AU8933001A - 3' genomic promoter region and polymerase gene mutations responsible for attenuation in viruses of the order designated mononegavirales - Google Patents

Description

S&FRef: 457034D1

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

ORIGINAL

Name and Address of Applicants: American Cyanamid Company Five Giralda Farms Madison New Jersey 07940 United States of America a Actual Inventor(s): Address for Service: The Government of the United States of America as represented by The Department of Health and Human Services Suite 325 6011 Executive Boulevard Rockville Maryland 20852 United States of America Stephen A. Udem, Mohinderjit S. Sidhu, Joanne M.

Tatem, Brian R. Murphy, Valerie B. Randolph Spruson Ferguson St Martins Tower,Level 31 Market Street Sydney NSW 2000 (CCN 3710000177) 3' Genomic Promoter Region and Polymerase Gene Mutations Responsible for Attenuation in Viruses of the Order Designated Mononegavirales Invention Title: 0* The following statement is a full description of this invention, including the best method of performing it known to me/us:- Documents rcceived on: L 8 OV 2001 Batch No: 5845c

I

3' GENOMIC PROMOTER REGION AND POLYMERASE

GENE

MUTATIONS RESPONSIBLE FOR ATTENUATION IN VIRUSES OF THE ORDER DESIGNATED

MONONEGAVIRALES

Field Of The Invention This invention relates to isolated, recombinantly-generated, attenuated, nonsegmented, negative-sense, single stranded RNA viruses of the Order designated Mononegavirales having at least one attenuating mutation in the 3' genomic promoter region and having at least one attenuating mutation in the RNA polymerase gene. This invention was made with Government support under a grant awarded by the Public Health Service. The Government has certain rights in the invention.

Background Of The Invention 20 20 Enveloped, negative-sense, single stranded •RNA viruses are uniquely organized and expressed. The genomic RNA of negative-sense, single stranded viruses serves two template functions in the context of a nucleocapsid: as a template for the synthesis of 25 messenger RNAs (mRNAs) and as a template for the synthesis of the antigenome strand. Negativesense, single stranded RNA viruses encode and package their own RNA dependent RNA Polymerase. Messenger RNAs are only synthesized once the virus has been uncoated 30 in the infected cell. Viral replication occurs after synthesis of the mRNAs and requires the continuous synthesis of viral proteins. The newly synthesized antigenome strand serves as the template for generating further copies of the strand genomic

RNA.

2 The polymerase complex actuates and achieves transcription and replication by engaging the cisacting signals at the 3' end of the genome, in particular, the promoter region. Viral genes are then transcribed from the genome template unidirectionally from its 3' to its 5' end. There is always less mRNA made from the downstream genes the polymerase gene relative to their upstream neighbors the nucleoprotein gene Therefore, there is always a gradient of mRNA abundance according to the position of the genes relative to the 3'-end of the genome.

Based on the revised reclassification in 1993 by the International Committee on the Taxonomy of Viruses, an Order, designated Mononegavirales, has been established. This Order contains three families of enveloped viruses with single stranded, nonsegmented RNA genomes of minus polarity (negative-sense). These families are the Paramyxoviridae, Rhabdoviridae and :oo. Filoviridae. The family Paramyxoviridae has been further divided into two subfamilies, Paramyxovirinae and Pneumovirinae. The subfamily Paramyxovirinae contains three genera, Paramyxovirus, Rubulavirus and Morbillivirus. The subfamily Pneumovirinae contains the genus Pneumovirus.

The new classification is based upon morphological criteria, the organization of the viral genome, biological activities and the sequence relationships of the proteins. The morphological distinguishing feature among enveloped viruses for the S 30 subfamily Paramyxovirinae is the size and shape of the nucleocapsids (diameter 18mm, Imm in length, pitch of nm), which have a left-handed helical symmetry. The biological criteria are: 1) antigenic cross-reactivity between members of a genus, and 2) the presence of neuraminidase activity in the genera Paramyxovirus, 3 Rubulavirus and its absence in genus Mooillivirus. In addition, variations in the coding potential of the P gene are considered, as is the presence of an extra gene (SH) in Rubulaviruses.

Pneumoviruses can be distinguished from Paramyxovirinae morphologically because they contain narrow nucleocapsids. In addition, pneumoviruses have major differences in the number of protein-encoding cistrons (10 in pneumoviruses versus 6 in Paramyxovirinae) and an attachment protein that is very different from that of Paramyxovirinae. Although the paramyxoviruses and pneumoviruses have six proteins that appear to correspond in function P, M, G/H/HN, F and only the latter two proteins exhibit significant sequence relatedness between the two subfamilies. Several pneumoviral proteins lack counterparts in most of the paramyxoviruses, namely the nonstructural proteins NS1 and NS2, the small hydrophobic protein SH, and a second protein M2. Some S. 20 paramyxoviral proteins, namely C and V, lack counterparts in pneumoviruses. However, the basic genomic organization of pneumoviruses and paramyxoviruses is the same. The same is true of rhabdoviruses and filoviruses. Table 1 presents the current taxonomical classification of these viruses, together with examples of each genus.

Table 1 Classification of Nonsegmented, negative-sense, single stranded RNA Viruses of the Order Mononegavirales Family Paramvxoviridae Subfamily Paramyxovirinae Genus Paramyxovirus Sendai virus (mouse parainfluenza virus type 1) 4 Human parainfluenza virus (PIV) types 1 and 3 Bovine parainfluenza virus (BPV) type 3 Genus Rubulavirus Simian virus 5 (SV) (Canine parainfluenza virus type 2) Mumps virus Newcastle disease virus (NDV) (avian Paramyxovirus 1) Human parainfluenza virus types 2, 4a and 4b Genus Morbillivirus Measles virus (MV) Dolphin Morbillivirus Canine distemper virus (CDV) Peste-des-petits-ruminants virus Phocine distemper virus Rinderpest virus SSubfamily Pneumovirinae 20 Genus Pneumovirus Human respiratory syncytial virus (RSV) Bovine respiratory syncytial virus Pneumonia virus of mice Turkey rhinotracheitis virus Family Rhabdoviridae Genus Lyssavirus Rabies virus Genus Vesiculovirus Vesicular stomatitis virus Genus Ephemerovirus Bovine ephemeral fever virus Family Filovirdae Genus Filovirus Marburg virus 5 For many of these viruses, no vaccines of any kind are available. Thus, there is a need to develop vaccines against such human and animal pathogens. Such vaccines would have to elicit a protective immune response in the recipient. The qualitative and quantitative features of such a favorable response are extrapolated from those seen in survivors of natural virus infection, who, in general, are protected from reinfection by the same or highly related viruses for some significant duration thereafter.

A variety of approaches can be considered in seeking to develop such vaccines, including the use of: purified individual viral protein vaccines (subunit vaccines); inactivated whole virus preparations; and live, attenuated viruses.

Subunit vaccines have the desirable feature of being pure, definable and relatively easily produced in abundance by various means, including recombinant Oo.DNA expression methods. To date, with the notable 9* e 20 exception of hepatitis B surface antigen, viral subunit •vaccines have generally only elicited short-lived and/or inadequate immunity, particularly in naive recipients.

"Formalin inactivated whole virus preparations of polio (IPV) and hepatitis A have proven safe and :efficacious. In contrast, immunization with similarly inactivated whole viruses such as respiratory syncytial virus and measles virus vaccines elicited unfavorable immune responses and/or response profiles which predisposed vaccinees to exaggerated or aberrant disease when subsequently confronted with the natural or "wild-type" virus.

Early attempts (1966) to vaccinate young children using a parenterally administered formalininactivated RSV vaccine. Unfortunately, several field 6 trials of this vaccine revealed serious adverse reactions the development of a severe illness with unusual features following subsequent natural infection with RSV (Bibliography entries It has been suggested that this formalinized RSV antigen elicited an abnormal or unbalanced immune response profile, predisposing the vaccinee to RSV disease Thereafter, live, attenuated RSV vaccine candidates were generated by cold passage or chemical mutagenesis. These RSV strains were found to have reduced virulence in seropositive adults.

Unfortunately, they proved either over or underattenuated when given to seronegative infants; in some cases, they also were found to lack genetic stability Another vaccination approach using parenteral administration of live virus was ineffective and efforts along this line were discontinued Notably, these live RSV vaccines were never associated S: with disease enhancement as observed with the formalin- .20 inactivated RSV vaccine described above. Currently, there are no RSV vaccines approved for administration to humans, although clinical trials are now in progress with cold-passaged, chemically mutagenized strains of RSV designated A2 and B-l.

Appropriately attenuated live derivatives of wild-type viruses offer a distinct advantage as vaccine candidates. As live, replicating agents, they initiate infection in recipients during which viral gene products are expressed, processed and presented in the 30 context of the vaccinee's specific MHC class I and II molecules, eliciting humoral and cell-mediated immune responses, as well as the coordinate cytokine patterns, which parallel the protective immune profile of survivors of natural infection.

7 This favorable immune response pattern is contrasted with the delimited responses elicited by inactivated or subunit vaccines, which typically are largely restricted to the humoral immune surveillance arm. Further, the immune response profile elicited by some formalin inactivated whole virus vaccines, e.g., measles and respiratory syncytial virus vaccines developed in the 1960's, have not only failed to provide sustained protection, but in fact have led to a predisposition to aberrant, exaggerated, and even fatal illness, when the vaccine recipient later confronted the wild-type virus.

While live, attenuated viruses have highly desirable characteristics as vaccine candidates, they have proven to be difficult to develop. The crux of the difficulty lies in the need to isolate a derivative of the wild-type virus which has lost its diseaseproducing potential virulence), while retaining sufficient replication competence to infect the 20 recipient and elicit the desired immune response o profile in adequate abundance.

Historically, this delicate balance between virulence and attenuation has been achieved by serial S• passage of a wild-type viral isolate through different 25 host tissues or cells under varying growth conditions (such as temperature) This process presumably favors oo 0 the growth of viral variants (mutants), some of which have the favorable characteristic of attenuation.

Occasionally, further attenuation is achieved through 30 chemical mutagenesis as well.

This propagation/passage scheme typically leads to the emergence of virus derivatives which are temperature sensitive, cold-adapted and/or altered in their host range one or all of which are changes 8 from the wild-type, disease-causing viruses i.e., changes that may be associated with attenuation.

Several live virus vaccines, including those for the prevention of measles and mumps (which are paramyxoviruses), and for protection against polio and rubella (which are positive strand RNA viruses), have been generated by this approach and provide the mainstay of current childhood immunization regimens throughout the world.

Nevertheless, this means for generating attenuated live virus vaccine candidates is lengthy and, at best, unpredictable, relying largely on the selective outgrowth of those randomly occurring genomic mutants with desirable attenuation characteristics.

The resulting viruses may have the desired phenotype in vitro, and even appear to be attenuated in animal models. However, all too often they remain either under- or overattenuated in the human or animal host for whom they are intended as vaccine candidates.

20 Even as to current vaccines in use, there is still a need for more efficacious vaccines. For example, the current measles vaccines provide reasonably good protection. However, recent measles epidemics suggest deficiencies in the efficacy of 25 current vaccines. Despite maternal immunization, high rates of acute measles infection have occurred in children under age one, reflecting the vaccines, inability to induce anti-measles antibody levels comparable to those developed following wild-type 30 measles infection As a result, vaccineimmunized mothers are less able to provide their infants with sufficient transplacentally-derived passive antibodies to protect the newborns beyond the first few months of life.

9 Acute measles infections in previously immunized adolescents and young adults point to an additional problem. These secondary vaccine failures indicate limitations in the current vaccines' ability to induce and maintain antiviral protection that is both abundant and long-lived (11,12,13). Recently, yet another potential problem was revealed. The hemagglutinin protein of wild-type measles isolated over the past 15 years has shown a progressively increasing distance from the vaccine strains (14).

This "antigenic drift" raises legitimate concerns that the vaccine strains may not contain the ideal antigenic repertoire needed to provide optimal protection. Thus, there is a need for improved vaccines.

Rational vaccine design would be assisted by a better understanding of these viruses, in particular, by the identification of the virally encoded determinants of virulence as well as those genomic *changes which are responsible for attenuation.

Summary Of The Invention Accordingly, it is an object of this invention to identify those regions of the genome of the RNA viruses of the Order Mononegavirales where mutations result in attenuation of those viruses.

It is a further object of this invention to produce recombinantly-generated viruses which incorporate such attenuating mutations in their genomes.

It is still a further object of this invention to formulate vaccines containing such attenuated viruses.

These and other objects of the invention as discussed below are achieved by the generation and 10 isolation of recombinantly-generated, attenuated, nonsegmented, negative-sense, single stranded RNA viruses of the Order Mononegavirales having at least one attenuating mutation in the 3' genomic promoter region and having at least one attenuating mutation in the RNA polymerase gene.

In the case of measles virus, at least one attenuating mutation in the 3' genomic promoter region is selected from the group consisting of nucleotide 26 (A nucleotide 42 (A T or A C) and nucleotide 96 (G where these nucleotides, as well as others delineated in this application (unless stated otherwise), are presented in positive strand, antigenomic, that is, message (coding) sense, and at least one attenuating mutation in the RNA polymerase gene is selected from the group consisting of nucleotide changes which produce changes in an amino acid selected from the group consisting of residues 331 (isoleucine threonine), 1409 (alanine threonine), 20 1624 (threonine alanine), 1649 (arginine methionine), 1717 (aspartic acid alanine), 1936 (histidine tyrosine), 2074 (glutamine arginine) and 2114 (arginine lysine) In the case of human parainfluenza virus type 3, at least one attenuating mutation in the 3' genomic promoter region is selected from the group consisting of nucleotide 23 (T nucleotide 24 (C -4 T), nucleotide 28 (G T) and nucleotide 45 (T and at least one attenuating mutation in the RNA polymerase 30 gene is selected from the group consisting of nucleotide changes which produce changes in an amino acid selected from the group consisting of residues 942 (tyrosine histidine), 992 (leucine 11 phenylalanine) ;and 155 8 (threonine isoleucine) In the case of human respiratory syncytial virus subgroup B, at least one attenuating mutation in the 31 genomic promoter region is selected from the group consisting of nucleotide 4 (C -4 G) and the insercion, of an additional A in the stretch of A's at nucleotides 6-11, and at least one attenuating mutation in the RNA polymerase gene is selected from the group consisting of nucleotide changes which produce changen in an amino acid selected from the group consisting of residues 353 (arginine -4 lysinle) 451 (lysine arginine) 1229 (aspartic acid -4 asparagine) 2029 (threonine -4 isoleucine) and 2050 (asparagine aspartic acid).

In another embodiment of this invention, attenuated virus is used to prepare vaccines which elicit a protective immune response against the wildtype form of the virus.

In yet another embodiment of this invention, an isolated, positive strand, antigenomic message sense nucleic acid molecule (or an isolated, negative strand *genomic sense nucleic acid molecule) having the complete viral nucleotide sequence (whether of wildtype virus or virus attenuated by non-recombinant means) is manipulated by introducing one or more of the attenuating mutations described in this application to generate an isolated, recombinant2.y-generate~d attenuated virus. This virus is then uned to prepare vaccines wh~ich elicit a protective immune response against the wild-type form of the virus.

Xn still another embodiment of this invention, such a complete wild-type or vaccine viral nucleotide sequence in used: to design PCR primers for use in a PCR assay to detect the presence of the 12 corresponding virus in a sample; or to design and select peptides for use in an ELISA to detect the presence of the corresponding virus in a sample.

Brief Description Of The Fiqures Figure 1 depicts the passage history of the Edmonston measles virus The abbreviations have the following meanings: HK human kidney; HA human amnion; CE(am) chick embryo; CEF chick embryo fibroblast; DK dog kidney; WI-38 human diploid cells; SK sheep kidney; plaque cloning. The number following each abbreviation represents the number of passages.

Figure 2 depicts a map of the measles virus genome showing putative cis-acting regulatory elements at and near the genome and antigenome termini. Top a schematic map of the measles virus genome, beginning at the 3' end with 52 nucleotides of leader sequence (1) 20 and ending at the 5' terminus with 37 nucleotides of trailer sequence Gene boundaries are denoted by 99"" vertical bars; below each gene is the number of cistronic nucleotides. Bottom an expanded schematic 9 9. view of the 3' extended genomic promoter regions of genome and antigenome, showing the position and sequence of the two highly conserved domains, A and B.

0" The intervening intergenic trinucleotide is denoted as o* well. Nascent 5' RNAs encompassing the A' to B' regions are presumed to contain the regulatory sequence 30 at which the N protein encapsidation initiates.

Figure 3 depicts a genetic map of the RSV subgroup B wild-type strains designated 2B and 18537 (top portion), the intergenic sequences of those strains (middle portion) and the 68 nucleotide overlap between the M2 and L genes (bottom portion). The RSV 13 2B stain has six fewer nucleotides in the G gene, encoding two fewer amino acid residues in the G protein, as compared to the 18537 strain. The 2B strain has 145 nucleotides in the 5' trailer region, as compared to 149 nucleotides in the 18537 strain. The 2B strain has one more nucleotide in each of the NS-1, NS-2 and N genes, and one fewer nucleotide in each of the M and F genes, as compared to the 18537 strain.

Detailed Description Of The Invention Transcription and replication of negativesense, single stranded RNA viral genomes are achieved through the enzymatic activity of a multimeric protein acting on the ribonucleoprotein core (nucleocapsid).

Naked genomic RNA cannot serve as a template. Instead, these genomic sequences are recognized only when they are entirely encapsidated by the N protein into the I* nucleocapsid structure. It is only in that context :0 20 that the genomic and antigenomic terminal promoter g" "sequences are recognized to initiate the transcriptional or replication pathways.

All paramyxoviruses require the two viral g*o proteins, L and P, for these polymerase pathways to o 25 proceed. The pneumoviruses, including RSV, also require the transcription elongation factor, M2, for the transcriptional pathway to proceed efficiently.

Additional cofactors may also play a role, including perhaps the virus-encoded NS1 and NS2 proteins, as well 30 as perhaps host-cell encoded proteins.

However, considerable evidence indicates that it is the L protein which performs most, if not all, the enzymatic processes associated with transcription and replication, including initiation, and termination of ribonucleotide polymerization, capping and 14 polyadenylation of mRNA transcripts, methylation and perhaps specific phosphorylation of P proteins. The L protein's central role in genomic transcription and replication is supported by its large size, sensitivity to mutations, and its catalytic level of abundance in the transcriptionally active viral complex (16).

These considerations led to the proposal that L proteins consist of a linear array of domains whose concatenated structure integrates discrete functions Indeed, three such delimited, discrete elements within the negative-sense virus L protein have been identified based on their relatedness to defined functional domains of other well-characterized proteins. These include: a putative RNA template 15 recognition and/or phosphodiester bond formation domain; an RNA binding element; and an ATP binding domain. All prior studies of L proteins of nonsegmented negative-sense, single stranded

RNA

viruses have revealed these putative functional elements (17).

e Without being bound by the following, it is reasonable to presume that these non-protein coding, promoter and other cis-acting genomic regulatory domains are important determinants of the efficiency 25 with which transcription and replication by measles virus (MV) and other viruses of the Order Mononegavirales are actualized, in association with the L protein, and that they may therefore be virulence determinants for these viruses as well.

In summary, the invention is believed to encompass a coordinate set of changes between the cisacting regulatory signal genomic promoter region) and the polymerase gene which results in attenuation of the virus while retaining sufficient ability of the virus to replicate. Attenuation is 15 optimized by rational mutations of the 3' genomic promoter region and the polymerase gene, which provide the desired balance of replication efficiency: so that the virus vaccine is no longer able to produce disease, yet retains its capacity to infect the vaccinee's cells, to express sufficiently abundant gene products to elicit the full spectrum and profile of desirable immune responses, and to reproduce and disseminate sufficiently to maximize the abundance of the immune response elicited.

Without being bound by the following, attenuating mutations in the extended promoter (3' genomic promoter region) and in the polymerase gene are believed to affect the display of cis-acting signals 15 and the conformation of the polymerase complex engaging S: these signals. For example, when encapsidated, the Se promoter RNA is coiled in a helical array. Changes in oe e promoter sequence may affect the relative positions at which the conserved signals are displayed relative to one another. Specifically, the measles wild-type 3' genomic promoter region has a pyrimidine (uracil) at positions 26 and 42 (the antigenomic message sense sequences have the purine adenine). The vaccine strains have purines at those positions (the 25 antigenomic message sense sequences have the corresponding pyrimidines; see Table 3 in Example 1 below). The larger purines may change the distance and/or angular display between the conserved domains of the promoter in measles, positions 1-11 and 87- 98), resulting in an altered spatial presentation of the cis-acting signals to the polymerase.

Animal studies have demonstrated a decrease in viral replication sufficient to avoid illness but adequate to elicit the desired immune response. This likely represents a decrease in transcription, a 16 decrease in gene expression of virally encoded proteins, a decrease in antisense templates and, therefore, the production of fewer new genomes. The resulting attenuated viruses are significantly less virulent than the wild-type.

The attenuating mutations described herein may be introduced into viral strains by two methods: Conventional means such as chemical mutagenesis during virus growth in cell cultures to which a chemical mutagen has been added, selection of virus that has been subjected to passage at suboptimal temperature in order to select temperature sensitive and/or cold adapted mutations, identification of mutant virus that produce small plaques in cell culture, and 15 passage through heterologous hosts to select for host .range mutations. These viruses are then screened for e.e\ .attenuation of their biological activity in an animal model. Attenuated viruses are subjected to nucleotide sequencing of their 3' genomic promoter region and polymerase genes to locate the sites of attenuating o mutations. Once this has been done, method is then •carried out.

A preferred means of introducing ee: attenuating mutations comprises making predetermined 25 mutations using site-directed mutagenesis. These mutations are identified either by method or by reference to closely-related viruses whose attenuating mutations are already known. One or more mutations are introduced into each of the 3' genomic promoter region and the polymerase gene. Cumulative effects of different combinations of coding and non-coding changes can also be assessed.

The mutations to the 3' genomic promoter region and polymerase gene are introduced by standard recombinant DNA methods into a DNA copy of the viral 17 genome. This may be a wild-type or a modified viral genome background (such as viruses modified by method thereby generating a new virus. Infectious clones or particles containing these attenuating mutations are generated using the cDNA "rescue" system, which has been applied to a variety of viruses, including Sendai virus measles virus (19); respiratory syncytial virus rabies (21); vesicular stomatitis virus (VSV) and rinderpest virus these references are hereby incorporated by reference. See, for measles virus rescue, published International patent application WO 97/06270, designating the United States for PIV-3 rescue, U.S. provisional patent application 60/047575 for 15 RSV rescue, published International patent application S: WO 97/12032, designating the United States these applications are hereby incorporated by reference.

Oe Briefly, all Mononegavirales rescue systems can be summarized as follows: Each requires a cloned DNA equivalent of the entire viral genome placed between a suitable DNA-dependent RNA polymerase promoter the T7 RNA polymerase promoter) and a self-cleaving ribozyme sequence the hepatitis delta ribozyme) which is inserted into a propagatable S* 25 bacterial plasmid. This transcription vector provides the readily manipulable DNA template from which the RNA polymerase T7 RNA polymerase) can faithfully transcribe a single-stranded RNA copy of the viral antigenome (or genome) with the precise, or nearly precise, 5' and 3' termini. The orientation of the viral genomic DNA copy and the flanking promoter and ribozyme sequences determine whether antigenome or genome RNA equivalents are transcribed. Also required for rescue of new virus progeny are the virus-specific trans-acting proteins needed to encapsidate the naked, 18 single-stranded viral antigenome or genome RNA transcripts into functional nucleocapsid templates: the viral nucleocapsid (N or NP) protein, the polymerase-associated phosphoprotein and the polymerase protein. These proteins comprise the active viral RNA-dependent RNA polymerase which must engage this nucleocapsid template to achieve transcription and replication.

The trans-acting proteins required for measles virus rescue are the encapsidating protein

N,

and the polymerase complex proteins, P and L. For PIV- 3, the encapsidating protein is designated NP, and the polymerase complex proteins are also referred to as P and L. For RSV, the virus-specific trans-acting 15 proteins include N, P and L, plus an additional protein, M2, the RSV-encoded transcription elongation factor.

Typically, these viral trans-acting proteins are generated from one or more plasmid expression vectors encoding the required proteins, although some Sor all of the required trans-acting proteins may be produced within mammalian cells engineered to contain and express these virus-specific genes and gene o*e: products as stable transformants.

25 The typical (although not necessarily exclusive) circumstances for rescue include an appropriate mammallian cell milieu in which T7 polymerase is present to drive transcription of the antigenomic (or genomic) single-stranded RNA from the viral genomic cDNA-containing transcription vector.

Either cotranscriptionally or shortly thereafter, this viral antigenome (or genome) RNA transcript is encapsidated into functional templates by the nucleocapsid protein and engaged by the required polymerase components produced concurrently from co- 19 transfected expression plasmids encoding the required virus-specific trans-acting proteins. These events and processes lead to the prerequisite transcription of viral mRNAs, the replication and amplification of new genomes and, thereby, the production of novel viral progeny, rescue.

For the rescue of rabies, VSV and Sendai, T7 polymerase is provided by recombinant vaccinia virus VTF7-3. This system, however, requires that the rescued virus be separated from the vaccinia virus by physical or biochemical means or by repeated passaging in cells or tissues that are not a good host for poxvirus. For MV cDNA rescue, this requirement is avoided by creating a cell line that expresses T7 15 polymerase, as well as viral N and P proteins. Rescue is achieved by transfecting the genome expression vector and the L gene expression vector into the helper cell line. Advantages of the host-range mutant of the vaccinia virus, MVA-T7, which expresses the T7 RNA polymerase, but does not replicate in mammalian cells, 'i .e are exploited to rescue RSV, Rinderpest virus and MV.

After simultaneous expression of the necessary encapsidating proteins, synthetic full length antigenomic viral RNA are encapsidated, replicated and S 25 transcribed by viral polymerase proteins and replicated genomes are packaged into infectious virions. In addition to such antigenomes, genome analogs have now *been successfully rescued for Sendai and PIV-3 (25,27).

The rescue system thus provides a composition which comprises a transcription vector comprising an isolated nucleic acid molecule encoding a genome or antigenome of a nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales having at least one attenuating mutation in the 3' genomic promoter region and having at least one attenuating 20 mutation in the RNA polymerase gene, together with at least one expression vector which comprises at least one isolated nucleic acid molecule encoding the transacting proteins necessary for encapsidation, transcription and replication N, P and L for measles virus; NP, P and L for PIV-3; N, P, L and M2 for RSV). Host cells are then transformed or transfected with the at least two expression vectors just described. The host cells are cultured under conditions which permit the co-expression of these vectors so as to produce the infectious attenuated virus.

The rescued infectious virus is then tested for its desired phenotype (temperature sensitivity, 1 5 cold adaptation, plaque morphology, and transcription and replication attenuation), first by in vitro means.

The mutations at the cis-acting 3' genomic promoter region are also tested using the minireplicon system where the required trans-acting encapsidation and polymerase activities are provided by wild-type or vaccine helper viruses, or by plasmids expressing the N, P and different L genes harboring gene-specific attenuating mutations (19,28).

If the attenuated phenotype of the rescued 25 virus is present, challenge experiments are conducted with an appropriate animal model. Non-human primates provide the preferred animal model for the pathogenesis of human disease. These primates are first immunized with the attenuated, recombinantly-generated virus, then challenged with the wild-type form of the virus.

Monkeys are infected by various routes, including but not limited to intranasal, intratracheal or subcutaneous routes of inoculation (29).

Experimentally infected rhesus and cynomolgus macaques have also served as animal models for studies of 21 vaccine-induced protection against measles Protection is measured by such criteria as disease signs and symptoms, survival, virus shedding and antibody titers. If the desired criteria are met, the attenuated, recombinantly-generated virus is considered a viable vaccine candidate for testing in humans. The "rescued" virus is considered to be "recombinantlygenerated", as are the progeny and later generations of the virus, which also incorporate the attenuating mutations.

Even if a "rescued virus is underattenuated or overattenuated relative to optimum levels for vaccine use, this is information which is valuable for developing such optimum strains.

15 Optimally, a codon containing an attenuating point mutation may be stabilized by introducing a second or a second plus a third mutation in the codon without changing the amino acid encoded by the codon bearing only the attenuating point mutation.

Infectious virus clones containing the attenuating and .stabilizing mutations are also generated using the cDNA "rescue" system described above.

Measles virus serves as a useful model for this invention, because sequence data are now available 25 as described herein for the disease-causing wild-type virus and for the disease-preventing vaccines which have a demonstrated history of efficacy.

Measles virus was first isolated in tissue culture in 1954 (31) from an infected patient named David Edmonston. This Edmonston strain of measles became the progenitor for many live-attenuated measles vaccines including Moraten, which is the current vaccine in the United States (Attenuvax'M; Merck Sharp Dohme, West Point, PA) and was licensed in 1968 and has proven to be efficacious.

22 Aggressive immunization programs instituted in the mid to late 1960s resulted in the precipitous drop in reported measles cases from near 700,000 in 1965 to 1500 in 1983. In parallel, other vaccine strains were also developed from the Edmonston strain (see Fig. Schwarz (Institut Merieux, Lyon, France), Zagreb (Zagreb, Yugoslavia) and AIK-C (Japan). These other vaccines have also proven to be efficacious and have been used extensively. An early, reactogenic, underattenuated vaccine strain (RubeovaxM: Merck Sharp Dohme) produced measles-like illness in children and its use thus was discontinued. It, however, was further attenuated successfully to produce the Moraten vaccine strain (see Fig. 1) Live measles virus 15 vaccine provides a success story of the development of an efficacious vaccine and provides a model for understanding the molecular mechanisms of viral vaccine attenuation among nonsegmented, negative-sense, single stranded RNA viruses.

Because of its significance as a major cause of human morbidity and mortality, measles virus (MV) has been quite extensively studied. MV is a large, relatively spherical, enveloped particle composed of S. two compartments, a lipoprotein membrane and a 25 ribonucleoprotein particle core, each having distinct biological functions The virion envelope is a ~host cell-derived plasma membrane modified by three virus-specified proteins: The hemagglutinin

(H;

approximately 80 kilodaltons and fusion (F 1 2 approximately 60 kD) glycoproteins project on the virion surface and confer host cell attachment and entry capacities to the viral particle (16).

Antibodies to H and/or F are considered protective since they neutralize the virus' ability to initiate infection (34,35,36). The matrix approximately 37 23 kD) protein is the amphipathic protein lining the membrane's inner surface, which is thought to orchestrate virion morphogenesis and thus consummate virus reproduction The virion core contains the 15,894 nucleotide long genomic RNA upon which template activity is conferred by its intimate association with approximately 2600 molecules of the approximately 60 kD nucleocapsid protein (38,39,40). Loosely associated with this approximately one micron long helical ribonucleoprotein particle are enzymatic levels of the viral RNA dependent RNA polymerase

(L;

approximately 240 kD) which in concert with the polymerase cofactor approximately 70 kD), and perhaps yet other virus-specified as well as 15 host-encoded proteins, transcribes and replicates the MV genome sequences (41).

To date, the entire nucleotide sequences (only for the Edmonston B laboratory strain and the AIK-C vaccine strain), coding potential, and organization of the MV genome have been reported (33).

The six virion structural proteins are encoded by six contiguous, non-overlapping genes which are arrayed as follows: Two additional MV gene products of as yet uncertain function have also been 25 identified. These two nonstructural proteins, known as C (approximately 20 kD) and V (approximately 45 kD), are both encoded by the P gene, the former by a second reading frame within the P mRNA; the latter by a cotranscriptionally edited P gene-derived mRNA which encodes a hybrid protein having the amino terminal sequences of P and a new zinc finger-like cysteine-rich carboxy terminal domain (16).

In addition to the sequences encoding the virus-specified proteins, the MV genome contains distinctive non-protein coding domains resembling those 24 directing the transcriptional and replicative pathways of related viruses (16,42). These regulatory signals lie at the 3' and 5' ends of the MV genome and in short internal regions spanning each intercistronic boundary.

The former encode the putative promoter and/or regulatory sequence elements directing genomic transcription, genome and antigenome encapsidation, and replication. The latter signal transcription termination and polyadenylation of each monocistronic viral mRNA and then reinitiation of transcription of the next gene. In general, the MV polymerase complex appears to respond to these signals much as the RNA-dependent RNA polymerases of other non-segmented negative strand RNA viruses (16,42,43,44).

1 5 Transcription initiates at or near the 3' end of the MV genome and then proceeds in a 5' direction producing monocistronic mRNAs (40,42,45). As the polymerase traverses the MV genomic template, it encounters putative stop/start signals which, in 3' to 5' order, are: a semi-conserved transcription termination/polyadenylation signal (A/G U/C UA A/U NN

A

4 where N may be any of the four bases) at which each monocistronic RNA is completed; a non-transcribed intergenic trinucleotide punctuation mark (CUU; except 25 at the H:L boundary where it is CGU); and a semiconserved start signal for transcription initiation of the next gene (AGG A/G NN C/A A A/G G A/U, where N may be any of the four bases) (45,46). Since some polymerase complexes fail to reinitiate, the abundance of each MV mRNA diminishes in parallel with the distance of the encoding gene from the genomic 3' end.

This mRNA gradient directly corresponds to the relative abundance of each virus-specified protein. This indicates that MV protein expression is ultimately controlled at the transcriptional level (44).

25 The 3' and 5' MV genomic termini contain non-protein coding sequences with distinct parallels to the leader and trailer RNA encoding regions of VSV Nucleotides 1-55 define the region between the genomic 3' terminus and the beginning of the N gene, while 37 additional nucleotides can be found between the end of the L gene and the 5' terminus of the genome. However, unlike VSV, or even the paramyxoviruses Sendai and NDV, MV does not transcribe these terminal regions into short, unmodified or sense leader RNAs (47,48,49). Instead, leader readthrough transcripts, including full-length polyadenylated leader:N, leader:N:P, leader:N:P:M, and of course full-length antigenome MV RNAs are 1 5 transcribed (48,49). Thus, the short leader transcript, the key operational element determining the switch from transcription to replication of the VSV single-stranded, negative polarity genome (50,51,52), seems absent in MV. This leads to consideration and exploration of alternative models for this crucial reproductive event (42).

Measles virus, as well as all other Mononegavirales except the rhabdoviruses, appears to have extended its terminal regulatory domains beyond 25 the confines of leader and trailer encoding sequences For measles, these regions encompass the 107 3' ~genomic nucleotides (the genomic promoter region", also referred to as the "extended promoter", which comprises 52 nucleotides encoding the leader region, followed by three intergenic nucleotides, and 52 nucleotides encoding the 5' untranslated region of N mRNA) and the 109 5' end nucleotides (69 encoding the 3' untranslated region of L mRNA, the intergenic trinucleotide and 37 nucleotides encoding the trailer).

Within these 3' terminal approximately 100 nucleotides 26 of both the genome and antigenome are two short regions of shared nucleotide sequence: 14 of 16 nucleotides at the absolute 3' ends of the genome and antigenome are identical. Internal to those termini, an additional region of 12 nucleotides of absolute sequence identity have been located. Their position at and near the sites at which the transcription of the MV genome must initiate and replication of the antigenome must begin, suggests that these short unique sequence domains encompass an extended promoter region.

These discrete sequence elements may dictate alternative sites of transcription initiation the internal domain mandating transcription initiation at the N gene start site, and the 3' terminal domain 15 directing antigenome production (42,48,53). In addition to their regulatory role as cis-acting determinants of transcription and replication, these 3' extended genomic and antigenomic promoter regions encode the nascent 5' ends of antigenome and genome RNAs, respectively. Within these nascent RNAs reside as yet unidentified signals for N protein nucleation, another key regulatory element required for nucleocapsid template formation and consequently for amplification of transcription and replication. Figure 25 2 schematically shows the location and sequence of these highly conserved, putative cis-acting regulatory domains.

Terminal non-protein coding regions similar in location, size and spacing are present in the genomes of other members of the genus Paramyxoviridae, though only 8-11 of their absolute terminal nucleotides are shared by MV (42,54). The genomic terminii of the Morbillivirus canine distemper virus (CDV) displays a greater degree of homology with its MV relative: 73% of the nucleotides of the leader and trailer sequences 27 of these two viruses are identical, including 16 of 18 at the absolute 3' termini and 17 of 18 at their ends No accessory internal CDV genomic domainsharing homology to that of the MV extended promoter has been found. However, there is a 20 nucleotide long stretch lying between CDV genomic nucleotides 85 and 104 and 15,587 and 15,606 in which 15 of the nucleotides are complementary (Gene Bank accession number AF 14953). This indicates that CDV, like MV contains an additional region within its non-coding 3' genomic and antigenomic ends that may provide important cis-acting promoter and/or regulatory signals Additionally, the precise length of the 3'leader region (55 nucleotides) is identical among 1 5 several members of the Family Paramyxoviridae (MV, CDV, PIV-3, BPV-3, SV and NDV). Further evidence for the importance of these extended, non-protein coding regions comes from analyses of a large number of distinct copy-back Defective Interfering Viruses (DIs) recently cloned from subacute sclerosing panencephalitis (SSPE) brain tissue. No DI with a stem shorter than the 95 5' terminal genomic nucleotides was found. This indicates that the minimal signals needed for MV DI RNA replication and encapsidation extend well 25 beyond the 37 nucleotide long trailer sequence to encompass the additional internal putative regulatory domain (56).

As exemplified in part by measles virus, this invention is directed to the concept that important virulence/attenuation determinants reside in viral genomic non-protein coding regulatory regions and in the transacting transcription/replication enzyme complex with which these cis-acting elements must interact. The cis-acting domains are found both at the 3' and 5' ends of the MV genome, flanking the six 28 contiguous genes encoding viral structural proteins; and within the MV genome as short regions encompassing internal intergenic boundaries. The former encode the putative promoter and/or regulatory sequence elements directing the vital processes of genomic transcription, genome and antigenome encapsidation, and replication.

The latter signal transcription termination and polyadenylation of each monocistronic viral mRNA and then reinitiation of transcription of the next gene.

The transcription/replication enzyme, RNA dependent

RNA

polymerase molecule can modulate transcription and/or replicative efficiency, thereby determining the abundance of cytopathic viral gene products and/or virion progeny.

15 Proof of the concept of this invention for measles virus is obtained by first determining the nucleotide sequences of the non-coding regulatory regions genomic promoter region) and the coding regions of the L gene (with predicted amino acid sequences) of the progenitor Edmonston wild-type

MV

isolate, together with available measles vaccine strains derived from this isolate (see Figure 1).

Independent other wild-type isolates were examined for comparative purposes as well.

25 The nucleotide sequences (in positive strand, antigenomic, message sense) of four wild-type and five *00* vaccine measles strains, as well as the deduced amino acid sequences of the RNA polymerase (L protein) of these measles viruses, are set forth as follows with reference to the appropriate SEQ ID NOS. contained herein: 29 Virus Nucleotide Sequence L Protein Sequence Wild-Type Edmonston SEQ ID NO:1 SEQ ID NO:2 1977 SEQ ID NO:3 SEQ ID NO:4 1983 SEQ ID NO:5 SEQ ID NO:6 Montefiore SEQ ID NO:7 SEQ ID NO:8 Vaccine Rubeovaxm SEQ ID NO:9 SEQ ID Moraten SEQ ID NO:11 SEQ ID NO:12 Zagreb SEQ ID NO:13 SEQ ID NO:14 AIK-C SEQ ID NO:15 SEQ ID NO:16 Each measles virus genome listed above is 15 15,894 nucleotides in length. Translation of the L gene starts with the codon at nucleotides 9234-9236; the translation stop codon is at nucleotides 15783- 15785. The translated L protein is 2,183 amino acids long.

Note that nucleotide 2499 of 1983 wild-type measles virus is indicated as in SEQ ID NO:5. In fact, the base is actually a mixture of and Also note that nucleotide 2143 of RubeovaxM vaccine virus is indicated as in SEQ ID NO:9. In nine S 25 clones sequenced, this base was in seven and in two; thus, this base can be or In addition, the Schwarz vaccine virus genome is identical to that of the Moraten vaccine virus genome (SEQ ID NO:11), except that at nucleotides 4917 and 4924, Schwarz has a instead of a Nucleotide differences distinguishing the 3' genomic promoter region and nucleotide and amino acid differences distinguishing the L gene and L protein sequences of the Edmonston wild-type isolate, vaccine strains and other independently isolated wild-type 30 viruses were then compared and aligned (see Tables in Example 1 below).

As shown in Table 3, there were three mutations from the 3' genomic promoter region (in antigenomic, message sense) of the progenitor wild-type MV isolate and the derivative vaccine strains: At nucleotide position 26, from to at position 42, from to or from to and in the case of Zagreb only, at position 96, from to In addition, the other examined wild-type isolates differed from both the progenitor wild-type isolate and the vaccine strains at position 50 by having

"A"

instead of The predicted amino acid sequences of the L 15 genes of measles vaccine strains (Rubeovax', Moraten, Schwarz, AIK-C and Zagreb) and wild-type isolates (1977, 1983 and Montefiore), differ from the progenitor strain (Edmonston) at 49 positions in the 2183 amino acid long open reading frame (see Tables 4 and 5 in Example 1 below).

These amino acid differences can be divided into four categories: Positions where one vaccine strain :differs from the progenitor, as well as from other 25 vaccine and wild-type strains, suggesting a potential attenuation site.

Specific differences between all wildtype and all vaccine sequences; these may also constitute important attenuation sites.

3) Residues where chronologically newer wildtypes differ from older wild-types; which may be attributable to genetic drift.

Positions where one or more vaccine strains and/or wild-type strains have common amino acids and differ from all the other strains; these 31 changes may represent lineage-specific, potentially attenuating changes within the vaccine strains and relatedness among the wild-type isolates, respectively.

There were four category changes where one vaccine differed from the other vaccines, as well as the wild-type strains. Two of these were in Moraten and Schwarz (amino acids 331 and 2114) and two were in AIK-C (1624 and 2074). These mutations are of special interest because all of these viruses are good vaccines. Thus, these positions are sites for attenuation.

Only one position, 1717, fits into category with all wild-types having aspartic acid and all vaccines having alanine. Interestingly, this position 15 is in one of two areas where the L genes of measles and canine distemper virus (which are otherwise highly homologous) do not show exceptional conservation. This difference makes it more likely that 1717 is a key position for an attenuating mutation in measles.

There were five positions, 149, 636, 720, 2017 and 2119, where both chronologically newer wildtypes (1983 and Montefiore) differ from older wildtypes (Edmonston and 1977), which therefore fit into category These differences suggest genetic drift 25 rather than denoting sites of attenuating mutations.

Not included in this total are 16 positions where Montefiore (the 1989 isolate) differed from the rest (see Table These could be either genetic drift (category or random change (category The remaining 23 positions are category with one or more of the viruses differing from the consensus.

Three of these positions (1409, 1649, 1936) are potentially attenuating category mutations.

These are changes where two vaccine strains have a common change from the progenitor wild-type strain.

32 These changes may be connected with the vaccine lineage leading to the Rubeovax"T and Moraten vaccines (Figure 1).

Applicants have found that their AIK-C vaccine strain nucleotide sequence differs from the published sequence (33) at 21 positions, including one insertion and one deletion. Several of these differences result in coding changes including two in the L gene (at amino acids 1477 and 2008).

Thus, the additional changes accrued within the L gene sequence as the measles progenitor strain is progressively attenuated to achieve a replicative capacity optimized for live vaccine purposes appears to be constrained and delimited. Presumably, this limited 15 tolerance in the number and location of L gene changes is imposed not only by the need to preserve the multifunctional capacities of the polymerase, but also by the preexisting 3' promoter changes with which the evolving L protein must interact to achieve transcription and replication. In other words, optimal virus attenuation requires coordinate linked) changes in the polymerase protein and the cis-acting regulatory elements on which it acts.

The 3'-leader displays the least tolerance 25 for change, allowing highly selected changes during the attenuation process at nucleotide position 26 (always the change of from to and at position 42 (the change of from to or from to (in antigenomic, message sense). In the case of Zagreb only, there is a single further change, from to "A" at position 96, which may be important when combined with Zagreb L gene-specific changes. The 3'-leader region seems to have undergone only one instance of genetic drift since 1954, with a change of to "A" at position 50 (see Table 3) 33 The net change in the 3' genomic promoter region during the attenuation process is the replacement of two pyrimidines by two purines in genomic sense in all MV vaccine strains. The coevolution of the L gene during these attenuation processes is believed to reflect selection of subtle changes favoring reproduction of the viruses in different host cells. All the vaccine strains were grown in chick embryo (CE) or chick embryo fibroblast (CEF) cells during their attenuation process (Figure In addition, some vaccine strains have been exposed to unique host cells; Zagreb vaccine was grown in dog kidney cells and human diploid cells, while the AIK-C vaccine was adapted to sheep kidney 15 cells. Moraten and RubeovaxM were exclusively developed in CE and CEF.

Some of the lineage-specific L gene changes (position 1649 in Rubeovax'", Moraten and Schwarz vaccines and the change at position 1717 in all vaccines) represent a subset-of adaptations of the L gene to the 3 '-leader to modulate the transcription/replication processes for vaccine attenuation. Additionally, individual vaccine-specific changes (category may provide additional fine tune 25 modulation of virus replication/transcription for each vaccine strain.

Based on Table 3 and the foregoing discussion, the key attenuating mutations for the MV 3' genomic promoter region are nucleotide 26 (A T), nucleotide 42 (A or A C) and nucleotide 96 (G A) (in antigenomic, message sense).

Based on Table 4 and the foregoing discussion, the key attenuating sites for the L protein are as follows: amino acid residues 331 (isoleucine threonine), 1409 (alanine threonine), 1624 34 (threonine -+alanine), 1649 (arginine methionine), 1717 (aspartic acid alanine), 1936 (histidine tyrosine), 2074 (glutamine arginine) and 2114 (arginine lysine). It is understood that the nucleotide changes responsible for these amino acid changes are not limited to those set forth in Table 4 of Example 1 below; all changes in nucleotides which result in codons which are translated into these amino acids are within the scope of this invention.

Human parainfluenza virus type 3 (HPIV-3) is another nonsegmented, negative-sense, single stranded enveloped RNA virus. HPIV-3 belongs to the Family Paramyxoviridae (see Table The genome of HPIV-3 is 15,462 nucleotides long and encodes six non-overlapping 15 protein-encoding genes Five of the genes encode a single virion structural protein each, which are designated NP (corresponding to the N protein of MV), S. M, F, HN (hemagglutinin-neuraminidase) and L. The sixth mRNA encodes the P protein, and by an overlapping 5' proximal open reading frame (ORF) encodes the C protein, and by the RNA editing mechanism, also encodes the D protein.

Like MV, HPIV-3 consists of a 3 '-nonprotein coding leader region of 55 nucleotides, but unlike 25 measles (where it is 37 nucleotides), it has a 44 nucleotide long 5'-trailer region. The polymerase o*o transcribes the genome in a linear, sequential, startef stop manner which is guided by transcription signals in the RNA template.

Attempts to develop a live attenuated HPIV-3 vaccine by passaging the wild-type virus JS strain through cell culture at sub-optimal temperature has produced promising results Several "cold passage" (cp) mutants were isolated for evaluation from different passage levels of the JS strain. One such 35 mutant resulted from 45 serial passages and was designated This virus exhibited three interesting properties: cold adaptation the ability to replicate efficiently at the suboptimal temperature of temperature sensitivity inability to replicate in vitro at temperatures greater than or equal to 39°C; and small plaque morphology. This mutant appeared to be a promising vaccine candidate because: its ca, ts and small plaque phenotype is stable after passage in cell culture; its replication is restricted in both the upper and lower respiratory tract of hamsters; and it induced significant protection in hamsters against subsequent 15 challenge with wild-type HPIV-3 (58,59).

SEvaluation of this strain in the rhesus monkey showed the attenuation mutations in cp45 to be a combination of ts and non-ts mutations Subsequent evaluation in chimpanzees indicated that 20 cp45 appeared to be satisfactorily attenuated while still able to induce a high level of protection against wild-type virus challenge Later preliminary clinical evaluation of cp45 in seronegative human infants and small children suggested that this S 2 5 candidate vaccine strain is suitably infectious and attenuated, as well as being moderately immunogenic (61).

The cp45 strain has been grown in both fetal rhesus lung (FRhL) and Vero cells as follows: The PIV- 3 cp45 virus grown in FRhL cells was prepared by inoculating confluent FRhL cell monolayers in tissue culture flasks at an MOI 0.1-1.0. The infected cell cultures were fed with EMEM medium and incubated at 32 0 C. About seven days later, when maximal cytopathic effects (synctyia) were observed, the virus was 36 harvested by subjecting the cultures to one freeze-thaw cycle, pooling the fluids and then storing the virus at oC.

The PIV-3 cp45 virus grown in Vero cells was prepared by inoculating with virus a bioreactor culture of confluent monolayers of Vero cells on microcarrier beads which was continuously stirred. The infected bioreactor culture was maintained at 30°C. The virus was harvested 4-5 days later when syncytial CPE was observed. The culture fluid containing the virus was stored at -70 °C.

The nucleotide sequences (in positive strand, antigenomic, message sense) of the HPIV-3 JS wild-type strain (89) and the cp45 vaccine strain grown in FRhL 15 and Vero cells, as well as the deduced amino acid sequences of the RNA polymerase (L protein) of these HPIV-3 viruses, are set forth as follows with reference to the appropriate SEQ ID NOS. contained herein: 20 Virus Nucleotide Sequence L Protein Sequence Wild-Type JS SEQ ID NO:17 SEQ ID NO:18 Vaccine FRhL cp45 SEQ ID NO:19 SEQ ID "o Vero cp45 SEQ ID NO:21 SEQ ID NO:22 Each PIV-3 virus genome listed above is 15,462 nucleotides in length. Translation of the L gene starts with the codon at nucleotides 8646-8648; the translation stop codon is at nucleotides 15345- 15347. The translated L protein is 2,233 amino acids long.

As detailed in Example 2 and Table 6 therein below, based upon the differences between the wild-type 37 JS strain and the FRhL-g'rown cp 45 mutant vaccine strain, the key attenuating mutations for the HPIV-3 3' genomic promoter region are nucleotide 23 (T C), nucleotide 24 (C nucleot;.de 28 (C and nuclaotide 45 (T (in antigenomic, message sense) A9 also detailed in Example 2 and Table 6 therein below, key attenuating sites for the L protein of HPIv- 3 include the following: amino acid residues 942 (tyrosine *histidine), 992 (leucine -4 phenylalanine) and 1558 (threonine isoleucifle) It is understood that the nucleotide changes renponsible for these amino acid changes are not limited to those set forth in Exarple 2 below; all changes in nucleotides which result in codone which are translated into these amino acids are within the scope of this invention.

Human respiratory syncytial virus (REV) is yet another nonaegmentede' negative-sense, single stranded enveloped RNA virus. RSV belongs to the Subfamily Pneumovirinae and the genus Pneunovirus (see Table 1).

Two major subgroups of human RSV, designated A and B, have been identified based on reactivities of W. the F and G surface glycoproteins with monoclonal 2S antibodies (62) More recently, the A and B lineages of. RBV strains have been confirmed by sequence analysis (63,64). Bovine, ovine. and caprine atraini of this virus have also been isolated. The host specificity of the virus iis =onL clearly associated with the 0 attachment protein, which is highly divergent between 38 the human and the bovine/ovine strains (65,66), and may be influenced, at least in part, by receptor binding.

RSV is the primary cause of serious viral pneumonia and bronchiolitis in infants and young children. Serious disease, lower respiratory tract disease (LRD), is most prevalent in infants less than six months of age. It most commonly occurs in the nonimmune infant's first exposure to RSV. RSV additionally is associated with asthma and hyperreactive airways and it is a significant cause of mortality in "high risk" children with bronchopulmonary dysplasia and congenital heart disease (CHD). It is also one of the common viral respiratory infections predisposing to otitis media in children. In adults, S: 15 RSV generally presents as uncomplicated upper :respiratory illness; however, in the elderly it rivals influenza as a predisposing factor in the development of serious LRD, particularly bacterial bronchitis and pneumonia. Disease is always confined to the e 20 respiratory tract, except in the severely immunocompromised, where dissemination to other organs can occur. Virus is spread to others by fomites contaminated with virus-containing respiratory secretions, and infection initiates through the nasal, oral, or conjunctival mucosa.

RSV disease is seasonal and virus is usually isolated only in the winter months, from November to April in northern latitudes. The virus is ubiquitous, and over 90% of children have been infected at least once by 2 years of age. Multiple strains cocirculate. There is no direct evidence of antigenic drift (such as that seen with influenza A viruses), but sequence studies demonstrating accumulation of amino acid changes in the hypervariable regions of the G 39 protein and SH proteins suggest that immune pressure may drive virus evolution.

In mouse and cotton rat models, both the F and G proteins of RSV elicit neutralizing antibodies and immunization with these proteins alone provides longterm protection against reinfection (67,68).

In humans, complete immunity to RSV does not develop and reinfections occur throughout life (69,70); however, there is evidence that immune factors will protect against severe disease. A decrease in severity of disease is associated with two or more prior infections and there is evidence that children infected with one of the two major RSV subgroups may be somewhat protected against reinfection with the homologous 15 subgroup observations which suggest that a live attenuated virus vaccine may provide protection sufficient to prevent serious morbidity and mortality.

Infection with RSV elicits both antibody and cell mediated immunity. Serum neutralizing antibody to the 20 F and G proteins has been associated, in some studies, with protection from LRD, although reduction in upper respiratory disease (URD) has not been demonstrated.

High levels of serum antibody in infants is associated with protection against LRD, and adminstration of 25 intravenous immunoglobulin with high RSV neutralizing antibody titers has been shown to protect against severe disease in high risk children (70,72,73). The role of local immunity, and nasal antibody in particular, is being investigated.

The RSV virion consists of a ribonucleoprotein core contained within a lipoprotein envelope. The virions of pneumoviruses are similar in size and shape to those of all other paramyxoviruses.

When visualized by negative staining and electron microscopy, virions are irregular in shape and range in 40 diameter from 150-300 nm The nucleocapsid of this virus is a symmetrical helix similar to that of other paramyxoviruses, except that the helical diameter is 12-15 nm rather than 18nm. The envelope consists of a lipid bilayer that is derived from the host membrane and contains virally coded transmembrane surface glycoproteins. The viral glycoproteins mediate attachment and penetration and are organized separately into virion spikes. All members of paramyxovirus subfamily have hemagglutinating activity, but this function is not a defining feature for pneumoviruses, being absent in RSV but present in PVM Neuraminidase activity is present in members of the genera Paramyxovirus, Rubulavirus, and is absent in 15 Morbillivirus and Pneumovirus of mice (PVM) RSV possesses two subgroups, designated A and B. The wild-type RSV (strain 2B) genome is a single strand of negative-sense RNA of 15,218 nucleotides

(SEQ

ID NO:23) that are transcribed into ten major 20 subgenomic mRNAs. Each of the ten mRNAs encodes a major polypeptide chain: Three are transmembrane surface proteins F and SH); three are the proteins associated with genomic RNA to form the viral nucleocapsid P and two are nonstructural proteins (NS1 and NS2) which accumulate in the infected cells but are also present in the virion in trace amounts and may play a role in regulating transcription and replication; one is the nonglycosylated virion matrix protein and the last is M2, another nonglycosylated protein recently shown to be an RSVspecified transcription elongation factor (see Figure These ten viral proteins account for nearly all of the viral coding capacity.

The viral genome is encapsidated with the major nucleocapsid protein and is associated with 41 the phosphoprotein and the large polymerase protein. These three proteins have been shown to be necessary and sufficient for directing RNA replication of cDNA encoded RSV minigenomes Further studies have shown that for transcription to proceed with full processing, the M2 protein (ORF 1) is required (74).

When the M2 protein is missing, truncated transcripts predominate, and rescue of the full length genome does not occur (74).

Both the M (matrix protein) and the M2 proteins are internal virion-associated proteins that are not present in the nucleocapsid structure. By analogy with other nonsegmented negative-stranded

RNA

viruses, the M protein is thought to render the nucleocapsid transcriptionally inactive before packaging and to mediate its association with the viral envelope. The NS1 and NS2 proteins have only been detected in very small amounts in purified virions, and at this time are considered non-structural. Their 20 functions are uncertain, though they may be regulators of transcription and replication. Three transmembrane surface glycoproteins are present in virions: G, F, and SH. G and F (fusion) are envelope glycoproteins that are known to mediate attachment and penetration of the 25 virus into the host cell. In addition, these glycoproteins represent major independent immunogens The function of the SH protein is unknown, although a recent report has implicated its involvement in the fusion function of the virus (78).

The genomes of two wild-type RSV subgroup

B

strains (2B and 18537) have now been sequenced in their entirety (see SEQ ID NOS:23 and 25, discussed below).

Genomic RNA is neither capped nor polyadenylated (79).

In both the virion and intracellularly, genomic RNA is tightly associated with the N protein.

42 The 3' end of the genomic RNA consists of a 4 4 -nucleotide extragenic leader region that is presumed to contain the major viral promoter (Fig. The 3' genomic promoter region is followed by ten viral genes in the order 3 '-NS1-NS2-N-P-M-SH-G-F-M2-L-5' (Fig. 3).

The L gene is followed by a 145-149 nucleotide extragenic trailer region (see Figure Each gene begins with a conserved nine-nucleotide gene start signal 3'-GGGGCAAAU (except for the ten-nucleotide gene start signal of the L gene, which is 3'-GGGACAAAAU; differences underlined). For each gene, transcription begins at the first nucleotide of the signal. Each gene terminates with a semi-conserved 12-14 nucleotide gene end G U/G U/A ANNN U/A A 3 (where N can be 15 any of the four bases) that directs transcription termination and polyadenylation (Fig. The first nine genes are non-overlapping and are separated by intergenic regions that range in size from 3 to 56 nucleotides for RSV B strains (Fig. The intergenic 20 regions do not contain any conserved motifs or any obvious features of secondary structure and have been shown to have no influence on the preceding and succeeding gene expression in a minreplicon system (Fig. The last two RSV genes overlap by 68 nucleotides (Fig. The gene-start signal of the L gene is located inside of, rather than after, the M2 gene. This 68 nucleotide overlap sequence encodes the last 68 nucleotides of the M2 mRNA (exclusive of the Poly-A tail), as well as the first 68 nucleotides of the L mRNA.

Ten different species of subgenomic polyadenylated mRNAs and a number of polycistronic polyadenylated read-through transcripts are the products of genomic transcription (74).

Transcriptional mapping studies using UV light mediated 43 genomic inactivation showed that RSV genes are transcribed in their 3' to 5' order from a single promoter near the 3' end Thus, RSV synthesis appears to follow the single entry, sequential transcription model proposed for all Mononegavirales (16,81). According to this model, the polymerase

(L)

contacts genomic RNA in the nucleocapsid form at the 3' genomic promoter region and begins transcription at the first nucleotide. RSV mRNAs are co-linear copies of the genes, with no evidence of mRNA editing or splicing.

Sequence analysis of intracellular RSV mRNAs showed that synthesis of each transcript begins at the o first nucleotide of the gene start signal The S 15 end of the mRNAs are capped with the structure m7G(5')ppp(5')Gp (where the underlined G is the first template nucleotide of the mRNA) and the mRNAs are polyadenylated at their 3' ends Both of these modifications are thought to be made co- 20 transcriptionally by the viral polymerase. Three regions of the RSV 3' genomic promoter have been found to be important as cis acting elements These regions are the first ten nucleotides (presumably acting as a promoter), nucleotides 21-25, and the gene 25 start signal located at nucleotides 45-53 Unlike other Paramyxovirinae, such as measles, Sendai and PIV- 3, the remainder of the leader and non-coding region of NS1 gene of RSV was found to be highly tolerant of insertions, deletions and substitutions (83).

Additionally, by saturation mutagenesis (wherein each base is replaced independently by each of the other three bases and compared for translation and replication efficiencies) within the first 12 nucleotides of the 3' genomic promoter region, a Utract located at nucleotides 6-10 was shown to be 44 highly inhibitory to substitutions In contrast, the first five nucleotides were relatively tolerant of a number of substitutions and two of them at position four were up-regulatory mutations, resulting in a fourto 20-fold increase in RSV-CAT RNA replication and transcription. Using a bi-cistronic minireplicon system, gene-start and gene-end motifs were shown to be signals for mRNA synthesis and appear to be self contained and largely independent of the nature of adjoining sequence (84).

The L gene start signal lies 68 nucleotides upstream of the M2 gene-end signal, resulting in gene overlap (Fig. 3) The presence of the M2 gene-end signal within the L gene results in a high frequency of 15 premature termination of L gene transcripts. Full length L mRNA is much less abundant and is made when the polymerase fails to recognize the M2 gene-end motif. This results in much lower transcription of L mRNA. The gene overlap seems incompatible with a model 20 of linear sequential transcription. It is not known whether the polymerase that exits the M2 gene jumps backward to the L gene-start signal or whether there is a second, internal promoter for L gene transcription It is also possible that the L gene is 25 accessible by a small fraction of polymerases that fail to start transcription at the M2 gene-start signal and slide down the M2 gene to the L gene-start signal.

The relative abundance of each RSV mRNA decreases with the distance of its gene from the promoter, presumably due to polymerase fall-off during sequential transcription Gene overlap is a second mechanism that reduces the synthesis of full length L mRNA. Also, certain mRNAs have features that might reduce the efficiency of translation. The initiation codon for SH mRNA is in a suboptimal Kozak 45 sequence context, while the G ORF begins at the second methionyl codon in the mRNA.

RSV RNA replication is thought (74) to follow the model proposed from studies with vesicular stomatitis virus and Sendai virus (16,81). This involves a switch from the stop-start mode of mRNA synthesis to an antiterminator read-through mode. This results in synthesis of positive sense replicationintermediate (RI) RNA that is an exact complementary copy of genomic RNA. This serves in turn as the template for the synthesis of progeny genomes. The mechanism involved in the switch to the antiterminator mode is proposed to involve cotranscriptional encapsidation of the nascent RNA by N protein (16,81).

15 RNA replication in RSV like other nonsegmented negative-strand RNA viruses is dependent on ongoing protein synthesis Predicted RI RNA has been detected for the standard virus as well as RSV-CAT minigenome (74,85). RI RNA was 10-20 fold less o 20 abundant intracellularly than was the progeny genome both for the standard and the minigenome system. The nucleotide sequences (in positive strand, antigenomic, message sense) of various wild-type, vaccine and revertant RSV strains, as well as the deduced amino 25 acid sequences of the RNA polymerase (L protein) of these RSV viruses, are set forth as follows with reference to the appropriate SEQ ID NOS. contained herein: 46 Virus Wild-Type 2B 18537 Vaccine 2B33F 2B20L Revertant 2B33F TS(+) 2B20L TS(+) Nucleotide Sequence SEQ ID NO:23 SEQ ID NO:25 SEQ ID NO:27 SEQ ID NO:29 L Protein Sequence SEQ ID NO:24 SEQ ID NO:26 SEQ ID N0:28 SEQ ID N0:30 SEQ ID NO:31 SEQ ID NO:33 SEQ ID N0:32 SEQ ID N0:34 Each RSV virus genome that is 2,166 amino acids long.

other nucleotide information is encodes an L protein Genome length and as follows: Virus Wild-Type 2B 18537 Vaccine 2B33F 2B20L Revertant 2B33F TS(+) 2B20L TS(+) Genome Length 15218 15229 15219 15219 15219 15219 L Start Codon 8502-8504 8509-8511 8503-8505 8503-8505 8503-8505 8503-8505 L Stop Codon 15000-15002 15007-15009 15001-15003 15001-15003 15001-15003 15001-15003 r As detailed in Example 3 (especially Tables 7 and 8) below, the key attenuating mutations for the RSV subgroup B 3' genomic promoter region are nucleotide 4 (C and the insertion of an additional A in the stretch of A's at nucleotides 6-11 (in antigenomic 47 message sense). As also detailed in Example 3 below, the key potentially attenuating sites for the L protein of RSV are as follows: amino acid residues 353 (arginine lysine), 451 (lysine arginine), 1229 (aspartic acid asparagine), 2029 (threonine isoleucine) and 2050 (asparagine aspartic acid). It is understood that the nucleotide changes responsible for these amino acid changes are not limited to those set forth in Example 3 below; all changes in nucleotides which result in codons which are translated into these amino acids are within the scope of this invention.

The attenuated viruses of this invention exhibit a substantial reduction of virulence compared 15 to wild-type viruses which infect human and animal hosts. The extent of attenuation is such that symptoms of infection will not arise in most immunized individuals, but the virus will retain sufficient replication competence to be infectious in and elicit 20 the desired immune response profile in the vaccinee.

The attenuated viruses of this invention may be used to formulate a vaccine. To do so, the attenuated virus is adjusted to an appropriate concentration and formulated with any suitable vaccine 25 adjuvant, diluent or carrier. Physiologically acceptable media may be used as carriers. These include, but are not limited to: an appropriate isotonic medium, phosphate buffered saline and the like. Suitable adjuvants include, but are not limited to MPL T (3-O-deacylated monophosphoryl lipid A; RIBI ImmunoChem Research, Inc., Hamilton, MT) and IL-12 (Genetics Institute, Cambridge,

MA)

In one embodiment of this invention, the formulation including the attenuated virus is intended for use as a vaccine. The attenuated virus may be mixed 48 with cryoprotective additives or stabilizers such as proteins albumin, gelatin), sugars sucrose, lactose, sorbitol), amino acids sodium glutamate), saline, or other protective agents. This mixture is maintained in a liquid state, or is then dessicated or lyophilized for transport and storage and mixed with water immediately prior to administration.

Formulations comprising the attenuated viruses of this invention are useful to immunize a human or animal subject to induce protection against infection by the wild-type counterpart of the attenuated virus. Thus, this invention further provides a method of immunizing a subject to induce protection against infection by an RNA virus of the S 15 Order Mononegavirales by administering to the subject "an effective immunizing amount of a vaccine formulation incorporating an attenuated version of that virus as described hereinabove.

A sufficient amount of the vaccine in an 20 appropriate number of doses must be administered to the subject to elicit an immune response. Persons skilled in the art will readily be able to determine such amounts and dosages. Administration may be by any conventional effective form, such as intranasally, S 25 parenterally, orally, or topically applied to any mucosal surface such as intranasal, oral, eye, vaginal or rectal surface, such as by an aerosol spray. The preferred means of administration is by intranasal administration.

In another embodiment of this invention, an isolated nucleic acid molecule having the complete viral nucleotide sequence of either the wild-type viruses or vaccine viruses described herein is used to generate oligonucleotide probes (from either positive strand antigenomic message sense or negative strand 49 complementary genomic sense) and to express peptides (from positive strand antigenomic message sense only), which are used to detect the presence of those wildtype virus and/or vaccine strains in samples of body fluids and tissues. The nucleotide sequences are used to design highly specific and sensitive diagnostic tests to detect the presence of the virus in a sample.

Polymerase chain reaction (PCR) primers are synthesized with sequences based on the viral wild-type or vaccine sequences described herein. The test sample is subjected to reverse transcription of RNA, followed by PCR amplification of selected cDNA regions corresponding to the nucleotide sequence described e herein which have nucleotides which are distinct for a 15 defined strain of virus. Amplified PCR products are identified on gels and their specificity confirmed by hybridization with specific nucleotide probes.

ELISA tests are used to detect the presence of antigens of the wild-type or vaccine viral strains.

20 Peptides are designed and selected to contain one or more distinct residues based on the wild-type or vaccine sequences described herein. These peptides are then coupled to a hapten keyhole limpet hemocyanin (KLH) and used to immunize animals 25 rabbits) for the production of monospecific polyclonal antibody. A selection of these polyclonal antibodies, or a combination of polyclonal and monoclonal antibodies can then be used in a "capture ELISA" to detect antigens produced by those viruses.

Samples of the Moraten measles virus vaccine strain were deposited by Applicants with the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Maryland 20852, under the provisions of the Budapest Treaty for the Deposit of Microorganisms for the Purposes of Patent Procedures 50 ("Budapest Treaty") and have been assigned ATCC accession number VR2587. Samples of the HPIV-3 virus Vero-grown cp45 vaccine strain were deposited by Applicants with the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Maryland 20852, under the provisions of the Budapest Treaty and have been assigned ATCC accession number VR2588.

Samples of the 2B wild-type RSV virus were deposited by Applicants with the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Maryland 20852, under the provisions of the Budapest Treaty and have been assigned ATCC accession number VR2586.

Given these three deposited strains and the sequence information for these and other strains 15 provided herein, one can use site-directed mutagenesis and rescue techniques described above to introduce mutations (or restore a wild-type genotype) of all the strains described herein, as well as taking these strains and making additional mutations from the panel 20 of mutations set forth in Tables 3, 4 and 6-8 below.

In order that this invention may be better understood, the following examples are set forth. The examples are for the purpose of illustration only and are not to be construed as limiting the scope of the 25 invention.

Examples Standard molecular biology techniques are utilized according to the protocols described in Sambrook et al. (86).

51 Example 1 Measles Moraten MV vaccine virus was grown once, directly from the Attenuvax TM vaccine vial (Lot #0716B), the Schwarz vaccine virus was grown once (Lot 96G04/M179 G41D), while the Zagreb and RubeovaxM vaccine viruses were each grown twice in the Vero cells before RNAs were made for sequence analysis.

MV

wildtype isolate Montefiore (56) was passed 5-6 times in Vero cells before extraction of RNA materials and similarly, MV wildtype isolates 1977, 1983 (14) were grown 5-7 times before extracting materials for analysis. Edmonston wild-type isolate received from 15 Dr. J. Beeler (CBER) (see Fig. 1) was the original Edmonston isolate already passaged seven times in human kidney cells and three times in Vero cells before receipt and further passaged once in Vero cells before using for sequence analysis.

20 RNA was prepared by infecting Vero cells at a multiplicity of infection of 0.1 to 1.0 and allowed to reach maximum cytopathology before being harvested. Total RNA from measles virus-infected cells was extracted using TrizolM reagent (Gibco-BRL).

25 The total RNA isolated from Vero cell passage material was amplified by the Reverse Transcriptase-PCR (Perkin-Elmer/Cetus) procedure using measles (Edmonston B strain specific primer pairs spanning the 3' and 5' promoter regions and the L gene of the viral genome. Table 2 presents these primer sequences. The primers of SEQ ID NOS:35-54, 74, 77 and 78 are in antigenomic message sense. The primers of SEQ ID NOS:55-73, 75, 76 and 79 are in genomic negative-sense.

52 Table 2 Primers for PCR and Sequencing MV L Genes and Genomic Termini 9 0 4 7

CATATCACTCACTCTGGGATGGAG

9 0 7 0 (SEQ ID 9 3 7 1

TCAGAACATCAAGCACCGCC

9 3 9 0 (SEQ ID NO:36) 9 7 4 1

ACAGTCAAGACTGAGATGAG

9 7 60 (SEQ ID NO:37) 1 000 1

AAGAGTCAGATACATGTGGA

1 0 0 2 0 (SEQ ID NO:38) 1 0 3 1 ACATGAATCAGCCTAAAGTC10370 (SEQ ID NO:39) 1 06 7 4

CCGAAAGAGTTCCTGCGTTACGACC

1 0 69 8 (SEQ ID 1 1 8 3 CAGTCCACACAAGTACCAGG11102 (SEQ ID NO:41) 14

,,GTCAGAAGCTGTGGACCATC,,

4 (SEQ ID NO:42) 1 1 8 4 1

AATATTGCTACAACAATGGC

1 1 8 6 0 (SEQ ID NO:43) 121 ACTCTTCATTCCTAGACTGG (SEQ ID NO:44) 1 2 5 4 2 GTCCAATTATGACTATGAAC (SEQ ID 12891AGACAGACATGAAGCTTGC 1 2 9 (SEQ ID NO:46) 1 32 CCAACAAGGAATGCTTCTAG1325, (SEQ ID NO:47) 13 5 5 1

ACAGCACTATCTATGATTGACCTGG

1 3 5 7 5 (SEQ ID NO:48) 13 9 3 0GCAACATGGTTTACACATGC 1 3 949 (SEQ ID NO:49) 1 4 2

AGATTGAGAGTTGATCCAGG

1 4 2 9 9 (SEQ ID 5555 1 4 2 9 AGGAGATACTTAAACTAAGC144, (SEQ ID NO:51) S 1 4 9 8 1

TAAGCTTATGCCTTTCAGCG

1 5 0 0 0 (SEQ ID NO:52) 1

S

337

TTAACGGACCTAAGCTGTGC

15356 (SEQ ID NO:53) 1 5671 GAAACAGATTATTATGACGG15690 (SEQ ID NO:54)

S

9 2 0CGGGCTATCTAGGTGAACTTCAGG (SEQ ID 0

ATTTGGATATGGAATATGAG

9 4 1 (SEQ ID NO:56) 9 8 4

ACTCAACTGAACTACCAGTG

8 2 1 (SEQ ID NO:57) 1 1

,,AAGAACATCATGTATTTCAG

1 1 62 (SEQ ID NO:58) 1 0 5 4 9 TTATCAACGCACTGCTCATG10530 (SEQ ID NO:59) 1 D9 19 ATTTTCAGCAATCACTTGGCATGCC10895 (SEQ ID 1 12 80GCCTCTGTGCAAACAAGCTG11261 (SEQ ID NO:61) 1 16 3 ,TCTCTAGTTACTCTAGCAGC11619 (SEQ ID Nb:62) 1 2 o 1 oAGGTCGTTGTTTGTGAGGAG11991 (SEQ ID NO:63) 1 2 361

TCGTCCTCTTCTTTACTGTC

1 2 3 4 2 (SEQ ID NO:64) 53 12 8 CCGTCCTCGAGCTAGCCTCG167 (SEQ ID NO: 1 3 0 5 2 CTCCTCCAGGCTCACATTGG103(E ID NO:66) 1 3 4 2 GGGTTGGTACATAGCTCTGC130 (SEQ ID NO:67) 1 3 7 7 CACCCATCTGATATTTCCCTGATGG1374 (SEQ ID NO:68) 1 4 99TGGTTGACAGTACAAATCTG108 (SEQ ID NO:69) 1 4 4 0CTGAAATGGGAAGATTGTGC144 (SEQ ID ,,,,,AGCAATCTACACTGCCTACC140 (SEQ ID NO:71) 15180TCACAGATGATTCATTATC11 (E ID NO:72) 155 3 GATCCTAGATATAAGTTCTC151 (SEQ ID NO:73) I0 IACCAACAAAGTTGGGTAAGG2 (SEQ ID NO:74) GGGGGATCC1 0 0

ATCCCTAATCCTGCTCTTGTCCC

78 (SEQ ID 2 0 0 GATTCCTCTGATGGCTCCAC18 (SEQ ID NO:76) 7 2 TAACAGTCAAGGAGACCAG17 (E ID NO:77) GGGAAGCTTj AACCCTAATCCTGCCCTAGGTGG112 (SEQ ID NO: 78) 158 9 4 ACCAGACAAAGCTGGGATAGA1,7 (SEQ ID NO:79) Overlapping PCR fragments of the complete viral genome were directly sequenced without cloning to 20 achieve the consensus sequence, by the dideoxy terminator cycle sequencing method using both strands (ABI PRISM 377 sequencer and A13I PRISM sequencing Kit).

To determine the sequence at the absolute termini, a ligation procedure described previously was used To test this hypothesis, the nucleotide sequences were determined for the non-protein coding regulatory regions and the L gene of the progenitor Edmonston wild-type MV isolate, for the available vaccine strains derived from this isolate, as well as for other wild-type strains. Nucleotide (in antigenomic, message sense) and amino acid differences were then compared and aligned as set forth in Tables (differences are in italics): 54 Table 3 Differences in MV 3' Genomic Promoter Region Nucleotide Sequence Virus Edmonston w-t Vaccines: RubeovaxM Nucleotide number: 26 42 50 .96 A A G G Mora ten Schwarz Zagreb

AIK-C

G G G G G G G A G G Wild-Types: 1977 1983 Montefiore A G A G A G Table 4 Differences in MV L Nucleotides and Amino Acids Between Edmonston Wild-Type and Vaccine Strains 331 1409 1624 1649 1717 1887 193 6 2 074 2 114 Edmuonston w-t ATT GCA ACC AGG GAT AAC CAT CAA AGA Mutation ACT ACA GCC ATG GCT GAC TAT CGA AAA Edmonston w-t I A T R D N H Q R Rubeovax" vac. I A T M A D H Q R Moraten vac. T A T M A D H Q K Schwarz vac. T A T M A D H Q K Zagreb vac. I T T R A N H Q R AIK-C vac. I T A R A N Y R R Table Differences in MV L Nucleotides and Amino Acids Between Wild-Type Strains 81 Edinonston w-t GCC Mutation ACC Edmonston w-t A 1977 w-t A 1983 w-t T Montefiore w-t A 618 Edmonston w-t GTC Mutation GCC Edmonston w-t V 1977 w-t A 1983 w-t V Montefiore w-t V 122 149 GAT GTT AAT ATT D V N V D I D I 252

ACA

GCA

T

T

T

A

331

ATT

GTT

I

V

441

AAA

AGA

K

K

K

R

447

AAA

AGA

K

K

K

R

500 513 570 GAT GTG AAA AAT ATG AAT D V K D M K N M N D M K 637 641 645 GTA GAC GAT ATA AAT AAT V D D I D N V D D V N D 613

TAC

CAC

y

Y

621 623 626 628 632 636 AGT AGG AGA GCA ATA CAA AAT AAG AAA GAA GTA CAT S R R A I Q N R R A I Q S K R A I H S R K E V H 650

ATG

ATA

M

M

M

I

S S S S. 652 Edmonston w-t GCT Mutation ACC Edmonston w-t A 1977 w-t A 1983 w-t A Montefiore w-t T 1860 Edmonston w-t GTA Mutation ATA Ednionston w-t V 1977 w-t V 1983 w-t V Montefiore w-t I Table 5 (continued) Differences in MV L Nucleotides and Amino Acids Between Wild-Type Strains 720 723 794 914 970 1044 1294 1569 1705 1745 ATC TAT CGG CGG GCC GGA AGC GTT ATC AAT GTC TGC TGG CAG TCA AGA ACC ATT GTC ACT I Y R R A G S V I N I C W Q A G S V I N V C R R S G T I I N V C R R A R S V V S 1865 1936 TTC CAT TAC TAT F H Y H F Y F H 2007

GAC

GGC

D

D

D

G

2013 2017 GAT ACT GOT ATT D T D T G I D I 2030

AAT

AGT

N

N

N

S

2096

ATA

GTA

I

2119

AAG

CGG

K

K

R

R

2165

GTC

ATC

V

V

I

V

58 Example 2 PIV-3 A comparison of sequences (in antigenomic message sense) of the parental wild-type JS strain of PIV-3 virus and the FRhL-grown and Vero-grown forms of the cp45 mutant are set forth in Table 6. Where a codon change does not result in an amino acid change, Table 6 states "none", followed by the name of the unchanged amino acid.

*o* 9 9* 9 59 Table 6 and FRhL-grown cp45 JS Sequence Comparison of Verc atrains Gene Region NP UTh N4P coding P coding X coding F coding HN coding L coding Nucleotide Position 24 28 62 397 1275 2080 4347 5536 6329 6419 6847 7956 9323 9971 11469 11621 12581 13318 is FRhL cp4 5 Ve ro cp4 5 Codon Change Amino Acid Change (number in L) GTC -4- TCT AAT

CC

GCT

AAC

CCC 4 ACC AA C AAI

ATA

OCA GGT GTT TAT GAA

TAC-

TTG TTC ACT

GTA

ACA

GGC

GCT

TAC

GAG

CAC

TTT

TTT

ATT

Val -4Ala Ser -*Ala none /Asn.

Pro Thr none/Asn le -4 Val Ala Thr none/Gly Val k Ala none/Tyr (226) none/Glu (442) Tyr -*His (942) Leu -+Phe (992) none/Phe (1312) Thr Ile (1558) mutations 20 60 Sequence analysis of the parental wild-type 3'S strain of PIV-3 virus and the M1Lht-grown cp 4 5 mutant showed that the latter contained 20 nucleotide changen.

Four changes were in the noncoding 31-leader region at nucleotide positions 23 (T 24 (C T) 28 (0 T) and 45 (T A) (in antigelomiC, message aiense') When considered in the genomic, negative sense, the change at position 28 fro= the smaller pyrimidine to the larger purine may change the size of the region flanked by the conserved regions of the 3' genomic promoter region, resulting in an altered spatial presentation of the cis-acting signals to the polymerase.

Nine changes were coding changes in the NP, M, F, 1fl and L genes. The other ise ven changes were non-coding or silent changes in the NP, P, F, HflN and L genes or the NP unt-ranslated region (UTR) The mutant has been demonstrated to have poor transcription activity at non-permissive temperatures due to its ta phenotype This ts phenotype has now been mapped to the viral L gene (88) Because the cp 4 5 virus has been shown to function normally with regard to mutations in the RN and F~ g'lycoproteins this supports the implication that mutations in the 3' leader and L gene contributed to the attenuating phenotype of this virus.

Thus, the four 3' leader specific ,changes in FRhL-grown cp45 and the three coding changes in the L gene at &Mino acid positions 942 (Tyr -+His) 992 (Leu -+Phe) and 1558 (Thr -+Ile) contributed significantly to the attenuation phenotype of the candidate cp 4 vaccine strain.

The first two amino acid changes in the L protein (at positions 942 and 992) map to one of the highly conserved areas among all Paramyxovirus L genes. The third amino acid change (at position 1558) maps to the area joining two conserved blocks corresponding to the change at amino acid 1717 in the HV vaccine strains The published literature (89) sets forth only 18 changes between the antigenomic message sense sequences of the JS and FRhL-grown cp45 strains. Sixteen of these changes were found by applicants.

The published literature did not report four changes found by applicants: in the 3' leader at nucleotide 45 (T in the NP UTR at nucleotide 62 (A or the 0o changes in amino acids in the NF protein resulting from the changes at nucleotide 397 (T leading to the amino acid change (Val Ala) and nucleotide 1275 (T G), leading to the amino acid change (Ser Ala) (nucleotide changes in antigenomic, message sense).

a .o g* a a o *ooo (R:\LIBZ]05589.doc:lam 62 Example 3 RSV Subqroup B The temperature-sensitive (ts) phenotype is strongly associated with attenuation in vivo; in addition, some non-ts mutations may also be attenuating. Identification of ts and non-ts attenuating mutations was achieved by sequence analysis and evaluation of ts, cold-adapted and in vivo growth phenotypes of RSV mutants and revertants.

The genomes of the following five RSV 2B strains have now been completely sequenced: 2B parent, 2B33F, one revertant designated 2B33F 2B20L and one revertant designated 2B20L The 2B33F and 2B20L strains are ts and ca and are described in U.S.

Serial No. 08/059,444 which is hereby incorporated by reference. After identifying regions where mutations in 2B33F and 2B20L are located, nine additional isolates of 2B33F "revertants" obtained 20 following in vitro passaging at 39 0 C and in vivo passaging in African Green Monkeys or chimpanzees, and nine additional isolates of 2B20L "revertants" obtained following in vitro passaging at 39 0 C have been sequenced in those regions. The ts, ca, and 25 attenuation phenotypes of many of these revertants have now been characterized and assessed. Correlations between phenotype ts, vaccine attenuation and sequence *changes have been identified.

A summary of results is presented in Tables 30 7-12.

63 Table 7 Sequence comparison between RSV 2B and 2B33F strains Nuc. Nuc 3' end RSV 2B of vRNAI leotide changes Gene/ region Genomic Promoter

M

SH

L

r

RSV

2B33F 4 6 4175 4199 4329 4409 4420 4442 4454 4484 4497 4505 4525 4526 4542 4561 4575 4598 9559 9 853 12186 14587 15071 C1T G ease to IS W ofS se.

T

T

T

T

T

T

T

T

T

T

T

T

T

T

T

T

G

A

G

C

A

extra A

C

C

C

C

C

C

C

C

C

C

C

C

C

C

C

C

A

G

A

T

G

RSV 2B33F 5a revertant

G

extra A

C

C

C

C

C

C

C

C

C

C

C

C

C

C

C

C

A

A

A

T

Amino acid changes non- coding non- coding non- coding non-coding Phe-Leu none Ile (36) Ile-Thr none His (47) none Cys (51) none Tyr (61) Stop-Gin (66) none Ser (68) Ile-Thr Ile-Thr Stop-Gin (81) Leu-Pro (87) Trp-Arg (92) none Thr (99) Arg-Lys (353) Lys-Arg (451)* Asp-Asn (1229) Thr-Iie (2029) non- coding

G

1~ I a ease.

For 2B33F and 2B33F nuci. pos. numbers are one larger than f or 2B for M, SH L genes At pos. 9853, the Lys-Arg change has reverted back to Lys in the 2B33F strain 64 Table 8 Sequence comparison between RSV 2B and 2B20L strains Nuci.

pos. t Nucleotide changes Gene/ region Genomi c Promoter

L

3'1 end of vRNA 4 6 8963 13347 14587 14649 14650 RSV 2 B

C

C

A

C

A

A

RSV

2B20L

G

extra A

T

A

T

G

A

RSV 2B20L R1 r ever tan t

G

extra A

T

G

T

G

T

Amino acid changes non- coding* non-coding* none Thr (154) Asn-Asp (1616) Thr-Ile (2029) Asn-Asp (2050) Asn-Asp-Val (2050) I 4

C

For 2B20L and 2B20L nucl. pos. numbers are one larger than for 2B for L gene mutation is common in 2B33F and 2B20L strains At pos. 14650, the mutation suppresses the ts phenotype in 2B20L revertant ~0 ~0 0 0* 0 0*0 0 *Table 9 RS 2B s an Reetn Strain Sample Source In Vitro Phenotype In Vjvo Growt h* tsca Cotton Rat AGM 39/32 0 C EOP 20/32 0 C Nasal Lungs Nasal Bronchial plaque morph Yield turbinates Wash Lavage RSV 2B Wild-type Parent 0.7 0.0001 5.58 5.8a 5.80 4.76 Strain (WT) 3 .9b 5 2 b (4/4) (4/4) RSV 2B33F ca, ts mutant isolated 0.00007 0.04 6a 3 .0e <0.9' from 2B cold-passaged (sp/int/wt) <1 .9b <1l.2 b (0/4) x 3(1/4) (0/4) RSV 2B33F 5a 2B33F spinner passage, 0.5 0.03 1l. 7" 3 .5a 4 .2e 4.Qe plaque picked at 39'C (WT) (4/4) RSV 2B33F 4a 2B33F spinner passage, 0.7 0.01 -1.71 3.8' ND ND plaque picked at 39'C (WT) (4/4) RSV 2B33F 3b 2B33F spinner passage, 0.5 0.04 2.96 ND ND plaque picked at 39'C (WT) (4/4) AGM pp2 2B33F-infected AGM 0.3 0.00002 2 0 .b 1.6b ND N #A2,d7 nasal wash (sp,int) (4/4) plaque picked at 32'C Tal 9 (continued RS 2B s an Reetn Strain Sample Source In Vitro Phenotype In Vivo Growth* tsca Cotton Rat AGM 39/32-C EOP 20/32-C Nasal Lungs Nasal Bronchial plaque morph Yield turbinates Wash Lavage AGM pp4 2B33F-infected AGM 0.1 0.008 D N #A2,d7 nasal wash (sp,int) (4/4) plaque picked at 32 0

C

AGM pp6 2B33F-infected AGM 0.000004 -0.00005 j.S5b<1.l NDD #A4,d12 nasal wash (wt) (0/4) plaque picked at 32'C AGM pp7 2B33F-infected AGM 0.000004 0.007 l1.

4 b<1.bNDD #A4,d12 nasal wash (sp/int/wt) (0/4) plaque picked at 32*C Chimp pplA 2B33F-infected Chimp 0.5 Nl ND D N #1552, d4 tracheal (WTr) lavage plaque picked at 32'C Chimp pp3A 2B333F-infected Chimp 0.7 ND 2.4' :0c ND ND #1560, d6 tracheal

(T

lavage (3/4) plaque picked at 32'C Chimp pp5A 2B33F-infected Chimp 0.7 N 2.3c 3.0 ND ND #1563, dlO nasal swab (T plaque picked at 32 0 C (4/4) a. *ee a a a RS 2B s an Reetn Strin

I

S amplie Source In Vitro Phenotype ts ca 39/32 0 C EOP 20/32-C plaque morph] Yield In Vi vo Cotton Rat Nasal 1 T L-, Growth* 4 RSV 2B20L RSV 2B20L Ri TS RSV 2B20L R2

TS(+)

RSV 2B20L R9 TS RSV 2B20L R10 TS ca, ts mutant isolated from 2B cold-passaged x 20 2B20L spinner passage, plaque picked at 39'C 2B20L spinner passage, plaque picked at 39 0

C

2B20L spinner passage, plaque picked at 39 0

C

2B20L spinner passage, plaque picked at 39*C 0.0002 (int/wt) 0.6 0.02 turbinates <1 9 d (0/4) (0/4)

AGM

N asal Bronchial Wash Lavage (0n/2) (0/2) ND 12 .3c 15 (ND IND (4/4) 06N 2.5c 2 .70 ND ND

(WT)

(4/4) 0.8ND_22c4.O

NDD

(WT)

0.7ND26'32 ND D (WT)(44(4 In Vivo growth measured in log 10 mean virus t ND not done WT wild-type plaque size aDose 106*7 PFU IN bDose 103'6 PFU IN d Dose 105'9 PFU IN e Dose 106'6 PFU IN+IT iter infected/# total) sp small plaque size int =intermediate plaque size CDose 1063 PFU IN Dose 106" PFU IN+IT 68 Table 2B33F Revertants vitro ~2 AGM ppjAChimp 4a 3b p2 pp4 P6 p 1A 3 base no.t

M

4176,4200 S S S S S S S S S S

SH

14 bases* S S S S S S S S S S

L

9560 S S S S S S S S S S 9854 2B 2B 2B 2B S S S ND 2B 2B 12187 S S S S S S S S S S 14588 S S S S S S S ND S S 15072 S S S S S S S S S S Phenotype ts {2B 2B 2B r r S S 2B 2B 2B ca S S S 2B S 2B S ND ND ND Attenuated r r r S S ND r r t These 2B33F revertant base nos. are one larger than for 2B for M, SH and L genes *bases 4330,4410,4421,4443,4455,4485,4498,4506,4526,4527,4543, 4562,4576,4599 S same base as 2B33F 2B reversion to 2B base or complete reversion in phenotype r moderate reversion in phenotype slight reversion in phenotype ND not donA 69 Table 11 2B20L Revertants base no.t In vitro Isolates R1 R2 R3A R4A R5A R6A R7A R8A R9A

LL

8964 S S S S S S S S S S 13348 C* S ND S S ND S S S S 14588 S S S S S S S S S S 14650 S S 2B S 2B 2B S S 2B 2B 14651 A* A* S A* S S A* A* S S Phenotype_ ts 2B 2B ND ND ND ND ND ND 2B 2B lAttenuated r r ND ND ND ND ND ND r r t These 2B20L revertant base nos. are one larger than for 2B for L genes S same base as 2B20L 2B reversion to 2B base r moderate reversion in phenotype base change, different from 2B or 2B20L ND not done Table 12 RSV 2B, ts and Revertant Strains: Phenotype Summary Virus Isolate Source In Vi tro In Vivo Phenotype Attenuation ts ca Cotton AGM I Rat RSV 2B j wild-type Parent Strain I I RSV 2B33F ca, ts mutant isolated from 2B, cold-passaged x 33 RSV 2B33F -5a 2B33F spinner passage TS(4-) plaque picked at 39*C SV B3F 4 2B33F pinner passage ND TS(+)plaque picked at 39*C RSV 2B33F -3b 2B33F spinner passage

ND

plaque picked at 39'c AGM pp2 2E33F-infected AGM A2,

ND

d7 nasal wash plaque picked at 32'C AGM pp4 2B33F-infected AGM A2,

ND

d7 nasal wash plaque picked at 32*C AGM pp6 2B33F-infected AGM. A4,

ND

d12 nasal wash plaque picked at 32'C AGM pp7 2B33F-infected AGM A4,

ND

d12 nasal wash plaque picked at 32'C Chimp pplA 2B33F-infected chimp ND ND ND #1552, d4 tracheal lavage, plaque picked at 32 0

C

Chimp pp3A 2B33F-infected chimp ND

ND

#1560, d6 tracheal lavage, plaque picked at 32'C Chimp pp5A 2B33F-infected chimp ND

ND

#1563, dlO tracheal lavage, plaque picked at 32*C 71 Table 12 (continued) RSV 2B, ts and Revertant Strains: Phenotype Summary Virus isolate Source In Vi tro In Vv Phenotype Attenuation ts ca Cotton

AGM

Rat RSV 2B20L ca, ts mutant isolated from 2B, cold-passaged x RSV 2B20L RI 2B20L spinner passage ND

ND

plaque picked at 39 0

C

RSV 2B20L R2 2B20L spinner passage ND

ND

plaque picked at 39 0

C

RSV 2B20L R9 2B2aL spinner passage

N

TS plaque picked at 39'C RSV 2B20L Ri0 2B20L spinner passage ND

ND

plaque picked at 39'C ND =not done -=Wild-type phenotype, not temperature sensitive, not cold adapted, not attenuated to increasing levels of temperature sensitivity, coldadaptation or attenuation 9 .9 9* 9 9.

9 9* 9 99999.

9 99 9.

9999 991.9 72 Several significant observations can be drawn from these data: a. As shown in Tables 7 (for 2B33F) and 8 (for 2B20L), there are relatively few sequence changes identified in the two mutant strains: RSV 2B33F differs from parental RSV 2B by two changes at the 3' genomic promoter region, two changes at the non-coding of the M gene, and four coding changes plus one non-coding (poly(A) motif) change in the RNA dependent RNA polymerase coding L gene. In addition, 14 changes mapped to the SH gene alone. RSV 2B20L differs from its RSV 2B parent only at seven nucleotide positions, of which three are common with 2B33F virus, including two changes at the 3' genomic promoter and one coding change in the L gene. Two additional unique changes of 2B20L virus mapped to the coding region of the L gene.

Potentially attenuating mutations at the non-coding 3' genomic promoter region and the RNA dependent RNA 20 polymerase gene have been identified.

b. Two ts mutations can be identified in the L gene of the attenuated virus strains 2B33F and 2B20L: In 2B33F, a mutation at nucleotide position 9853 (A G) leading to a coding change in L protein at amino acid 451 (Lys ->Arg) is clearly associated with the ts and attenuation phenotypes. Reversion at this site alone in the 2B33F 5a strain is 30 responsible for complete restoration of growth at 39 0

C

(Table 9) and partial reversion in attenuation in animals. This association with the ts and attenuation phenotypes was also supported by partial sequence analyses of six additional "full TS revertants" (designated 4a, 3b, pp2, 3A, 5a, 5A) isolated from cell 73 culture and from chimps, in which only the nucleotide 9853 mutation reverted (Tables 10-12) (note that one AGM (African Green Monkey) isolate which reverted at 9853 only partially reverted in ts phenotype). This amino acid 451 mutation (Lys ->Arg) is amenable to stabilization in cDNA infectious clone constructs, by inserting a second mutation to stabilize the codon, thereby lessening the likelihood that it will revert back to Lys.

(ii) In 2B20L, a mutation at base 14,649 (A leading to a coding change in the L protein (amino acid position 2,050, Asn ->Asp) appears to be associated with the ts and attenuation phenotypes. This aspartic acid at the amino acid 2050 invariably reverts back (Asp ->Asn) in revertants or changes to a different amino acid (Asp Val) by nucleotide substitution at position 14,650 (A (Tables 8, 11). The above observation is based on complete 20 sequence analysis on the revertant R1 and partial sequence of several additional revertants (R2, R4A, R7A, R8A) at selected regions (Table 11). An additional mutation is seen in the R1 revertant at nucleotide postion 13,347 (amino acid 1616, Asn Asp) associated with the above reversion. However, the effect of this mutation on the ts phenotype is not

O

known; the L gene of other revertants has not been sequenced completely.

c. Three base changes are common to 2B33F and 2B20L strains of virus: A change at position 14,587 (C with a corresponding change (Thr Ile) at amino acid 2029 is 74 present in both 2B33F and 2B20L (Tables This nucleotide substitution was found to be present in of the population of the progenitor RSV2B strain and may have been preferred during the attenuation process. No wildtype base was found in the 2B33F and 2B20L virus.

(ii) Two mutations are seen in the 2B33F and 2B20L 3' genomic promoter region: nucleotide 4 (C and the insertion of an extra A in the stretch of A's at positions 6-11 (in antigenomic, message sense). When the sequences of selected revertants were analyzed, these mutations were seen to have been retained in the 2B33F TS(+)5a (Table 7) and the 2B20L TS(+)R1 (Table 8) revertants. These non-coding, cisacting mutations remained associated with partial viral attenuation.

Expression using the minireplicon RSV-CAT system for the analysis of these cis-acting changes has 20 shown the 3' genomic promoter nucleotide 4 (C G) change to be an upregulation of transcription/replication in this in vitro system when the 2B progenitor virus or either of the 2B33F or 2B33F provided helper L gene functions (the N, P and M2 genes are identical in these viruses) Complementation analysis of the 2B33F 3' genomic promoter and the helper functions provided by the progenitor RSV2B virus or the 2B33F and 2B33F TS(+) viruses by this RSV-CAT minireplicon system has also 30 been conducted. All three viruses supported both the 2B and 2B33F 3' genomic promoter mediated transcription/replication functions. However, the 2B33F and 2B33F viruses preferred their 2B33F 3' genomic promoters. This analysis clearly shows coevolution of 3' genomic promoter changes during the 75 vaccine attenuation process, along with the RNA dependent RNA polymerase gene. Reversion of ts phenotype in the 2B33F mutant 5a by reversion of the single L protein amino acid 451 (Arg -*Lys) by sequence analysis was clearly demonstrated by support of transcription/replication functions of RSV-CAT minireplicon at 37°C. The 2B33F virus did not provide helper functions to the RSV-CAT minireplicon (with 2B or 2B33F 3' genomic promoters) at 37°C.

d. A biased hypermutation of SH seen in 2B33F is present in all 2B33F revertants, regardless of phenotype, and is not seen in 2B20L, which is ts, ca, and attenuated. Thus, there are no data at this time that associate this mutation with any biological phenotype.

Another wild-type RSV designated 18537 was also sequenced and compared to the sequence of the wild-type RSV 2B strain. With one exception, at all 20 the critical residues described above, the two wild- Stype strains were identical. For 2B, the codon ACA at nucleotides 14586-14588 encodes a Thr at amino acid 2029 of the L protein, while for 18537, the codon ATT .at nucleotides 14593-14595 encodes an Ile at amino acid 2029 (the L gene start codon is at nucleotides 8509- 8511 in 18537, compared to 8502-8504 in 2B).

Example 4 PCR Assay to Detect Measles Virus A 21 year old patient was admitted to a hospital with a three week history of progressive nonproductive cough, shortness of breath, and fever. His symptoms failed to improve following treatment with clarithromycin for seven days or after a similar course 76 of treatment with atovaquone. Concomitant complaints of right upper quadrant abdominal pain proved recalciltrant to omeprazole and antacids. Relevant past medical history included Factor VIII deficiency and HIV infection diagnosed 3-4 years prior to this hospital admission. One year earlier, he had received a booster immunization of measles-mumps-rubella

(MMR)

vaccine as required for college enrollment.

Bronchoalveolar lavage and transbronchial biopsies performed two days after admission to the hospital demonstrated reactive hyperplasia and alveolar lining cell desquamation with minimal chronic inflammation. No microorganisms were revealed by Gram, methenamine silver, or PAS stains. CT scans of the chest showed multiple, ill-defined, confluent nodules at the left lung base. Despite administration of empiric antimicrobials for opportunistic bacterial, mycobacterial, and fungal pathogens commonly responsible for pulmonary complications of advanced HIV S 20 disease, the patient became and remained febrile to :39 0 C. A left-sided pleural effusion developed; diagnostic thoracentesis showed it to be exudative but otherwise non-diagnostic. Bronchoalveolar lavage performed three weeks later only demonstrated alveolar histiocytes, some of which were hemosiderin laden, a few lymphocytes, and neutrophils. FITE, AFB, and methanamine silver stains again were negative.

Two weeks thereafter, a wedge resection of the left lung was performed through CT-guided 30 minithoracotomy. Multiple tissue sections revealed nodular areas of acute and chronic inflammation with regions of necrosis and fibrosis. Numerous multinuclated giant cells were present, some of which contained both intracytoplasmic and intranuclear inclusions suggestive of measles virus giant cell 77 pneumonia. Special stains for bacteria, fungi, P.

carinii, and acid fast organisms again gave negative results. Electron microscopic examination of sections of this lung biopsy revealed particles morphologically consistent with paramyxoviruses such as measles virus.

Serum anti-measles IgM titers determined by a solid phase hemadsorbant assay were negative, as was a subsequent IgM capture immunoassay.

Two weeks later, Rhesus monkey kidney (RMK) tissue culture cells inoculated with the patient's lung biopsy material revealed cytopathic changes characteristic of measles virus infection.

Confirmation was obtained using an immunofluorescence assay with monoclonal antibodies directed to measles virus. Based upon this diagnosis, oral ribavirin 1000mg B.I.D. was given for 14 days. Unfortunately, the patient progressively deteriorated, eventually dying two months later.

In order to ascertain the nature of the 20 measles virus present in the patient, reverse transcription and PCR amplification of virus obtained from infected tissues were performed, followed by sequence analysis. The measles virus isolated from Rhesus monkey kidney cells inoculated with tissue from this patient's lung biopsy was propagated by two serial passages in the continuous Vero (monkey kidney) tissue culture cell line. Total infected cell RNA was extracted at the second Vero cell passage using TRIzol reagent (Life Technologies, Grand Island, NY) according S 30 to the manufacturer's protocol. Total RNA was similarly extracted from the patient's lung biopsy material. The measles virus vaccine strain (Moraten) currently used in the United States as a component of the trivalent MMR vaccines, was obtained in its univalent form (Attenuvax, Merck, Sharpe, Dohme) 78 This virus was passaged once in Vero cells and total vaccine infected cellular RNA then was extracted as described above.

Each of these RNA preparations was reverse transcribed (RT) to cDNA using random hexameric primers and Maloney murine leukemia virus reverse transcriptase (Perkin-Elmer/Cetus RT-PCR kit reagents, Perkin-Elmer- Cetus, Branchburg, NJ). The cDNA then was amplified by PCR using measles virus-specific oligodeoxynucleotide primer pairs whose design was based on the Edmonston measles virus sequence described above. These PCR products comprised a set of overlapping DNA fragments spanning the entire 15,894 nucleotide long measles genome. A consensus genomic sequence was established by direct analysis of each PCR product, without cloning, using the dideoxy terminator cycle-sequencing method established by the manufacturer (ABI PRISM 377 sequencer and ABI PRISM DNA sequencing kit; Perkin- Elmer/Cetus, Foster City, CA). Both strands of the 20 PCR-amplified DNA products were analyzed to eliminate possible sequencing ambiguities.

The nucleotide sequences of selected regions of the measles virus genomes present in the patient's viral isolate, as well as in the diseased lung tissue, S 25 were compared with that of the Moraten vaccine virus, as well as with the nucleotide sequences of other o *measles virus wild-type and vaccine strains. This sequence analysis revealed identity to the Moraten vaccine strain rather than demonstrating relatedness to 30 past or currently circulating wild-type viruses or other measles vaccine strains.

79 Example ELISA to Detect RSV An ELISA test is used to detect the presence of RSV. Peptides are designed and selected based on homologies to the RSV sequences described herein to be specific for all subgroup B strains, or for individual wild-type, vaccine or revertant RSV subgroup B strains described herein. These peptides are then coupled to KLH and used to immunize rabbits for the production of monospecific polyclonal antibody. A selection of these polyclonal antibodies, or a combination of polyclonal and monoclonal antibodies is then used in a "capture ELISA" to detect the presence of an RSV antigen.

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U.S. Patent Application No. 08/059,444.

i o Page(s) 4 b 21 are claims pages they appear after the sequence listing 86 SEQUENCE LISTING GENERAL INFORMATION: APPLICANT: Udem, Stephen A.

Sidhu, Mohinderjit S.

Tatem, Joanne M.

Murphy, Brian R.

Randolph, Valerie B.

(ii) TITLE OF INVENTION: 3' Genomic Promoter Region and Polymerase Gene Mutations Responsible for Attenuation in Viruses of the Order Designated Mononegavirales (iii) NUMBER OF SEQUENCES: 79 (iv) CORRESPONDENCE

ADDRESS:

ADDRESSEE: American Home Products Corporation STREET: One Campus Drive CITY: Parsippany STATE: New Jersey COUNTRY: United States ZIP: 07054 COMPUTER READABLE

FORM:

MEDIUM TYPE: Floppy disk S(B) COMPUTER: IBM PC compatible OPERATING SYSTEM:

PC-DOS/MS-DOS

SOFTWARE: PatentIn Release Version #1.30 (vi) CURRENT APPLICATION DATA: APPLICATION NUMBER: US FILING DATE:

CLASSIFICATION:

(viii) ATTORNEY/AGENT

INFORMATION:

NAME: Gordon, Alan M.

REGISTRATION NUMBER: 30,637 REFERENCE/DOCKET NUMBER: 33,294 PCT (ix) TELECOMMUNICATION

INFORMATION:

TELEPHONE: 973/683-2157 S(B) TELEFAX: 973/683-4117 INFORMATION FOR SEQ ID NO:1: SEQUENCE CHARACTERISTICS: LENGTH: 15894 base pairs TYPE: nucleic acid STRANDEDNESS: single 87 TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: ACCAAACAA.A GTTGGGTAAG GATAGATCAA TCAATGATCA TATTCTAGTG

CACTTAGGAT

TCAAGATCCT

TAAGGAGCTT

GTGGAGCCAT

TTACCACTCG

GCGGGCCCAA

GTCAATTGAT

TCCAGAGTGA

ATGAGGCGGA

GATGGTTCGA.

TGATTCTGGG

CAGACACGGC

TAGTTGGTGA

AGGACCTCTC

GAA.ACAAACC

GATTAGCCAG

GACTGCATGA

AAATGGGGGA

GTGCAGGATC

ACTCCATGGG

GGCAAGAGAT

GTATCACTGC

ATTATCAGGG

AGCATTGTTC

CAGAGGAATC

ATCCAGACTT

ACTAACAGGG

TCAGAGGATC

CCAGTCACAA

CCAATACTTT

GAACAAGGAA

TACCATCCTA

AGCTGATTCG

ATTTAGATTG

CTTACGCCGA

CAGGATTGCT

TTTTATCCTG

ATTTGCTGGT

AACTGCACCC

ATACCCTCTG

AGGTTTGAAC

GGTAAGGAGG

CGAGGATGCA

ACAAGAGCAG

AA.AAGAAACA

AAACACATTA

CTGGACCGGT

GCACTAATAG

ACCGATGACC

TCTGGCCTTA

TCACATGATG

ATCTCAGATA

GCCCAAATTT

GAGCTAAGAA

GAGAGAAAAT

TTCATGGTCG

GAAATGATAT

ACTATTAAGT

GAGTTATCCA

TACATGGTAA

CTCTGGAGCT

TTTGGCCGA.T

TCAGCTGGAA

AGGCTTGTTT

GATTAGGGAT

AGGACAAACC!

TTATAGTACC

TGGTCAGGTT

GTATATTATC

CTGACGTTAG

CCTTCGCATC

ATCCAATTAG

TTGAAGTGCA

GGGTCTTGCT

GGTGGATA;A

GGTTGGATGT

CTCTAATCCT

GTGACATTGA

TTGGGATAGA

CACTTGAGTC

TCCTGGAG,

ATGCCATGGG

CTTACTTTGA

AGGTCAGTTC

CAGAGATTGC

ATCCGAGATG

ACCCATTACA

AA.TCCCTGGA

AATTGGAAAC

CTTATTTGTG

CATA.AGGCTG

AAGAGGTACC

TAGTGATCAA

AGACCCTGAG

CGCAAAGGCG

GTACACCCAA

GGTGAGGAAC

GGATATCAAG

TACATATATC

AACTATGTAT

CTTGATGAAC

CTCAATTCAG

AGTAGGAGTG

TCCAGCATAT

CACATTGGCA

AATGCATACT

GCCACACTTT

TCAGGATCCG

GATTCCTCAA

CCGGATGTGA

GAGTCTCCAG

TTAGAGGTTG

AACATGGAGG

TCCAGGTTCG

GGATTCAACA

GTTACGGCCC

CAAAGAAGGG

AGGATTGCCG

AGAACACCCG

GTAGAGGCAG

CCTGCTCTTG

CTTTACCAGC

AACAAGTTCA

GAACTTGAAA

TTTAGATTAG

TCTGAACTCG

ACTGAGGACA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 88 0*

AGATCAGTAG

GTGAGAATGA

GAGAAGCCAG

CCCATCTTCC

CGCAGGACAG

CGGAAGAACA

ACTAGGTGCG

AAAACTTAGG

GAGCCGATGG

CTCAAGGCCG

ATATCAGACA

GGTCTCAGCA

CGCGGCCAGG

AATCTCCAGG

GCGGTTAAGG

AGCACCCTCT

GATACCGAGG

GCTTCTGATG

AGAGGCAACA

GGTAGGGCCA

TTTGGAACGG

CCCTCGGAAC

GCCGCACTGA

AATAATGAAG

AA;AACAGCCT

CTGCTGTTAT

AGCGGTTGGA

GCTACCGAGA

GGAGAGCTAC

AACCGGCACA

TCGAAGGTCA

AGGCTCAGAC

AGAGGCCGAG

AACCAGGTCC

CAGAAGAGCA

AGCCCATCGG

ACCCAGGACA

AACCATGCCT

GACCTGGAGA

CATCAAGCAC

GAATCC;AAGA

CAGGAGGAGA

GATATGCTAT

TTGAAACTGC

ACTTTCCGAA

GCACTTCCGA

AGATCGCGTC

CATCAGGGCC

TACAGGAGTG

AAGGGGGAGA

TGGCCAAAT

TGAAGGGAGA

CCCAGACAAG

TTGGGGGGCA

AGAGAAACCG

CCCCTAGACA

GCTGACGCCC

ACGGACACCC

GACCAGAACA

ACACAGCCGC

GGCACGCCAT

CTCACTGGCC

GGAGCGAGCC

CTCAGCAATT

GAGCGATGAC

TGGGTTACAG

TGCTGACTCT

CAATGAATCT

CACTGACCGG

AGAAGGAGGG

GCTTGGGAAA

GACACCCATT

TTTATTGACA

AGGTGCACCT

GACACCCGAA

CTATTATGAT

ACACGAGGAT

AGTTGAGTCA

CCCAAGTATC

AGGAAGATAG

GGCCCAGCAG

TTGACACTGC

TGCTTAGGCT

CTATAGTGTA

ACATCCGCCT

CAGCCCATCA

GTCAAAAACG

ATCGAGGALAG

ACCTGCAGGG

GGATCAACTG

GACGCTGAAA

TGTTATTATG

ATCATGGTTC

GAAAACAGCG

GGATCTGCTC

GAGATCCACG

ACTCTCAATG

AAA.AAGGGCA

GGTGGTGCAA

GCGGGGAATG

TCTGGTACCA

GATGAGCTGT

AATCAGAAGA

ATTAAGAAGC

ATTTCTACAC

GAGGGTCAA.A

AGCAAGTGAT

ATCGGAGTCC

GCA.AGCCATG

CAATGACAGA

ACCCTCCATC

ACCATCCACT

GACTGGAATG

CTATGGCAGC

AAGAGAAGGC

AAGGCGGTGC

CTTTGGGAAT

TTTATGATCA

AATCAGGCCT

ATGTGGATAT

CCATCTCTAT

AGCTCCTGAG

TTCCTCCGCC

CAGACGCGAG

CCCAATGTGC

TCCCCGAGTG

CAATCTCCCC

TCTCTGATGT

TAATCTCCAA

AGATCAACAG

GGTGATCAAA

CAGAGTCGAG

GCGAGAGCTG

AGCCAAGATC

GCAGGAATCT

AATCTTCTAG

ATTGTTATAA

CCCACGATTG

CATCCGGGCT

ATGGTCAGAA

AGGCAGTTCG

ACCTCGCATC

CCCCCCALAGA

CAGCGGTGAA

TGATGGTGAT

TGGCGAACCT

GGGGTTCAGG

ACTCCAATCC

CCCGGACCCC

ATTAGCCTCA

TCGAAAGTCA

TGTGAGCAAT

GAGATCCCAG

CCAAGATATT

GCTAGAATCA

GCAAAATATC

1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 89

AGCATATCCA

AAGGATCCCA

GGCAGAGATT

CTCCAAGGAA

CTAAAGCCGA

GCATCACGCA

CGTTACCTGA

CAGATGCTGA

CCAGTCGACC

GCCTCCCAAG

AAGGGTCGAT

TCAGAGTCAT

TGCTGGGGGT

CCCTGCCCTT

CTGAGCTTGA

ACAACACCCC

TCAACGCAAA

TCCGTGTTGT

GAAGAATGCT

GGATTGACAA

CAACATTTAT

ATTATTGCAA

GCACCAGTCT

GGTTCAAGAA

TCTGGAGGAG

AAGAATTCCG

CCCTGGAAGG

ACGACCCCAC

CAGGCCGAGC

TGACAAATGG

TCGGGAAAAA

GTGTALATCCG

TGACTCTCCT

TGAAGATAAT

CAACTAGTAC

TTCCACAATG

CGCTCCGATA

AGATCCTGGT

TGTTGAGGGC

AGGTGTTGGC

CATAGTTGTT

ACTAACTCTC

CCAAGTGTGC

TTATATGAGC

GGAATTCAGA

GGCGATAGGC

GGTCCACATC

AATGAAAATC

TCACATTAGA

GACCTTATGT

CAGATGCAAG

CATTTACGAC

ACACCTCTCA

TGCAGATGTC

ACTGGCCGAA

ACGGACCAGT

GATGAGCTCA

CTCCATTATA

TGATGATATC

AATGAAGTAG

AACCTAAATC

ACAGAGATCT

CAACCCACCA

CTAGGCGACA

AGCGATCCCC

AGATCCACAG

AGACGTACAG

CTCACACCTT

AATGCGGTTA

ATCACCCGTC

TCGGTCAATG

CCTGGGAAGA

GGGAACTTCA

GAAAAGATGG

AGCACAGGCA

TACCCGCTGA

ATAGTAAGAA

GACGTGATCA

AGCATCATGA

GAAATCAATC

GTTCTCAAGA

TCCAGAGGAC

GCCGTCGGGT

AAATCCAGCC

AAAGGAGCCA

CTACAGCTCA

CATTATAAAA

ACGACTTCGA

CCTACAGTGA

GGAAGGATGA

TAGGGCCTCC

CAAAGCCCGA

CAGGGCTCAA

GGAGAAAGGT

ATCTGATACC

TTTCGGATAA

CAGTGGCCTT

TCATCGACAA

GGAGA.ALAGAA

GCCTGGTTTT

AGATGAGCAA

TGGATATCAA

TCCAGGCAGT

TAAATGATGA

TCGCCATTCC

CCGACTTGAA

AACCCGTTGC

AGCTGCTGAA

TTGTTCCTGA

GGCTAGAGGA

ATGATCTTGC

ACTTACCTGC

AACTTAGGAG

CAAGTCGGCA

TGGCAGGCTG

ATGCTTTATG

AATCGGGCGA

AGAACTCCTC

TGAAAA1ACTG

CCTAACAACA

GCTCGATACC

CGGGTATTAC

CAACCTGCTG

TACAGAGCAA

GAGTGAAGTC

TGCACTTGGT

GACTCTCCAT

TGAAGACCTT

TTGCAGCCA

CCAAGGACTA

TGGACTTGGG

ACCCATCATA

CAGCCGACAA

GGAATTTCAG

CACCGGCCCT

GGATCGGAAG

CAAGTTCCAC

CAACCCCATG

CAAAGTGATT

TGGGACATCA

GTGCCCCAGG

TACATGTTTC

GCATTTGGGT

AAAGAGGCCA

GTGTTCTACA

GGGAGTGTCT

CCGCAGAGGT

ACCGTTCCTA

GTGACCCTTA

CTTCCTGAGG

TACTCTGCCG

GGGATAGGGG

GCACAACTCG

AATCGATTAC

TCAGTTCCTC

TTCAAAGTTC

2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 90 TGTAGACCGT AGTGCCCAGC AATGCCCGAA AACGACCCCC CTCACAATGA CAGCCAGA.AG 4500

S.

4 S. S 4

S

S.

S.

GCCCGGACA.A

GCCGACGGCA

CCACCAGCCA

TGCCCCCGAT

ATTGGAAGGC

GACCGAGGTG

ACTAAACAAA

CGGCGCCGCG

CCCCGGTGCC

AATCCAAGAC

GAGGAAGCCC

GGGCCACCAG

ACCCCAGCCC

CGAAGGACCC

CTCCTCCTTT

CCCACCCCTA

GGTCTCAAGG

ACCGGTCA;A

AGCTACAAAG

ATAACTCTCC

ACAGTTTTGG

CAGAGTGTAG

GCCCTAGGCG

CTGAACTCTC

GAGGCAATCA

AA.AAGCCCCC

AGCGCGAACA

CCCCAATCTG

CCAAACCACC

CCCTCCCCCT

ACCCALACCGC

ACTTAGGGCC

CCCCCAACCC

CACAGGCAGG

GGGGGGGCCC

ACCCACCCCA

CTCCCAGACT

CGATCCGGCG

CCGAACCGCA

TCTCGAAGGG

AAGGAGACAC

TGAACGTCTC

TCCATTGGGG

TTATGACTCG

TCAATAACTG

AACCAATTAG

CTTCAAGTAG

TTGCCACAGC

AAGCCATCGA

GACAAGCAGG

TCCGAAAGAC

CCAGGCGGCC

CATCCTCCTC

AACCG CAT CC

CTTCCTCAAC

AGGCATCCGA

AAGGAACATA

CCGACAACCA

GACACCAACC

CCCCAAAAAA

CACACGACCA

CGGCCATCAC

GGGAGCCACC

AAGGACATCA

ACCAAAAGAT

CGGGAATCCC

TGCCATATTC

CAATCTCTCT

TTCCAGCCAT

CACGAGGGTA

AGATGCACTT

GAGACACAAG

TGCTCAGATA

CAATCTGAGA

GCAGGAGATG

TCCACGGACC

CCAGCACAGA

GTGGGACCCC

CCACCACCCC

ACAAGAACTC

CTCCCTAGAC

CACACCCAAC

GAGGGAGCCC

CCCGAACAGA

AGGCCCCCAG

CGGCAACCAA

CCCGCAGA;A

CAACCCGAAC

GTATCCCACA

CAATCCACCA

AGAATCAAGA

ATGGCAGTAC

AAGATAGGGG

CAATCATTAG

GAGATTGCAG

AATGCAATGA

AGATTTGCGG

ACAGCCGGCA

GCGAGCCTGG

ATATTGGCTG

AAGCGAGAGG

ACAGCCCTGA

CGAGGACCAA

CGGGAAAGAA

CACAACCGAA

AGATCCTCTC

AGAACCCAGA

CCAACCAATC

CCCAGCACCC

GGGCCGACAG

ACCAGAACCC

GGAAJAGGCCA

CAGCACCCAA

GCCTCTCCAA

CACCCGACGA

CTCATCCAAT

TGTTAACTCT

TGGTAGGAAT

TCATAAAATT

AATACAGGAG

CCCAGAATAT

GAGTAGTCCT

TTGCACTTCA

AAACTACTAA

TTCAGGGTGT

CCAGCCAGCA

CACAAGGCCA

CCCCCAAGGC

ACCCCCAGCA

CCGCACAAGC

TCCCCGGCAA

CCCCGGCCCA

CCGCCGGTTC

AACCATCGAC

CCAGCACCGC

AGACCACCCT

CAACCCGCGC

GAGCGATCCC

GTCCCCCGGT

CACTCAACTC

GTCCATCATG

CCAGACACCC

AGGAAGTGCA

AATGCCCAAT

ACTACTGAGA

AAGACCGGTT

GGCAGGTGCG

CCAGT6CATG

TCAGGCAATT

CCAAGACTAC

4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000

S

4 5O S 4

S.

91 *0@e *e 4 4 04 @9 4 4 4 4. 9 .9 4 4 *4 9 44.4 9 9&*4 *99*44 4 94*444 9 4.

4 9 94 9 *fl.

ATCAATAATG

CTCGGGCTCA

CGGGACCCCA

ATCAATAAGG

AGCAGAGGAA

AGTATAGCCT

GTCTCGTACA

CAAGGGTACC

GTGTGCAGCC

TCCACCAAGT

TCACAAGGGA

ACGATCATTA

GTAGTCGAGG

TACTTGCACA

AATCTGGGGA

CAGATATTGA

GTGTGTCTTG

AACAAAAAGG

ACATCAAAAT

CACAAGTCTC

TATCTCCGGC

ATCATCCACA

TCCCAAGGGA

TTTGCTGGCT

CATTAGACTT

TCTAGATGTA

AGCTGATACC

AATTGCTCAG

TATCTGCGGA

TGTTAGAAA-A

TAAAGGCCCG

ATCCGACGCT

ACATAGGCTC

TTATCTCGAA

AAAATGCCTT

CCTGTGCTCG

ACCTAATAGC

ATCAAGACCC

TGAACGGCGT

GAATTGACCT

ATGCAATTGC

GGAGTATGAA

GAGGGTTGAT

GAGAACAAGT

CCTATGTAAG

CTCTTCGTCA

TTCCCTCTGG

ATGTCACCAC

AGTAGGATAG

GTTCTGTTTG

CATCGGGCAG

ACTAACTCAA

GTCTATGAAC

ATACTATACA

GATATCTATC

GCTCGGATAC

GATAACTCAC

GTCCGAGATT

TCAAGAGTGG

TTTTGATGAG

GTACCCGATG

TACACTCGTA

CAATTGTGCA

TGACAAGATC

GACCATCCAA

CGGTCCTCCC

TAAGTTGGAG

AGGTTTATCG

AGGGATCCCC

TGGTATGTCA

GTCGCTCTGA

TCAAGCAACC

CCGAACAATA

AACGAGACCG

TCATTAACAG

TCATGTCTCT

CCATCTACAC

TCGAGCATCA

CAACTATCTT

GAAATCCTGT

CAGGCTTTGA

AGTGGAGGTG

GTCGACACAG

AAGGGGGTGA

TATACCACTG

TCATCGTGTA

AGTCCTCTGC

TCCGGGTCTT

TCAATCCTTT

CTAACATACA

GTCGGGAGCA

ATATCATTGG

GATGCCAAGG

AGCACTAGCA

GCTTTAATAT

AGACCAGGCC

TCCTCTACAA

ACCGCACCCA

TCGGTAGTTA

GATAALATGCC

AGAACATCTT

GAGCTTGATC

CGCAGAGATC

GGTCAAGGAC

GTGATTTAAT

CATTATTTGG

GCTATGCGCT

ATTTACTGGG

AGTCCTACTT

TTGTCCACCG

TGCCCAAGTA

CTTTCATGCC

TCCAAGAATG

TTGGGAACCG

GCAAGTGTTA

TTGCTGCCGA

GGAGGTATCC

AGAGGTTGGA

AkATTGTTGGA

TAGTCTACAT

GTTGCTGCAG

TAAAGCCTGA

CTCTTGAAAC

GCATCAAGCC

ATTAAAACTT

TTCTACAAAG

ATGATTGATA

GGGTTGCTAG

CATAAAAGCC

GTGCTGACAC

CGGCCAGAAG

CCCCAGCTTA

TGGAGGAGAC

CATCTTAGAG

CATTGTCCTC

GCTAGAGGGG

TGTTGCAACC

AGAGGGGACT

CCTCCGGGGG

GTTCATTTTA

CACAACAGGA

TCACTGCCCG

AGACGCTGTG

CGTAGGGACA

GTCATCGGAC

CCTGATTGCA

GGGGCGTTGT

TCTTACGGGA

ACAAATGTCC

CACCTGAAAT

AGGGTGCAAG

ATAACCCCCA

GACCTTATGT

CCATTGCAGG

TCAGCACCAA

CACTCTTCAA

6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 92 44000 0 0 00 0 00 00 0000

AATCATCGGT

CATCTCTGAC

TTGGTGTATC

GGCTGCTGAA~

CAATCAGTTC

ATTCTCAAAC

ATCTATAGTC

TAATCTGAGC

AGGTGTTATC

GCAACCAGTC

AGCCCTTTGT

CAGCTTCCAG

CCCCTTATCA

TATCGCTGAC

AATGGAGACA

CGAGTGGGCA

GAGTCTGACA

CGGTTCAGGG

GCCAATGAAG

GGTTAGTCC

AACATACCTA

ACCTGGTCAA

TGTGGTTTAT

GCCTATWAG

CTGGTGCCGT

GATGAAGTGG

AAGATTAAAT

AACCCGCCAG

GAGCTCATGA

CTAGCTGTCT

ATGTCGCTGT

ACTATGACAT

AGCAAAAGGT

AGAAATCCGG

AGTAATGATC

CACGGGGAAG

CTCGTCAAGC

ACGGATGATC

AATCAAGCAA,

TGCTTCCAAC

CCATTGAAGG

GTTGAGCTTA

ATGGACCTAT

AACCTAGCCT

AACCTCTTCA

CCTGCGGAGG

GATCTCCAAT

TACGTTTACA

GGGGTCCCCA

CACTTCTGTG

GCCTGAGGAC

TCCTTA.ATCC

AGAGA.ATCAA

ATGCATTGGT

CAAAGGGAAA

CCCTGTTAGA

CCCAGGGALAT

CAGAGTTGTC

GTTTGGGGGC

TCAGCAACTG

ATTCTATCAC

TAGGTGTCTG

CAGTGATAGA

AATGGGCTGT

AGGCGTGTAA

ATAACAGGAT

AAATCAAAAT

ACAAATCCAA~

TAGGTGTALAT

CTGTCCCAAT

TGGATGGTGA

ATGTTTTGGC

GCCCAGGCCG

TCGAATTACA

TGCTTGCGGA

ACCTCAGAGA

GGATAGGGAC

ATTGGATTAT

GAACTCAACT

CTGCTCAGGG

CTTGTATTTA

GTATGGGGGA

ACAACTGAGC

TCCGGTGTTC

TATGGTGGCT

AATTCCCTAT

GAAATCCCCA

CAGGCTTTAC

CCCGACAACA

GGGTAAAATC

TCCTTCATAC

TGCTTCGGGA

CCACAACAAT

CAACACATTG

TAAGGAAGCA

TGTCAAACTC

AACCTACGAT

CTCATTTTCT

AGTGGAATGC

CTCAGAATCT

TTCACTGACC

TACGACTTCA

GATCAATACT

CTACTGGAGA

CCCACTACAA

AGTCGAGGTT

ACTTACCTAG

ATGTACCGAG

CATATGACAA

TTGGGGGAGC

CAGGGATCAG

ACCGACATGC

CTCTCATCTC

CGAACAGATG

CAAGCACTCT

GGGGTCTTGT

TTCGGGCCAT

GTGTATTGGC

GAGTGGATAC

GGCGAAGACT

AGTTCCAATC

ACTTCCAGGG

TACTTTTATC

TTCACATGGG

GGTGGACATA

TAGTGAAATT

GAGATCTCAC

GTGCAGATGT

CCAGAACAAC

TCAGAGGTCA

ACAATGTGTC

TGGAAAAGCC

TGTTTGAAGT

ACTATCTTGA

TCAAACTCGC

GGAAAGGTGT

AATCCTGGGT

ACAGAGGTGT

ACAAGTTGCG

GCGAGAATCC

CTGTTGATCT

TGATCACACA

TGACTATCCC

CGAGATTCAA

GCCATGCCCC

TGGTGATTCT

TTGAACATGC

CTTTTAGGTT

PLCCAAAAACT

TCACTCACTC

7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 TGGGATGGTG GGCATGGGAG TCAGCTGCAC AGTCACCCGG GAAGATGGAJ,

CCAATCGCAG

93 ATAGGGCTGC TAGTGAACCA ATCACATGAT GTCACCCAGA CATCAGGCAT

ACCCACTAGT

9180 .v r.

4 9.

9 9

GTGAAATAGA

CGCTATCTGT

ATAAGATAGT

CTACACTGTG

TAAACAATGT

CTCATATTCC

CGAGGAAGAT

AGGTTTTCCA

AGGACATCAA

AGCCCTTTCT

CCCATACTTG

TGCTAATCTC

TGACATTTGA

CCGCTATGAC

AACTGATAGA

TGGAGCCTCT

CTTTCCTTAA

ATGAAGGTAC

TACATCTGAC

CAGTAACGGC

AGACTCTGAT

GGCACGGAGG

ATGCTCAAGC

TTGCTGGAGT

ACCTAAAGGA

*CATCAGAATT

CAACCAGATC

AGCCATCCTG

TCAGAACATC

GGAAGTTGGG

ATATCCAAAr

CCGTGAACTC

ATGCTTAAGG

GGAGAAAGTT

GTTTTGGTTT

CCATAGGAGG

TCGTGACCTT

ACTGGTTTTG

TATTGATGCT

TGGTTTCTTC

TTCACTTGCT

CCACTGCTTT

TTATCATGAG

AGGGGAGATT

TGCTGAAAAT

GAA.AGGTCAT

CAGTTGGCCA

TTCAGGTGAA

GAAATTTGGC

CAAGGCACTT

AAGAAAAACG

TTATACCCTG

GAGTATGCTC

AAGCACCGCC

AATGTCATCA

TGTAATCAGG

CTCAAAAAGG

GACACTAACT

ATTAACTTGG

AC-AGTCAAGA

AGACACACAC

GTTGCTATAA

ATGTATTGTG

AGGTATACAG

CCTGCACTCG

TACCTGCAGC

ACTGAAATAC

TTAATTGAAG

TTCTCATTTT

GTTAGGAAAT

GCCATATTTT

CCGCTGACCC

GGGTTAACAC

TGCTTTATGC

GCTGCTCTC

TAGGGTCCAA

AAGTTCACCT

GAGTCCCTCA

TAAAAAACGG

AGTCCAAGCT

ATTTATTTAA

GGAATTCGCT

CACGGCTTGG

GAGTTTACAT

CTGAGATGAG

CTGTATTCTT

TCAGTAAAGA

ATGTCATAGA

AGCTTCTAGG

GGAATCCA~c

TGAGGGATAT

ATGATGTTCT

CTCTAGATTA

TCAGAAGTTT

ACATGAATA

GTGGA.ATCAT

TCCCCCTGCA

ATGAGCAGTG

CTCTTAGCCT

AAAGGGAATG

GTGGTTCCCC

AGATAGCCCG

CGCTTACAGC

ATTTTCCAAC

TAGGAGTTAT

CATAGAAGAC

GTACTCCAAA

CCTAGGCTCC

GCACAGCTCC

GTCAGTGATT

CACTGGTAGT

GTCTCAACAT

GGGGAGGTTA

AAGAGTCAGA

TTATCAAATT

AACAGTAGAA

TGACCAAAAC

CATTTTCATA

CGGCCACCCC

GCCTAAAGTC

AATCAACGGC

rGCTGCAGAC

CGTTGATAAC

GGATAGTGAT

GGATTCAGTT I

GTTATGGACT

ATAGTTACCA

CTGGAGGACC

CAXATGATTA

CCGGCCCACT

AAAGAGTCAA

GTCAGTGATA

GAATTGAGGG

CAGTGGTTTG

AAATCACAAA

TCAGTTGAGT

GTATATTACC

ATGACAGAGA

TACATGTGGA

GTAGCCATGC

CTCAGAGGTG

GGGTTTTCTG

PCTGATGACA

AGACTTGAAG

ATTGTGTATG

TATCGTGACA

kCAATCCGGA

EGGAAATCTT

!TGACAATGT

~ACCCGAALAG

9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 94

AGTTCCTGCG

TTAATGATTC

TCCATGACCC

GTAGACTTTT

TAATCTCAAA

ATTTGACTAA

GTCACAGGGG

GGAACGTGAG

ACACTGATCA

ATCTCAAGAA

TAAATGAGAT

CTGTCCTGTA

ATAAAGTCCC

GTCAGAAGCT

GAGTAAGGAT

TACCCAGCAC

ACTTTGTAAT

CAATTGTTTC

TGTCCCAATC

AAACAAGGGC

ATGACCGTTA

CTCTTGGCTT

ACAACGACCT

TGAATATGAG

ATCTCAAGAG

TTACGACCCT

GAGCTTTGAC

TGAGTTCA.AC

TGCTAAAATG

CGGGATTGGC

GGCACTCCAC

GGGGCCAGTC

AGCAGCAAAA

TCCGGAGAAT

GTACTGCCTT

TTACGGATTG

TGTAAGTGAC

CAATGATCAA

GTGGACCATC

TGCTTCGTTA

ATGGCCCTAC

TCTTAGGCA.A

ATCACATTTT

ACTCAAGAGC

AGCATGCAGT

CCTTGCATAT

CACAATCAAT

CTTAATAAGG

CAGGCTGTTT

AATGATTCTC

CCCAAGGGAA

CCATATGATG

CTGTCTTACA

ACTTACAAAA

AAATATTTTA

ACTCTAGCTG

TTAAAAACCT

GGGTTTATAG

ATGGAAGCTT

AATTGGAGAT

CCCTCATTTT

CCTCATTGCC

ATCTTCATTA

AGCACCATTC

GTGCA.AGGGG

AACCTTAAGA

AGGCTACATG

TTTGTCTATT

ATCGCAAGAT

AATATTGCTA

TCCCTGAACG

TCILACCATGA

ATGGCACTGT

GTCAGAAACA

GCCTCACTAA

CCGGGTCACG

TGATAATGTA

GCCTGAAAGA

TGAGGGCATG

AGGACAATGG

TCTCAGGAGT

ACTCCCGAALG

GGTTCCCTCA

ACGAGACAGT

ATGAGACCAT

TCCAGTGGCT

CCCCCGACCT

AGTACCCTAT

CCTATCTATA

ACAATCAGAC

AACGGGAAGC

ATATTGGCCA

CAAAAGGAAT

GTGTATTCTG

CAACA.ATGGC

TCCTAAAAGT

CCCGGGATGT

TGCCCGCTCC

TCGGTGATCC

TGCCTGAAGA

GAGGCTTGTA

TGTTGTAAGT

AKAGGAGATC

CCAAGTGATT

GATGGCCAAG

CCCCAAAGAT

CCCAGTCCAC

AGTAATTCGG

CAGTGCATTT

CAGCTTGTTT

GCATAAGAGG

TGACGCCCAT

GGGAGGTATA

CCTGGCTGCT

CATAGCCGTA

TGCTAGAGTA

TCACCTCAAG

ATATTATGAT

GTCAGAGACT

TAAAAGCATC

GATACAGCAA

AGTCATACCC

TATTGGGGGG

AGTAACATCA

GACCCTCCAT

GATGTTTTCC

GGAGCTTACC

AAGGAAACAG

GCTGAAAATC

GATGAGCACG

CTCAAAGAAA

ACAAGTACCA

CAGGACCAAG

ATCACGACTG

GCACAGAGGC

CTTGAGACCT

ATCCCGTTAT

GAAGGGTATT

TATGAGAGCG

ACAAAAAGGG

ACTAGAGATT

GCAAATGAGA

GGGCTACTTG

ATAGTTGATG

GAGAGAGGTT

ATTCTGATCT

CTCCTCACA.A

ATGAATTATC

TCAATTGCTG

CAAGTAATGA

10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 CACAACAACC GGGGGACTCT TCATTCCTAG ACTGGGCTAG CGACCCTTAC TCAGCAAATC 95 TTGTATGTGT CCAGAGCATC ACTAGACTCC TCAAGAACAT AACTGCAAGG

TTTGTCCTGA

C C C. C

C

C

C

C

TCCATAGTCC

AGGGACTGGC

TCCTGGATCA

AAGGCCTGAT

TGTCCAATTA

GAAATGTCCT

ATATGTGGGC

TAGAATCTAT

GATCAGTCAA

AGGAAACATC

TGAAGCTTGC

CAGTGTACTC

CTAGGCAAAG

CGACTAATTT

CCCTTGTCCG

CAGATAAGAA

TTTTAGAAAC

TTCACGTCGA

CCCGCAAGCT

CTTTAATTGA

AATTTGTTAC

CTATGATTGA

TAGGGGATGA

TCACTATCTA

AAACCCAATG

GGCATTCCTC

TAGTGTCACA

TCGAGCCAGC

TGACTATGAA

CATTGACAAAJ

GAGGCTAGCT

GCGAGGCCAC

CTACGGATGG

ATCCTTGAGA

CTTCGTAAGA

ATGGGCTTAC

GGCCAATGTG

AGCGCATAGG

AGTGGCGAGG

GGTTGATACT

ATTGTTTCGA

AACAGATTGT

AGAGCTGAGG

CAGAGATGCA

ATGGTCCACA

CCTGGTAACA

CGATATCAAT

CTTGGGCCAG

TTAAAAGGAT

ATGGACAGGC

GGGGCAAGAG

ATGAGGAAGG

CAATTCAGAG

GAGTCATGTT

CGAGGACGGC

CTTATTCGGC

TTTTTTGTCC

GTCCCATATA

GCCCCAAGTC

GGTGATGATG

AGCCTGGAGG

TTGAGGGATC

TATACCACAA

AACTTTATAT

CTCGAGAAAG

TGCGTGATCC

GCAGAGCTAT

ACAAGGCTAT

CCCCA.ACTAT

AAATTTGAGA

AGTTTCATAA

TGTGCGGCCA

*TATTCCATGA

ATATTATAGT

AGTCTATTGC

GGGGGTTAAC

CAGGGATGGT

CAGTGCAGCT

CTATTTACGG

GTCATGAGAC

CCTCGGGTTG

TTGGTTCTAC

GATCCTTGCG

ATAGCTCTTG

AGCTAAGGGT

GTAGCACTCA

TCTCCAACGA

ACCAACAAGG

ATACCGGATC

CGATGATAGA

GTACCAAcCCC

ACACCCAGAG

ATCACATTTT

AGGACCATAT

CTGAGTTTCT

TCAATTGGGC

TGACAGTAA

ACCTAGGGCA

AGGCATGCTG

CTCTCGAGTG

OCTATTGACA

GGCGAGAGCT

CCTTGAGGTC

ATGTGTCATC

CCAACTGGAT

CACTGATGAG

ATCTGCTGTT

GAACGAAGCC

GATCACTCCC

AGTGAAATAC

CAATCTCTCA

AATGCTTCTA

ATCTAACACG

TCATCCCAGG

ATTGATATAT

CCATAGGAGG

AGCTAAGTCC

GAATGAAATT

GCTCATAGAG

1ATTTGATGTA

GAAGAGGACG

GCTCATGAAA

GATACCACAA

ATAACCAGAT

GGAAGAAAGA

CTAAGAAGCC

CCTGATGTAC

TGCGAGTGTG

GATATTGACA

AGAACAGACA

AGAATAGCAA

TGGTTGTTGG

ATCTCAACTT

TCAGGTACAT

TTTGTCATAT

GGGTTGGGTG

GTATTACATC

ATACCCAGCT

GATAATGCAC

CACCTTGTGG

ACAGCACTAT

rcAGCTCTCA

CCAAGATTAT

7ATTATCATA 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 GACCATCAGG GAAATATCAG ATGGGTGAGC TGTTGTCATC GTTCCTTTCT

AGAATGAGCA

96

AAGGAGTGTT

GGCATTGTGG

CAACTGTGTG

AAGAGTTAGA

GATTCGACAA

GGACCTGCCC

ATATCAAGGC

TTGTAGACCA

GATTGAGAGT

CAAAGATCGG

ATGATGTTGC

GGGGCAATCT

CTTGCTACAA

ACGGCTTGTT

AACTAAACAA

AATTAGCACC

TTGTCAA&GT

TCAATTTCAT

AGACCTTGCC

TGGCTCTGCT

GGGATTTTGT

TATACCCTAG

AGGCTAACCG

GGACTTCACC

CAkTTGTGGG

CTATAGAGCA

TAAGGTGCTT

TATTATAGAG

CAACATGGTT

AGAGTTCACA

CATCCAGGCA

ACCAATTCGA

AGAGGCTAGG

TTACTCATGC

TGATCCAGGA

CAGCAACAAC

AAAATTGCTC

CGCCAATTAT

AGCTGTTGAG

CTTGGGTGAG

GTGCTTCTAT

CTATCCCTCC

GCTCTTTAAC

AGTTAGTAAT

TAACAAAGAT

CCTGGGCAAA

TCAGGGATTT

ATACAGCA.AC

GCTAATGAAT

TGGACTTATA

AGACGCAGTT

GGTGCTGATC

GTCAATGCTC

CCTATCCATG

TACACATGCT

TTTCTCTTGT

AAACACTTAT

GGTCTAAGAC

TTATCTCCAG

TCTCTGACTT

TTCATTTTCG

ATCTCAAATA

AAAGATATCA

GAAATCCATG

ATATCAACAT

GGATCGGGTT

AATAGTGGGG

GAAGTTGGCC

GGGAGGCCCG

ATCCCTACCT

ACTATAGAGA

ATAGGATCAA

ATAAGTTATG

TTCATATCTA

CCTGAAAAGA

GGTCACATCC

AGTAGAGGTG

AATTGCGGGT

TAAGCCACCC

GTCCTTCACT

ATATGACCTA

GTGAAAGCGA

GTGTTCTGGC

CGGTAGAGAA

CAGGATCTTC

ATCTCCGGCG

ACGCCCTCGC

TGAGCATCAA

ACACAAGCAA

CTTTCCGCAG

TAATTAGGAG

CTATGTTGAT

TTTCCGCCAA

TTGTCGAACA

AAGTCACGTG

CTAGTGTGGG

AGCTAGAGGA

TACTGGTGAT

TAGGGTCTCA

CTGAATCTTA

TTAAGCAGCA

TATCCATTAA

ATATCAATCC

TGGCAATTAA

AAAGATCTAC

TGATGCTCAA

CCTCGACCTG

CGAGGATGTA

AGATTTGTAC

ATGTGCAGTT

GTGGAACATA

AGGATCGATC

TGAGGTmAT

GGATTTCAGA

GCACAATCTT

AATCGGGTTG

ATGCCTTGAG

CACTTATAAG

TTCTAGATCT

CAGAATGGGA

GGTAGGCAGT

GTTTATCCAT

ATTGGCAGCC

TAAGCTTATG

TTATAGAGAA

TTTGGTTATG

GATAATTGAA

GCAACTAAGC

TACTCTGAAA

CGGACCTAAG

AAGAAATTCT

AACTTGCACA

TTGTTGAATG

GTACCGGACA

TGTCAACCAG

CTAACCGACC

AATCCAATTA

AAACAGATAA

GTCAGTCAGC

CCCCCACACG

CCCATTTCAG

AACTCATCTG

CCAGGGGAAG

GAGATACTTA

GGTCAA-AGGG

GTAGGTAATA

GTAGATTGCT

TCAGATATAG

ATCTTATCGA

CCTTTCAGCG

GTGAACCTTG

ACAGATCTCA

TCATCTGTGA

TGCATACAAG

AAACTTACAC

CTGTGCAAAG

13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15240 15300 15360 4 97 AATTGATCCA CCATGATGTT GCCTCAGGGC AAGATGGATT TCTACAGGGA GTTGGCAAGA TTCAXAGACA ACCAAAGAAG CTTACCCCGT ATTGGTA.AGT AGCAGGCAAC GAGAACTTAT TTTGGGGGCA CATTCTTCTT TACTCCGGGA ACAGAAAGTT ATCTCAAGTC CGGCTATCTG ATACTAGACT TACACCAGAA CCAAGTCAGA GAAACAGATT ATTATGACGG GGGGTTTGAA TAACAGTCAA GGAGACCAAA GAATGGTATA AGTT.AGTCGG ACTAATTGGT TGAACTCCGG AACCCTAATC CTGCCCTAGG TATATTAAAG AAAACTTTGA AAATACGAAG TTTCTATTCC INFORMATION FOR SEQ ID NO:2: SEQUENCE CHARACTERISTICS: LENGTH: 2183 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein

GCTTAATTCT

TCAACAAGGG

ATCTAGGATC

GATAAATAAG

TATCTTCGTT

ACGTGAGTGG

ATACAGTGCC

TGGTTAGGCA

CAGCTTTGTC

ATACTCATCC

ATGTTCCACG

ACCCGCAAAT

TTTATCCAGA

AAGAATCTAT

GTTTTTAAGG

CTGATTAAGG

TTATTTGCAA

TGGT

15420 15480 15540 15600 15660 15720 15780 15840 15894 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: Met Asp Set Leu Ser Val Asn Gin Ile Leu 1 5 10 Asp Ser Pro Ile Val Thr Asn Lys Ile Val 25 Arg Val Pro His Ala Tyr Ser Leu Giu Asp 35 40 Ile Lys His Arg Leu Lys Asn Gly Phe Ser 55 Asn Val Giu Val Gly Asn Val Ile Lys Ser 70 Ala His Ser His Ile Pro Tyr Pro Asn Cys 90 Tyr Pro Giu Val His Leu Ala Ile Leu Pro Thr Leu Asn Gin Met Giu Tyr Ala Cys Gin Asn Ile Ile Asn Lys Leu Arg Ser Tyr Pro Asn Gin Asp Leu Phe 98 Ile Giu Asp Lys Giu Ser Thr Arg Lys Ile Arg Glu Leu Leu Lys Lys 100 105 110

C

C C C .C Gly Arg Ile 145 Trp Ser Pro Leu Phe 225 Thr Arg Gly Al a Leu 305 Phe Ile Phe Asn Asp 130 Lys Phe Val1 Val1 Val 210 Giu Giu Val Asn Tyr 290 Asn Ser Phe Arg Ser 115 Thr Giu Giu Ile Phe 195 Ala Leu Thr Arg Pro 275 Leu His Asp Ile Ser Leu Tyr Asn Ser Lys Val Pro Phe 165 Lys Ser 180 Phe Thr Ile Ile Val Leu Ala Met 245 Tyr Met 260 Thr Tyr Gin Leu Cys Phe Glu Gly 325 Thr Asp 340 Phe Gly Ser Arg Ile i50 Lau Gin Gly Ser Met 230 Thr Trp Gin Arg Thr 310 Thr Asp His Lys Val 120 Leu Gly 135 Asn Leu Phe Trp Thr His Ser Ser 200 Lys Giu 215 Tyr Cys Ile Asp Lys Leu Ile Val 280 Asp Ile 295 Giu Ile Tyr His Ile His Pro Arg S er Leu Gly Phe Thr 185 Val Ser Asp Ala Ile 265 Ala Thr His Glu Leu 345 Lau Asp Gly Val Thr 170 Cys Giu Gin Val Arg 250 Asp Met Val Asp Lau 330 Thr Glu Lys Ser Tyr 155 Val His Leu His Ile 235 Tyr Gly Leu Giu Val 315 Ile Gly Al a Val Glu 140 Met Lys Arg Leu Val 220 Giu Thr Phe Glu Leu 300 Lau Glu Giu Val Phe 125 Leu His Thr Arg Ile 205 Tyr Gly Giu Phe Pro 285 Arg Asp Ala Ile Thr 365 Gin Arg Ser Glu Arg 190 Ser Tyr Arg Leu Pro 270 Lau Gly Gin Lau Phe 350 Ala Cys Giu Ser Met 175 His Arg Leu Lau Lau 255 Ala Ser Ala Asn Asp 335 Ser Ala Leu Asp Gin 160 Arg Thr Asp Thr Met 240 Gly Lau Leu Phe Gly 320 Tyr Phe Glu 355 360 Asn Val Arg Lys Tyr Met Asn Gin Pro Lys Val Ile Val Tyr Glu Thr 99 370 Leu Met Lys Gly Arg Ala His Gly Lys 465 Pro Arg Val Asn Leu 545 Glu Met Val Val Val 625 Asp Al a Glu Cys 450 Asp Lys Leu Ile Leu 530 Phe Asn Al a Ser Leu 610 Arg Arg Asp Gin 435 Phe Lys Glu Val Met 515 Ser Al a Leu Lys Gly 595 Lys Al a His Thr 420 Cys Met Ala Phe Asp 500 Tyr Tyr Lys Ile Asp 580 Val Thr Ala His Ala Ile 390 Gly Gly Ser 405 Ile Arg Asn Val Asp Asn Pro Leu Ser 455 Leu Ala Ala 470 Leu Arg Tyr 485 Val Phe Leu Val Val Ser Ser Leu Lys 535 Met Thr Tyr 550 Ser Asn Gly 565 Glu His Asp Pro Lys Asp Tyr Ser Arg 615 Lys Gly Phe 630 Phe Trp Ala Trp 440 Leu Leu Asp Asn Gly 520 Glu Lys Ile Leu Leu 600 S er Ile Cys Pro Gin 425 Lys Asp Gin Pro Asp 505 Al a Lys Met Gly Thr 585 Lys Pro Gly Gly Pro 410 Al a Ser Ser Arg Pro 490 Ser Tyr Glu Arg Lys 570 Lys Giu Val Phe Met 650 Ile 395 Leu Ser Phe Asp Glu 475 Lys Ser Leu Ile Al a 555 Tyr Al a Ser His Pro 635 Ile Thr Gly Ala Leu 460 Trp Gly Phe His Lys 540 cys Phe Leu His Thr 620 Gin Ile Leu Giu Gly 445 Thr Asp Thr Asp Asp 525 Glu Gin Lys His Arg 605 Ser Val Asn Pro Gly 430 Val Met Ser Gly Pro 510 Pro Thr Val Asp Thr 590 Gly Thr Ile Gly Leu 415 Leu Lys Tyr Val Ser 495 Tyr Glu Gly Ile Asn 575 Leu Gly Arg Arg Tyr 400 His Thr Phe Leu Tyr 480 Arg Asp Phe Arg Al a 560 Gly Ala Pro Asn Gln 640 Asp Gin Asp Thr Asp His Pro Giu Asn Glu Ala Tyr Glu Thr Val 655 100 Ser Ala Phe Ile Thr Thr Asp Leu Lys Lys Tyr Cys Leu Asn Trp Arg 660 665 670 Tyr Giu Thr Ile Ser Leu Phe Ala Gin Arg Leu Asn Giu Ile Tyr Giy 675 680 685 Leu Pro Ser Phe Phe Gin Trp Leu His Lys Arg Leu Giu Thr Ser Vai 690 695 700 Leu Tyr Val Ser Asp Pro His Cys Pro Pro Asp Leu Asp Ala His Ile 705 710 715 720 Pro Leu Tyr Lys Val Pro Asn Asp Gin Ile Phe Ile Lys Tyr Pro Met 725 730 735 Giy Gly Ile Giu Gly Tyr Cys Gin Lys Leu Trp Thr Ile Ser Thr Ile 740 745 750 Pro Tyr Leu Tyr Leu Ala Ala Tyr Giu Ser Gly Vai Arg Ile Ala Ser 755 760 765 Leu Val Gin Gly Asp Asn Gin Thr Ile Ala Val Thr Lys Arg Val Pro 770 775 780 Ser Thr Trp Pro Tyr Asn Leu Lys Lye Arg Giu Ala Ala Arg Val Thr 785 790 795 800 Arg Asp Tyr Phe Val Ile Leu Arg Gin Arg Leu His Asp Ile Gly His .805 810 815 His Leu Lye Ala Aen Giu Thr Ile Val Ser Ser His Phe Phe Vai Tyr 820 825 830 Ser Lys Giy Ile Tyr Tyr Asp Giy Leu Leu Val Ser Gin Ser Leu Lye 835 840 845 **Ser Ile Ala Arg Cys Val Phe Trp Ser Giu Thr Ile Val Asp Giu Thr **850 855 860 Arg Ala Ala Cys Ser Asn Ile Ala Thr Thr Met Ala Lye Ser Ile Giu 865 870 875 880 Arg Gly Tyr Asp Arg Tyr Leu Ala Tyr Ser Leu Asn Val Leu Lys Val 885 890 895 Ile Gin Gin Ile Leu Ile Ser Leu Gly Phe Thr Ile Asn Ser Thr Met 900 905 910 Thr Arg Asp Val Val Ile Pro Leu Lou Thr Asri Asn Asp Leu Leu Ile 915 920 929; 101 Arg Met Ala Leu Leu Pro Ala Pro Ile Gly Gly Met Asn Tyr Leu Asn 930 935 940 Met Ser Arg Leu Phe Val Arg Asn Ile Gly Asp Pro Val Thr Ser Ser 945 950 955 960 Ile Ala Asp Leu Lys Arg Met Ile Leu Ala Ser Leu Met Pro Giu Giu 965 970 975 Thr Leu His Gln Val Met Thr Gin Gin Pro Giy Asp Ser Ser Phe Leu 980 985 990 Asp Trp Ala Ser Asp Pro Tyr Ser Ala Asn Leu Vai Cys Val Gin Ser 995 1000 1005 Ile Thr Arg Leu Leu Lys Asn Ile Thr Ala Arg Phe Val Leu Ile His 1010 loi5 1020 Ser Pro Asn Pro Met Leu Lys Gly Leu Phe His Asp Asp Ser Lys Giu 1025 1030 1035 1040 Glu Asp Glu Giy Leu Ala Ala Phe Leu Met Asp Arg His Ile Ile Val 1045 1050 1055 Pro Arg Ala Ala His Glu Ile Leu Asp His Ser Val Thr Gly Ala Arg .1060 1065 1070 Giu Ser Ile Ala Gly Met Leu Asp Thr Thr Lys Giy Leu Ile Arg Ala ***1075 1080 1085 Ser Met Arg Lys Gly Gly Leu Thr Ser Arg Val Ile Thr Arg Leu Ser 1090 1095 1100 Asn Tyr Asp Tyr Giu Gin Phe Arg Ala Gly Met Val Leu Leu Thr Gly 1105 1110 1115 1120 Arg Lys Arg Asn Val Leu Ile Asp Lys Giu Ser Cys Ser Val Gin Leu 1125 1130 1135 Ala Arg Ala Leu Arg Ser His Met Trp, Ala Arg Leu Ala Arg Gly Arg C1140 1145 1150 *Pro Ile Tyr Gly Leu Glu Val Pro Asp Val Leu Giu Ser Met Arg Gly 1155 1160 1165 His Leu Ile Arg Arg His Glu Thr Cys Val Ile Cys Giu Cys Gly Ser 1170 1175 1180 Val Asn Tyr Giy Trp Phe Phe Val Pro Ser Gly Cys Gin Leu Asp Asp 1185 1190 1195 1200 Ile Asp Lys Glu Thr Ser Ser Leu Arg Val Pro Tyr Ile Gly Ser Thr 102 1205 1210 1215 Thr Asp Giu Arg Thr Asp Met Lys Leu Ala Phe Val Arg Ala Pro Ser 1220 1225 1230 Arg Ser Leu Arg Ser Ala Val Arg Ile Ala Thr Val Tyr Ser Trp Ala 1235 1240 1245 Tyr Gly Asp Asp Asp Ser Ser Trp Asn Giu Ala Trp Leu Leu Ala Arg 1250 1255 1260 Gin Arg Ala Asn Val Ser Leu Giu Glu Leu Arg Val Ile Thr Pro Ile 1265 1270 1275 1280 Ser Thr Ser Thr Asn Leu Ala His Arg Leu Arg Asp Arg Ser Thr Gin 1285 1290 1295 Val Lys Tyr Ser Gly Thr Ser Leu Val Arg Val Ala Arg Tyr Thr Thr 1300 1305 1310 Ile Ser Asn Asp Asn Leu Ser Phe Val Ile Ser Asp Lys Lys Val Asp 1315 1320 1325 Thr Asn Phe Ile Tyr Gin Gin Gly Met Leu Leu Gly Leu Gly Val Leu 1330 1335 1340 Giu Thr Leu Phe Arg Leu Glu Lys Asp Thr Gly Ser Ser Asn Thr Val 1345 1350 1355 1360 *Leu His Leu His Val Glu Thr Asp Cys Cys Val Ile Pro Met Ile Asp 1365 1370 1375 *His Pro Arg Ile Pro Ser Ser Arg Lys Leu Glu Leu Arg Ala Giu Leu **.1380 1385 1390 Cys Thr Asn Pro Leu Ile Tyr Asp Asn Ala Pro Leu Ile Asp Arg Asp 1395 1400 1405 **Ala Thr Arg Leu Tyr Thr Gin Ser His Arg Arg His Leu Val Giu Phe 1410 1415 1420 Val Thr Trp Ser Thr Pro Gin Leu Tyr His Ile Leu Ala Lys Ser Thr 1425 1430 1435 1440 Ala Leu Ser Met Ile Asp Leu Val Thr Lys Phe Giu Lys Asp His Met 1445 1450 1455 Aen Glu Ile Ser Ala Leu Ile Gly Asp Asp Asp Ile Asn Ser Phe Ile 1460 1465 1470 Thr Giu Phe Leu Leu Ile Giu Pro Arg Leu Phe Thr Ile Tyr Leu Gly 147 5 1480 1485 103 Gin Cys Ala Ala Ile Asn Trp Ala Phe Asp Val His Tyr His Arg Pro 1490 1495 1500 Ser Gly Lys Tyr Gin Met Gly Glu Leu Leu Ser Ser Phe Leu Ser Arg 1505 1510 1515 1520 Met Ser Lys Gly Val Phe Lys Val Leu Val Asn Ala Leu Ser His Pro 1525 1530 1535 Lys Ile Tyr Lys Lys Phe Trp His Cys Gly Ile Ile Giu Pro Ile His 1540 1545 1550 Gly Pro Ser Leu Asp Ala Gin Asn Leu His Thr Thr Val Cys Asn Met 1555 1560 1565 Val Tyr Thr Cys Tyr Met Thr Tyr Leu Asp Leu Leu Leu Asn Giu Giu 1570 1575 1580 Leu Glu Glu Phe Thr Phe Leu Leu Cys Giu Ser Asp Giu Asp Val Val 1585 1590 1595 1600 Pro Asp Arg Phe Asp Asn Ile Gin Ala Lys His Leu Cys Val Leu Ala 1605 1610 1615 Asp Leu Tyr Cys Gin Pro Gly Thr Cys Pro Pro Ile Arg Gly Leu Arg 1620 1625 1630 :cPro Vai Giu Lys Cys Ala Val Leu Thr Asp His Ile Lys Ala Glu Ala 1635 1640 1645 Arg Leu Ser Pro Ala Gly Ser Ser Trp Asn Ile Asn Pro Ile Ile Val 1650 1655 1660 .*Asp His Tyr Ser Cys Ser Leu Thr Tyr Leu Arg Arg Gly Ser Ile Lys 1665 1670 1675 1680 **Gin Ile Arg Leu Arg Val Asp Pro Gly Phe Ile Phe Asp Ala Leu Ala 1685 1690 1695 Giu Val Asn Val Ser Gin Pro Lys Ile Gly Ser Asn Asn Ile Ser Asn 1700 1705 1710 Met Ser Ile Lys Asp Phe Arg Pro Pro His Asp Asp Val Ala Lys Leu 1715 1720 1725 Leu Lys Asp Ile Asn Thr Ser Lys His Asn Leu Pro Ile Ser Gly Giy 1730 1735 1740 Asn Leu Ala Asn Tyr Giu Ile His Aia Phe Arg Arg Ile Gly Leu Asn 1745 1750'1- )D 1700 104 Ser Ser Ala Cys Tyr Lys Ala Vai Giu Ile Ser Thr Leu Ile Arg Arg 1765 1770 1775 Cys Leu Giu Pro Gly Glu Asp Gly Leu Phe Leu Giy Giu Gly Ser Gly 1780 1785 1790 Ser Met Leu Ile Thr Tyr Lye Giu Ile Leu Lys Leu Asn Lys Cys Phe 1795 1800 1805 Tyr Asn Ser Giy Val Ser Ala Asn Ser Arg Ser Gly Gin Arg Giu Leu 1810 1815 1820 Ala Pro Tyr Pro Ser Glu Val Giy Leu Val Glu His Arg Met Gly Val 1825 1830 1835 1840 Gly Asn Ile Val Lys Val Leu Phe Asn Gly Arg Pro Giu Val Thr Trp 1845 1850 1855 Val Gly Ser Val Asp Cys Phe Asn Phe Ile Val Ser Asn Ile Pro Thr 1860 1865 1870 Ser Ser Vai Gly Phe Ile His Ser Asp Ile Giu Thr Leu Pro Asn Lys 1875 1880 1885 *Asp Th~r Ile Giu Lys Leu Giu Giu Leu Ala Ala Ile Leu Ser Met Ala .1890 1895 1900 Leu Leu Leu Gly Lye Ile Gly Ser Ile Leu Val Ile Lys Leu Met Pro *1905 1910 1915 1920 Phe Ser Gly Asp Phe Val Gin Gly Phe Ile Ser Tyr Val Gly Ser His 1925 1930 1935 Tyr Arg Giu Val Asn Leu Val Tyr Pro Arg Tyr Ser Aen Phe Ile Ser 1940 1945 1950 Thr Glu Ser Tyr Leu Val Met Thr Asp Leu Lye Ala Asn Arg Leu Met 1955 1960 1965 Asn Pro Giu Lye Ile Lye Gin Gin Ile Ile Giu Ser Ser Val Arg Thr 1970 1975 1980 *Ser Pro Gly Leu Ile Gly His Ile Leu Ser Ile Lye Gin Leu Ser Cys 1985 1990 1995 2000 Ile Gin Ala Ile Val Gly Asp Ala Val Ser Arg Gly Asp Ile Aen Pro 2005 2010 2015 Thr Leu Lye Lye Leu Thr Pro Ile Glu Gin Val Leu Ile Asn Cys Gly 2020 2025 2030 Leu Ala Ile Asn Gly Pro Lys Leu Cys Lys Glu Leu Ile His His Asp 105 2035 2040 2045 Val Ala Ser Giy Gin Asp Gly Leu Leu Asn Ser Ile LeU Ile Leu Tyr 2050 2055 2060 Arg Giu Leu Ala Arg Phe Lys Asp Asn Gin Arg Ser Gin Gin Gly Met 2065 2070 2075 2080 Phe His Ala Tyr Pro Val Leu Val Ser Ser Arg Gin Arg Glu Leu Ile 2085 2090 2095 Ser Arg Ile Thr Arg Lys Phe Trp, Gly His Ile Leu Leu Tyr Ser Gly 2100 2105 2110 Asn Arg Lys Leu Ile Asn Lys Phe Ile Gin Asn Leu Lys Ser Gly Tyr 2115 2120 2125 Leu Ile Leu Asp Leu His Gin Asn Ile Phe Val Lys Asn Leu Ser Lys 2130 2135 2140 Ser Giu Lys Gin Ile Ile Met Thr Gly Gly Leu Lys Arg Giu Trp Val 2145 2150 2155 2160 Phe Lys Val Thr Val Lys Glu Thr Lys Giu Trp Tyr Lys Leu Val Gly 2165 2170 2175 Tyr Ser Ala Leu Ile Lys Asp 2180 INFORMATION FOR SEQ ID NO;3: SEQUENCE CHARACTERISTICS: LENGTH: 15894 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) SEQUENCE DESCRIPTION: SEQ ID NO:3: ACCAAACAAA GTTGGGTAAG GATAGATCAA TCAATGATCA TATTCTAGTA CACTTAGGAT TCAAGATCCT ATTATCAGGG ACAAGAGCAG GATTAGGGAT ATCCGAGATG GCCACACTTC 120 TAAGGAGCTT AGCATTGTTC AAAAGAAACA AGGACAAACC ACCCATTACA TCAGGATCCG 180 GTGGAGCCAT CAGAGGAATC AAACACATTA TTATAGTACC AATCCCGGGA GATTCCTCAA 240 106

TTACCACTCG

GCGGGCCCAA

GTCAATTGAT

TCCAGAGTGA

ATGAGGCGGA

GATGGTTCGA

TGATTCTGGG

CAGACACGGC

TAGTTGGTGA

AGGACCTCTC

GGAACAAACC

GATTAGCCAG

GACTGCATGA

AAATGGGGGA

GTGCAGGATC

ACTCCATGGG

GGCAAGAGAT

GTATCACTGC

GGATCAGTAG

ATGAAAATGA

GAGAAGCCAG

CCCATCCTCC

CGCAGGACAG

CGGAAGAACA

ACTAGGTGCA

AAAACTTAGG

ATCTAGACTT

ACTAACAGGG

TCAGAGGATC

CCAGTCACAA

CCAATATTTT

GAACAAGGAA

TACCATCCTA

AGCTGATTCG

ATTTAGATTG

CTTACGCCGA

CAGGATTGCT

TTTTATCCTG

ATTTGCTGGT

AACTGCACCA

ATACCCTCTG

AGGTTTGAAC

GGTGAGGAGG

CGAAGATGCA

AGCGGTTGGA

GCTACCGAGA

AGAGAGCTAC

AACCGACACA

TCGAAGGTCA

AGGCTCAGAC

AGAGGCCGAG

AACCAGGTCC

CTGGACCGGT

GCACTAATAG

ACCGA'rGACC

TCTGGCCTTA

TCACATGATG

ATCTCAGATA

GCTCAAATTT

GAGCTA.AGAA

GAGAGAAAAT

TTCATGGTCG

GAAATGATAT

ACTATTAAGT

GAGTTATCCA

TACATGGTAA

CTCTGGAGCT

TTTGGCCGAT

TCAGCTGGAA

AGGCTTGTTT

CCCAGACAAT

TGGGGGGGTA

AGAGAAACCA

CCCTTAGACA

GCTGACGCcC

ACGGACACCC

GACCAGAACA

ACACAGCCGC

TGGTCAGGTT

GTATATTATC

CTGACGTTAG

CCTTCGCATC

ATCCAAGTAG

TTGAAGTGCA

GGGTCTTGCT

GGTGGATAAA

GGTTGGATGT

CTCTAATCCT

GTGACATTGA

TTGGGATAGA

CACTTGAGTC

TCCTGGAGAA

ATGCCATGGG

CTTACTTCGA

AGGTCAGTTC

CAGAGATCGC

CCCAAGTGTC

AGGA.AGATAT

GGCCCAGCAG

TTGACACTGC

TGCTCAGGCT

CTAGAGTGTA

ACATCCGCCT

CAGCCCACCA

AATTGGAAAC

CTTATTTGTG

CATAAGGCTG

ALAGAGGTACC

TAGTGATCAA

AGACCCTGAG

CGCAA.AGGCG

GTACACCCAA

GGTGAGGAAC

GGATATCALAG

TACATATATC

AACTATGTAT

CTTGATGAAT

CTCAATTCAG

AGTAGGAGTG

TCCAGCATAT

CACATTGGCA

AATGCATACT

ATTCCTACAC

GAGGGTCAAA

AGCAAGTGAC

ATCGGAGTCC

GCAAGCCATG

CAATGACAGA

ACCCTCCATC

ACCATCCACT

CCGGATGTGA

GAGTCTCCAG

TTAGAGGTTG

AACATGGAGG

TCCAGGTTCG

GGATTCAACA

GTTACGGCCC

CAAAGAAGGG

AGGATTGCCG

AGAACACCCG

GTAGAGGCAG

CCTGCTCTTG

CTTTACCAGC

AACAAGTTCA

GAACTTGAAA

TTCAGACTAG

TCTGAACTCG

ACAGAGGACA

GGTGATCAAA

CAGAGTCGGG

GCGAGAGCTA

AGCCAAGATC

GCAGGAATCT

GATCTTCTAG

ATTGTTATAA

CCCACGATTG

300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 107 GGGCCGATGG CAGAAGAGCA GGCACGCCAT GTCAAAAACG GACTGGAATG CATCCGGGCT

CTCAAGGCCG

ATATCAGACA

GGTCTCAGCA

CGCGGTCAGG

AATCTCCAGG

GCGGTTAAGG

AGCACCCTCT

GATACCGAGG

GCTTCTGATG

AGAGGCAACA

GGTAGGGCCA

TTTGGAACGG

CCCTCGGAAC

GCCGTACTGA

AATAATGAAG

AAALACAGCCT

CTGCTGTTAT

AGCATATCCA

AAGGATCCCA

GGCAGAGATT

ATCCAAGGAA

CTAAAGCCGA

GCATCACGCA

CGTTACCTGA

CAGATGCTGA

AGCCCATCGG

ACCCAGGACA

AACCATGCCT

GATCTGGAGA

CATCAAGCAC

GAATCCAAGA

CAGGAGGAGA

GATATGCTAT

TTGAA.ACTGC

ACTTTCCAAA

GCACTTCCGA

AGATCGCGTC

CATCAGGGCC

TACAGGAGTG

AAGGGGGAGA

TGGCCAAAAT

TGAAGGGGGA

CCTTGGAAGG

ACGACCCCAC

CAGGCCGAGC

TGACAAATGG

TCGGGAAAAA

GTGTAATCCG

TGACTCTCCT

TGAAGATAAT

CTCACTGGCC

GGAGCGAGCC

CTCAGCAATT

GAGCGATGAC

TGGGTTACAG

TGCTGACTCT

CAATGA.ATCT

CACTGACCGG

AGILAGGAGGG

GCTTAGGAAA

GACACCCATT

TTTATTGACA

AGGTGCACCT

GACACCCGAA

TTATTATGAT

ACACGAGGAT

AGTTGAGTCA

ACACCTCTCA

TGCAGATGTC

ACTGGCTGAA

ACGGACCAGT

GATGAGCTCA

CTCCATTATA

TGATGACATC

AATGAAGTAG

ATCGAGGAAG

GCCTGCA.AGG

GGATCAACTG

GACGCTGAAA

TGTTATTATG

ATCATGGTTC

GAAAACAGCG

GGATCTGCTC

GAGATCCACG

ACTCTCAATG

AAAAAGGGCA

GGTGGTGCAA

GCGGGGAATG

TCTGGTACCA

GATGAGCTGT

AATCAGAAGA

ATCAAGAAGC

AGCATCATGA

GAAATCAATC

GTTCTCAAGA

TCCAGAGGAC

GCCGTCGGGT

AAATCCAGCC

AAAGGAGCCA

CTACAGCTCA

CTATGGCAGC

ILAGAGAAGGC

AAGGCGGTGC

CTTTGGGAAT

TTTATGATCA

ALATCAGGCCT

ATGTGGATAT

CCATCTCTAT

AGCTCCTGAG

TTCCCCCGCCC

CAGACGCGAG

CCCAATGTGC

TCCCCGAGTG

CAATCTCCCC

TCTCTGATGT

TAATCACCAA

AGATCAACAG

TCGCCATTCC

CCGACTTGAA

AACCCGTTGC

AGCTGCTGAA

TTGTTCCGGA

GGCTAGAGGA

ACGATCTTGC

ACTTACCTGC

ATGGTCAGAA

AAGCAGTCCG

ACCTCGCATC

CCCCTCAGGA

CAGCGGTGAA

TGATGGTGAT

TGGCGALACCT

GGGGTTCAGG

ACTCCAATCC

CCCGGACCCT

ATTAGCCTCA

TCGAAAGTCA

TGTGAGCAAT

GAGATCCCAG

CCAAGATATT

GCTAGAATCA

GCAAAATATC

TGGACTTGGG

ACCCATCATA

CAGCCGACAA

GGAATTTCAG

CACCGGCCCT

GGATCGGAAG

CAAGTTCCAC

CAACCCCATG

1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 108 CCAGTCGACC TAGCTAATAC AACCTAAATC CATTATAAAA AACTTAGGAG CA.A1GTGATT

GCCTCCCAAG

AAGGGTCGAT

TCAGAGTCAT

TGCTGGGGGT

CTCTGCCCTT

CTGAGCTTGA

ACAACACCCC

TCAACGCAAA

TCCGTGTTGT

GAAGAATGCT

GGATTGACAA

CAACATTTAT

ATTATTGCAA

GCACCAGTCT

GGTTCAAGAA

TCTGGAGGAG

AAGAATTCCG

TGTAGACCGT

GCCCGGAAAA

GCTGACGGCA

CCACCAGCCA

TGCCCCCCAC

ACTGGAAGAG

GACCGAGGTG

TTCCACAATG

CGCTCCGATA

AGATCCTGGT

TGTTGAGGAC

AGGTGTTGGC

CATAGTTGTT

ACTAACTCTC

CCAAGTGTGC

TTATATGAGC

GGAATTCAGA

GGCGATTGGC

GGTCCACATC

AATGAAAATC

TCACATTAGA

GACCCTATGT

CAGATGCAAG

CATTTACGAC

AGTGCCCAGC

AAAGGCCCCC

AGCACGAACA

TCCCAATCTG

CCAAACCACC

CCCTTCCCCT

ACCCAACCGC

ACAGAGATCT

CAACCCACCA

CTAGGCGACA

AGCGATCTCC

AGATCCACAG

AGACGTACAG

CTCATACCTT

AATGCGGTTA

ATCACCCGTC

TCGGTCAATG

CATGGGAAGA

GGGAACTTCA

GAAAAGATGG

AGCACAGGCA

TACCCACTGA

ATAGTAAGA

GACGTTATCA

AATGCCCGAA

TCCGAA.AGAC

CCAGGCGGCC

CATCCTCCTC

AACCGCATCC

TTCCCTCAAC

AGGCACCCGA

ACGACTTCGA

CCTACAGTGA

GAAAAGATGA

TAGGGCCTCC

CAAAACCCGA

CAGGGCTCAA

GGAGAAAGGT

ATCTGATACC

TTTCAGATAA

CAGTGGCCTT

TCATCGACAA

GGAGAXAGAA

GCCTGGTTTT

AAkATGAGCAA

TGGATATCAA

TCCAGGCAGT

TAAATGATGA

GACGACCCTC

TCCACAGACC

CCAGCACAcIA

GTAGGACCCC

CTACCACCCC

ACAAGAACTC

CTCCCTAGAC

CAAGTCGGCA

TGGCAGGCTG

ATGTTTTATG

A.ATCGGGCGA

AGAACTCCTC

TGAAAAACTG

CCTAACAACA

GCTGGATACC

CGGGTATTAC

CAACCTGCTG

TGCAGAGCAA

AAGTGAAGTC

TGCACTTGGT

GACTCTCCAT

TGAAGACCTT

TTTGCAGCCA

CCAAGGATTA

CTCACAATGA

AAATGAGAGG

ACAGCCCTGA

CGAGGACCAA~

CGGGAAAGAA

CACAACCGAA

PGATCCTCTC

TGGGACATCA

GTGCCCCAGG

TACATGTTTC

GCATTTGGGT

AAAGAGGCCA

GTGTTCTACA

GGGAGTGTCT

CCGCAGAGGT

ACCGTTCCTA

GTGACCCTTA

CTTCCTGAGG

TACTCTGCCG

GGGATAGGGG

GCACAACTCG

AATCGATTAC

TCAGTTCCTC

TTCAAAGTTC

CAGCCAGAAG

CCAGCCAGCA

CATAAGGCCA

CCCCCAAiGGT kCCCCCAGCA 7CACACAAGC

CCCTGGCAA

3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 ACTAAACAAA ACTTAGGGCC AAGGAACATA CACACCCAAC AGAACCCAGA CCCCGGCCCA 4920 109 a a a. a.

a a a a a a a..

a a a a a.

a

CGGCGCCGCG

CCCCGGTGCC

AATCCAAGAC

GAGGAAGCCC

GGGCCACCAG

ACCCCAGCCC

CGAAGGACCC

CTCTTCCTCT

CCCGTCCCTA

GGTCTCAAGG

ACCGGTCA;A

AGCTACAILAG

ATAACTCTCC

ACAGTTTTGG

CAGAGTGTAG

GCCCTAGGCG

CTGAACTCTC

GAGGCAATCA

ATCAATAATG

CTCGGGCTCA

CGGGACCCCA

ATCAATAAGG

AGCAGAGGIA

AGTATAGCCT

GTCTCGTACA

CAAGGGTACC

CCCCCAACCC

CACAGGCAGG

GGGGGGGCCC

ACCCACCCCA

TTCCCAGACT

CGATCCGGCG

CCGAACCGCA

TCTCGAAGGG

AAGGAGACAC

TGAACGTCTC

TCCATTGGGG

TTATGACTCG

TCAATAACTG

AACCAATTAG

CTTCALAGTAG

TTGCCACAGC

AAGCCATCGA

GACAAGCAGG

AGCTGATACC

AATTGCTCAG

TATCTGCGGA

TGTTAGAAAA

TAAAGGCCCG

ACCCGACGCT

ACATAGGCTC

TTATCTCGAA

CCGACAACCA

CACACCAACC

CCC CAAAAAA

CACACGACCA

CGGCCATCAC

GGCAGCCACC

AAGGACATCA

ACTAAAAGAT

CGGGAATCCC

TGCCATATTC

CAATCTCTCT

TTCCAGCCAT

CACGAGGGTA

AGATGCACTT

GAGACACAAG

TGCTCAGATA

CAATCTGAGG

GCAGGAGATG

GTCTATGAAC

ATACTATACA

GATATCTATC

GCTCGGATAT

GATAACTCAC

GTCCGAGATC

TCAAGAGTGG

TTTTGATGAG

GAGGGAGCCc

CCCGAACAGA

AGGCCCCCAG

CGACAACCAA

CCCGCAGAAA

CALACCCTAAC

GTATCCCACA

CAATCCACCA

GGAATTAAGA

ATGGCAGTAC

AAGATAGGGG

CAATCATTAG

GAGATTGCAG

AATGCAATGA

AGATTTGCAG

ACAGCCGGCA

GCAAGTCTGG

ATATTGGCTG

CAACTATCTT

GAAATCCTGT

CAGGCTTTGA

AGTGGAGGTG

GTCGAkCACAG

AAGGGGGTGA

TATACGACTG

TCATCGTGTA

CCAACCAATC

CCCAGCACCC

GGGCCGACAG

ACCAGAACCC

GGAAAGGCCA

CAGCACCCAA

GCCTCTCCAA

CATCCGACGA

CTCATCCAAT

TGTTAACTCT

TGGTAGGAAT

TCATAAAATT

AATACAGGAG

CCCAGAATAT

GAGTAGTCCT

TTGCACTTCA

AAACTACTAA

TTCAGGGTGT

GTGATTTAAT

CATTATTTGG

GCTATGCGCT

ATTTACTGGG

AGTCCTACTT

TTGTCCACCG

TGCCCAAGTA

CTTTCATGCC

CCGCCGGCTC

AGCCATCGAC

CCAGCACCGC

AGACCACCCT

CAACCTGCGC

GAGCGATCCC

GTCCCCCGGT

CACTCAACTC

GTCCATCATG

CCAAACACCC

AGGAAGTGCA

AATGCCCAAT

ACTACTGAGA

AAGACCGTTT

GGCAGGTGCG

CCAGTCCATG

TCAGGCAATT

CCAAGACTAC

CGGCCAGAAG

CCCTAGCTTA

CGGAGGAGAT

CATCTTAGAG

CATTGTCCTC

GCTAGAGGGG

TGTTGCAACC

AGAGGGGACT

4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 110 p.

GTGTGCAGCC

TCCACCAAGT

TCACAAGGGA

ACGATCATTA

GTAGTCGAGG

TACTTGCACA

AkATCTGGGGA

CAGATATTGA

GTGTGTCTTG

AACAAAAAGG

ACATCGAAAT

CACAAGTCTC

TATCTCCGGC

ATCATCCACA

TCCCAAGGGA

TTTGCTGGCT

CATTAGACTT

TCTAGATGTA

AATCATCGGT

CATCTCTGAC

TTGGTGTATC

GGCTGCTGAA

C.AATCAGTTC

ATTCTCAAAC

ATCTATAGTC

TAATCTGAGC

AAAATGCCTT

CCTGTGCTCG

ACCTA.ATAGC

ATCAAGACCC

TGAACGGCGT

GAATTGACCT

ATGCAATTGC

GGAGTATGAA

GAGGGTTGAT

GAGAACAAGT

CCTATGTAAG

CTCTTCGTCA

TCCCCTTTGG

ATGTCACCAC

AGTAGGATAG

GTTCTGTTCG

CATCGGGCAG

ACTALACTCAA

GATGAAGTGG

AAGATTAXAT

AACCCGCCAG

GAGCTCATGA

CTAGCTGTCT

ATGTCGCTGT

ACTATGACAT

AGCAAAGGGT

GTACCCGATG

TACACTCGTA

CAATTGTGCA

TGACILAGATC

GACCATCCAA

CGGTCCTCCC

TAAGTTGGAG

AGGTTTGTCG

AGGGATCCCC

TGGTATGTCA

GTCGCTCTGA

TCAAGCAACC

CCGAACAATA

ALACGAGACCG

TTATCAACAG

TCATGTTTCT

CCATCTACAC

TTGAGCATCA

GCCTGAGGAC

TCCTTAACCC

AGAGAATCAA

ATGCATTGGT

CAAAGGGAAA

CCCTGTTGGA

CCCAGGGAAT

CAGAGTTGTC

AGTCCTCTGC

TCTGGGTCTT

TCAATCCTTT

CTAACATACA

GTCGGGAGCA

ATATCATTGG

GATGCCAAGG

AGCACTAGCA

GCTTTAATAT

AGACCAGGCC

TCCTCTACIA

ACCGCATCCA

TCGGTAGTTA

GATAA.ATGCC

AGAACACCTT

GAGCTTGATC

CGCAGAGATC

GGTCAAGGAC

ACCTCAGAGA

GGATAGGGAG

ATTGGATTAT

GAACTCAACT

CTGCTCAGGG

CTTGTATTTA

GTACGGGGGA

ACAACTGAGC

TCCAAGAATG

TTGGGAkACCG

GCAAGTGTTA

TTGCTGCCGA

GGAGGTATCC

AGAGGTTGGA

AATTGTTGGA

TAGTCTACAT

GTTGCTGCAG

TAAAGCCTGA

CTCTTGGAAC

GCATCAAGCC

ATTAAAACTT

TTCTACAAAG

ATGATTGATA

GGGTTGCTAG

CATAAAAGCC

GTGCTGACAC

TTCACTGACC

TACGACTTCA

GATCAATACT

CTACTGGAGA

CCCACTACAA

AGTCGAGGTT

ACTTACCTAG

ATGTACCGAG

CCTCCGGGGG

GTTCATTTTG

CACAACAGGA

TCACTGCCCG

AGACGCTGTG

CGTAGGGACA

GTCATCGGAC

CCTGATTGCA

GGGGCGTTGT

TCTTACAGGA

ACAAATGTCC

CACCTGAAAT

AGGGTGCAAG

ATAACCCCCA

GACCTTATGT

CAATTGCAGG

TCAGCACCAA

CACTCTTCAA

TAGTGAAATT

GAGATCTCAC

GTGCAGATGT

CCAGAACAAC

TCAGAGGTCA

ACAATGTGTC

TGGAAAAGCC

TGTTTGAAGT

6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 ill1 AGGTGTTATC AGAkATCCGG GTTTGGGGGC TCCGGTGTTC CATATGACAA ACTATTTTGA 8100

GCAACCAGTC

AGCCCTTTGT

CAGCTTTCAG

AGTAATGATC

CACGGGGGAG

CTCGTCAAGC

CCCCTTCTCA ACGGATGACC too* 0*S 060 S 00.055 0:00.:

TATCGCTGAC

AATGGAGACA

CGAGTGGGCA

GAGTCTA.ACA

CGGTTCAGGG

GCCAATGAAG

GGTTAGTCCC

AACATACCTA

ACCTGGTCAA

TGTGGTTTAT

GCCTATAAAG

CTGGTGCCGT

TGGGATGGTG

ATAGGGCTGC

GTGAAATAGA

CGCTATCTGT

ACAAGATAGT

CTACACTGTG

TAAACAATGT

CTCATATTCC

CGAGGAAGAT

AATCAAGCAA

TGCTTCCAGC

CCATTGAAGG

GTTGAGCTTA

ATGGACCTAT

AACCTAGCCC

AACCTCTTCA

CCTGCGGAGG

GATCTCCAAT

TACGTTTACA

GGGATCCCCA

CACTTCTGTG

GGCATGGGAG

CAGTGAACCA

CATCAGAATT

CAACCAGATC

AGCCATCCTG

TCAGAACATC

GGAAGTTGGG

ATATCCAAAC

CCGTGAACTC

TCAGCAACTG

ATTCTATCAC

TAGGTGTCTG

CAGTGATAGA

AATGGGCTAT

AGGCGTGTAI.

ATAACAGGAT

AAATCAAAAT

ACAAGTCCAA

TAGGTGTA.AT

CTGTCCCAAT

TGGATGGTGA

ATCTTTTGGC

GCCCAAGCCG

TCGAkATTACA

TGCTTGCGGA

rCAGCTGCAC kTCACATGAT

PAGAAAAACG

rTATACCCCG 3AGTATGCTC kAGCACCGCC

!LATGTCATCA

EGTAATCAGG

:TCAAAAAGG

TATGGTGGCT

AATTCCCTAT

GAAATCCCCA

CAGGCTTTAC

CCCGACAACA

GGGTAAAATC

TCCTTCATAC

TGCTTCGGGA

CCACAACA.AT

CAACACATTG

TAAGGAAGCA

TGTCAAACTC

AACCTACGAT

CTCATTTTCT

AGTGGAATGC

CTCAGAATCT

AGTCACCCGG

GTCACCCAGA

TAGGGTCCAA

AAGTTCACCT

GAGTCCCTCA

TAAAAAACGG

PGTCCAAGCT

PTTTATTTAA

GAAATTCGCT

TTGGGGGAGC

CAGGGATCAG

ACCGACATGC

CTCTCATCTC

AGAACAGATG

CAAGCACTCT

GGAGTCTTGT

TTCGGGCCAT

GAGTATTGGC

GAGTGGATAC

GGCGAAGACT

AGTTCCAATC

ACTTCCAGGG

TACTTTTATC

TTCACATGGG

GGTGGACATA

GAAGATGGAA

CATCAGGCAT

GTGGTTCCCC

AGATAGCCCG

CGCTTACAGC

ATTTTCCAAC

TAGGAGTTAT

CATAGAAGAC1

GTACTCTAAAC

TCAA.ACTCGC

GGAAAGGTGT

AATCCTGGGT

ACAGAGGTGT

ACAAGTTGCG

GCGAGAATCC

CTGTTGATCT

TGATCACACA

TGACTATCCC

CGAGATTCAA

GCCATGCCCC

TGGTGATCCT

TTGAACATGC

CTTTTAGGTT

ACCAA.AAACT

TCACTCACTC

CCAATAGCAG

PCCCACTAGT

GTTATGGACT

kTAGTTACCA

CTGGAGGACC

7AAATGATTA

XGGCCCACT

LZLAGAGTCAA

;TCAGTAATA

8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 112 000S 0 0@e* @0 08 0 0 @6 @0 S S 5 00 00 S

S.

0 0 0

S

@05660

S

0 *000

AGGTTTTCCA

AGGACATCAA

AGCCCTTTCT

CCCATACTTG

TGCTAATCTC

TAACATTTGA

CTGCTATGAC

AATTGATAGA

TGGAGCCTCT

CTTTCCTTAA

ATGAAGGTAC

TACACCTGAC

CAGTAACGGC

AGACTCTGAT

GGCACGGAGG

ATGCTCAAGC

TTGCTGGAGT

ACCTAAAGGA

AGTTCCTGCG

TTAATGATTC

TCCATGACCC

GTAGACTTTT

TAATCTCAAA

ATTTGACTAA

GTCACAGAGG

GGAACGTGAG

ATGCTTGAGG

GGAGAAAGTT

GTTTTGGTTT

CCATAGGAGG

TCGTGACCTT

GCTGGTTTTG

CATTGATGCT

TGGTTTCTTC

TTCACTTGCT

CCACTGCTTT

TTATCACGAG

AGGGGAGATT

TGCTGAAAAT

GAAAGGTCAT

CAGTTGGCCA

CTCAGGTGAA

GAAATTTGGC

CAAGGCACTT

TTACGACCCC

GAGCTTTGAC

TGAGTTCAAC

TGCTAAAATG

CGGGATTGGC

GGCACTCCAC

GGGGCCAGTC

GGCAGCAAAA

GACACTAATT

ATTAACTTGG

ACAGTCAAGA

AGACACACAC

GTTGCTATAA

ATGTATTGTG

AGATATACAG

CCTGCACTCG

TACCTGCAGC

ACTGAAATAC

TTAGTTGAAG

TTCTCATTTT

GTTAGGAAAT

GCCATATTTT

CCGCTGACCC

GGATTAACAC

TGCTTCATGC

GCTGCTCTCC

CCCAAGGGAA

CCATATGATA

CTGTCTTACA

ACTTACAAAA

AALATATTTTA

ACTCTGGCTG

CTAAAAACCT

GGGTTTATAG

CACGGCTTGG

GAGTTTACAT

CTGAGATGAG

CTGTATTCTT

TCAGTAAAGA

ATGTCATAGA

AGCTTCTAGG

GGAATCCAAC

TGAGGGATAT

ATGATGTTCT

CTCTAGATTA

TCAGAAGTTT

ACATGAATCA

GTGGAATCAT

TCCCCCTGCA

ATGAGCAGTG

CTCTTAGCCT

AAAGGGAATG

CCGGGTCACG

TGATAATGTA

GCCTGAAAGA

TGAGGGCATG

AGGACAATGG

TCTCAGGAGT

ACTCCCGAAG

GGTTCCCTCA

TCTAGGCTCC

GCACAG CTC C

GTCAGTGATT

CACTGGTAGT

GTCTCAACAT

GGGGAGGTTA

AAGAGTCAGA

TTATCAAATT

AACGGTAGAA

TGACCAA.AAC

CATTTTCATA

CGGCCACCCC

GCCTAAAGTC

AATCAACGGC

TGCTGCAGAC

CGTTGATAAC

GGATAGTGAT

GGA'rTCAGTT

GAGGCTTGTA

TGTTGTAAGT

AAAGGAGATC

CCAAGTGATT

GATGGCCAAG

CCCTAAAGAT

CCCAGCCCAC

GATAATTCGG

GA.ATTGAGGG

CAATGGTTTG

AAATCACAAA

TCAGTTGAGT

GTATATTACC

ATGACAGAGA

TACATGTGGA

GTAGCCATGC

CTCAGAGGTG

GGGTTTTCTG

ACTGATGACA

AGACTTGAAG

ATTGTGTATG

TATCGTGACA

ACAATCCGGA

TGGAAATCTT

CTGACAATGT

TACCCGAAAG

GATGTTTTCC

GGAGCTTACC

AAGGAAACAG

GCTGAAAATC

GATGAGCACG

CTCAAAGAAA

ACAAATACCA

CAGGACCAAG

9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 see*0 113

ACACTAATCA

ATCTCAAGAA

TAAATGAGAT

CTGTCCTGTA

GCAAAGTCCC

GTCAGAAGCT

GAGTAAGGAT

TACCCAGCAC

ACTTTGTA-AT

CAATTGTTTC

TGTCCCAATC

AAACAAGGGC

ATGACCGTTA

CTCTTGGCTT

ACAACGACCT

TGAATATGAG

ATCTCAAGAG

CACAGCAACC

TTGTATGTGT

TCCACAGTCC

AGGGACTGGC

TCCTGGATCA

AAGGCCTGAT

TGTCCAATTA

GAAATGTCCT

ATATGTGGGC

TCCGGAG2AAT

GTACTGCCTT

TTACGGATTA

TGTAAGTGAC

CAATGACCAA

GTGGACCATC

TGCTTCATTA

ATGGCCTTAC

TCTTAGGCAA

ATCACATTTT

ACTCAAGAGC

AGCATGCAGT

CCTTGCATAT

CAC2AATCAAT

CTTAATAAGG

CAGGCTGTTT

AATGATTCTC

GGGGGACTCT

CCAGAGCATC

AAACCCAATG

AGCATTCCTC

TAGTGTCACA

TCGAGCCAGC

TGACTATGAA

CATTGACAAA

GAGGCTAGCT

ATGGAAGCTT

AATTGGAGAT

CCCTCATTTT

CCTCATTGCC

ATCTTCATTA

AGCACCATTC

GTGCAAGGGG

AACCTTAAGA

AGGCTACATG

TTTGTTTATT

ATCGCAAGAT

AATATTGCTA

TCCCTGAACG

TCAACCATGA

ATGGCACTGT

GTCAGAAACA

GCATCACTGA

TCATTCCTAG

ACTAGACTCC

TTAAAGGGAT

ATGGACAGGC

GGGGCAAGAG

ATGAGGAAGG

CAATTCAGAG

GAGTCATGTT

CGAGGACGGC

ACGAGACAGT

ATGAGACCAT

TTCAGTGGCT

CCCCCGACCT

AGTACCCTAT

CCTATTTATA

ACAATCAGAC

AATGGGAAC

ACATTGGCCA

CAAAAGGAAT

GTGTATTCTG

CAACAATGGC

TCCTAAAAGT

CCCAGGATGT

TGCCCGCTCC

TCGGTGATCC

TGCCTGAAGA

ACTGGGCTAG

TCAAGAACAT

TATTCCATGA

ATATTATAGT

AGTCTATTGC

GGGGGTTAAC

CAGGGATGGT

CAGTGCAGCT

CTATTTACGG

CAGTGCATTT

CAGCTTGTTT

GCATAAGAGG

TGACGCCCAT

GGGAGGTATA

CCTGGCTGCT

CATAGCTGTA

TGCTAGAGTA

TCACCTCALAG

ATATTATGAT

GTCAGAGACT

TAAALAGCATC

GATACAGCAG

AGTCATACCC

TATTGGGGGG

AGTAACATCA

GACCCTCCAT

CGACCCTTAC

AACTGCAAGG

TGACAGTAAA

ACCTAGGGCA

AGGCATGCTA

CTCTCGAGTG

GCTATTAACA

GGCGAGAGCC

CCTTGAGGTC

ATCACAACTG

GCACAGAGGC

CTTGAGACCT

ATCCCGTTAT

GAAGGGTATT

TATGAGAGCG

ACAAAAGGG

ACTAGAGATT

GCAAATGAGA

GGGCTACTTG

ATAGTTGATG

GAGAGAGGTT

ATTCTGATCT

CTCCTCACAA

ATGAATTATC

TCAATTGCTG

CAAGTAATGA

TCAGCAAATC

TTTGTCCTAA

GAAGAGGACG

GCTCATGAAA

GATACCACAA

ATAACCAGAT

GGAAGAAAGA

CTAAGAAGCC

CCTGATGTAC

11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 114

*O.

i

TAGAATCTAT

GATCAGTCAA

AGGAAACATC

TGAAGCTTGC

CAGTGTACTC

CAAGGCAAAG

CGACTAATTT

CCCTTGTCCG

CAGATAAGAA

TTTTAGAAAC

TTCACGTCGA

CTCGCAAGCT

CTTTAATTGA

AATTTGTTAC

CTATGATTGA

TAGGGGATGA

TCACTATCTA

GACCATCAGG

AAGGAGTGTT

GGCACTGTGG

CAACTGTGTG

AAGAGTTAGA

GATTCGACAA

GGACCTGCCC

ATATCAAGGC

GCGAGGCCAC

CTACGGATGG

ATCCTTGAGA

CTTCGTAAGA

ATGGGCTTAC

GGCTAATGTG

AGCACATAGG

AGTGGCAAGG

GGTTGATACT

ATTGTTTCGA

AACAGATTGT

AGAGCTGAGG

CAGAGATGCA

ATGGTCCACA

CCTGGTAACA

CGATATCAAT

CTTGGGCCAG

GAAATATCAG

TAAGGTGCTT

TATTATAGAG

CAACATGGTT

AGAGTTTACA

CATCCAGGCA

ACCAATTCGA

GGAGGCTAGG

CTTATTCGGC

TTTTTTGTCC

GTCCCATATA

GCCCCAAGTC

GGTGATGATG

AGCCTGGAGG

TTGAGGGATC

TATACCACAA

AACTTTATAT

CTCGAGAAAG

TGCGTGATCC

GCAGAGCTGT

ACAAGGCTAT

CCCCA.ACTAT

AAATTTGAGA

AGTTTCATAA

TGTGCGGCCA

ATGGGTGAGC

GTCAATGCTC

CCTATCCATG

TACACATGCT

TTTCTTTTGT

AAACACTTGT

GGTCTAAGAC

TTATCTCCAG

GTCATGAGAC

CCTCGGGTTG

TTGGTTCTAC

GATCCTTGCG

ATAGCTCTTG

AGCTAAGGGT

GTAGCACTCA

TCTCCAkACGA

ACCAACAAGG

ATACCGGATC

CAATGATAGA

GTACCAACCC

ACACCCAGAG

ATCACATTCT

AGGACCATAT

CTGAGTTTCT

TCAATTGGGC

TGTTGTCATC

TA-AGCCAccc

GTCCTTCACT

ATATGACCTA

GTGAAAGTGA

GTGTTCTGGC

CGGTAGAGAA

CAGGATCTTC

ATGTGTCATC

CCALACTGGAT

CACTGATGAG

ATCTGCTGTT

GAACGAAGCC

GATCACTCCC

AGTGAAATAC

CAATCTCTCA

AATGCTCCTA

ATCTAACACG

TCATCCCAGG

ATTGATATAT

CCATAGGAGG

AGCTAAGTCC

GAATGAAATT

GCTTATAGAG

ATTTGATGTA

GTTCCTTTCT

AAAGATCTAC

TGATGCTCAA

CCTCGACCTG

CGAGGATGTA

AGATTTGTAC

ATGTGCAGTT

GTGGAILCATA

TGCGAGTGTG

GATATTGACA

AGA.ACAGACA

AGA)ATAGCAA

TGGTTGTTGG

ATCTCAACTT

TCAGGTACAT

TTTGTCATAT

GGGTTGGGCG

GTATTACATC

ATACCCAGCT

GATAATGCAC

CACCTTGTAG

ACAGCACTAT

TCAGCTCTCA

CCAAGATTAT

CATTATCATA

AGAATGAGCA

AAGAAATTCT

AACTTGCACA

TTGTTGAATG

GTACCGGACA

TGTCAACCAG

CTALACCGACC

AATCCAATTA

12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 TTGTAGACCA TTACTCATGC TCTCTGACTT ATCTTCGGCG AGGATCGATC AAACAGATAA 115

GATTGAGAGI

CAAAGATCGG

ATGATGTTGC

GGGGCAATCT

CTTGCTACAA

ACGGCTTATT

AACTA.AACAA

AATTAGCACC

TTGTCAAGGT

TCAATTACAT

AGACCTTACC

TGGCTCTGCT

GGGATTTTGT

TATACCCCAG

AGGCTAACCG

GGACTTCACC

CAATTGTGGG

CTATAGAGCA

AATTGATCCA

TCTACAGGGA

CTTACCCCGT

TTTGGGGGCA

ATCTCAAGTC

CCA.AGTCAGA

TAACAGTCAA

o

*TGATCCAGGA

CAGCAACAAC

AAA.ATTGCTC

CGCCAATTAT

AGCTGTTGAG

CTTGGGTGAG

GTGCTTCTAT

CTATCCCTCC

GCTCTTTAAC

AGTTAGTAAT

TAACAAAGAT

CCTGGGCAAA

TCAGGGATTT

ATACAGCAAC

GCTAATGAAT

TGGACTTATA

AGACGCAGTT

GGTGCTGATC

CCATGATGTT

GTTGGCAAGA

ATTGGTAAGT

CATTCTTCTT

CGGTTATCTG

GAAACAGATT

GGAGACCAAG

TTCATTTTCG

ATCTCAAATA

AILAGATATCA

GAAATCCATG

ATATCAACAT

GGATCGGGTT

AATAGTGGGG

GAAGTTGGCC

GGGAGGCCCG

ATCCCTACCT

ACTATAGAGA

ATAGGATCAA

ATAAGTTATG

TTCATATCTA

CCTGAAAAGA

GGTCACATCC

AGTAGAGGTG

AATTGCGGGT

GCCTCAGGGC

TTCAAGGACA

AGCAGGCAAC

TACTCCGGGA

ATACTAGACT

P.TTATGACGG

GAATGGTATA

ACGCCCTCGC

TGAGCATCAA

ATACAAGCAA

CTTTCCGCAG

TAATTAGGAG

CTATGTTGAT

TCTCTGCCAA

TTGTCGAACA

AAGTCACATG

CTAGTGTGGG

AGCTAGAGGA

TACTGGTGAT

TAGGGTCTCA

CTGAATCTTA

TTILAGCAGCA

TATCCATTAA

ATATCAATCC

TGGCAATTIA

AAGATGGATT

ACCAAAGAAG

GAGAACTTAT

ACAGAAAGTT

TACACCAGAA

GGGGTTTGAA

kGTTAGTCGG

TGAGGTAAAT

GGATTTCAGA

GCACAATCTT

AATCGGGTTG

ATGCCTTGAG

CACTTATAAG

TTCTAGATCT

CAGAATGGGA

GGTAGGCAGT

GTTTATCCAT

ATTGGCAGCC

TAAGCTTATG

TTATAGAGAA

TTTGGTTATG

GATAATTGAA

GCAACTAAGC

TACTCTGAAA

CGGACCTAAA

GCTTAATTCT

TCAACAAGGG

ATCTAGAATC

GATAAATAAG

TATCTTCGTT

A.CGTGAGTGG

kTACAGTGCC

GTCAGTCAGC

CCCCCACACG

CCCATTTCTG

AACTCATCTG

CCAGGGGAAG

GAGATACTTA

GGTCAAAGGG

GTAGGTAATA

GTAGATTGCT

TCAGATATAG

ATCTTATCGA

CCTTTCAGCG

GTGAACCTTG

ACAGATCTCA

TCATCTGTGC

TGCATACAAG

AAACTTACAC

CTGTGCAAAG

ATACTCATCC

1iTGTTCCACG

ACTCGCAAAT

rTTATCCAGA

PLAGAATCTAT

GTTTTTAAGG

TGATTAAGG

14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15240 15300 15360 15420 15480 15540 15600 15660 15720 15780 15840 ACTA.ATTGGT TGAACTCCGG AACCCTAATC CTGCCCCAGG TGGTTAGGCA

TTATTTGTAA

116 TATATTAAAG AAAACTTTGA AAATACGAAG TTTCTATTCC CAGCTTTGTC

TGGT

INFORMATION FOR SEQ ID NO:4: SEQUENCE CHARACTERISTICS: LENGTH: 2183 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: 15894 Met Asp Ser Leu Ser Val Asn Gin Ile Leu *e 1 Asp Arg Ile Asn 65 Ala Ile Gly Arg Ile 145 Trp Ser Val Lys 50 Val His Glu Asn Asp 130 Lys Phe Pro Pro His Giu Ser Asp Ser 115 Thr Glu Glu Ile Val His Ala Arg Leu Val Gly His Ile Lys Giu 100 Leu Tyr Asn Ser Lys Val Pro Phe 165 Thr Tyr Lys Asn 70 Pro Ser Ser Arg Ile 150 Leu Asn Ser Asn 55 Val Tyr Thr Lys Leu 135 Asn Phe Lys Leu 40 Gly Ile Pro Arg Val 120 Gly Leu Trp 10 Ile Val 25 Glu Asp Phe Ser Lys Ser Asn Cys 90 Lys Ile 105 Ser Asn Leu Gly Gly Val Phe Thr 170 Tyr Al a Pro Asn Lys 75 Aen Arg Lys Ser Tyr 155 Val Pro Ile Thr Gin Leu Gin Giu Val Glu 140 Met Lys Glu Val Leu Glu Leu Cys Met Ile Arg Ser Asp Leu Leu Leu 110 Phe Gin 125 Leu Arg His Ser Thr Glu His Leu Tyr Ala Gin Asn Ile Asn Tyr Pro Phe Asn Lys Lys Cys Leu Glu Asp Ser Gin 160 Met Arg 175 Ser Val Ile Lys 180 eSer Gin Thr His Thr Cys His Arg Arg Arg His Thr 10185io 117 Pro Val Phe Phe Thr Gly Ser Ser Val Glu Leu Leu Ile Ser Arg Asp .L -11 n 205 9*

C

S

Leu Phe 225 Thr Arg Gly Al a Leu 305 Phe Ile Phe Asn Leu 385 Arg Ala His Val 210 Giu Giu Val.

Asn Tyr 290 Asn Ser Phe Arg Val 370 Met Asp Al a Giu Al a Leu Thr Arg Pro 275 Leu His Asp Ile Ser 355 Arg Lys Arg Asp Gin 435 Ile Val Ala Tyr 260 Thr Gin Cys Glu Thr 340 Phe Lys Gly His Thr 420 Cys Ile Leu Met 245 Met Tyr Leu Phe Gly 325 Asp Giy Tyr His Giy 405 Ile Val Ser Met 230 Thr Trp, Gin Arg Thr 310 Thr Asp His Met Al a 390 Gly Arg Asp Lys 215 Tyr Ile Lys Ile Asp 295 Glu Tyr Ile Pro Asn 375 Ile S er Asn Asn Glu Cys Asp Leu Val 280 Ile Ile His His Arg 360 Gin Phe Trp Al a Trp 440 Ser Asp Ala Ile 265 Ala Thr His Glu Leu 345 Leu Pro Cys Pro Gin 425 Lys Gin Val Arg 250 Asp Met Val Asp Leu 330 Thr Glu Lys Gly Pro 410 Ala Ser His Ile 235 Tyr Gly Leu Giu Val1 315 Val Gly Ala Val1 Ile 395 Leu Ser Phe Val 220 Glu Thr Phe Giu Leu 300 Leu Giu Glu Val Ile 380 Ile Thr Gly Ala Tyr Giy Giu Phe Pro 285 Arg Asp Ala Ile Thr 365 Val Ile 1Leu Glu 4~45 Tyr Arg Leu Pro 270 Leu Gly Gin Leu Phe 350 Ala Tyr Asn Pro Giy 430 Val LeL Leu Leu 255 Al a Ser Al a Asn Asp 335 Ser Al a Glu Gly Leu 415 ELeu Lys Thr Met 240 IGly Leu Leu Phe Gly 320 Tyr Phe Giu Thr Tyr 400 His Thr Phe Gly Cys Phe Met Pro Leu Ser Leu Asp Ser Asp Leu Thr Met Tyr Leu 450 455 Az 118 Lys 465 Pro Arg Met Asn Leu 545 Glu Met Val1 Val Val 625 Asp Ser p.....Tyr Leu 705 Pro Gly Asp Lys Leu Ile Leu 530 Phe Asn Ala Ser Leu 610 Arg Gin Al a Glu Pro 690 Tyr Leu Gly Lys Glu Vai Met 515 Ser Al a Leu Lys Gly 595 Lys Ala Asp Phe Thr 675 Ser Val Cys Ile Leu Leu 485 Val Val1 Ser Met Ser 565 Giu Pro Tyr Lys Asn 645 Thr Ser Phe Asp Val 725 Gly Ala 470 Arg Phe Val Leu Thr 550 Asn His Lys Ser Gly 630 His Thr Leu Gin Pro 710 Pro Tyr Al a Tyr Leu S er Lys 535 Tyr Gly Asp Asp Arg 615 Phe Pro Asp Phe Trp 695 His Asn Cys Arg Pro 490 Ser Tyr Giu Arg Lys 570 Lys Glu Al a Phe Met 650 Lys Arg Lys Pro Ile 730 Leu Glu 475 Lys Ser Leu Ile Ala 555 Tyr Ala Ser His Pro 635 Glu Tyr Leu Arg Asp 715 Phe Trp Trp Gly Phe His Lys 540 Cys Phe Leu His Thr 620 Gin Al a Cys Asn Leu 700 Leu Ile Thr Asp Thr Asp Asp 525 Glu Gin Lys His Arg 605 Asn Ile Tyr Leu Glu 685 Glu Asp Lys Ile Ser Gly Pro 510 Pro Thr Val Asp Thr 590 Gly Thr Ile Giu Asn 670 Ile Thr Al a Tyr Ser Val1 Ser 495 Tyr Giu Gly Ile Asn 575 Leu Gly Arg Arg Thr 655 Trp Tyr Ser His Pro 735 Thr Tyr 480 Arg Asp Phe Arg Ala 560 Gly Ala Pro Asn Gin 640 Val Arg Gly Val Ile 720 Met Ile 119 a Pro Leu Ser 785 Arg His Ser Ser Arg 865 Arg Ile Thr Arg Met 945 Ile Thr Asp Tyr Val 770 Thr Asp Leu Lys Ile 850 Ala Giy Gin Gin Met 930 Ser Al a Leu Trp Leu 755 Gin Trp Tyr Lys Gly 835 Ala Ala Tyr Gin Asp 915 Ala Arg Asp His Ala 995 740 Tyr Gly Pro Phe Al a 820 Ile Arg Cys Asp Ile 900 Val Leu Leu Leu Gin 980 Ser Leu Asp Tyr Val 805 Asn Tyr Cys Ser Arg 885 Leu Val Leu Phe Lys 965 Val Asp Ala Asn Asn 790 Ile Glu Tyr Val Asn 870 Tyr Ile Ile Pro Val 950 Arg Met Pro Al a Gin .775 Leu Leu Thr Asp Phe 855 Ile Leu Ser Pro Ala 935 Arg Met Thr Tyr Tyr 760 Thr Lys Arg Ile Gly 840 Trp Ala Al a Leu Leu 920 Pro Asn Ile Gin Ser 745 Giu Ile Lys Gin Val 825 Leu Ser Thr Tyr Gly 905 Leu Ile Ile Leu Gin 985 Ala Ala Val Thr 780 Trp Giu Ala 795 Arg Leu His 810 Ser Ser His Leu Val Ser Giu Thr Ile 860 Thr Met Aia 875 Ser Leu Asn 890 Phe Thr Ile Thr Asn Asn Gly Gly Met 940 Gly Asp Pro 955 Ala Ser Leu 970 Pro Gly Asp Asn Leu Val Lys Arg Ala Arg Asp Ile Phe Phe 830 Gin Ser 845 Val Asp Lys Ser Val Leu Asn Ser 910 Asp Leu 925 Asn Tyr Val Thr Met Pro Ser Ser 990 Cys Val 1005 Val Vai Gly 815 Val Leu Giu Ile Lys 895 Thr Leu Leu Ser Giu 975 Phe Gln Pro Thr 800 His Tyr Lys Thr Glu 880 Val Met Ile Asn Ser 960 Giu Leu Ser 750 Ser Gly Val Arg Ile Ala Ser 1000 Ile Thr Arg Leu Leu Lys Asn Ile Thr Ala Arg Phe Val Leu Ile His 1010 1015 1020 120 Ser Pro Asn Pro Met Leu Lys Gly Leu Phe His Asp Asp Ser Lys Glu 1025 1030 1035 1040 Giu Asp Giu Gly Leu Ala Ala Phe Leu Met Asp Arg His Ile Ile Val 1045 1050 1055 Pro Arg Ala Ala His Glu Ile Leu Asp His Ser Val Thr Gly Ala Arg 1060 1065 1070 Giu Ser Ile Ala Gly Met Leu Asp Thr Thr Lys Gly Leu Ile Arg Ala 1075 1080 1085 Ser Met Arg Lys Gly Gly Lou Thr Ser Arg Val Ile Thr Arg Leu Ser 1090 1095 1100 Asn Tyr Asp Tyr Giu Gin Phe Arg Ala Gly Met Val Leu Leu Thr Gly 1105 1110 1115 1120 Arg Lys Arg Asn Val Lou Ile Asp Lys Giu Ser Cys Ser Val Gin Leu 1125 1130 1135 Aia Arg Ala Leu Arg Ser His Met Trp, Ala Arg Leu Ala Arg Gly Arg 1140 1145 1150 Pro Ile Tyr Gly Lou Giu Val Pro Asp Val Leu Glu Ser Met Arg Gly 1155 1160 1165 His Leu Ile Arg Arg His Glu Thr Cys Val Ile Cys Giu Cys Gly Ser 1170 1175 1180 Val Asn Tyr Gly Trp Phe Phe Val Pro Ser Gly Cys Gin Lou Asp Asp 1185 1190 1195 1200 Ile Asp Lys Giu Thr Ser Ser Lou Arg Val Pro Tyr Ile Gly Ser Thr 1205 1210 1215 Thr Asp Glu Arg Thr Asp Met Lys Lou Ala Phe Val Arg Ala Pro Ser *1220 1225 1230 Arg Ser Lou Arg Ser Ala Val Arg Ile Ala Thr Val Tyr Ser Trp Ala 1235 1240 1245 Tyr Gly Asp Asp Asp Ser Ser Trp Am-i Giu Ala Trp Lou Lou Ala Arg 1250 1255 1260 Gin Arg Ala Asn Val Ser Lou Glu Giu Lou Arg Val Ile Thr Pro Ile 1265 1270 1275 1280 Ser Thr Sor Thr Asn Lou Ala His Arg Lou Arg Asp Arg Ser Thr Gin 1285 1290 1295 121 Val Lys Tyr Ser Gly Thr Ser Leu Val Arg Val Ala Arg Tyr Thr Thr 1300 1305 1310 Ile Ser Asn Asp Asn Leu Ser Phe Val Ile Ser Asp Lys Lys Val Asp 1315 1320 1325 Thr Asn Phe Ile Tyr Gin Gin Gly Met Leu Leu Gly Leu Gly Val Leu 1330 1335 1340 Glu Thr Leu Phe Arg Leu Giu Lys Asp Thr Gly Ser Ser Asn Thr Val 1345 1350 1355 1360 Leu His Leu His Val Giu Thr Asp Cys Cys Vai Ile Pro Met Ile Asp 1365 1370 1375 His Pro Arg Ile Pro Ser Ser Arg Lys Leu Giu Leu Arg Ala Giu Leu 1380 1385 1390 Cys Thr Asn Pro Leu Ile Tyr Asp Asn Ala Pro Leu Ile Asp Arg Asp 1395 1400 1405 Ala Thr Arg Leu Tyr Thr Gin Ser His Arg Arg His Leu Val Giu Phe 1410 1415 1420 Val Thr Trp Ser Thr Pro Gin Leu Tyr His Ile Leu Ala Lys Ser Thr 1425 1430 1435 1440 Ala Leu Ser Met Ile Asp Leu Val Thr Lys Phe Glu Lys Asp His Met 1445 1450 1455 Glu Ile Ser Ala Leu Ile Gly Asp Asp Asp Ile Asn Ser Phe Ile 1460 1465 1470 *Thr Glu Phe Leu Leu Ile Giu Pro Arg Leu Phe Thr Ile Tyr Leu Gly **,1475 1480 1485 Gin Cys Ala Ala Ile Ann Trp Ala Phe Asp Val His Tyr His Arg Pro *1490 1495 1500 Ser Gly Lys Tyr Gin Met Gly Giu Leu Leu Ser Ser Phe Leu Ser Arg 1505 1510 1515 1520 ***Met Ser Lys Gly Val Phe Lys Val Leu Val Asn Ala Leu Ser His Pro 1525 1530 1535 Lys Ile Tyr Lys Lys Phe Trp His Cys Gly Ile Ile Glu Pro Ile His 1540 1545 1550 Gly Pro Ser Leu Asp Ala Gin Asn Leu His Thr Thr Val Cys Asn Met 1555 1560 1565 Val Tyr Thr Cys Tyr Met Thr Tyr Leu Asp Leu Leu Leu Asn Giu Glu 122 1570 1575 1580 Leu Glu Glu Phe Thr Phe Leu Leu Cys Glu Ser Asp Glu Asp Val Val 1585 1590 1595 1600 Pro Asp Arg Phe Asp Asn Ile Gin Ala Lys His Leu Cys Val Leu Ala 1605 1610 1615 Asp Leu Tyr Cys Gin Pro Gly Thr Cys Pro Pro Ile Arg Gly Leu Arg 1620 1625 1630 Pro Val Glu Lys Cys Ala Val Leu Thr Asp His Ile Lys Ala Glu Ala 1635 1640 1645 Arg Leu Ser Pro Ala Gly Ser Ser Trp Asn Ile Asn Pro Ile Ile Val 1650 1655 1660 Asp His Tyr Ser Cys Ser Leu Thr Tyr Leu Arg Arg Gly Ser Ile Lys 1665 1670 1675 1680 Gin Ile Arg Leu Arg Val Asp Pro Gly Phe Ile Phe Asp Ala Leu Ala 1685 1690 1695 Glu Val Asn Val Ser Gin Pro Lys Ile Gly Ser Asn Asn Ile Ser Asn 1700 1705 1710 ***Met Ser Ile Lys Asp Phe Arg Pro Pro His Asp Asp Val Ala Lys Leu 1715 1720 1725 *Leu Lys Asp Ile Asn Thr Ser Lys His Asn Leu Pro Ile Ser Gly Gly *1730 1735 1740 Asn Leu Ala Asn Tyr Giu Ile His Ala Phe Arg Arg Ile Gly Leu Asn *1745 1750 1755 1760 Ser Ser Ala Cys Tyr Lys Ala Val Giu Ile Ser Thr Leu Ile Arg Arg 1765 1770 1775 **Cys Leu Giu Pro Gly Glu Asp Gly Leu Phe Leu Gly Giu Gly Ser Gly 1780 1785 1790 Ser Met Leu Ile Thr Tyr Lys Glu Ile Leu Lys Leu Asn Lys Cys Phe .*1795 1800 1805 Tyr Asn Ser Gly Val Ser Ala Asn Ser Arg Ser Gly Gin Arg Glu Leu 1810 1815 1820 Ala Pro Tyr Pro Ser Glu Val Gly Leu Val Glu His Arg Met Gly Vai 1825 1830 1835 1840 Gly Asn Ile Val Lys Val Leu Phe Asn Gly Arg Pro Giu Val Thr Trp 1845 1850 1855 123 Val Gly Ser Val Asp Cys Phe Asn Tyr Ile Val Ser Asn Ile Pro Thr 1860 1865 1870 Ser Ser Val Gly Phe Ile His Ser Asp Ile Giu Thr Leu Pro Asn Lys 1875 1880 1885 Asp Thr Ile Giu Lys Leu Giu Giu Leu Ala Ala Ile Leu Ser Met Ala 1890 1895 1900 Leu Leu Leu Gly Lys Ile Gly Ser Ile Leu Val Ile Lys Leu Met Pro 1905 1910 1915 1920 Phe Ser Gly Asp Phe Vai Gin Gly Phe Ile Ser Tyr Val Gly Ser His 1925 1930 1935 Tyr Arg Giu Val Asn Leu Val Tyr Pro Arg Tyr Ser Asn Phe Ile Ser 1940 1945 1950 Thr Giu Ser Tyr Leu Val Met Thr Asp Leu Lys Ala Asn-Arg Leu Met 1955 1960 1965 Asn Pro Giu Lys Ile Lys Gin Gn Ile Ile Giu Ser Ser Val Arg Thr 1970 1975 1980 Ser Pro Gly Leu Ile Gly His Ile Leu Ser Ile Lys Gin Leu Ser Cys 1985 1990 1995 2000 Ile Gin Ala Ile Val Gly Asp Ala Val Ser Arg Gly Asp Ile Asn Pro *2005 2010 2015 Thr Leu Lys Lys Leu Thr Pro Ile Giu Gin Val Leu Ile Asn Cys Gly 2020 2025 2030 Leu Ala Ile Asn Gly Pro Lys Leu Cys Lys Giu Leu Ile His His Asp 2035 2040 2045 Val Ala Ser Gly Gin Asp Gly Leu Leu Asn Ser Ile Leu Ile Leu Tyr *.2050 2055 2060 *.Arg Giu Leu Ala Arg Phe Lys Asp Asn Gin Arg Ser Gin Gin Gly Met 2065 2070 2075 2080 *Phe His Ala Tyr Pro Val Leu Val Ser Ser Arg Gin Arg Giu Leu Ile 2085 2090 2095 Ser Arg Ile Thr Arg Lys Phe Trp Gly His Ile Leu Leu Tyr Ser Gly 2100 2105 2110 Asn Arg Lys Leu Ile Asn Lys Phe Ile Gin Asn Leu Lys Ser Gly Tyr 2115 2120 2125 124 Leu Ile Leu Asp Leu His Gin Asn Ilie Phe Val Lys Asn Leu Ser Lys 2130 2135 2140 Ser Glu Lys Gin Ile Ile Met Thr Gly Gly Leu Lys Arg Giu Trp Vai 2145 2150 2155 2160 Phe Lys Val Thr Val Lys Giu Thr Lys Glu Trp Tyr Lys Leu Val Giy 2165 2170 2175 Tyr Ser Ala Leu Ile Lys Asp 2180 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 15894 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID ACCAAACAAA GTTGGGTAAG GATAGATCAA. TCAATGATCA

TCAAGATCCT

TAAGGAGCTT

GTGGAGCCAT

TTACCACTCG

GCGGGCCCAA

GTCAATTGAT

TCCAGAGTGA

ATGAGGCGGA

GATGGTTCGA

TGATTCTGGG

CAGACACGGC

ATTATCAGGG

AGCATTGTTC

CAGAGGAATC

ATCCAGACTA

ACTA-ACAGGG

TCAGAGGATC

CCAGTCACAA

CCAATACTTT

GAACAAGGAA

TACCATTCTA

AGCTGATTCG

ACAAGAGCAG

AAAAGAAACA.

AAACACATTA

CTGGACCGGT

GCACTAATAG

ACCGATGACC

TCTGGCCTTA.

TCACATGATG

ATCTCAGATA

GCCCAAATTT

GAGCTAAGAA

GATTAGGGAT

AGGACAALACC

TTATAGTACC

TGGTCAGGTT

GTATATTATC

CTGACGTTAG

CCTTCGCATC

ATCCAAGTAG

TTGAAGTGCA

GGGTCTTGCT

GGTGGATAAA

TATTCTAGTA

ATCCGAGATG

ACCCATTACA

AATCCCTGGA

AATTGGAAAC

CTTGTTTGTG

CATCAGGCTG

AAGAGGTACC

TAGTGATCAA

AGACCCTGAG

CGCGILAGGCG

GTACACCCAA

CACTTAGGAT

GCCACACTTT

TCAGGATCCG

GATTCCTCAA

CCGGATGTGA

GAGTCTCCAG

TTAGAGGTTG

AACATGGAGG

TCCAGGTCCG

GGATTCA-ACA

GTTACGGCCC

CAAAGAAGGG

120 180 240 300 360 420 480 540 600 660 720 p TAGTTGGTGA ATTCAGATTG GAGAGAAAAT GGTTGGATGT GGTGAGGAAC AGGATTGCCG 125 AGGACCTCTC CTTACGCCGA TTCATGGTCG CTCTAATCCT GGATATCAAG AGGACACCCG 0*

GGAACAAACC

GATTAGCCAG

GACTGCATGA

AAATGGGAGA

GTGCAGGATC

ACTCCATGGG

GGCAAGAGAT

GTATCACTGC

GGACCAGTAG

GTGAGAATGA

GAGAAGCCAG

CCCATCTTCC

CGCAGGACAG

TGGAAGAACA

ACTAGGTGCG

AAPLACTTAGG

GGGCCGATGG

CTCAAGGCCG

ATATCAGACA

GGTCTCAGCA

TGCGGTCAGG

AATCTCCAGG

GCGGTTAAGG

AGCACCCTCT

GATACCGAGG

AAGGATTGCT

TTTTATCCTA

ATTTGCTGGT

AACTGCACCC

ATACCCCCTG

AGGTTTGAAC

GGTGAGGAGG

TGAGGATGCA

AGCGGTTGGA

GCTACCAGGA

GGAGAGCTAC

AACCAGCGCA

TCGACGGTCA

AGGCTCAGAC

AGAGGCCGAG

AACCAGGTCC

CAGAAGAGCA

AGCCCATCGG

ACCCAGGACA

AACCATGCCT

GATCTGGAGA

CATCAAGCAC

GAATCCAAGA

CAGGAGGAGA

GATATGCTAT

GAAATGATAT

ACTATTAAGT

GAGTTATCCA

TACATGGTAA

CTCTGGAGCT

TTTGGTCGAT

TCAGCTGGGA

AGGCTTGTTT

CCCAGACAAG

TTGGGGGGCA

AGAGAALACCG

CCCCTAGACA

GCTGACGCCC

ACGGACACCC

GACCAGAACA

ACACAGCCGC

GGCACGCCAT

CTCACTGGCC

GGACCGAACC

CTCAGCAATT

GAGCGATGAC

TGGGTTACAG

TGCTGACTCT

CGATGAATCT

CACTGACCGG

GTGACATTGA

TTGGGATAGA

CACTTGAGTC

TCCTGGAGAA

ATGCCATGGG

CTTACTTTGA

A.AGTCAGTTC

CAGAGATTGC

CCCAAGTGTC

AGGAAGATAG

GGTCTAGCAG

TTGACACTGC

TGCTCAGGCT

CTAGGGTGTA

ACATCCGCCT

CAGCCAACCA

GTCAAAAACG

GTCGAGGALAG

ACCCGCAAGG

GGATCAACTG

AACGCTGAAA

TGTTATCATG

ATCATGGTTC

GAAAACAGCG

GGATCTGCTC

TACATATATC

AACTATGTAT

CTTGATGAAT

CTCAATTCAG

AGTAGGGGTG

TCCAGCATAT

CACATTAGCA

AATGCACACT

ATTTCTACAC

GAGGGTCAAA

AGCAAGCGAT

ATCGGAGTCA

GCAAGCCATG

CAATGACAGA

ACCCTCCATC

ACCATCCACT

GACTGGAATG

CCATGGCAGC

AAGAGGAGGC

ALAGGCAGTGC

CTTTGGGAAT

TTTATGATCA

AATCAGGCCT

ATGTGGATAT

CCATCTCTAT

GTAGAGGCAG

CCTGCTCTTG

CTTTACCAGC

AACAAGTTCA

GAACTTGAAA

TTTAGATTAG

TCTGAACTCG

ACTGAGGACA

GGTGATCA;A

CAGAGTCGGG

GCGAGAGCTG

GGCCAAGATC

GCAGGAATCT

GATCTTCTAG

ATTGTTATAA

CCTACGACTG

CATCCGGGCT

ATGGTCACAA

AGGCAGTTCG

ACCTCGCATC

CCCCTCAAGA

CAGCGGTGAA

TGATGjGTGAT

TGGCGAACCT

GGGGTTCAGG

900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 126

GCTTCTGATG

AGAGGCAACA

GGTAGGGCCA

TTTGGAGCGG

TTGAAACTGC

ACTTCCCGAA

GCACTTCCGA

AGATCGCGTC

CCCTCGGAAC

CATCAGGGCC

GCCGCACTGA

AATAATGAAG

AAAACAGCCT

CTGCTGTTAT

AGCATATCCA

AAGGATCCCA

GGCAGAGATT

CTCCAAGGAA

CTAAAGCCGA

GCATCACGCA

CGTTACCTGA

CAGATGCTGA

CCAATCGACC

GCCTCCCAAG

AAGGGTCGAT

TCAGAGTCAT

TGCTGGGGGT

CCCTGCCCTT

CTGAGCTTGA

ACAACACCCC

TCAACGCAAA

TACAGGAGTG

AAGGGGGAGA

TGGCCAAAAT

TGAAGGGAGA

CCCTGGAAGG

ACGACCCCAC

CAGGCCGAGC

TGACAAATGG

TCGGGAAAAA

GTGTAATCCG

TGACTCTCCT

TGAAGATAAT

TAATTAGTAC

TTCCACAATG

CGCTCCGATA

AGATCCTGGT

TGTTGAGGAC

AGGTGTTGGT

CATAGTCGTT

ACTAACTCTC

CCAAGTGTGC

AGAAGGAGGG

GCTTGGGAAA

GACACCCATT

TTTATTGACA

AGGTGCACCT

GACACCCGAA

TTATTATGAT

ACACGAGGAT

AGTTGAGTCA

ACACCTCTCA

TGCAGATGTC

ACTGGCCGAA

ACGGACCAGT

GATGAGCTCA

CTCCATTATA

TGATGATATC

PLATGAAGTAG

kGCCTAIAATC PiCAGAGATCT

:!PACCTACCA

7TAGGCGACA kGCGATCCCC kGATCCACAG kGACGTACAG 7TCACACCTT

LATGCGGTTA

GAGATCCACG

ACTCTCAATG

AAA.AAGGGGA

GGTGGTGCAjA

GTGGGGAATG

TCTGGTACCA

GATGAGCTGT

AATCAGAAGA

ATTAAAAAGC

AGCATCATGA

GAACTCAATC

GTTCTCAAGA

TCCAGAGGAC

GCCGTCGGGT

AAATCCAGCC

AAAGGAGCCA

CTACAGCTCA

CATTATAAAA

ACGACTTCGA

CCTACAGTGA

GGAAGGATGA

TAGGGCCTCC

CAAAACCCGA

CAGGGCTCA

'GAGAAAGGT

kTCTGATACC

AGCTCCTGAG

TTCCTCCGCC

CAGACGCGAG

CCCAATGTGC

TCCCCGAGTG

CILATCTCCCC

TCTCCGATGT

TAATCTCCIJ

AGATCILACAG

TCGCCATTCC

CCGACCTGA

AACCCGTTGC

AGCTGCTGA

TTGTTCCTGA

GGCTAGAGGA

ACGATCTTGC

ACTTACCTGC

A.ACTTAGGAG

CAAGTCGGCA

TGGCAGGCTG

ATGCTTTACG

AATCGGGCGA

PGAACTCCTC3 rGAAAAACTGC ::CTAACAA&CA

C

;CTGGATACC

C

ACTCCA.ATCT

CCCGAACCCC

ATTAGCCTCA

TCGAAAGTA

TGTGACAT

GAGATCCCAG

CCALAGACATC

GCTAGAATCA

GCAAAATATC

TGGACTTGGG

ACCCATCATA

CAGCCGACA.A

GGAATTTCAA

CACCGGCCCC

GGATCGGAAG

CAAGTTCCAC

CAACCTCATG

CAAAGTGATT

rGGGACATCA 3TGCCCCAGG rACATGTTTC

;CATTTGGGT

LZLAGAGGCCA

TGTTCTACA

;GGAGTGTCT

CGCAGAGGT

2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 a 127 4

C

TCCGTGTTGT

GAAGAATGCT

GGATTGACAA

CAACATTTAT

ATTATTGCAA

GCACCAGTCT

GGTTCAAAAA

TCTGGAGGAG

AAGAATTCCG

TGTAGACCGT

GCCCGGACA.A

GCTGACGGCA

CCACCAGCCA

CGCCCCCGAC

ACTGGAAGGC

GATCGAGGTG

ACTAAACAAA

CGGCGCCGCG

CCCCGGTGCC

AATTCAAGAC

GAGGAAGCCC

GGGCCACCAG

ACCCCTGCCC

CGAAGGGCCC

CTCCCCCTCT

CCCACCCCTA

TTATATGAGC

AGAATTCAGA

AGCGATTGGC

GGTCCACATC

AATGAAAATC

TCACATTAGA

GACCTTATGT

CAGATGCAAG

CATTTACGAC

AGTGCCCAGC

AAAAG CC CCC

AGCGTGAACA

TCCCAATCTG

CCAGACCACC

CCCTCCCCCT

ACCCAACCGC

ACTTAGGGCC

CCCCCACCTC

CACAGGCAGG

GGGGGGCCCC

ACCCACCCCA

TTCCCAGACT

TGATCCGGTG

CCGAACCGCA

TCTCGAAGGG

AAGGAGACAC

ATCACCCGTC

TCGGTCAATG

CCTGGGAAGA

GGGAACTTCA

GAAAAGATGG

AGCACAGGCA

TACCCACTGA

ATAGTA.AGAA

GACGTGATCA

AATACCCGAA

TCCAAAAGAC

CCAGGCGGCC

CGTCCTCCTC

AACCGCATCC

TTCCCTCAAC

AGGCATCCGA

AAGGAACATA

CCGACAACCA

CACACCAACC

CCCCAAAAAA

CACACGACCA

CGGCCATCAC

GGCGGCCACC

AAAGACATCA

ACCAAAAGAT

CGGGAATCCC

TTTCGGATAA

CAGTGGCTTT

TCATCGATAA

GGAGAAAGAA

GCCTGGTTTT

AAATGAGCAA

TGGATATCAA

TCCAGGCAGT

TAA.ATGATGA

AACGACCCCC

TCCACGGACC

TGGGCACAGA

GTGGGAC CCC

CCACAGCCCC

GCAAGAACTC

CTCCCTAGAC

CACACCCGAC

GAGGGAGCCC

CTCGAACAGA

AGGCCCCCAG

CAGGAACCGA

CCCGCAGA-

CAACCCGAAC

GTATCCCACA

CAATCCACCA,

AGAATCAAGA

CGGGTATTAC

CAACCTGCTG

TGCAGAGCAA

GAGTGAAGTC

TGCACTTGGT

GACTCTCCAT

TGAAGACCTT

TTTGCAGCCA

CCAAGGACTA

CTCATAATGA

AAGTGAGAGG

ACAGCCCCGA

CGAGGACCAA

CGGGAAAGAG

CACALACCGAA

AGATCCTCTC

AGAACCCAGA

CCAACCAATC

CCCAGCACCC

GGGCCGACAG

ACCAGAATCC

GGAAAGGCCA

CAGCACCCAA

GCCTCTCCAA

CACCCGACGA

CTCATCCAAT

ACCGTTCCTA

GTGACCCTTA

CTTCCTGAGG

TACTCTGCTG

GGGATAGGGG

GCACAACTCG

AATCGATTAC

TCAGTTCCCC

TTCAAAGTTC

CAGCCAGAAG

CCAGCCAGCA

CACAAGGCAA

CCCCCAAGGT

ACCCCCAGCA

CCGCACAAGC

CCCCCGGCAA

CCCCGGCCCA

CCGCCGGCTC

AGCCATCGAC

CCAGCACCGC

AGACCACCCT

CAACCCGCGC

GAGCGATCCC

GTCCCCCGGT

CACTCAATTC

GTCCATCATG

3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 128 4 *4 4* 4

GGTCTCAAGG

ACCGGTCAAA

AGCTACAAAG

ATAACTCTCC

ACAGTTTTGG

CAGAGTGTAG

GCCCTAGGCG

TTGAACTCTC

GAGGCAATCA

ATCAATAATG

CTAGGGCTCA

CGGGACCCCA

ATCAATAAGG

AGCAGAGGAA

AGTATAGCCT

GTCTCGTACA

CAAGGGTACC

GTGTGCAGCC

TCCACCAAGT

TCACAAGGGA

ACGATCATTA

GTGGTCGAGG

TACTTGCACA

AATCTGGGGA

CAGATATTGA

TGAACGTCTC

TCCATTGGGG

TTATGACTCG

TCAATAACTG

AACCAATTAG

CTTCAAGTAG

TTGCCACAGC

AAGCCATCGA

GACAAGCAGG

AGCTGATACC

AATTGCTCAG

TATCTGCGGA

TGTTAGAAAA

TAAAGGCCCG

ATCCGACGCT

ACATAGGCTC

TTATCTCGAA

AA]LATGCCTT

CCTGTGCTCG

ATCTAATAGC

ATCAGGACCC

TGAACGGCGT

GAATTGACCT

ATGCAATTGC

GGAGTATGAA

TGCCATATTC

CAATCTCTCT

TTCCAGCCAT

CACGAGGGTA

AGATGCACTT

GAGACACAAG

TGCTCAGATA

CAATCTGAGA

GCAGGAGATG

GTCTATGAAC

ATACTATACA

GATATCTATC

GCTCGGATAC

GATAACTCAC

GTCCGAGATT

TCAAGAGTGG

TTTTGATGAG

GTACCCGATG

TACACTTGTA

CAATTGTGCA

TGACAAGATC

GACCATCCAA

CGGTCCTCCC

TAAGTTGGAG

AGGTTTATCG

ATGGCAGTAC

AAGATAGGGG

CAATCATTAG

GAGATTGCAG

AATGCAATGA

AGATTTGCTG

ACAGCCGGCA

GCGAGCCTGG

ATATTGGCTG

CAACTATCTT

GAAATCCTGT

CAGGCTTTGA

AGTGGAGGTG

GTCGACACAG

AAGGGGGTGA

TATACCACTG

TCATCGTGTA

AGTCCTCTGC

TCCGGGTCTT

TCAATCCTTT

CTAACATACA

GTCGGGAGCA

ATATCATTGG

GATGCCAAGG

AGCACTAGCA

TGTTAACTCT

TGGTAGGGAT

TCATAAAATT

AATACAGGAG

CCCAGAATAT

GAGTTGTCCT

TTGCACTTCA

AAACTACTAA

TTCAGGGTGT

GTGATTTAAT

CACTATTTGG

GCTATGCGCT

ATTTACTGGG

AGTCCTACTT

TTGTCCACCG

TGCCCAAGTA

CTTTCATGCC

TCCAAGAATG

TTGGGAACCG

GCAAGTGTTA

TTGCTGCCGA

GGCGGTATCC

AGAGGTTGGA

AATTGTTGGA

TAGTTTACAT

CCAAACACCC

AGGAAGTGCA

AATGCCCAAT

ACTACTGAGA

AAGACCGGTT

GGCGGGTGCG

CCAGTCCATG

TCAGGCAATT

CCAAGACTAC

CGGCCAGAAG

CCCCAGCTTA

TGGAGGAGAT

CATCTTAGAG

CATTGTACTC

GCTAGAAGGG

TGTTGCAACC

AGAGGGGACT

CCTCCGGGGG

GTTCATTTTA

CACAACAGGA

TCACTGCCCG

GGACGCTGTG

CGTAGGGACA

GTCATCGGAC

CCTGATTGCA

5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 4* 4 GTGTGTCTTG GAGGGTTGAT AGGGATCCCC GCTTTAATAT GTTGCTGCAG GGGGCGTTGT 129 AACAAAAAGG GAGAACAAGT TGGTATGTCA AGACCAGGCC TAAAGCCTGA TCTTACAGGA S 5.55

S*

S

5* S S

S

5555

S

S.*

S

5S S 55

ACATCAAAAT

CACAAGTCTC

TGTCTCCGGA

ATCATCCACA

TCCTAGGGGA

TTTGCTGGCT

CATAAGACTT

TCTAGATGTA

GATCATCGGT

CATCTCTGAC

TTGGTGTATC

GGCTGCTGAA

CAATCAGTTC

ATTCTCAAAC

ATCTATAGTC

TAATCTGAGC

AGGTGTTATC

GCAACCAGTC

AGCCCTTTGT

CAGCTTCCAG

CCCCCTATCA

TATCGCTGAC

AATGGAGACA

CGAGTGGGCA

GAGTCTGACA

CCTATGTAAG

CTCTTCGTCA

TTCCCTCTGG

ATGTCACCAC

AGTAGGATAG

GTTCTATTCG

CATCGGGCAG

ACTAACTCAA

GATGAAGTGG

AAGATTAAAT

AACCCGCCAG

GAkACTCATGA

CTAGCTGTCT

ATGTCGCTGT

ACTATGACAT

AGTAAAGGGT

AGAILATCCGG

AGTAATGATT

CACAGGGAAG

CTCGTCAAGC

ACGGATGATC

AATCAAGCAA

TGCTTCCAGC

CCATTGAAGG

GTTGAGCTTA

GTCGCTCTGA

TCAAGCIAACC

CCGAACAATA

AACGAGACCG

TTATTAACAG

TCATGTTTCT

CCATCTACAC

TCGAGCATCA

GCCTGAGGAC

TCCTTALATCC

AGAGAATCIA

ATGCATTGGT

CAAAGGGAAA

CCCTGTTGGA

CCCAGGGAAT

CAGAGTTGTC

GTTTGGGGGC

TCAGCAACTG

ATTCTATCAC

TAGGTGTCTG

CAGTGATAGA

AATGGGCTGT

AGGCGTGTAA

ATAACAGGAT

AAATCAAAAT

TCCTCTACAA

ACCGCATCCA

TCGGTAGTTA

GATAAATGCC

AGAACATCTT

GAGCTTGATC

CGCAGAGATC

GGTCAAGGAC

ACCTCAGAGA

GGATAGGGAG

ATTGGATTAT

GAACTCAACT

CTGCTCAGGG

CTTGTATTTA

GTACGGGGGA

ACAACTGAGC

TCCGGTGTTC

CATGGTGGCT

AATTCCCTAT

GAAATCCCCA

CAGGCTCTAC

CCCGACAACA

GGGTAAAATC

TCCTTCATAC

TGCTTCAGGA

CTCTTGAAAC

GCATCGAGCC

ATTAAA.ACTT

TTCTACAAAG

ATGATTGATA

GGGTTGCTAG

CATAA.AAGCC

GTGCTGACAC

TTCACCGACC

TACGACTTCA

GATCAATACT

CTACTGGAGG

CCCACTACAA

AILTCGAGGTT

ACTTACCTAG

ATGCACCGAG

CATATGACAA

TTGGGGGAGC

CAGGGATCAG

ACCGACATGC

CTCTCATCTC

CGGACAGATG

CAAGCACTCT

GGGGTCTTGT

TTCGGGCCAT

ACAAATGTCC

CACCTGAAAT

AGGGTGCAAG

ACAACCCCCA

GACCTTATGT

CCATTGCAGG

TCAGCACCAA

CACTCTTCA.A

TAGTGAAATT

GAGATCTCAC

GTGCAGATGT

CCAGGGTAAC

TCAGAGGTCA

ACAATGTGTC

TGGAAAAGCC

TGTTTGAAGT

ACTATTTTGA

TCAAATTCGC

GGAAAGGTGT

AATCCTGGGT

ACAGAGGCGT

ACAAGTTGCG

GCGAGAATCC

CTGTTAATCT

TGATCACACA

7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 -130 .fr..

CGGTTCAGGG

GCCAATGAAG

GGTTAGTCCC

AACATACCTA

ACCTGGTCAA

TGTGGTTTAT

GCCTATAAGG

CTGGTGCCGT

TGGGATGGTG

ATAGGGCTGC

GTGAAATAGA

CGCTATCTGT

ATAAGATAGT

CTACACTGTG

TAAACAATGT

CTCATATTCC

CAAGGAAGAT

AGGTTTTCCA

AGGACATCA.A

AGCCCTTTCT

CCCATACTTG

TGCTAATCTC

TGACGTTTGA

CCGCTATGAC

AACTGATAGA

TGGAGCCTCT

ATGGACCTAT

AACCTAGCCT

TACCTCTTCA

CCTGCGGAGG

GATCTCCA.AT

TACGTTTACA

GGGGTCCCCA

CACTTCTGTG

GGCATGGGAG

CAGTGAACCA

CATCAGAATT

CAACCAGATC

AGCTATCCTG

TCAGAACATC

GGAAGTTGGG

ATATCCAAAT

CCGTGAGCTC

ATGCCTGAGG

GGAGAAAATT

GTTTTGGTTT

CCATAGGAGG

TCGTGACCTT

ACTGGTCTTG

CATTGATGCT

TGGTTTCTTC

TTCACTTGCT

ACAAATCCAA

TAGGTGTAAT

CTGTTCCAAT

TGGATGGTGA

ATGTTTTGGC

GCCCAAGCCG

TCGAATTACA

TGCTTGCGGA

TCAGCTGCAC

ATCACATGAT

AAGAAAAACG

TTATACCCTG

GAGTATGCTC

AAGCACCGCC

AATGTCATCA

TGTAATCAGG

CTCAAAAAGG

GACACTAACT

ATTAACTTGG

ACAGTCAAGA

AGACACACAC

GTTGCTATAA

ATGTATTGTG

AGGTATACAG

CCTGCACTCG

TACCTGCAGC

CCACAACAAT

CAACACATTG

TAAGGAAGCA

TGTCAAACTC

AACCTATGAT

CTCATTTTCT

AGTGGAATGC

CTCAGA.ATCT

AGTCACTCGG

GTCACCCAGA

TAGGGTCCAA

AAGTTCACCT

GAGTCCCTCA

TAAAAAACGG

AGTCCAAGCT

ATTTATTTAA

GAAATTCGCT

CACGGCTTGG

GAGTTTACAT

CTGAGATGAG

CAGTATTCTT

TCAGTAAAGA

ATGTCATAGA

AGCTTCTAGG

GGAATCCAAC

TGAGGGATAT

GTGTATTGGC

GAGTGGATAC

GGCGAGGACT

AGTTCCAATC

ACTTCCAGAG

TACTTTTATC

TTCACATGGG

GGTGGATATA

GAAGATGGAA

CATCAGGCAT

GTGGTTCCCC

AGATAGCCCG

CGCATACAGC

ATTTTCCAAC

TAGGAGTTAT

CATAGAAGAC

GTACTCCAAA

CCTAGGCTCC

GCACAGCTCC

GTCAGTGATT

CACTGGTAGT

GTCTCJZLCAT

GGGGAGGTTA

AAGAGTCAGA

TTACCA.AATT

AACAGTAGAA

TGACTATCCC

CGAGATTCAA

GCCATGCCCC

TGGTGATTCT

TTGAACATGC

CTTTTAGGTT

ACCAAAAACT

TCACTCACTC

CCAACCGCAG

ACCCACTAGT

CTTATGGACT

ATAGTTACCA

CTGGAGGACC

CAAATGATTA

CCGACCCACT

AAAGAGTCAA

GTCAGTGATA

GA.ATTGAGGG

CAATGGTTTG

AAkATCACAAA

TCAGTTGAGT

GTATATTACC

ATGACAGAGA

TACATGTGGA

GTAGCCATGC

CTCAGAGGTG

8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 4* 131 CTTTCCTTA-A CCACTGCTTT ACTGAAATAC ATGATGTTCT TGACCAAAAC GGGTTTTCTG ATGAAGGTAC TTATCATGAG off, eoo.*: foe.

0 so #009

TACATCTGAC

CAGTAACGGC

AGACTCTGAT

GGCACGGAGG

ATGCTCAAGC

TTGCTGGAGT

ACCTAILAGGA

AGTTCCTGCG

TTAATGATTC

TCCATGACCC

GTAGACTTTT

TAATCTCAAA

ATTTGACTAA

GTCACAGGGG

AGAACGTGAG

ACACTGATCA

ATCTCAAGAA

TAAATGAGAT

CTGTCCTCTA

GCAAAGTCCc

GTCAGAAGCT

GAGTAAGGAT

TACCCAGCAC

ACTTTGTAAT

AGGGGAGATT

TGCTGAAAAT

GAAAGGTCAT

CAGTTGGCCA

TTCAGGTGA.A

GAAATTTGGC

CAAGGCACTT

TTACGACCCT

GAGCTTTGAC

TGAGTTCAAC

TGCTAAAATG

CGGGATTGGC

GGCACTCCAC

GGGGCCAGTC

AGCAGCAAAA

TCCGGAGAAT

GTACTGCCTT

TTACGGATTA

TGTA-AGTGAC

CAATGACCAA

GTGGACCATC

TGCTTCGTTA

ATGGCCTTAC

TCTTAGGCAA

TTAATTGAAG

TTCTCATTTT

GTTAGGAAAT

GCCATATTCT

CCCCTGACCC

GGGTTALACAC

TGCTTTATGC

GCTGCTCTCC

CCCAAAGGAA

CCATATGACA

CTGTCTTACA

ACTTACAAA-A

A.ATTATTTTA

ACTCTAGCTG

TTAAAAACCC

GGGTTTATAG

ATGGAGGCTT

AATTGGAGAT

CCCTCATTTT

CCTCATTGCC

ATCTTCATTA

AGCACCATTC

GTGCAAGGGG

AACCTTAAGA

AGGCTACATG

CCCTAGATTA

TCAGAAGTTT

ACATGAATCA

GTGGAATCAT

TCCCCCTGCA

ATGAGCAGTG

CTCTTAGCCT

AAAGGGAATG

CTGGGTCACG

TGATAATGTA

GCCTGAAAGA

TGAGGGCATG

AGGACAATGG

TCTCAGGAGT

ACTCCCGAAG

GATTCCCTCA

ACGAGACAGT

ATGAGACCAT

TCCAGTGGCT

CCCCTGACCT

AGTACCCTAT

CCTATTTATA

ACAATCAGAC

AACGGGAAGC

ACATAGGCCA

CATTTTCATA

CGGCCACCCC

GCCTAAAGTC

AATCAACGGC

TGCTGCAGAC

CGTTGATAAC

GGATAGTGAT

GGATTCAGTT

GAGGCTTGTA

TGTTGTAAGT

AAAGGAGATC

CCAAGTGATT

GATGGCCAAG

CCCCAAAGAT

CCCAGTCCAC

TGTAATTCGG

CAGTGCATTT

CAGCTTATTT

GCATAAGAGG

TGACGCCCAT

GGGAGGTATA

CCTGGCTGCT

CATAGCCGTA

TGCTAGAGTA

TCACCTCAAG

ACTGATGACA

AGACTTGAAG

ATTGTGTATG

TATCGTGACA

ACAATCCGGA

TGGAAATCTT

CTGACAATGT

TACCCGA;LAG

AATGTTTTCC

GGAGCTTACC

AAGGAAACAG

GCTGAAAATC

GACGAGCACG

CTCAAAGAAA

ACAAGTACCA

CAGGACCAAG

ATCACGACTG

GCACAAAGGC

CTTGAAACCT

GTCCCGTTAT

GAAGGGTATT

TATGAGAGCG

ACAAAAAGGG

ACTAGAGATT

GCAAATGAGA

10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 132 e.g.

S

00Se 0O Ce S 0

S

S@ 55 S C

S

CbS.

0@ 55 5

CO

5 S Ce

S

S CC S 55 5 0005 5 5555 0

S.O.S.

0 50 6C S 00 0000

C

6060

CAATTGTCTC

TGTCCCAATC

AAACAAGGGC

ATGACCGTTA

CTCTTGGCTT

ACAACGATCT

TGAATATGAG

ATCTCAAGAG

CACAACAACC

TTGTATGCGT

TCCATAGTCC

AGGGACTGGC

TCCTGGATCA

AAGGCCTGAT

TGTCCAATTA

GAAATGTCCT

ATATGTGGGC

TAGAA.TCTAT

GATCAGTCAA

AGGAAACATC

TGAAGCTTGC

CAGTGTACTC

CAAGGCAAAG

CGACTAATTT

CCCTTGTCCG

ATCACATTTT

ACTCA.AGAGC

AGCATGCAGT

CCTTGCATAT

CACAATCAAT

CTTAATAAGG

CAGGCTGTTT

AATGATTCTC

GGGGGACTCT

CCAGAGCATC

AAACCCA.ATG

GGCATTCCTC

TAGTGTCACA

TCGAGCCAGC

TGACTATGAA

CATTGACAAA

AAGGCTAGCT

GCGAGGCCAC

CTACGGATGG

ATCCTTGAGA

CTTCGTAAGA

ATGGGCTTAT

GGCCAATGTG

AGCGCATAGG

AGTGGCAAGG

TTTGTCTATT

ATCGCAAGAT

A.ATATTGCTA

TCCCTGAACG

TCAACCATGA

ATGGCACTGT

GTCAGAAACA

TCATCACTA.A

TCATTCCTAG

ACTAGACTCC

TTAAAAGGGT

ATGGACAGGC

GGGGCAAGAG

ATGAGGAAGG

CAPLTTTAGAG

GAGTCATGTT

CGAGGACGGC

CTTATTCGGC

TTTTTTGTCC

GTCCCATATA

GCCCCAAGTC

GGTGATGATG

AGCCTGGAGG

TTGAGGGATC

TATACCACAA

CAAAAGGAAT

GTGTATTCTG

CAACAATGGC

TCCTAAAAGT

CCCGGGATGT

TGCCCGCTCC

TCGGTGATCC

TGCCTGAAGA

ACTGGGCTAG

TCAAGAACAT

TATTCCATGA

ATATTATAGT

AGTCTATTGC

GGGGGTTAAC

CAGGGATGGT

CAGTGCAGCT

CTATTTACGG

GCCATGAGAC

CCTCGGGTTG

TTGGTTCTAC

GATCCTTGCG

ATAGCTCTTG

AGCTAAGGGT

GTACCACTCA

TCTCCAACGA

ATATTATGAT

GTCAGAGACT

TAA.AAGCATC

GATACAGCAA

AGTCATACCC

TATCGGGGGG

AGTAACATCA

GACCCTTCAT

CGACCCTTAC

AACTGCAAGG

TGACAGTAAA

ACCTAGGGCA

AGGCATGCTA

CTCTCGAGTG

GCTATTGACA

GGCTAGAGCC

CCTTGAGGTC

ATGTGTCATC

CCAACTGGAT

CACTGATGAG

ATCTGCTGTT

GAACGAAGCC

GATCACTCCC

AGTGAALATAC

CAATCTCTCA

GGGCTACTTG

ATAGTTGATG

GAGAGAGGTT

ATCCTGATCT

CTCCTCACAA

ATGAATTATC

TCAATTGCTG

CAAGTAATGA

TCAGCAAATC

TTTGTCCTGA

GAAGAGGACG

GCTCATGAAA

GATACCACAA

ATAACCAGAT

GGAAGAAAGA

CTAAGAAGCC

CCTGATGTAC

TGCGAGTGTG

GATATTGACA

AGAACAGACA

AGAATAGCAA

TGGTTGTTGG

ATCTCAACTT

TCAG~jTACAT

TTTGTCATAT

11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 CAGATAAGAA GGTTGATACT AACTTTATAT ACCAACAGGG AATGCTTCTA GGGTTGGGTG 133

TTTTAGAAAC

TTCACGTCGA

CCCGCAAGCT

CTTTAATTGA

AATTTGTTAC

CTATGATTGA

TAGGGGATGA

TCACTATCTA

GACCATCAGG

AAGGAGTGTT

GGCATTGTGG

CAACTGTGTG

AAGAGTTAGA

GATTCGACAA

GGACCTGCCC

ATATCAAGGC

TTGTAGACCA

GATTGAGAGT

CAAAGATCGG

ATGATGTTGC

GGGGTAATCT

CTTGCTACAA

ACGGCTTGTT

AACTAAACAA

AATTAGCACC

TTGTCAAAGT

ATTGTTTCGA

AACAGATTGT

AGAGCTTAGG

CAGAGATGCA

ATGGTCCACA

CCTGGTAACA

CGATATCAAT

CTTGGGCCAG

GAAATATCAG

TAAGGTGCTT

TATTATAGAG

CAACATGATT

AGAGTTCACA

TATCCAGGCA

ACCAATTCGA

AGAGGCTAGG

TTACTCATGC

TGATCCAGGA

CAGCAACAAC

AAALATTGCTC

CGCCAATTAT

AGCTGTTGAG

CTTGGGTGAG

GTGCTTCTAT

CTATCCCTCC

GCTCTTTAAC

CTCGAGAAAG

TGCGTGATCC

GCAGAGCTAT

ACAAGGCTAT

CCCCA.ACTAT

AAATTTGAGA

AGTTTCATAA

TGTGCAGCCA

ATGGGTGAGC

GTCAATGCTC

CCTATCCATG

TACACATGCT

TTTCTTCTGT

AAACACTTGT

GGTCTACGAC

TTATCTCCAG

TCTCTGACTT

TTCATTTTTG

ATCTCAAATA

AAAGATATCA

GAAATCCACG

ATATCAACAT

GGGTCGGGTT

AATAGTGGGG

GAAGTTGGTC

GGGAGGCCCG

ATACCGGATC

CGATGATAGA

GTACCAACCC

ACACCCAGAG

ATCACATTTT

AGGACCATAT

CTGAGTTTCT

TCAATTGGGC

TGTTGTCTTC

TAAGCCACCC

GTCCTTCACT

ATATGACCTA

GTGAAAGCGA

GTGTTCTAGC

CTGTAGAGAA

CAGGGTCTTC

ATCTCCGGCG

ACGCCCTCGC

TGAGCATCAA

ACACAAGCAA

CTTTCCGCAG

TAATTAGGAG

CTATGTTGAT

TTTCCGCCAA

TTGTCGAACA

AAGTCACGTG

ATCTAA-CACG

TCATCCCAGG

ATTGATATAT

CCATAGGAGG

AGCTAAGTCC

GAATGA.AATT

GCTTATAGAG

ATTTGATGTA

GTTCCTTTCT

AAAGATCTAC

TGATGCTCAA

CCTCGACCTG

CGAGGATGTA

AGATTTGTAC

ATGTGCAGTT

GTGGAACATA

AGGATCGATC

TGAGGTAAAT

GGATTTCAGA

GCACAATCTT

AATCGGGTTA

ATGCCTTGAG

CACTTATAAG

TTCTAGATCT

CAGAATGGGA

GGTAGGCAGT

GTATTACATC

ATACCCAGCT

GATAATGCAC

CACCTTGTGG

ACAGCACTAT

TCAGCTCTCA

CCAAGATTAT

CATTATCATA

AGAATGAGCA

AAGAAATTCT

AACTTACACA

TTGTTGAATG

GTACCGGACA

TGTCAACCAG

CTAACCGATC

AATCCAATTA

AALACAGATAA

GTCAGTCAGC

CCTCCACACG

CCCATTTCAG

AACTCATCCG

CCAGGGGAAG

GAGATACTAA

GGTCAALAGGG

GTAGGTAATA

GTAGATTGCT

13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 134

TCAATTTCAT

AGACCTTACC

TGGCTCTGCT

GGGATTTTGT

TCTACCCTAG

AAGCTAACCG

GGACTTCACC

CAATTGTGGG

CTATAGAGCA

AATTGATCCA

TCTACAGGGA

CTTACCCCGT

TTTGGGGGCA

ATCTCAAGTC

CTAAGTCAGA

TAACAATCAA

ATTAATTGGT

AGTCAGTAAT

TAACAAAGAT

CCTTGGCAAA

TCAGGGATTT

ATACAGCAAC

GCTAATGAAT

TGGACTTATA

AGACGCAGTT

GGTGCTGATC

CCATGATGTT

GTTGGCAAGA

ATTGGTAAGT

TATTCTTCTT

CGGTTACCTG

GAAACAGATT

GGAGACCAAA

TGGACTCCGG

ATCCCTACCT

ACTATAGAGA

ATAGGATCAA

ATAAGTTATG

TTCATATCTA

CCTGAAAAGA

GGTCACATCC

AGTAGAGGTG

AATTGCGGGT

GCCTCAGGGC

TTCAAAGACA

AGCAGGCAAC

TACTCCGGGA

ATACTAGACT

ATTATGACGG

GAATGGTATA

GACCCTAATC

CTAGTGTGGG

AGCTAGAGGA

TACTGGTGAT

TAGGGTCTTA

CTGAATCTTA

TTAAGCAGCA

TATCCATTAA

GTATCAACCC

TGGCAATTAA

AAGATGGATT

ACCA.AAGAAG

GAGAACTTAT

ACAGAAAGTT

TACACCAGAA

GGGGTTTAAA

AGTTAGTCGG

CTGCCCTAGG

TTTCTATTCC

GTTTAT CCAT

ATTAGCAGCC

TAAGCTTATG

TTATAGAGAA

TTTAGTCATG

GATAATTGAA

GCAACTAAGC

TATTCTGAAG

CGGACCTAAA

GCTTAACTCT

TCA-ACAAGGG

ATCTAGGATC

GATAAATCGG

TATCTTCGTT

ACGTGAGTGG

ATACAGTGCC

TAGTTAGGCA

CAGCTTTGTC

TCAGATATAG

ATCTTATCGA

CCTTTCAGCG

GTGAACCTTG

ACAGATCTCA

TCATCTGTGC

TGCATACAAG

AA.ACTTACAC

CTGTGCAAAG

ATACTCATCC

ATGTTCCATG

ACCCGCAAAT

TTTATCCAGA

AAGAATCTAT

GTTTTTAAGG

CTGATTAAGG

TTATTTGCAA

TGGT

14880 14940 15000 15060 15120 15180 15240 15300 15360 15420 15480 15540 15600 15660 15720 15780 15840 15894 a a.

a a a.

a TATATTAAAG AAAACTTTGA AAATACGAAG INFORMATION FOR SEQ ID NO:6: SEQUENCE CHARACTERISTICS: LENGTH: 2183 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: 135 Met Asp Arg Ile Asn Thr Ile Gly .Arg 145 Trp Ser Pro Leu Phe 225 Thr Arg Gly Asp Ser Val Lys Val His Glu Asn Asp 130 Lys Phe Vai Val Val 210 Giu Glu Val Asn Ser Pro Pro His Giu Ser Asp Ser 115 Thr Giu Giu Ile Phe 195 Al a Leu Thr Arg Pro Leu Ile His Arg Val His Lys 100 Leu Asn Lys Pro Lys 180 Phe Ile Val Al a Tyr 260 Thr Ser Val Al a Leu Gly Ile Giu Tyr Ser Ile Phe 165 Ser Thr Ile Leu Met 245 Met Tyr Val Thr Tyr Lys Asn 70 Pro Ser Ser Arg Ile 150 Leu Gin Gly Ser Met 230 Thr Trp Gin Asn Asn Ser Asn Val Tyr Thr Lys Leu 135 Asn Phe Thr Ser Lys 215 Tyr Ile Lys Ile Gin Lys Leu Gly Ile Pro Arg Vai 120 Gly Leu Trp His Ser 200 Glu Cys Asp Leu Val Leu 10 Val Asp Ser Ser Cys 90 Ile Asp Gly Val Thr 170 Cys Giu Gin Val Arg 250 Asp Met Tyr Al a Pro Asn Lys 75 Asn Arg Lys Ser Tyr 155 Val1 HisB Leu His Ile 235 Tyr Gly Leu Pro le Thr Gin Leu Gin Giu Val Giu 140 Met Lys Arg Leu Val 220 Glu Thr Phe Glu Val Giu Cys Ile Ser Leu Leu 110 Gin Arg S er Glu Arg 190 Ser Tyr Arg Leu Pro 270 Leu His Tyr Gin Ile Tyr Phe Lys Cys Giu Ser Met 175 His Arg Leu Leu Leu 255 Ala Ser Leu Ala Asn Asn Pro Asn Lys Leu Asp Gin 160 Arg Thr Asp Thr Met 240 Gly Leu Leu 136 275 280 285 Ala Tyr Leu Gin Leu Arg Asp Ile Thr Val Giu Leu Arg Giy Ala Phe 290 295 300 Leu Asn His Cys Phe Thr Giu Ile His Asp Val Leu Asp Gin Asn Gly 305 310 315 320 Phe Ser Asp Giu Gly Thr Tyr His Giu Leu Ile Giu Ala Leu Asp Tyr 325 330 335 Ile Phe Ile Thr Asp Asp Ile His Leu Thr Gly Giu Ile Phe Ser Phe 340 345 350 Phe Arg Ser Phe Giy His Pro Arg Leu Glu Ala Val Thr Ala Ala Giu 355 360 365 Asn Val Arg Lys Tyr Met Asn Gin Pro Lys Val Ile Val Tyr Giu Thr 370 375 380 Leu Met Lys Giy His Ala Ile Phe Cys Gly Ile Ile Ile Asn Gly Tyr S385 390 395 400 Arg Asp Arg His Gly Gly Ser Trp Pro Pro Leu Thr Leu Pro Leu His *405 410 415 *Ala Ala Asp Thr Ile Arg Asn Ala Gin Ala Ser Giy Glu Gly Leu Thr 420 425 430 His Giu Gin Cys Val Asp Asn Trp Lys Ser Phe Ala Gly Val Lys Phe 435 440 445 Gly Cys Phe Met Pro Leu Ser Leu Asp Ser Asp Leu Thr Met Tyr Leu 450 455 460 Lys Asp Lys Ala Leu Ala Ala Leu Gin Arg Giu Trp Asp Ser Val Tyr 465 470 475 480 Pro Lye Giu Phe Leu Arg Tyr Asp Pro Pro Lys Gly Thr Gly Ser Arg *485 490 495 Arg Leu Val Asn Val, Phe Leu Asn Asp Ser Ser Phe Asp Pro Tyr Asp 500 505 510 Met Ile Met Tyr Val Vai Ser Giy Ala Tyr Leu His Asp Pro Glu Phe 515 520 525 Asn Leu Ser Tyr Ser Leu Lye Glu Lye Glu Ile Lye Glu Thr Gly Arg 530 535 540 Leu Phe Ala Lys Met Thr Tyr Lys Met Arg Ala Cys Gin Val Ile Ala 545 550 555 560 137 Giu Asn Leu Ile Ser Asn Gly Ile Cly Asn Tyr Phe Lys Asp 565 570 Asn Gly 575 Met Val Val Val 625 Asp Ser Tyr Leu Leu 705 Pro Gly Pro Leu Ser 785 Arg Ala Ser Leu 610 Arg Gin Aila Glu Pro 690 Tyr Leu Giy Tyr Val 770 Thr Asp Lys Giy 595 Lys Ala Asp Phe Thr 675 Ser Val Cys Ile Leu 755 Gin Trp Tyr Asp Giu 580 Vai Pro Thr His Aia Lys Thr Asp 645 Ile Thr 660 Ile Ser Phe Phe Ser Asp Lys Val 725 Giu Giy 740 Tyr Leu Giy Asp Pro Tyr Phe Vai 805 His Lye Ser Giy 630 His Thr Leu Gin Pro 710 Pro Tyr Aia Asn Aen 790 Ile Asp Asp Arg 615 Phe Pro Asp Phe Trp 695 His Aen Cys Aia Gin 775 Leu Leu Leu Leu 600 Ser Ile Giu Leu Aila 680 Leu Cys Asp Gin Tyr 760 Thr Lys Arg Thr 585 Lye Pro Giy Asn Lye 665 Gin His Pro Gin Lys 745 Giu Ile Lye Gin Lye Giu Val Phe Met 650 Lye Arg Lye Pro Ile 730 Leu Ser Aia Arg Arg 810 Al a S er His Pro 635 Giu Tyr Leu Arg Asp 715 Phe Trp Gly Vai Giu 795 Leu Leu His Thr 620 His Ala Cys Asn Leu 700 Leu Ile Thr Val Thr 780 Ala His His Arg 605 Ser Val Tyr Leu Giu 685 Giu Asp Lys le Arg 765 Lys Ala Asp Thr 590 Giy Thr Ile Glu Asn 670 Ile Thr Ala Tyr Ser 750 Ile Arg Arg Ile Leu Gly Lys Arg Thr 655 Trp Tyr Ser His Pro 735 Thr Ala Val Val Gly 815 Al a Pro Asn Gin 640 Val Arg Gly Val Val 720 Met Ile Ser Pro Thr 800 His His Leu Lye Aia Aen Glu Thr Ile Val Ser Ser His Phe 820 825 Phe Val Tyr 830 138 Ser Lys Gly Ile Tyr Tyr Asp Gly LeU Leu Val Ser Gin Ser Leu Lys 835 840 845 Ser Ile Ala Arg Cys Val Phe Trp Ser Glu Thr Ile Val Asp Giu Thr 850 855 860 Arg Ala Ala Cys Ser Asn Ile Ala Thr Thr Met Ala Lys Ser Ile Giu 865 870 875 880 Arg Gly Tyr Asp Arg Tyr Leu Ala Tyr Ser Leu Asn Val Leu Lys Val 885 890 895 Ile Gin Gin Ile Leu Ile Ser Leu Gly Phe Thr Ile Asn Ser Thr Met 900 905 910 Thr Arg Asp Vai Vai Ile Pro Leu Leu Thr Asn Asn Asp Leu Leu Ile 915 920 925 Arg Met Ala Leu Leu Pro Aia Pro Ile Gly Gly Met Asn Tyr Leu Asn 930 935 940 Met Ser Arg Leu Phe Vai Arg Asn Ile Gly Asp Pro Val Thr Ser Ser 945 950 955 960 Ile Ala Asp Leu Lys Arg Met Ile Leu Ser Ser Leu Met Pro Giu Giu 965 970 975 Thr Leu His Gin Val Met Thr Gin Gin Pro Gly Asp Ser Ser Phe Leu 980 985 990 Asp Trp Ala Ser Asp Pro Tyr Ser Ala Asn Leu Val Cys Val Gin Ser 995 1000 1005 Ile Thr Arg Leu Leu Lys Asn Ile Thr Ala Arg Phe Val Leu Ile His 1010 1015 1020 Ser Pro Asn Pro Met Leu Lys Giy Leu Phe His Asp Asp Ser Lys Giu 1025 1030 1035 1040 Giu Asp Giu Gly Leu Ala Ala Phe Leu Met Asp Arg His Ile Ile Val *.1045 1050 1055 Pro Arg Ala Ala His Giu Ile Leu Asp His Ser Vai Thr Gly Ala Arg 1060 1065 1070 Giu Ser Ile Ala Gly Met Leu Asp Thr Thr Lys Gly Leu Ile Arg Ala 1075 1080 1085 Ser Met Arg Lys Gly Gly Leu Thr Ser Arg Val Ile Thr Arg Leu Ser 1090 1095 1100 Asn Tyr Asp Tyr Glu Gin Phe Arg Ala Gly Met Val Leu Leu Thr Gly 139 1105 1110 1115 1120 Arg Lys Arg Asn Val Leu Ile Asp Lys Glu Ser Cys Ser Val Gin Leu 1125 1130 1135 Ala Arg Ala Leu Arg Ser His Met Trp Ala Arg Leu Ala Arg Gly Arg 1140 1145 -1150 Pro Ile Tyr Gly Leu Glu Val Pro Asp Val Leu Glu Ser Met Arg Gly 1155 1160 1165 His Leu Ile Arg Arg His Glu Thr Cys Val Ile Cys Glu Cys Gly Ser 1170 1175 1180 Val Asn Tyr Gly Trp Phe Phe Val Pro Ser Gly Cys Gin Leu Asp Asp 1185 1190 1195 1200 Ile Asp Lys Giu Thr Ser Ser Leu Arg Val Pro Tyr Ile Gly Ser Thr 1205 1210 1215 Thr Asp Giu Arg Thr Asp Met Lys Leu Ala Phe Val Arg Ala Pro Ser 1220 1225 1230 .Arg Ser Leu Arg Ser Ala Val Arg Ile Ala Thr Val Tyr Ser Trp Ala 1235 1240 1245 Tyr Gly Asp Asp Asp Ser Ser Trp Aen Glu Ala Trp Leu Leu Ala Arg 1250 1255 1260 Gin Arg Ala Asn Val Ser Leu Giu Glu Leu Arg Val Ile Thr Pro Ile 1265 1270 1275 1280 Ser Thr Ser Thr Asn Leu Ala His Arg Leu Arg Asp Arg Thr Thr Gin 1285 1290 1295 Val Lys Tyr Ser Gly Thr Ser Leu Val Arg Val Ala Arg Tyr Thr Thr 1300 1305 1310 Ile Ser Asn Asp Asn Leu Ser Phe Val Ile Ser Asp Lys Lys Val Asp *1315 1320 1325 Thr Asn Phe Ile Tyr Gin Gin Gly Met Leu Leu Gly Leu Gly Val Leu 1330 1335 1340 Glu Thr Leu Phe Arg Leu Glu Lye Asp Thr Gly Ser Ser Asn Thr Val 1345 1350 1355 1360 Leu His Leu His Val Glu Thr Asp Cys Cys Val Ile Pro MetIle Asp 1365 1370 1375 His Pro Arg Ile Pro Ser Ser Arg Lye Leu Glu Leu Arg Ala Glu Leu 1380 1385 1390 140 Cys Thr Asn Pro Leu Ile Tyr Asp Asn Ala Pro Leu Ile Asp Arg Asp 1395 1400 1405 Ala Thr Arg Leu Tyr Thr Gin Ser His Arg Arg His Leu Val Giu Phe 1410 1415 1420 Val Thr Trp Ser Thr Pro Gin Leu Tyr His Ile Leu Ala Lys Ser Thr 1425 1430 1435 1440 Ala Leu Ser Met Ile Asp Leu Val Thr Lys Phe Glu Lys Asp His Met 1445 1450 1455 Asn Glu Ile Ser Ala Leu Ile Gly Asp Asp Asp Ile Asn Ser Phe Ile 1460 1465 1470 Thr Giu Phe Leu Leu Ile Giu Pro Arg Leu Phe Thr Ile Tyr Leu Gly 1475 1480 1485 Gin Cys Ala Ala Ile Asn Trp Ala Phe Asp Val His Tyr His Arg Pro 1490 1495 1500 Ser Gly Lys Tyr Gin Met Gly Giu Leu Leu Ser Ser Phe Leu Ser Arg 1505 1510 1515 1520 *Met Ser Lys Gly Val Phe Lys Val Leu Val Asn Ala Leu Ser His Pro *1525 1530 1535 Lys Ile Tyr Lys Lys Phe Trp His Cys Gly Ile Ile Giu Pro Ile His 1540 1545 1550 Gly Pro Ser Leu Asp Ala Gin Asn Leu His Thr Thr Val Cys Asn Met 1555 1560 1565 Ile Tyr Thr Cys Tyr Met Thr Tyr Leu Asp Leu Leu Leu Asn Giu Glu *1570 1575 1580 Leu Giu Giu Phe Thr Phe Leu Leu Cys Glu Ser Asp Glu Asp Val Val 1585 1590 1595 1600 Pro Asp Arg Phe Asp Asn Ile Gin Ala Lys His Leu Cys Val Leu Ala 1605 1610 1615 Asp Leu Tyr Cys Gin Pro Gly Thr Cys Pro Pro Ile Arg Gly Leu Arg 1620 1625 1630 Pro Val Giu Lys Cys Ala Val Leu Thr Asp His Ile Lys Ala Giu Ala 1635 1640 1645 Arg Leu Ser Pro Ala Gly Ser Ser Trp Asn Ile Asn Pro Ile Ile Val 1650 1655 1660 141 Asp His Tyr Ser Cys Ser Leu Thr Tyr Leu Arg Arg Gly Ser Ile Lys 1665 1670 1675 1680 Gin Ile Arg Leu Arg Val Asp Pro Gly Phe Ile Phe Asp Ala Leu Ala 1685 1690 1695 Giu Val Asn Val Ser Gin Pro Lys Ile Gly Ser Asn Asn Ile Ser Asn 1700 1705 1710 Met Ser Ile Lys Asp Phe Arg Pro Pro His Asp Asp Val Ala Lys Leu 1715 1720 1725 Leu Lys Asp Ile Asn Thr Ser Lys His Asn Leu Pro Ile Ser Gly Gly 1730 1735 1.740 Asn Leu Ala Asn Tyr Giu Ile His Ala Phe Arg Arg Ile Gly Leu Asn 1745 1750 1755 1760 Ser Ser Ala Cys Tyr Lys Ala Val Glu Ile Ser Thr Leu Ile Arg Arg 1765 1770 1775 Cys Leu Giu Pro Gly Glu Asp Gly Leu Phe Leu Gly Glu Gly Ser Giy 1780 1785 1790 Ser Met Leu Ile Thr Tyr Lys Glu Ile Leu Lys Leu Asn Lys Cys Phe 1795 1800 1805 **Tyr Asn Ser Gly Vai Ser Ala Asn Ser Arg Ser Giy Gin Arg Giu Leu 1810 1815 1820 Ala Pro Tyr Pro Ser Glu Val Gly Leu Val Glu His Arg Met Gly Val 1825 1830 1835 1840 Gly Asn Ile Val Lys Val Leu Phe Asn Gly Arg Pro Glu Val Thr Trp *1845 1850 1855 Val Gly Ser Val Asp Cys Phe Asn Phe Ile Vai Ser Asn Ile Pro Thr 1860 1865 1870 Ser Val Gly Phe Ile His Ser Asp Ile Giu Thr Leu Pro Asn Lys 1875 1880 1885 Asp Thr Ile Glu Lys Leu Giu Glu Leu Ala Ala Ile Leu Ser Met Ala 1890 1895 1900 Leu Leu Leu Gly Lys Ile Gly Ser Ile Leu Val Ile Lys Leu Met Pro 1905 1910 1915 1920 Phe Ser Gly Asp Phe Val Gin Gly Phe Ile Ser Tyr Val Gly Ser Tyr 1925 1930 1935 Tyr Arg Giu Val Asn Leu Val Tyr Pro Arg Tyr Ser Asn Phe Ile Ser 142 1940 1945 1950 Thr Glu Ser Tyr Leu Val Met Thr Asp Leu Lys Ala Asn Arg Leu Met 1955 1960 1965 Asn Pro Giu Lys Ile Lys Gin Gin Ile Ile Giu Ser Ser Val Arg Thr 1970 1975 1980 Ser Pro Gly Leu Ile Gly His Ile Leu Ser Ile Lys Gin Leu Ser Cys 1985 1990 1995 2000 Ile Gin Ala Ile Val Gly Asp Ala Val Ser Arg Gly Gly Ile Asn Pro 2005 2010 2015 Ile Leu Lys Lys Leu Thr Pro Ile Giu Gin Val Leu Ile Asn Cys Gly 2020 2025 2030 Leu Ala Ile Asn Gly Pro Lys Leu Cys Lys Giu Leu Ile His His Asp 2035 2040 2045 Val Ala Ser Giy Gin Asp Gly Leu Leu Asn Ser Ile Leu Ile Leu Tyr 2050 2055 2060 *Arg Giu Leu Ala Arg Phe Lye Asp Asn Gin Arg Ser Gin Gin Giy Met 2065 2070 2075 2080 Phe His Ala Tyr Pro Val Leu Val Ser Ser Arg Gin Arg Giu Leu Ile *..2085 2090 2095 Ser Arg Ile Thr Arg Lys Phe Trp Gly His Ile Leu Leu Tyr Ser Gly 2100 2105 2110 Asn Arg Lys Leu Ile Asn Arg Phe Ile Gin Asn Leu Lye Ser Gly Tyr 2115 2120 2125 *Leu Ile Leu Asp Leu His Gin Asn Ile Phe Val Lys Asn Leu Ser Lys 2130 2135 2140 Ser Giu Lye Gin Ile Ile Met Thr Gly Gly Leu Lye Arg Giu Trp Val *2145 2150 2155 2160 C..Phe Lys Vai Thr Ile Lye Giu Thr Lye Giu Trp Tyr Lye Leu Val Gly 2165 2170 2175 Tyr Ser Ala Leu Ile Lye Asp 2180 INFORMATION FOR SEQ ID NO:7: SEQUENCE CHARACTERISTICS: LENGTH: 15894 base pairs TYPE: nucleic acid 143 STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: ACCAAACAAA GTTGGGTAAG GATAGATCAA TCAATGATCA TATTCTAGTA CACTTAGGAT

TCAAGATCCT

TGAGGAGCTT

GTGGAGCCAT

TTACCACTCG

GCGGGCCCAA

GTCAATTGAT

TTCAGAGTGA

ATGAGGCGGA

GATGGTTCGA

TGATTCTGGG

CAGACACGGC

TAGTTGGTGA

AGGACCTCTC

GGAACAAACC

GATTAGCCAG

GACTGCATGA

AAATGGGAGA

GCGCAGGATC

ACTCCATGGG

GGCAAGAGAT

ATTATCAGGG

AGCATTGTTC

CAGAGGAATC

ATCCAGACTA

ACTAACAGGG

TCAGAGGATC

CCAGTCACAA

CCAATACTTT

GAACAAGGAA

TACCATTCTA

AGCTGATTCG

ATTTAGATTG

TTTACGCCGA

TAGGATTGCT

TTTTATCTTG

ATTTGCTGGT

AACTGCACCC

ATACCCTCTG

AGGTTTGAAC

GGTGAGGAGG

ACAAGAGCAG

AAAAGAAACA

AAACACATTA

CTGGACCGGT

GCACTAATAG

ACCGATGACC

TCTGGCCTTA

TCACATGATG

ATCTCAGATA

GCCCAGATCT

GAGCTAAGAA

GAGAGAAAAT

TTCATGGTGG

GAAATGATAT

ACTATTAAGT

GAGTTATCCA

TACATGGTAA

CTCTGGAGCT

TTTGGTCGAT

TCAGCTGGAA

GATTAGGGAT

AGGACAXACC

TTATAGTACC

TGGTCAGGTT

GTATATTATC

CTGACGTTAG

CCTTCGCATC

ATCCAAGCAG

TTGAAGTGCA

GGGTCTTGCT

GGTGGATAAA

GGTTGGATGT

CTCTAATCCT

GTGACATTGA

TTGGGATAGA

CACTTGAGTC

TCCTAGAGAA

ATGCCATGGG

CTTACTTTGA

AGGTCAGTTC

ATCC!GAGATG

ACCCATTACA

AATTCCTGGA

AATTGGAAAC

CTTATTTGTG

CATCAGGCTG

AAGAGGTACC

TAGTGATCAA

AGATCCTGAG

CGCAAAGGCG

GTACACCCAA~

GGTGAGGAAC

GGATATCAAG

TACATATATC

AACTATGTAT

CTTGATGAAT

CTCAATTCAG

AGTAGGAGTG

TCCAGCATAT

CACATTGGCA

GCCACACTTT

TCAGGATCCG

GATTCCTCAA

CCGGATGTGA.

GAGTCTCCAG

TTAGAGGTTG

AACATGGAGG

TCCAGGTCCG

GGATTCAACA

GTTACGGCCC

CAAAGAAGGG

AGGATTGCCG

AGGACACCCG

GTAGAGGCAG

CCTGCTCTTG

CTTTACCAGC

AACAAGTTCA

GAACTTGAAA

TTTAGATTAG

TCCGAACTCG

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 144 a

GTATCACTGC

GGATCAGTAG

GTGAGAATGA

GAGAAGCCAG

CCCATCCTCC

CGCAGGACAG

TGGAAGAACA

ATTAGGTGCG

AAAACTTAGG

GAGCCGATGG

CTCAAGGCCG

ATATCAGACA

GGTCTCAGCA

CGCGGTCAGG

AATCTCCAGG

GCGGTTAAGG

AGCACCCTCT

GATACCGAGG

GCTTCTGATG

AGAGGCAACA

AGTAGGGCCA

TTTGGAACGG

CCCTCGGAAC

GCCGCACTGA

AATAATGAAG

AAAACAGCCT

CGAGGATGCA

AGCGGTCGGA

GCTACCAGGA

GGAGAGCTAC

AACCAGCATG

TCGA.AGGTCA

AGGCTCAGAC

AGAGGCCGAG

AACCAGGTCC

CAGAAGAGCA

AGCCCATCGG

ATCCAGGACA

AACCATGCTT

GATCTGGAGA

CATCAAGCAC

GAATCCAAGA

CAGGAGGAGA

GATATGCTAT

TTGAAACTGC

ACTTTCCGAA

GCACTTCCGA

AGATCGCGTC

CGTCAGGGCC

TACAGGAGTG

AAGGGGGAGA

TGGCCAAAAT

AGGCTTGTTT

CCCAGACAAG

TTGGGGGGCA

AGAGAAACCG

CCCCTAGACA

GCTGACGCTC

ACGGACACCC

GACCAGA.ACA

ACACAGCCGC

GGCACGCCAT

CTCACTGGCC

GGACCGAGCC

CTCAGCAATT

AAGCGATGAC

TGGGTTACAG

TGCTGACTCT

CGATGAATCT

CACTGACCGG

AGAAGGAGGG

GCTTGGGAAA

GACACCCATT

TTTATTGACA

AGATGCACCT

GACACCCGAA

CTATTATGAT

ACACGAGGAT

CAGAGATTGC

CCCAAGTATC

AGGAAGACAG

AGTCCAGCAG

TTGACACTGC

TGCTCAGGCT

CTAGGGTATA

ACATCCGCCT

CAGCCAACCA

GTCAAAAACG

GTCGAGGAAG

GCCTGCAAGG

GGATCAACTG

GACGCTGAAA

TGTTATCATG

ATCATGGTTC

GAAAACAGCG

GGATCTGCTC

GAGATCCACG

ACTCTCAATG

AAAA.AGGGGA

GGTGGTGCAA

GCGGGGAATG

TCTGGTACCA

GATGAGCTGT

AATCAGAAGA

AATGCATACT

ATTTCTACAC

GAGGGTCAA

AGCAAGTGAT

ATCGGAGTCA

GCAAGCCATG

CAATGACAGA

ACCCTCCATC

ACCATCCACT

GACTGGAATG

CCATGGCAGC

AAGAGGAGGC

AAGGCGGTGC

CTTTGGGAAT

TTTATGATCA

AATCAGGCCT

ATGTGGATAT

CCATCTCTAT

AGCTCCTGAA

TTCCTCCGCC

CAGACGCGAG

CCCAATGTGC

TCCCCGAGTG

CAATCTCCCC

TCTCCGATGT

TALATCTCCAA~

ACTGAGGACA

GGTGATCAAA

CAGAGTCGGG

GCGAGAGCTG

GGCCALAGATC

GCAGGAALTCT

GATCTTCTAG

ATTGTTATAA

CCCACGACTG

CATCCGGGCT

ATGGTCAGAA

AGGCAGTTCG

ALCCTCGCATC

CCCCTCAAGA

CAGCGGTGAA

TGATGGTGAT

TGGCGAACCT

GGGGTTCAGG

ACTCCAATCC

CCCGA.ACCCC

ATTGGCCTCA

TCGAAAGTCA

TGTGAGCAAT

GAGATCCCAG

CCAAGACATC

GCTAGAATCA

1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 a.

145

TTGCTGTTAT

AGCATATCCA

AAGGATCCCA

GGCAGAGATT

CTCCAGGGAA

CTAAAGCCGA

GCATCACGCA

CGTTACCTGT

CAGATGCTGA

CCAGTCGAC

GCCTCCTAAG

AAGGGTCGAT

TCAGAGTCAT

TGCTGGGGGT

CCCTGCCCTT

CTGAGCTTGA

ACAACACCCC

TCAATGCAAA

TCCGTGTTGT

GAAGAATGCT

GGATTGACAA

CAACATTTAT

ATTATTGCAA

GCACCAGTCT

GGTTCAAGAA

TCTGGAGGAG

TGAAGGGAGA

CCCTGGAAGG

ACGACCCCAC

CAGGCCGAGC

TGACTAATGG

TCGGGAAAA.A

GTGTAATCCG

TGACTCTCCT

TGAAGATAAT

TAATTAGTAC

TTCCACAATG

CGCTCCGATA

AGATCCTGGT

TGTTGAGGAC

AGGTGTTGGT

CATAGTTGTT

ACTALACCCTC

CCAAGTGTGC

TTATATGAGC

GGAATTCAGA

GGCGATTGGC

GGTCCACATC

AATGAAAATC

TCACATTAGA

GACCTTATGT

CAGATGCAAG

AGTTGAGTCA

ACACCTCTCA

TGCAGATGTC

ACTGGCCGAA

ACGGACCAGT

GGTGAGCTCA

CTCCATTATA

TGATGATATC

AATGAAGTAG

AACCTAAATC

ACAGAGATCT

CA.ACCTACCA

CTAGGTGATA

AGAGATCCCC

AGATCCACAG

AGACGTACAG

CTCACACCTT

AATGCGGTTA

ATCACCCGTC

TCGGTCAATG

CCTGGGAAGA

GGGAACTTCA

GAAAAGATGG

AGCACAGGCA

TACCCACTGA

ATAGTAAGAA

ATTAAGAAGC

AGCATCATGA

GAACTCAATC

GTTCTCAAGA

TCCAGAGGAC

GCCGTCGGGT

AALATCCAGCC

AAAGGAGCCA

CTACAGCTCA

CATTATAAAA

ACGACTTCGA

CCTACAGTGA

GGAAGGATGA

TAGGGCCTCC

CAAAACCCGA

CAGGGCjTCAA

GGAGAAAGGT

ATCTAATACC

TTTCGGATAA

CAGTGGCCTT

TCATCGACAA

GGAGAAAGAA

GCCTGGTTTT

AAATGAGCAA

TGGATATCAA

TCCAGGCAGT

AGATCAACAG

TTGCCATTCC

CCGACCTGAA

AGCCCGTTGC

AGCTGCTGAA

TTGTCCCTGA

GGCTAGAGGA

ACGATCTTGC

ACTTACCTGC

AACTTAGGAG

CAAGTCGGCA

TGGCAGGCTG

ATGCTTTATG

AATCGGGCGA

GGAACTCCTC

TGAAAAACTG

CCTAACAACA

GCTGGACACC

CGGGTATTAC

CAACCTGCTA

TGCAGAGCAA

GAGTGAAGTC

TGCACTTGGT

GACTCTCCAT

TGAAGACCTT

TTTGCAGCCA

GCAAAATATC

TGGACTTGGG

ACCCATCATA

CAGCCGACA.A

GGAATTTCAA

CACCGGCCCT

GGATCGGAAG

CAAGTTCCAC

CAACCCCATG

CAAAGTGATT

TGGGACATCA

GTGCCCCAGG

TACATGTTTC

GCATTCGGGT

AAAGAGGCCA

GTGTTCTACA

GGGAGTGTCT

CCGCAGAGGT

ACCGTTCCCA

GTGACCCTCA

CTTCCTGAGG

TACTCTGCCG

GGGATAGGGG

GCACAACTCG

AATCGGTTAC

TCAGTTCCTC

2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 146 9 9 9* 9 .99 9 9 9 9 9 9 9.

9

AAGAATTCCG

TGTAGACCGT

GCCCGGACAA

GCCGACAGCA

CCACCAGCCA

CGCTCCGGAC

ACTGGAAGGC

GACCGAGGTG

ACTAAACAAA

CGGCACCGCG

CCCCGGTGCC

AATCCAAGAC

GAGGAAGCCC

GGGCCACCAG

ACCCCAGGCC

TGGGGGACCC

CTCCTCCTCT

CCCACCCCTA

GGTCTCAAGG

ACCGGTCAAA

AGCTACAAAG

ATAACTCTCC

ACAGTTTTGG

CAGAGTGTAG

GCCCTAGGCG

CTGAACTCTC

CATTTACGAC

AGTGCCCAGC

AAAAG CCC CC

AGTGTGGACA

TCCCAATCCG

ACAGACCACC

CCCTTCCCCC

ACCCAACCGC

ACTTAGGGCC

CCCCCACCCC

CACAGGTAGG

GGGGGGCCCC

ACCCACCCCA

CTCCCAGACT

CGATCCGGCG

CCAAACCGCA

TCTCGAAGGG

AAGGAGACAC

TGAATGTCTT

TCCATTGGGG

TTATGACTCG

TCAATAACTG

AACCAATTAG

CTTCAAGTAG

TTGCCACAGC

AAGCCATCGA

GACGTGATCA

AATACCCGAA

TCCAAAAGAC

CCAGGCGGCC

CGTCCTCCTC

AGCCGCATCC

CTCCCCCAAC

AGGCATCCGA

AAGGAACACA

CCGAAAACCA

CACACCAACC

CCCCAAAA.AA

CACACGACCA

CGGCCATCAC

GGAAGCCACC

AAAGACATCA

ACCAAAAGAT

CGGGAATCCC

TGCCATATTC

CAATCTCTCT

TTCCAGCCAT

CACGAGGGTA

AGATGCACTT

GAGACACAAG

TGCTCAGATA

CAATCTGAGA

TAAATGATGA

AACGACCCCC

TTCACGGACC

CAkAGCACAGA

GTAGGACCCC

CCACAGCCCT

GCAAGAACCC

CTCCCTAGAC

CACACCCGAC

GAGGGAGCCC

CCCGAkACAGA

AGGCCCCCAG

CGGCAACCAA

CCCGAAAAAA

CAACCCGAAC

GTATCCCACC

CAATCCACCA

AGAATCAAGA

ATGGCAGTAC

AAGATAGGGG

CAATCATTGG

GAAATTGCAG

AATGCAATGA

AGATTTGCGG

ACAGCCGGCA

GCAAGCCTGG

CCAAGGACTA

CTCATAATGA

AAGCGAGAGG

ACAGCCCCGA

CGAGGACCAA

CGGGAAAGGA

CACAACCGAA

AGACCCTCCC

AGAACCCAGA

CCAACCAATC

CCCAGCACCC

GGGCCGACAG

ACCAGAGCCC

GGAAAGGCCA

CAGCACCCAA

GCCTCTCCAA

CATCCGACGA

CTCATCCAAT

TGTTAACTCT

TGGTAGGGAT

TCATAAAATT

AATACAGGAG

CCCAGAATAT

GAGTTGTCCT

TTGCACT'TCA

AAACTACTAA

TTCAAAGTTC

CAGCCAGAAG

CCAGCCAGCA

CACAAGGCCA

CCCCCAAGGT

ACCCCCAGCA

CCGCACAAGC

TCCCCGGCAT

CCCCGGCCCG

CCGCCGCCCC

AGCCACCGAC

CCAGCATCGC

AGACCACCCT

CAACCCGCGC

GAGCGATCCC

GTCCCCCGGT

CACTCAATTC

GTCCATCATG

CCAAACACCC

AGGAAGTGCA

AATGCCCAAT

ACTACTGAGA

AAGACCGGTT

GGCAGGTGCG

CCAGTCCATG

TCAGGCAATT

4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 147

GAGGCAATCA

ATCAATAATG

CTAGGGCTCA

CGGGACCCCA

ATCAATAAGG

AGCAGAGGAA

AGTATAGCCT

GTCTCGTACA

CAAGGGTACC

GTGTGCAGCC

TCCACCAAGT

TCACAAGGGA

ACGATCATTA

GTGGTCGAGG

TACCTGCACA

AATCTGGGGA

CAGATATTGA

GTGTGTCTTG

AACAAAAAGG

ACATCAAAAT

CACAAGTCTC

TGTCTCCGGC

ATCATCCACA

TCCTAAGGGA

TTTGCTGGCT

CATTAGACTC

GGCAAGCAGG

AGCTGATACC

AATTGCTCAG

TATCTGCGGA

TATTAGAAAA

TAAAGGCCCG

ATCCGACGCT

ATATAGGCTC

TTATCTCGAA

AAAATGCCTT

CCTGTGCTCG

ACCTAATAGC

ATCAAGACCC

TGAACGGTGT

GAATTGACCT

ATGCAATTGC

GGAGTATGAA

GAGGGTTGAT

GGGAACAAGT

CCTATGTAAG

CTCTCCGTCA

TTCCCTCTGG

ATGTCACCAC

AGTAGGATAG

GTTCTATTCG

CATCGGGCAG

GCAGGAGATG

GTCTATGAAC

ATACTATACA

GATATCCATC

GCTCGGATAC

GATAACTCAC

GTCCGAGATT

TCAAGAGTGG

TTTTGATGAG

GTACCCGATG

TACACTCGTA

CAATTGTGCA

TGACAAGATC

GACCATCCAA

CGGTCCTCCC

TAAGCTGGAG

AGGTTTATCG

AGGGATCCCC

TGGTATGTCA

GTCGCTCTGA

TCAAGCAACC

CCGAACGATA

ACCGAGACCG

TTATTAACAG

TCATGTTTCT

CCATCTACAC

ATATTGGCTG

CAACTATCTT

GAALATCCTGT

CAGGCTTTGA

AGTGGAGGTG

GTCGACACAG

AAGGGGGTGA

TATACCACTG

TCATCGTGTA

AGTCCTCTGC

TCCGGGTCTT

TCAATCCTCT

CTAACATACA

GTCGGGAGCA

ATATCATTGG

GATGCCAAGG

AGCACTAGCA

GCTTTAATAT

AGACCAGGCC

TCCCCTACA.A

ACCGCATCCA

TCGGTAGTTA

AATAAATGCC

AGAACATCTT

GAGCTTGATC

CGCAGAGATC

TTCAGGGTGT

GTGATTTAAT

CATTATTTGG

GCTATGCGCT

ATTTACTGGG

AGTCCTACTT

TTGTCCACCG

TGCCCAAGTA

CTTTCATGCC

TCCAAGAATG

TTGGGAACCG

GCAAGTGTTA

TTGCTGCCGA

GGAGGTATCC

AGAAGTTGGA

AATTGCTGGA

TAGTTTACAT

GTTGCTGCAG

TAAAGCCTGA

CTCTTGAAAC

GCATCAAGGC

ATTAAAACTT

TTCTACA7LAG

ATGATTGATA

GGGTTGCTAG

CATAAGAGCC

CCAAGACTAC

CGGCCAGAAG

CCCCAGCTTA

TGGGGGAGAT

CATCTTAGAG

CATTGTCCTC

GCTAGAGGGG

TGTTGCAACC

AGAGGGGACT

CCTCCGGGGG

GTTCATTTTA

CACAACAGGA

TCACTGCCCG

GGACGCGGTG

CGTAGGGACA

GTCATCGGAC

CCTGATTGCA

GGGGCGTTGT

TCTTACAGGG

ACAGATTTCC

CACCCGAAAT

AGGGTGCAAG

ACAACCCCCA

GACCTTATGT

CCATTGCAGG

TCAGCACCAA

6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 148 TCTAGATGTA ACTAACTCAA TCGAGCATCA GGTCAAGGAC GTGCTGACAC CACTCTTCAA *9e* 9*SR fl*q 00 0 *0

I

GATCATCGGT

CATCTCTGAC

TTGGTGTATC

GGCTGCTGAA

CAATCAGTTC

ATTCTCAAAC

ATCTATAGTC

TAATCTGAGC

AGGGGTTATC

GCAACCAGTC

AGCCCTCTGT

CAGCTTCCAG

CCCCCTATCA

TATCGCTGAC

AATGGAGACA

CGAGTGGGCA

GAGTCTGACA

CGGTTCAGGG

GCCAATGAAG

GGTTAGTCCC

AACATACCTA

ACCTGGTCAG

TGTGGTTTAT

GCCTATAAAG

CTGGTGCCGT

GATGAAGTGG

AA.AATTAAAT

AACCCGCCAG

GAACTCATGA

CTAGCTGTCT

ATGTCGCTGT

ACCATGACAT

AGTAAAGGGT

AGAALATCCGG

AGTAATGATT

CACAGGGAAG

CTCGTCAAGC

ACGGATGATC

AATCAAGCAA

TGCTTCCAGC

CCATTGAAGG

GTTGAGCTTA

ATGGACCTAT

AACCTAGCCT

AACCTCTTCA

CCTGCGGAGG

GATCTCAT

TATGTTTACA

GGGGTCCCAA

CACTTCTGTG

GCCTGAGGAC

TCCTTAATCC

AGAGAATCAA

ATGCATTGGT

CAAAGGGAAA

CCCTGTTGGA

CCCAGGGAAT

CAGAGTTGTC

GTTTGGGGGC

TCAGCAACTG

ATTCTGTCAC

TAGGTGTCTG

CAGTGATAGA

AATGGGCTGT

AGGCGTGTAA

ATAACAGGAT

AAATCAAA.AT

ACAAAACCAA

TAGGTGTAAT

CTGTTCCAAT

TGGATGGTGA

ATGTTTTGGC

GCCCAGGCCG

TCGAATTACA

TGCTTGCGGA

ACCTCAGAGA

GGATAGGGAG

ATTGGATTAT

GAACTCAACT

CTGCTCAGGG

CTTGTATTTA

GTACGGGGGA

ACAACTGAGC

TCCGGTGTTC

CATGGTGGCT

GGTTCCCTAT

GA.AATCCCCA

TAGGCTTTAC

CCCGACAACA

GGGTAAAAAC

TCCTTCATAC

TGCTTCAGGA

CCACAACAAT

CAACACATTG

CAAGGAAGCA

TGTCAAACTC

AACCTACGAT

CTCATTTTCT

AGTGGAATGC

TTCAGAATCT

TTCACTGACC

TACGACTTCA

GATCAATACT

CTACTGGAGG

CCCACTACAA

AGTCGAGGTT

ACTTACCTAG

ATGCACCGAG

CATATGACAA

TTGGGGGAGC

CAGGGGTCAG

ACCGACATGC

CTCTCATCTC

CGGACAGATG

CAAGCACTCT

GGGGTCTTGT

TTCGGGCCAT

GTGTATTGGC

GAGTGGATAC

GGCGAGGACT

AGTTCCAATC

ACTTCCAGGG

TACTTTTATC

TTCACATGGG

GGTGGACATA

TAGTGAAATT

GAGATCTCAC

GTGCAGATGT

CCAGGGCAAC

TCAGAGGTCA

ACAATGTGTC

TGGGAALAGCC

TGTTTGAAGT

ACTATTTTGA

TCAGGTTCGC

GGAAAGGTGT

AATCCTGGGT

ACAGAGGTGT

ACAAGTTGCG

GCGAGAATCC

CTGTTAATCT

TGATCACACA

TGACTATCCC

CGAGATTCAA

GCCATGCCCC

TGGTAATTCT

TTGA.ACATGC

CTTTTAGGTT

ACCAAAAACT

TCACTCACTC

7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 149 TGGGATGGTG GGCATGGGAG TCAGCTGCAC AGTCACTCGG GAAGATGGAA CCAATCGCAG 9120 *0Oe

S

OOSO

SC OS 0 5 00 5 0 0555 S S 5* 0 50

S

S.

ATAGGGCTGC

GTGAAATAGA

CGCTATCTGT

ATAAGATAGT

CTACACTGTG

TAAACAATGT

CTCATATTCC

CAAGGAAGAT

AGGTTTTCCA

AGGACATCAA

AGCCCTTTCT

CCCATACTTG

TGTTAATCTC

TGACGTTTGA

CCGCTATGAC

AACTGATAGA

TGGAGCCACT

CTTTCCTTAA

ATGAAGGTAC

TACATCTGAC

CAGTAACGGC

AGACTCTGAT

GGCACGGAGG

ATGCTCAAGC

TTGCTGGAGT

CAGTGAACCG

CATCAGAATT

CAACCAGATC

AGCTATCCTG

TCAGAACATC

GGAAGTTGGG

ATATCCAAAT

CCGTGAGCTC

ATGCCTGAGG

GGAGAAAATT

GTTTTGGTTT

CCATAGGAGG

TCGTGACCTT

ACTGGTTTTG

CATTGATGCT

TGGTTTCTTC

TTCACTTGCT

CCACTGCTTT

TTATCATGAG

AGGGGAGATT

TGCTGAAAAT

GAAGGGTCAT

CAGTTGGCCA

TTCAGGTGAA

GAGATTTGGC

ATCACATGAT

AAGAA.AAACG

TTGTACCCTG

GAGTATGCTC

AAGCACCGCC

AATGTCATCA

TGTAATCAGG

CTAAAAAAGG

GACACTAACT

ATTAACTTGG

ACAGTCAAGA

AGACACACAC

GTTGCTATAA

ATGTATTGTG

AGGTATGCAG

CCTGCACTCG

TACCTGCAAC

ACTGAA.ATAC

TTAATTGAAG

TTCTCATTTT

GTCAGGAAAT

GCCATATTTT

CCCCTGACCC

GGGTTAACAC

TGTTTTATGC

GTCACTCAGA

TAGGGTCCAA

AAGTTCACCT

GAGTCCCTCA

TAAAAAACGG

AGTCCAAGCT

ATTTATTTAA

GAALATTCGCT

CACGGCTTGG

GAGTTTACAT

CTGAGATGAG

CTGTATTCTT

TCAGTAAGGA

ATGTCATAGA

AACTTCTAGG

GGAATCCAAC

TGAGGGACAT

ATGATGTTCT

CCTTAGATTA

TCAGAAGTTT

ACATGAATCA

GTGGAATCAT

TCCCCCTGCA

ATGAGCAGTG

CTCTTAGCCT

CACCAGGCAT

GTGGTTTCCC

AGATAGCCCG

CGCTTACAGC

ATTCTCCAAC

TAGGAGTTAT

CATAGAAGAC

GTACTCCAAA

CCTAGGCTCC

GCACAGCTCC

GTCAGTGATT

CACTGGTAGT

GTCTCAACAT

GGGGAGGTTA

AAGAGTCAGA

TTATCAAATT

AACAGTAGAA

TGACCAAAAC

CATTTTCATA

CGGCCACCCC

GCCTAAAGTC

AATCAACGGC

TGCTGCAGAC

CGTTGATAAC

GGACAGTGAT

ACCCACTAGT

GTCATGGACT

ATAGTTACCA

CTTGAGGACC

CAAATGATTA

CCGGCCCACT

AAAGAGTCAA

GTCAGTGATA

GAATTGAGGG

CAATGGTTTG

AAATCACAAA

TCAGTTGAGC

GTATATTACC

ATGACAGAGA

TACATGTGGA

GTAGCTATGC

CTCAGAGGTG

GGGTTTTCTG

ACTGATGACA

AGACTTGAAG

ATTGTGTATG

TATCGTGACA

ACAATCCGGA

TGGAGATCAT

CTGACAATGT

9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 0

S

0

SOS...

O 5 5S C S

SS

5005 0 SOgO 150

ACCTAA.AGGA

AGTTCCTGCG

TTAATGATTC

TCCATGACCC

GTAGACTTTT

TAATCTCAkA

ATTTGACTAA

GTCACAGGGG

GGAACGTTAA

ACACTGATCA

ATCTCAAGAA

TAAATGAGAT

CTGTCCTCTA

GCAAAGTCCC

GTCAGAAGCT

GGGTAAGGAT

TACCCAGCAC

ACTTTGTAAT

CAATTGTTTC

TGTCCCAATC

AAACAAGGGC

ATGACCGTTA

CTCTTGGCTT

ACAACGATCT

TGAACATGAG

ATCTCAAGAG

CAAGGCACTT

TTACGATCCT

GAGCTTTGAC

TGAGTTCAAT

CGCTAAAATG

CGGGATTGGC

GGCACTCCAC

GGGGCCAGTC

AGCAGAAAAA

TCCGGAGAAT

GTACTGCCTT

TTACGGATTA

TGTAAGTGAT

CAATGACCAA

GTGGACCATC

TGCCTCGTTA

ATGGCCTTAC

TCTTAGGCAA

ATCACATTTT

ACTCAAGAGC

AGCATGCAGT

TCTTGCATAT

CACAATCAAT

CTTAATAAGG

CAGGCTGTTT

AATGATTCTC

GCTGCTCTCC

CCCAAGGGAA

CCATATGATA

CTGTCTTACA

ACTTACAA;A

AAGTATTTTA

ACTCTGGCTG

TTAAAAACCT

GGGTTTGTAG

ATAGAAACCT

AATTGGAGAT

CCCTCATTTT

CCTCATTGCC

ATCTTCATCA

AGCACCATTC

GTGCAAGGGG

AACCTTAAGA

AGGCTACATG

TTTGTCTATT

ATTGCAAGAT

AATATTGCTA

TCCCTGAACG

TCAACCATGA

ATGGCACTGT

GTCAGAkAACA

GCATCACTAA

AAAGGGAATG

CCGGGTCACG

TGATAATGTA

GCCTGAAAGA

TGAGGGCATG

AGGACAATGG

TCTCAGGAGT

ACTCCCGAAG

GATTCCCTCA

ACGAGACAGT

ATGAGACCAT

TTCAGTGGCT

CCCCCGACCT

AGTACCCTAT

CCTACTTATA

ACAATCAGAC

AACGGGAAGC

ACATTGGCCA

CAAAAGGAAT

GTGTATTCTG

CAACAATGGC

TCCTAAAAGT

CCCGAGATGT

TGCCCGCTCC

TCGGTGATCC

TGCCTGAAGA

GGATTCAGTT

GAGGCTTGTA

TGTCGTAAGT

AAAGGAGATC

CCAAGTGATC

GATGGCCAAG

CCCCAAAGAT

CCCAGTCCAC

TGTAATTCGG

CAGCGCATTT

CAGCTTATTT

GCATAAGAGG

TGACGCCCAT

GGGAGGTATA

CCTGGCTGCT

CATAGCCGTA

TGCTAGAGTA

TCACCTCAAG

ATATTATGAT

GTCAGAGACT

TAAAAGCATC

GATACAGCAA

AGTCATACCC

TATTGGGGGG

AGTAACATCA

GACCCTCCAT

TACCCGAAkAG

GATGTTTTCC

GGAGCCTACC

AAGGAAACAG

GCTGAAAATC

GATGAGCACG

CTCAAAGAAA

ACILAGTACCA

CAGAATCAAG

ATCACGACTG

GCACAGAGGC

CTTGAAACCT

GTCCCGTTAT

GAAGGGTATT

TATGAGAGCG

ACAAAAAGGG

ACTAGAGATT

GCAAATGAGA

GGGCTACTTG

ATAGTTGATG

GAGAGAGGTT

ATTTTGATCT

CTCCTCACAA

ATGAATTATC

TCAATTGCTG

CAAGTAATGA

10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 151

CACAACAACC

TTGTATGCGT

TCCATAGTCC

AGAGACTGGC

TCCTGGATCA

AAGGCCTGAT

TGTCCAATTA

GAAATGTCCT

ATATGTGGGC

TAGAATCTAT

GATCAGTCAA

AGGAAACATC

TGAAGCTTGC

CAGTGTACTC

CAAGGCAAAG

CGACTAATTT

CCCTTGTCAG

CAGATAAGAA

TTTTAGAAAC

TTCACGTCGA

CCCGCAAGCT

CTTTAATTGA

AATTTGTTAC

CTATGATTGA

TAGGGGATGA

TCACCATCTA

GGGGGACTCT

CCAGAGCATC

AAACCCAATG

GGCATTCCTC

TAGTGTCACA

TCGAGCCAGC

TGACTATGAA

CATTGACAAA

AAGACTAGCT

GCGAGGCCAC

CTACGGATGG

ATCCTTGAGA

CTTCGTAAGA

ATGGGCTTAC

GGCCAATGTG

AGCGCATAGG

AGTGGCAAGG

AGTTGATACT

ATTGTTTCGA

AACAGATTGT

AGAGCTGAGG

CAGAGATGCA

ATGGTCCACA

CCTGGTAACA

CGATATCAAT

CTTGGGCCAG

TCATTCCTAG

ACTAGACTCC

TTAAAAGGGT

ATGGACAGGC

GGGGCAAGAG

ATGAGGAAGG

CAATTTAGAG

GAGTCATGTT

CGAGGACGGC

CTTATTCGGC

TTTTTTGTCC

GTCCCATATA

GCCCCAAGTA

GGTGATGATG

AGCCTGGAGG

TTGAGGGATC

TATACCACAA

AACTTTATAT

CTCGAGAAAG

TGCGTGATCC

GCAGAGCTAT

ACAAGGCTAT

CCCCAACTAT

AAATTTGAGA

AGTTTCATAA

TGTGCAGCCA

ACTGGGCTAG

TCAAGAACAT

TATTCCATGA

ATATTATAGT

AGTCTATTGC

GGGGGTTAAC

CAGGGATGGT

CAGTGCAGCT

CTATTTACGG

GTCATGAGAC

CCTCGGGTTG

TTGGTTCTAC

GATCCTTGCG

ATAGCTCTTG

AGCTAAGGGT

GTAGCACTCA

TCTCCAACGA

ACCAACAAGG

ATACTGGATC

CGATGATAGA

GTACCAACCC

ACACCCAGAG

ATCACATTCT

AGGACCATAT

CTGAGTTTCT

TCAATTGGGC

CGACCCTTAC

AACTGCAAGG

TGACAGTAAA

ACCTAGGGCA

AGGCATGCTA

CTCTCGAGTG

GCTATTGACA

GGCTAGAGCC

CCTTGAGGTC

ATGTGTCATC

CCAACTGGAT

CACTGATGAG

ATCTGCCGTT

GAACGAAGCC

GATCACTCCC

AGTGAA.ATAC

CAATCTCTCA

AATGCTTCTA

ATCTAACACG

TCATCCCAGG

ATTGATATAT

CCATAGGAGG

AGCTAAGTCC

GAATGAAATT

GCTTATAGAG

ATTTGATGTA

TCAGCAAATC

TTTGTCCTAA

GAAGAGGACG

GCTCATGAAA

GATACCACAA

ATAACCAGAT

GGAAGAAAGA

CTAAGAAGCC

CCTGATGTAC

TGCGAGTGTG

GATATTGACA

AGAACAGACA

AGAATAGCAA

TGGTTGTTGG

ATCTCGACTT

TCAGGTACAT

TTTGTCATAT

GGGTTGGGTG

GTATTACATC

ATACCCAGCT

GATAATGCAC

CACCTTGTGG

ACAGCACTAT

TCAGCTCTCA

CCAAGATTAT

CATTATCATA

12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 152 GACCATCAGG GAAATATCAG ATGGGTGAGC TGTTGTCTTC GTTCCTTTCT

AGAATGAGCA

13800

AAGGAGTGTU

GGCATTGTGG

CAACTGTGTG

AAGAGTTAGA

GATTCGACAA

GGACCTGCCC

ATATCAAGGC

TTGTAGACCA

GATTGAGAGT

CAAAGGTCGG

ATGATGTTGC

GGGGTAGTCT

CTTGCTACAA

ACGGCTTGTT

AACTAAACAA

AATTAGCACC

TTGTCAAGGT

TCAATTTCAT

AGACCTTACC

TGGCTCTACT

GGGATTTTGT

TCTACCCTAG

AAGCTAACCG

GGACTTCACC

*TAAGGTGCTT

TATTATAGAG

CAACATGGTT

AGAGTTCACA

CATCCAGGCA

ACCGATTCGA

AGAGGCTAGG

TTACTCATGC

TGATCCAGGA

CAGCAACAAC

AAAATTGCTC

TGCCAATTAT

AGCTGTTGAG

CTTGGGTGAG

GTGCTTCTAT

CTATCCCTcC

GCTCTTTAAC

AGTCAGTAAT

CAACAAAGAT

CCTTGGCAA

TCAGGGATTT

GTACAGCAAC

GCTAATGAT

TGGACTTATA

GTCAATGCTC

CCTATCCATG

TACACATGCT

TTTCTTTTGT

AAACACTTGT

GGTCTAAGGC

TTATCTCCAG

TCTCTGACTT

TTCATTTTTG

ATCTCAAATA

AAAGATATCA

GAAATCCATG

ATATCAACAT

GGGTCGGGTT

AATAGTGGGG

GAAGTTGGCC

GGGAGGCCCG

ATCCCTACCT

ACTATAGAGA

ATAGGATCAA

ATAAGCTATG

TTCATATCTA

CCTGAAAAGA

GGTCACATCC

TAAGCCACCC

GTCCTTCACT

ATATGACCTA

GTGAAAGCGA

GTGTTCTGGC

CGGTAGAGAA

CAGGATCTTC

ATCTCCGTCG

ATGCCCTCGC

TGAGCATCAA

ACACAAGCA

CTTTCCGCAG

TAATTAGGAG

CTATGTTGAT

TTTCCGCCA

TTGTCGAACA

AAGTCACGTG

CTAGTGTGGG

AGTTAGAGGA

TACTGGTGAT

TAGGGTCTCAI

CTGAATCTTA I

TTAAGCAGCAC

TATCTATCAA C

AAAGATCTAC

TGATGCTCA

CCTTGACCTG

TGAGGATGTA

AGATTTGTAC

ATGTGCAGTT

GTGGAACATA

AGGATCTATC

TGAGGTAAAT

GGATTTCAGA

GCACAATCTT

AATCGGGTTA

ATGCCTTGAG

CACTTATAAG

TTCTAGATCT

CAGAATGGGA

GGTAGGCAGT

k.TTTATCCAT k.TTGGCAGCC

CAAGCTTATG

~TATAGAGAA

~TTAGTTATG2 7ATAATTGAA,

I

;CAACTAAGc I

AAGAAATTCT

AACTTGCACA

TTGTTGAATG

GTACCGGACA

TGTCAACCAG

CTAACCGATC

AATCCAATTA

AAACAGATAA

GTCAGTCAGC

CCTCCACACG

CCCATTTCAG

AACTCATCTG

CCAGGGGAAG

GAGATACTA

GGTCAAAGGG

GTAGGTAATA

ATAGATTGCT

rCAGATATAG kTCTTATCGA

CCTTTCAGCG

'TGAACCTTG

kCAGATCTCA

LCATCTGTGC

13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15240 CAATTGTGGG AGGCGCAGTT AGTAGAGGTG ATATCAACCC TATTCTGA

AAACTTACAC

15300 153

CTATAGAGCA

AATTAATCCA

TCTACAGGGA

CTTACCCCGT

TTTGGGGGCA.

ATCTCAAGTC

CCAAGTCAGA

TAACAGTCAA

ATTAATTGGT

GGTGCTGATC

CCATGATGTT

GTTGGCAAGA

ATTGGTAAGT

TATTCTTCTT

CGGTTATCTA

GAAACAGATT

GGAGACCAAA

TGAACTCCGG

AGTTGCGGGT

GCCTCAGGGC

TTCAAAGACA

AGTAGGCAAC

TACTCCGGGA

ATACTAGACT

ATTATGACGG

GAATGGTATA

AACCCTAATC

TGGCAATTAJA

AAGATGGATT

ACCAAAGAAG

GAGAACTTGT

ACAGAA.AGTT

TACACCAGAA

GGGGTTTAAA

AGTTAGTCGG

CTACCCTAGG

TTTCTATTCC

CGGACCTAAG

GCTTAACTCT

TCAACAAGGG

ATCTAGGATC

GATAAATCGG

TATCTTCGTT

ACGTGAGTGG

ATACAGCGCT

TAGTTAGGCA

CAGCTTTGTC

CTGTGCAAAG

ATACTCATCC

ATGTTCCACG

ACTCGCAAAT

TTTATCCAGA

AAGAATCTAT

GTTTTTA.AGG

CTGATTAAGG

TTATTTGCAA

TGGT

15360 15420 154 15540 15600 15660 15720 15780 15840 15894 TATATTAAAG AAAACTTTGA

AXATACGAAG

INFORMATION FOR SEQ ID NO:8: i)SEQUENCE

CHARACTERISTICS:

LENGTH: 2183 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (iMOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: Met Asp Ser Leu Ser Val Asn Gin Ile Leu Tyr 1 5 10 Asp Ser Pro Ile Val Thr Asn Lys Ile Val Ala 25 Arg Val Pro His Ala Tyr Ser Leu Glu Asp Pro 40 Ile Lys His Arg Leu Lys Asn Gly Phe Ser Asn 55 Asn Val Glu Val Gly Asn Val Ile Lys Ser Lys 70 75 Pro Glu Val His Leu Ile Leu Thr Leu Gin Met Leu Arg Glu Tyr Ala Cys Gln Asn Ile Ile Asn Ser Tyr Pro Leu Phe Asn Ala His Ser His Ile Pro Tyr Pro Asn Cys 90 Asn Ginx Asp 154 Ile Giu Asp Lys 100 Glu Ser Thr Arg Lys Ile Arg Giu Leu Leu Lys Lys 105 110 Gly Arg Ile 145 Trp Ser Pro Leu Phe 225 Thr Arg Gly Ala Leu 305 Phe Ile Phe Asn Asp 130 Lys Phe Val Vai Val 210 Giu Glu Val Asn Tyr 290 Asn Ser Phe Arg Ser 115 Thr Giu Giu Ile Phe 195 Ala Leu Thr Arg Pro 275 Leu His Asp Ile Ser 355 Leu Asn Lys Pro Lys 180 Phe Ile Val Al a Tyr 260 Thr Gin Cye Giu Thr 340 Phe Tyr Ser Ile Phe 165 Ser Thr Ile Leu Met 245 Met Tyr Leu Phe Gly 325 Asp Gly Ser Arg Ile 150 Leu Gin Gly Ser Met 230 Thr Trp Gin Arg Thr 310 Thr Asp His Lys Leu 135 Asn Phe Thr Ser Lys 215 Tyr Ile Lye Ile Asp 295 Glu Tyr Ile Pro Vai 120 Gly Leu Trp His Ser 200 Giu Cys Asp Leu Vai 280 Ile Ile His His Arg 360 Ser Leu Gly Phe Thr 185 Val Ser Asp Ala Ile 265 Ala Thr His Giu Leu 345 Leu Asp Giy Val1 Thr 170 Cye Giu Gin Val1 Arg 250 Asp Met Val Asp Leu 330 Thr Glu Lys Ser Tyr Val His Leu His Ile 235 Tyr Gly Leu Giu Val1 315 Ile Giy Al a Val Giu 140 Met Lys Arg Leu Val 220 Glu Ala Phe Giu Leu 300 Leu Glu Giu Val Phe 125 Leu His Thr Arg Ile 205 Tyr Gly Giu Phe Pro 285 Arg Asp Ala Ile Thr 365 Gin Arg Ser Glu Arg 190 Ser Tyr Arg Leu Pro 270 Leu Gly Gin Leu Phe 350 Ala Cys Giu Ser Met 175 His Arg Leu Leu Leu 255 Ala Ser Ala Asn Asp 335 Ser Ala Leu Asp Gin 160 Arg Thr Asp Thr Met 240 Giy Leu Leu Phe Gly 320 Tyr Phe Glu 155 Asn Leu 385 Arg Ala His Gly Lys 465 Pro Arg Met Asn *.oO Met Val Val Val 625 Asn Val 370 Met Asp Ala Glu Cys 450 Asp Lys Leu Ile Leu 530 Phe Asn Ala Ser Leu 610 Lys Gin Arg Lys Arg Asp Gin 435 Phe Lys Glu Val Met 515 Ser Ala Leu Lys Gly 595 Lys Ala Asp Lys Gly His Thr 420 Cys Met Ala Phe Asp 500 Tyr Tyr Lys Ile Asp 580 Val Thr Glu Thr Tyr His Gly 405 Ile Val Pro Leu Leu 485 Val Val Ser Met Ser 565 Glu Pro Tyr Lys Asp Met Ala 390 Gly Arg Asp Leu Ala 470 Arg Phe Val Leu Thr 550 Asn His Lys Ser Gly 630 His Asn 375 Ile Ser Asn Asn Ser 455 Ala Tyr Leu Ser Lys 535 Tyr Gly Asp Asp Arg 615 Phe Pro Pro Cys Pro Gin 425 Arg Asp Gin Pro Asp 505 Ala Lys Met Gly Thr 585 Lys Pro Gly Asn Lys Gly Pro 410 Ala Ser Ser Arg Pro 490 Ser Tyr Glu Arg Lys 570 Lys Glu Val Phe lle Val Ile 395 Leu Ser Phe Asp Glu 475 Lys Ser Leu Ile Ala 555 Tyr Ala Ser His Pro 635 Glu Ile 380 Ile Thr Gly Ala Leu 460 Trp Gly Phe His Lys 540 Cys Phe Leu His Thr 620 His Thr Val Ile Leu Glu Gly 445 Thr Asp Thr Asp Asp 525 Glu Gin Lys His Arg 605 Ser Val Tyr Tyr Asn Pro Gly 430 Val Met Ser Gly Pro 510 Pro Thr Val Asp Thr 590 Gly Thr Ile Glu Glu Thr Gly Tyr 400 Leu His 415 Leu Thr Arg Phe Tyr Leu Val Tyr 480 Ser Arg 495 Tyr Asp Glu Phe Gly Arg Ile Ala 560 Asn Gly 575 Leu Ala Gly Pro Arg Asn Arg Gin 640 Thr Val 156 650 p

C

p. p *ppp Ser Tyr Leu Leu 705 Pro Gly Pro Leu Ser 785 Arg His Ser Ser Arg 865 Arg Ile Ala Glu Pro 690 Tyr Leu Gly Tyr Val 770 Thr Asp Leu Lys Ile 850 Ala Gly Gin Phe Thr 675 Ser Val Cys Ile Leu 755 Gin Trp Tyr Lys Gly 835 Ala Ala Tyr Gin Thr Ser Phe Asp Val 725 Gly Leu Asp Tyr Val 805 Asn Tyr Cys Ser Arg 885 Leu Thr Leu Gin Pro 710 Pro Tyr Ala Asn Asn 790 Ile Glu Tyr Val Asn 870 Tyr Ile Phe Trp 695 His Asn Cys Ala Gin 775 Leu Leu Thr Asp Phe 855 Ile Leu Ser Ala 680 Leu Cys Asp Gin Tyr 760 Thr Lys Arg Ile Gly 840 Trp Ala Ala Leu Leu 920 665 Gin His Pro Gin Lys 745 Glu Ile Lys Gin Val 825 Leu Ser Thr Tyr Gly 905 Arg Leu Lys Arg Pro Asp 715 Ile Phe 730 Leu Trp Ser Gly Ala Val Arg Glu 795 Arg Leu 810 Ser Ser Leu Val Glu Thr Thr Met 875 Ser Leu 890 Phe Thr Asn Leu 700 Leu Ile Thr Val Thr 780 Ala His His Ser Ile 860 Ala Asn Ile Glu 685 Glu Asp Lys Ile Arg 765 Lys Ala Asp Phe Gin 845 Val Lys Val Asn 670 Ile Thr Ala Tyr Ser 750 Ile Arg Arg Ile Phe 830 Ser Asp Ser Leu Ser 910 Tyr Ser His Pro 735 Thr Ala Val Val Gly 815 Val Leu Glu Ile Lys 895 Thr Gly Val Val 720 Met Ile Ser Pro Thr 800 His Tyr Lys Thr Glu 880 Val Met Asp Leu Lys Lys Tyr Cys Leu Asn Trp Arg Thr Arg Asp Val Val Ile Pro Leu Thr Asn Asn Asp 925 Leu Leu Ile 157 Arg Met Ala Leu Leu Pro Ala Pro Ile Gly Gly Met Asn Tyr Leu Asn 930 935 940 Met Ser Arg Leu Phe Val Arg Asn Ile Gly Asp Pro Val Thr Ser Ser 945 950 955 960 Ile Ala Asp Leu Lys Arg Met Ile Leu Ala Ser Leu Met Pro Giu Giu 965 970 975 Thr Leu His Gin Val Met Thr Gin Gin Pro Gly Asp Ser Ser Phe Leu 980 985 990 Asp Trp Aia Ser Asp Pro Tyr Ser Aia Asn Leu Vai Cys Vai Gin Ser 995 1000 1005 Ile Thr Arg Leu Leu Lys Asn Ile Thr Ala Arg Phe Val Leu Ile His 1010 1015 1020 Ser Pro Asn Pro Met Leu Lys Gly Leu Phe His Asp Asp Ser Lys Giu 1025 1030 1035 1040 Glu Asp Glu Arg Leu Ala Ala Phe Leu Met Asp Arg His Ile Ile Val 1045 1050 1055 *Pro Arg Ala Ala His Glu Ile Leu Asp His Ser Val Thr Gly Ala Arg .*.1060 1065 1070 *..Glu Ser Ile Ala Gly Met Leu Asp Thr Thr Lys Gly Leu Ile Arg Ala .1075 1080 1085 **Ser Met Arg Lys Giy Gly Leu Thr Ser Arg Val Ile Thr Arg Leu Ser 1090 1095 1100 Asn Tyr Asp Tyr Giu Gin Phe Arg Ala Gly Met Val Leu Leu Thr Gly 1105 1110 1115 1120 Arg Lys Arg Asn Val Leu Ile Asp Lys Glu Ser Cys Ser Val Gin Leu **1125 1130 1135 Ala Arg Ala Leu Arg Ser His Met Trp Ala Arg Leu Ala Arg Gly Arg 1140 1145 1150 Pro Ile Tyr Gly Leu Giu Val Pro Asp Val Leu Giu Ser Met Arg Gly 1155 1160 1165 His Leu Ile Arg Arg His Giu Thr Cys Val Ilie Cys Giu Cys Gly Ser 1170 1175 1180 Val Asn Tyr Gly Trp, Phe Phe Val Pro Ser Gly Cys Gin Leu Asp Asp 1-10C 1190 1195 1200 158 Ile Asp Lys Glu Thr Ser Ser Leu Arg Val Pro Tyr Ile Gly Ser Thr 1205 1210 1215 Thr Asp Glu Arg Thr Asp Met Lys Leu Ala Phe Val Arg Ala Pro Ser 1220 1225 1230 Arg Ser Leu Arg Ser Ala Val Arg Ile Ala Thr Val Tyr Ser Trp Ala 1235 1240 1245 Tyr Gly Asp Asp Asp Ser Ser Trp Asn Glu Ala Trp Leu Leu Ala Arg 1250 1255 1260 Gin Arg Ala Asn Val Ser Leu Giu Glu Leu Arg Val Ile Thr Pro Ile 1265 1270 1275 1280 Ser Thr Ser Thr Asn Leu Ala His Arg Leu Arg Asp Arg Ser Thr Gin 1285 1290 1295 Val Lys Tyr Ser Gly Thr Ser Leu Val Arg Val Ala Arg Tyr Thr Thr 1300 1305 1310 Ile Ser Asn Asp Asn Leu Ser Phe Val Ile Ser Asp Lys Lye Val Asp 1315 1320 1325 Thr Asn Phe Ile Tyr Gin Gin Gly Met Leu Leu Gly Leu Gly Val Leu 1330 1335 1340 Glu Thr Leu Phe Arg Leu Glu Lys Asp Thr Gly Ser Ser Aen Thr Val *1345 1350 1355 1360 Leu His Leu His Val Glu Thr Asp Cye Cys Val Ile Pro Met Ile Asp 1365 1370 1375 His Pro Arg Ile Pro Ser Ser Arg Lys Leu Glu Leu Arg Ala Giu Leu 1380 1385 1390 Cys Thr Aen Pro Leu Ile Tyr Asp Asn Ala Pro Leu Ile Asp Arg Asp 1395 1400 1405 Ala Thr Arg Leu Tyr Thr Gin Ser His Arg Arg His Leu Val Giu Phe 1410 1415 1420 Val Thr Trp Ser Thr Pro Gin Leu Tyr His Ile Leu Ala Lys Ser Thr *1425 1430 1435 1440 Ala Leu Ser Met Ile Asp Leu Val Thr Lys Phe Glu Lys Asp His Met 1445 1.450 1455 Aen Giu Ile Ser Ala Leu Ile Gly Asp Asp Asp Ile Asn Ser Phe Ile 1460 1465 1470 Thr Glu Phe Leu Leu Ile Giu Pro Arg Leu Phe Thr Ile Tyr Leu Gly 159 1475 1480 1485 Gin Cys Ala Ala Ile Asn Trp Ala Phe Asp Val His Tyr His Arg Pro 1490 1495 1500 Ser Gly Lys Tyr Gin Met Gly Giu Leu Leu Ser Ser Phe Leu Ser Arg 1505 1510 1515 1520 Met Ser Lys Gly Val Phe Lys Val Leu Val Asrn Ala Leu Ser His Pro 1525 1530 1535 Lys Ile Tyr Lys Lys Phe Trp His Cys Gly Ilie Ile Giu Pro Ile His 1540 1545 1550 Gly Pro Ser Leu Asp Ala Gin Aen Leu His Thr Thr Val Cys Asn Met 1555 1560 1565 Val Tyr Thr Cys Tyr Met Thr Tyr Leu Asp Leu Leu Leu Asn Giu Giu 1570 1575 1580 Leu Glu Giu Phe Thr Phe Leu Leu Cys Giu Ser Asp Giu Asp Val Val 1585 1590 1595 1600 Pro Asp Arg Phe Asp Aen Ile Gin Ala Lys His Leu Cys Val Leu Ala 1605 1610 1615 Asp Leu Tyr Cys Gin Pro Gly Thr Cys Pro Pro le Arg Gly Leu Arg 1620 1625 1630 *SPro Val Giu Lys eye Ala Val Leu Thr Asp His Ile Lys Ala Giu Ala 1635 1640 1645 Arg Leu Ser Pro Ala Gly Ser Ser Trp Asn Ile Aen Pro Ile Ile Val 1650 1655 1660 Asp His Tyr Ser Cys Ser Leu Thr Tyr Leu Arg Arg Gly Ser Ile Lye 1665 1670 1675 1680 **Gin Ile Arg Leu Arg Val Asp Pro Gly Phe Ilie Phe Asp Ala Leu Ala 1685 1690 1695 Giu Val Aen Val Ser Gin Pro Lys Val Gly Ser Asn Aen Ile Ser Aen *SS1700 1705 1710 Met Ser Ile Lye Asp Phe Arg Pro Pro His Asp Asp Val Ala Lye Leu 1715 1720 1725 Leu Lye Asp Ile Asn Thr Ser Lye His Aen Leu Pro Ile Ser Gly Gly 1730 1735 1740 Ser Leu Ala Aen Tyr Giu Ile His Ala Phe Arg Arg Ile Gly Leu Asn .L 1% n 1750 1755 1760 160 Ser Ser Ala Cys Tyr Lys Ala Val Glu Ile Ser Thr Leu Ile Arg Arg 1765 1770 1775 Cys Leu Giu Pro Gly Giu Asp Gly Leu Phe Leu Gly Giu Gly Ser Gly 1780 1785 1790 Ser Met Leu Ile Thr Tyr Lys Giu Ile Leu Lys Leu Asn Lys Cys Phe 1795 1800 1805 Tyr Asn Ser Gly Val Ser Ala Asn Ser Arg Ser Gly Gin Arg Giu Leu 1810 1815 1820 Ala Pro Tyr Pro Ser Glu Val Gly Leu Val Glu His Arg Met Gly Val 1825 1830 1835 1840 Gly Asn Ile Val Lys Val Leu Phe Asn Gly Arg Pro Glu Val Thr Trp 1845 1850 1855 Val Gly Ser Ile Asp Cys Phe Asn Phe Ile Val Ser Asn Ile Pro Thr 1860 1865 1870 Ser Ser Val Gly Phe Ile His Ser Asp Ile Glu Thr Leu Pro Asn Lys 1875 1880 1885 Asp Thr Ile Glu Lys Leu Giu Glu Leu Ala Ala Ile Leu Ser Met Ala *1890 1895 1900 *Leu Leu Leu Gly Lys Ile Gly Ser Ile Leu Val Ile Lys Leu Met Pro *1905 1910 1915 1920 *Phe Ser Gly Asp Phe Val Gin Gly Phe Ile Ser Tyr Val Gly Ser His 1925 1930 1935 Tyr Arg Glu Val Asn Leu Val Tyr Pro Arg Tyr Ser Asn Phe Ile Ser 1940 1945 1950 Thr Giu Ser Tyr Leu Val Met Thr Asp Leu Lys Ala Asn Arg Leu Met 1955 1960 1965 Asn Pro Giu Lys Ile Lys Gin Gin Ile Ile Glu Ser Ser Val Arg Thr 1970 1975 1980 *Ser Pro Gly Leu Ile Gly His Ile Leu Ser Ile Lys Gin Leu Ser Cys 1985 1990 1995 2000 Ile Gin Ala Ile Val Gly Gly Ala Val Ser Arg Gly Asp Ile Asn Pro 2005 2010 2015 Ile Leu Lys Lys Leu Thr Pro Ile Giu Gin Val Leu Ile Ser Cys Giy 2020 2025 2030 161 Leu Ala Ile Aen Giy Pro Lys Leu Cys Lys Giu Leu Ile His His Asp 2035 2040 2045 Val Ala Ser Gly Gin Asp Gly Leu Leu Asn Ser Ile Leu Ile Leu Tyr 2050 2055 2060 Arg Giu Leu Ala Arg Phe Lys Asp Asn Gin Arg Ser Gin Gin Gly Met 2065 2070 2075 2080 Phe His Ala Tyr Pro Val Leu Val Ser Ser Arg Gin Arg Giu Leu Val 2085 2090 2095 Ser Arg Ile Thr Arg Lys Phe Trp Gly His Ilie Leu Leu Tyr Ser Gly 2100 2105 2110 Asn Arg Lys Leu Ile Asn Arg Phe Ile Gin Asn Leu Lys Ser Gly Tyr 2115 2120 2125 Leu Ile Leu Asp Leu His Gin Asn Ile Phe Val Lys Asn Leu Ser Lye 2130 2135 2140 Ser Glu Lys Gin Ile Ile Met Thr Gly Gly Leu Lys Arg Glu Trp Val 2145 2150 2155 2160 Phe Lys Val Thr Val Lye Giu Thr Lye Glu Trp, Tyr Lye Leu Val Gly 2165 2170 2175 *Tyr Ser Ala Leu Ile Lye Asp 2180 INFORMATION FOR SEQ ID NO:9: SEQUENCE CHARACTERISTICS: LENGTH: 15894 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) SEQUENCE DESCRIPTION: SEQ ID NO:9: ACCAA.ACAAA GTTGGGTAAG GATAGTTCAA TCAATGATCA TCTTCTAGTG CACTTAGGAT TCAAGATCCT ATTATCAGGG ACAAGAGCAG GATTAGGGAT ATCCGAGATG GCCACACTTT 120 TAAGGAGCTT AGCATTGTTC AAAAGAAACA AGGACAAACC ACCCATTACA TCAGGATCCG 180 GTGGAGCCAT CAGAGGAATC AAACACATTA TTATAGTACC AATCCCTGGA GATTCCTCAA 240 162

TTACCACTCG

GCGGGCCCAA

GTCAATTGAT

TCCAGAGTGA

ATGAGGCGGA

GATGGTTCGA

TGATTCTGGG

CAGACACGGC

TGGTTGGTGA

AGGACCTCTC

GAAACAAACC

GATTAGCCAG

GACTGCATGA

AAATGGGGGA

GTGCAGGATC

ACTCCATGGG

GGCAAGAGAT

GTATCACTGC

AGATCAGTAG

GTGAGAATGA

GAGAAGCCAG

CCCATCTTCC

CGCAGGACAG

CGGAAGAACA

ACTAGGTGCG

AAAACTTAGG

ATCCAGACTT

ACTAACAGGG

TCAGAGGATC

CCAGTCACAA

CCAATACTTT

GAACAAGGAA

TACCATCCTA

AGCTGATTCG

ATTTAGATTG

CTTACGCCGA

CAGGATTGCT

TTTTATCCTG

ATTTGCTGGT

AACTGCACCC

ATACCCTCTG

AGGTTTGAAC

GGTAAGGAGG

CGAGGATGCA

AGCGGTTGGA

GCTACCGAGA

GGAGAGCTAC

AACCGGCACA

TCGAAGGTCA

AGGCTCAGAC

AGAGGCCGAG

AACCAGGTCC

CTGGACCGGT

GCACTAATAG

ACCGATGACC

TCTGGCCTTA

TCACATGATG

ATCTCAGATA

GCCCAAATTT

GAGCTAAGAA

GAGAGAAAAT

TTCATGGTCG

GAAATGATAT

ACTATTAAGT

GAGTTATCCA

TACATGGTAA

CTCTGGAGCT

TTTGGCCGAT

TCAGCTGGAA

AGGCTTGTTT

CCCAGACAAG

TTGGGGGGCA

AGAGAAACCG

CCCCTAGACA

GCTGACGCCC

ACGGACACCC

GGCCAGAACA

ACACAGCCGC

TGGTCAGGTT

GTATATTATC

CTGACGTTAG

CCTTCGCATC

ATCCAATTAG

TTGAAGTGCA

GGGTCTTGCT

GGTGGATA.AA

GGTTGGATGT

CTCTAATCCT

GTGACATTGA

TTGGGATAGA

CACTTGAGTC

TCCTGGAGA.A

ATGCCATGGG

CTTACTTTGA

AGGTCAGTTC

CAGAGATTGC

CCCAAGTATC

AGGAAGATAG

GGCCCAGCAG

TTGACACTGC

TGCTTAGGCT

CTATAGTGTA

ACATCCGCCT

CAGCCCATCA

AATTGGAA-AC

CTTATTTGTG

CATAAGGCTG

AAGAGGTACC

TAGTGATCAA

AGACCCTGAG

CGCAAAGGCG

GTACACCCAA

GGTGAGGAAC

GGATATCAAG

TACATATATC

AACTATGTAT

CTTGATGAAC

CTCAATTCAG

AGTAGGAGTG

TCCAGCATAT

CACATTGGCA

AATGCATACT

ATTTCTACAC

GAGGGTCAAA~

AGCAAGTGAT

AACGGAGTCC

GCA.AGCCATG

CAATGACAGA

ACCCTCCATC

ACCATCCACT

CCGGATGTGA

GAGTCTCCAG

TTAGAGGTTG

AACATGGAGG

TCCAGGTTCG

GGATTCAACA

GTTACGGCCC

CAAAGAAGGG

AGGATTGCCG

AGAACACCCG

GTAGAGGCAG

CCTGCTCTTG

CTTTACCAGC

AACAAGTTCA

GAACTTGAAA

TTTAGATTAG

TCTG.AACTCG

ACTGAGGACA

GGTGATCAAA

CAGAGTCGAG

GCGAGAGCTG

AGCCAAGATC

GCAGGAATCT

AATCTTCTAG

ATTGTTATAA

CCCACGATTG

300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 163 GAGCCAATGG CAGAAGAGCA GGCACGCCAT GTCAAAA.ACG GACTGGAATG CATCCGGGCT

S*

S*

S

S..

S

*5SS

S

S.

S S

S.

S

5559

CTCAAGGCCG

ATATCAGACA

GGTCTCAGCA

CGCGGTCAGG

AATCTCCAGG

GCGGTTAAGG

AGCACCCTCT

GATACCGAGG

GCTTCTGATG

AGAGGCAACA

GGTAGGGCCA

TTTGGA.ACGG

CCCTCGGAAC

GCCGCACTGA

AATAATGAAG

AAA.ACAGCCT

CTGCTGTTAT

AGCATATCCA

AAGGATCCCA

GGCAGAGATT

CTCCAAGGAA

CTAALAGCCGA

GCATCACGCA

CGTTACCTGA

CAGATGCTGA

AGCCCATCGG

ACCCAGGACA

AACCATGCCT

GACCTGGAGA

CATCAAGCAC

GAATCCAAGA

CAGGAGGAGA

GATATGCTAT

TTGAAACTGC

ACTTTCCGAA

GCACTTCCGG

AGATCGCGTC

CATCAGGGCC

TACAGGAGTG

AAGGGGGAGA

TGGCCAAALAT

TGAAGGGAGA

CCCTGGALAGG

ACGACCCCAC

CAGGCCGAGC

TGACAAATGG

TCGGGAAAAA

GTGTAATCCG

TGACTCTCCT

TGAAGATAAT

CTCACTGGCC

GGAGCGAGCC

CTCAGCALATT

GAGCGATGAC

TGGGTTACAG

TGCTGACTCT

CAATGA.ATCT

CACTGACCGG

AGAAGGAGGG

GCTTGGGAAA

GACACCCATT

TTTATTGACA

AGGTGCACCT

GACACCCGALA

CTATTATGAT

ACACGAGGAT

AGTTGAGTCA

ACACCTCTCA

TGCAGATGTC

ACTGGCCGAA

ACGGACCAGT

GATGAGCTCA

CTCCATTATA

TGATGATATC

AATGAAGTAG

ATCGAGGAAG

ACCTGCAGGG

GGATCAACTG

GACGCTGAAA

TGTTATTACG

ATCATGGTTC

GAAAACAGCG

GGATCTGCTC

GAGATCCACG

ACTCTCAATG

AAAAAGGGCA

GGTGGTGCAA

GCGGGGAATG

TCTGGTACCA

GATGAGCTGT

AATCAGAAGA

ATTAAGAAGC

AGCATCATGA

GAAATCAATC

GTTCTCAAGA

TCCAGAGGAC

GCCGTCGGGT

AAATCCAGCC

AAAGGAGCCA

CTACAGCTCA

CTATGGCAGC

ALAGAGAAGGC

A.AGGCGGTGC

CTTTGGGAAT

TTTATGATCA

AATCAGGCCT

ATGTGGATAT

CCATCTCTAT

AGCTCCTGAG

TTCCTCCGCC

CAGACGCGAG

CCCAATGTGC

TCCCCGAGTG

CAATCTCCCC

TCTCTGATGT

TA.ATCTCCAA

AGATCAACAG

TCGCCATTCC

CCGACTTGAA

AkCCCGTTGC

AGCTGCTGAA

TTGTTCCTGA

GGCTAGAGGA

ATGATCTTGC

ACTTACCTGC

ATGGTCAGAA

AGGCAGTTCG

ACCTCGCATC

CCCCCCAAGA

CAGCGGTGAA

TGATGGTGAT

TGGCGAACCT

GGGGTTCAGG

ACTCCAATCC

CCCGGACCCC

ATTAGCCTCA

TCGAAAGTCA

TGTGAGCAAT

GAGATCCCAG

CCAAGATATT

GCTAGAATCA

GCAAAATATC

TGGACTTGGG

ACCCATCATA

CAGCCGACA

GGAATTTCAG

CACCGGCCCT

GGATCGGAAG

CAAGTTCCAC

CAACCCCATG

1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 164 9 9* 9 9 9* *9 9 9 9 9*9* 9 9.

.9 9 9* 9 9*9* 9 9*99 999999 9 ~9 9 9. 9 9*

CCAGTCGACC

GCCTCCCALAG

AAGGGTCGAT

TCAGAGTCAT

TGCTGGGGGT

CCCTGCCCTT

CTGAGCTTGA

ACAACACCCC

TCAACGCAAA

TCCGTGTTGT

GAAGAATGCT

GGATTGACAA

CAACATTTAT

ATTATTGCAA

GCACCAGTCT

GGTTCAAGAA

TCTGGAGGAG

AAGAATTCCG

TGTAGACCGT

GCCCGGACAA

GCCGACGGCA

CCACCAGCCA

TGCCCCCGAT

ATTGGAAGGC

GACCGAGGTG

CA.ACTAGTAC

TTCCACA.ATG

CGCTCCGATA

AGATCCTGGT

TGTTGAGGAC

AGGTGTTGGC

CATAGTTGTT

ACTAACTCTC

CCAAGTGTGC

TTATATGAGC

GGAATTCAGA

GGCGATAGGC

GGTCCACATC

AATGAAAATC

TCACATTAGA

GACCTTATGT

CAGATGCAAG

CATTTACGAC

AGTGCCCAGC

AA7LAGCCCCC

AGCGCGAACA

CCCCAATCTG

CCAAACCACC

CCCTCCCCCT

ACCCAACCGC

AACCTAAATC

ACAGAGACCT

CAACCCACCA

CTAGGCGACA

AGCGATTCCC

AGATCCACAG

AGACGTACAG

CTCACACCTT

AATGCGGTTA

ATCACCCGTC

TCGGTCAATG

CCTGGGAAGA

GGGAACTTCA

GAA.AAGATGG

AGCACAGGCA

TACCCGCTGA

ATAGTAAGAA

GACGTGATCA

AATGCCCGAA

TCCGAAAGAC

CCAGGCGGCC

CATCCTCCTC

AACCGCATCC

CTTCCTCAAC

AGGCATCCGA

CATTATAAAA

ACGACTTCGA

CCTACAGTGA

GGAAGGATGA

TAGGGCCTCC

CAAAGCCCGA

CAGGGCTCAA

GGAGAA.AGGT

ATCTGATACC

TTTCGGATAA

CAGTGGCCTT

TCATCGACAA

GGAGAAAGAA

GCCTGGTTTT

AA.ATGAGCAA

TGGATATCAA

TCCAGGCAGT

TAAATGATGA

AACGACC CC C

TCCACGGACC

CCAGCACAGA

GTGGGACCCC

CCACCACCCC

ACAAGAACTC

CTCCCTAGAC

AACTTAGGAG

CAAGTCGGCA

TGGCAGGCTG

ATGCTTTATG

AATCGGGCGA

AAAACTCCTC

TGAAAA.ACTG

CCTAACAACA

GCTCGATACC

CGGGTATTAC

CAACCTGCTG

TACAGAGCA

GAGTGA.AGTC

TGCACTTGGT

GACTCTCCAT

TGALAGACCTT

TTTGCAGCCA

CCAAGGACTA

CTCACAATGA

AAGCGAGAGG

ACAGCCCCGA

CGAGGACCAA

CGGGAAAGAA

CACAACCGAA

AGATCCTCTC

CAAAGTGATT

TGGGACATCA

GTGCCCCAGG

TACATGTTTC

GCATTTGGGT

AAAGAGGCCA

GTGTTCTACA

GGGAGTGTCT

CCGCAGAGGT

ACCGTTCCTA

GTGACCCTTA

CTTCCTGAGG

TACTCTGCCG

GGGATAGGGG

GCACAACTCG

AATCGATTAC

TCAGTTCCTC

TTCAAAGTTC

CAGCCAGAAG

CCAGCCAGCA

CACAAGGCCA

CCCCCAAGGC

ACCCCCAGCA

CCGCACAAGC

TCCCCGGCAA

3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 ACTAAACAAA ACTTAGGGCC AAGGAACATA CACACCCAA~C AGAACCCAGA CCCCGGCCCA 165 CGGCGCCGCG CCCCCAACCC CCGACAACCA GAGGGAGCCC CCAACCA.ATC CCGCCGGCTC CCCCGGTGCC

CACAGGCAGG

p p.

p p p. pp p p p pp p. p p* p p p.

p p p p p.

p *6

A.ATCCAAGAC

GAGGAAGCCC

GGGCCACCAG

ACCCCAGCCC

CGAAGGACCC

CTCCTCCTCT

CCCACCCCTA

GGTCTCAAGG

ACCGGTCAAA

AGCTACAAAG

ATAACTCTCC

ACAGTTTTGG

CAGAGTGTAG

GCCCTAGGCG

CTGAACTCTC

GAGGCAATCA

ATCAATAATG

CTCGGGCTCA

CGGGACCCCA

ATCAATAAGG

AGCGGAGGAA

AGTATAGCCT

GTCTCGTACA

CAAGGGTACC

GGGGGGGCCC

ACCCACCCCA

CTCCCAGACT

CGATCCGGCG

CCGAACCGCA

TCTCGAAGGG

AAGGAGACAC

TGAACGTCTC

TCCATTGGGG

TTATGACTCG

TCAATAACTG

AACCAATTAG

CTTCAAGTAG

TTGCCACAGC

AAGCCATCGA

GACAAGCAGG

AGCTGATACC

AATTGCTCAG

TATCTGCGGA

TGTTAGAAAA

TAAAGGCCCG

ATCCGACGCT

ACATAGGCTC

TTATCTCGAA

GACACCAACC

CCCCAAAAAA

CACACGACCA

CGGCCATCAC

GGGAGCCAcC

AAGGACACCA

ACCAAAAGAT

CGGGAATCCC

TGCCATATTC

CAATCTCTCT

TTCCAGCCAT

CACGAGGGTA

AGATGCACTT

GAGACACAAG

TGCTCAGATA

CAATCTGAGA

GCAGGAGATG

GTCTATGAAC

ATACTATACA

GATATCTATC

GCTCGGATAC

GATAACTCAC

GTCCGAGATT

TCAAGAGTGG

TTTTGATGAG

CCCGAACAGA

AGGCCCCCAG

CGGCAACCA3A

CCCGCAGAAA

CAACCCGAAC

GTATCCCACA

CAATCCACCA

AGAATCAAGA

ATGGCAGTAC

AAGATAGGGG

CAATCATTAG

GAGATTGCAG

AATGCAATGA

AGATTTGCGG

ACAGCCGGCA

GCGAGCCTGG

ATATTGGCTG

CAACTATCTT

GAAATCCTGT

CAGGCTTTGA

AGTGGAGGTG

GTCGACACAG

AAGGGGGTGA

TATACCACTG

TCATCGTGTA

CCCAGCACCC

GGGCCGACAG

ACCAGAACCC

GGAAAGGCCA

CAGCACCCAA

GCCTCTCCA

CACCCGACGA

CTCATCCAAT

TGTTAACTCT

TGGTAGGAAT

TCATAAAATT

AATACAGGAG

CCCAGAATAT

GAGTACTCCT

TTGCACTTCA

AAACTACTAA

TTCAGGGTGT

GTGATTTAAT

CATTATTTGG

GCTATGCGCT

ATTTACTGGG

AGTCCTACTT

TTGTCCACCG

TGCCCAAGTA

CTTTCATGCC

AACCATCGAC

CCAGCACCGC

AGACCACCCT

CAACCCGCGC

GAGCGATCCC

GTCCCCCGGT

CACTCAACTC

GTCCATCATG

CCAAACACCC

AGGAAGTGCA

ALATGCCCAAT

ACTACTGAGA

AAGACCGGTT

GGCAGGTGCG

CCAGTCCATG

TCAGGCAATT

CCAAGACTAC

CGGCCAGA.AG

CCCCAGTTTA

TGGAGGAGAC

CATCTTAGAG

CATTGTCCTC

GCTAGAGGGG

TGTTGCAACC

AGAGGGGACT

4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 166 -tee too..: 0 00 see.*

GTGTGCAGCC

TACACCAAGT

TCACAAGGGA

ACGATCATTA

GTAGTCGAGG

TACTTGCACA

AATCTGGGGA

CAGATATTGA

GTGTGTCTTG

AACAAAAAGG

ACATCAAAAT

CACAAGTCTC

TATCTCCGGC

ATCATCCACA

TCCCAAGGGA

TTTGCTGGCT

CATTAGACTT

TCTAGATGTA

AATCATCGGT

CATCTCTGAC

TTGGTGTATC

GGCTGCTGAA

CAATCAGTTC

ATTCTCAAAC

ATCTATAGTC

TAATCTGAGC

AAAATGCCTT

CCTGTGCTCG

ACCTALATAGC

ATCAAGACCC

TGAACGGCGT

GAATTGACCT

ATGCAATTGC

GGAGTATGAA

GAGGGTTGAT

GAGAACAAGT

CCTATGTAAG

CTCTTCGTCA

TTCCCTCTGG

ATGTCACCAC

AGTAGGATAG

GTTCTGTTTG

CATCGGGCAG

ACTAACTCAA

GATGAAGTGG

AAGATTAAAT

AACCCGCCAG

GAGCTCATGA

CTAGCTGTCT

ATGTCGCTGT

ACTATGACAT

AGCAAAAGGT

GTACCCGATG

TACACTCGTA

CAATTGTGCA

TGACAAGATC

GATCATCCAA

CGGTCCTCCC

TAAGTTGGAG

AGGTTTATCG

AGGGATCCCC

TGGTATGTCA

GTCGCTCTGA

TCALAGCAACC

CCGAACAATA

AACGAGACCG

TCATTAACAG

TCATGTTTCT

CCATCTACAC

TCGAGCATCA

GCCTGAGGAC

TCCTTAATCC

AGAGAATCAA

ATGCATTGGT

CAAAGGGAAA

CCCTGTTAGA

CCCAGGGAAT

CAGAGTTGTC

AGTCCTCTGC

TCCGGGTCTT

TCAATCCTTT

CTAACATACA

GTCGGGAGCA

ATATCATTGG

GATGCCAAGG

AGCACTAGCA

GCTTTAATAT

AGACCAGGCC

TCCTCTACAA

ACCGCACCCA

TCGGTAGTTA

GATAALATGCC

AGAACATCTT

GAGCTTGATC

CGCAGAGATC

GGTCAAGGAC

ACCTCAGAGA

GGATAGGGAG

ATTGGATTAT

GAACTCAACT

CTGCTCAGGG

CTTGTATTTA

GTATGGGGGA

ACAACTGAGC

TCCAAGAATG

TTGGGAACCG

GCAAGTGTTA

TTGCTGCCGA

GGAGGTATCC

AGAGGTTGGA

AATTGTTGGA

TAGTCTACAT

GTTGCTGCAG

TAAAGCCTGA

CTCTTGAA.AC

GCATCALAGCC

ATTAAAACTT

TTCTACAAAG

ATGATTGATA

GGGTTGCTAG

CATAAAAGCC

GTGCTGACAC

TTCACTGACC

TACGACTTCA

GATCAATACT

CTACTGGAGA

CCCACTACAA

GGTCGAGGTT

ACTTACCTAG

ATGTACCGAG

CCTCCGGGGG

GTTCATTTTA

CACAACAGGA

TCACTGCCCG

AGACGCTGTG

CGTAGGGACA

GTCATCGGAC

CCTGATTGCA

GGGGCGTTGT

TCTTACGGGA

ACAAATGTCC

CACCTGAAAT

AGGGTGCAAG

ATAACCCCCA

GACCTTATGT

CCATTGCAGG

TCAGCACCAA

CACTCTTCAA

TAGTGAAATT

GAGATCTCAC

GTGCAGATGT

CCAGAACAAC

TCAGAGGTCA

ACAkTGTGTC

TGGAAAAGCC

TGTTTGAAGT

6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 167 AGGTGTTATC AGAAATCCGG GTTTGGGGGC TCCGGTGTTC CATATGACAA ACTATCTTGA 0060

S

@000

OS

S S

S

@5 05 S 0

S

555.

OS

55 5 00 0 55

S

00 55 .5 5 @005 0 0055

S

005500 0

S

550500 9 6 S0 S S 5* 0005 0 0050

GCAACCAGTC

AGCCCTTTGT

CAGCTTCCAG

CCCCTTATCA

TATCGCTGAC

AATGGAGACA

CGAGTGGGCA

GAGTCTGACA

CGGTTCAGGG

GCCAATGAAG

GGTTAGTCCC

AACATACCTA

ACCTGGTCAA

TGTGGTTTAT

GCCTATAAAG

CTGGTGCCGT

TGGGATGGTG

ATAGGGCTGC

GTGAAATAGA

CGCTATCTGT

ATAAGATAGT

CTACACTGTG

TAAACAATGT

CTCATATTCC

CGAGGAAGAT

AGTAATGATC

CACGGGGAAG

CTCGTCAAGC

ACGGATGATC

AATCAAGCAA

TGCTTCCAAC

CCATTGAAGG

GTTGAGCTTA

ATGGACCTAT

AACCTAGCCT

TACCTCTTCA

CCTGCGGAGG

GATCTCCAAT

TACGTTTACA

GGGGTCCCCA

CACTTCTGTG

GGCATGGGAG

TAGTGAACCA

CATCAGAATT

CAACCAGATC

AGCCATCCTG

TCAGAACATC

GGAAGTTGGG

ATATCCAAAT

CCGTGAACTC

TCAGCAACTG

ATTCTATCAC

TAGGTGTCTG

CAGTGATAGA

AATGGGCTGT

AGGCGTGTAA

ATAACAGGAT

AAATCAAAAT

ACAAATCCAA

TAGGTGTAAT

CTGTCCCAAT

TGGATGGTGA

ATGTTTTGGC

GCCCAAGCCG

TCGAATTACA

TGCTTGCGGA

TCAGCTGCAC

ATCACATGAT

AAGAAAAACG

TTATACCCTG

GAGTATGCTC

AAGCACCGCC

AATGTCATCA

TGTAATCAGG

CTCAAAAAGG

TATGGTGGCT

AATTCCCTAT

GAAATCCCCA

CAGGCTTTAC

CCCGACAACA

GGGTAAAATC

TCCTTCATAC

TGCTTCGGGA

CCACAACAAT

CA-ACACATTG

TAAGGAAGCA

TGTCAAACTC

AACCTACGAT

CTCATTTTCT

AGTGGAATGC

CTCAGAATCT

AGTCACCCGG

GTCACCCAGA

TAGGGTCCAA

AAGTTCACCT

GAGTCCCTCA

TAAAAAACGG

AGTCCAAGCT

ATTTATTTAA

GGAATTCGCT

TTGGGGGAGC

CAGGGATCAG

ACCGACATGC

CTCTCATCTC

CGAACAGATG

CALAGCACTCT

GGGGTCTTGT

TTCGGGCCAT

GTGTATTGGC

GAGTGGATAC

GGCGAAGACT

AGTTCCAATC

ACTTCCAGGG

TACTTTTATC

TTCACATGGG

GGTGGACATA

GAAGATGGAA

CATCAGGCAT

GTGGTTCCCC

AGATAGCCCG

CG3CTTACAGC

ATTTTCCAAC

TAGGAGTTAT

CATAGAAGAC

GTACTCCAA

TCAA.ACTCGC

GGAILAGGTGT

AATCCTGGGT

ACAGAGGTGT

ACAAGTTGCG

GCGAGAATCC

CTGTTGATCT

TGATCACACA

TGACTATCCC

CGAGATTCAA

GCCATGCCCC

TGGTGATTCT

TTGAACATGC

CTTTTAGGTT

ACCAAAAACT

TCACTCACTC

CCA.ATCGCAG

ACCCACTAGT

GTTATGGACT

ATAGTTACCA

CTGGAGGACC

CAAPLTGATTA

CCGGCbCACT

AAAGAGTCAA

GTCAGTGATA

8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 168

I.

AGGTTTTCCA

AGGACATCAA

AGCCCTTTCT

CCCATACTTG

TGCTAATCTC

TGACATTTGA

CCGCTATGAC

A.ACTGATAGA

TGGAGCCTCT

CTTTCCTT;A

ATGAAGGTAC

TACATCTGAC

CAGTAACGGC

AGACTCTGAT

GGCACGGAGG

ATGCTCAAGC

TTGCTGGAGT

ACCTAAAGGA

AGTTCCTGCG

TTAATGATTC

TCCATGACCC

GTAGACTTTT

TAATCTCAAA

ATTTGACTAA

GTCACAGGGG

ATGCTTAAGG

GGAGAA.AGTT

GTTTTGGTTT

CCATAGGAGG

TCGTGACCTT

ACTGGTTTTG

TATTGATGCT

TGGTTTCTTC

TTCACTTGCT

CCACTGCTTT

TTATCATGAG

AGGGGAGATT

TGCTGAkAAT

GAAAGGTCAT

CAGTTGGCCA

TTCAGGTGAA

GAAATTTGGC

CAAGGCACTT

TTACGACCCT

GAGCTTTGAC

TGAGTTCAAC

TGCTAAAATG

CGGGATTGGC

GGCACTCCAC

GGGGCCAGTC

GACACTAACT

ATTAACTTGG

ACAGTCAAGA

AGACACACAC

GTTGCTATAA

ATGTATTGTG

AGGTATACAG

CCTGCACTCG

TACCTGCAGC

ACTGAAATAC

TTAATTGAAG

TTCTCATTTT

GTTAGGAAAT

GCCATATTTT

CCGCTGACCC

GGGTTAACAC

TGCTTTATGC

GCTGCTCTCC

CCCAAGGGAA

CCATATGATG

CTGTCTTACA

ACTTACAAAA

AAATATTTTA

ACTCTAGCTG

TTAAA.AACCT

CACGGCTTGG

GAGTTTACAT

CTGAGATGAG

CTGTATTCTT

TCAGTAAAGA

ATGTCATAGA

AGCTTCTAGG

GGAATCCAAC

TGAGGGATAT

ATGATGTTCT

CTCTAGATTA

TCAGAAGTTT

ACATGAATCA

GTGGAATCAT

TCCCCCTGCA

ATGAGCAGTG

CTCTTAGCCT

AAAGGGAATG

CCGGGTCACG

TGATAATGTA

GCCTGAAAGA

TGAGGGCATG

AGGACAATGG

TCTCAGGAGT

ACTCCCGAAG

CCTAGGCTCC

GCACAGCTCC

GTCAGTGATT

CACTGGTAGT

GTCTCAACAT

GGGGAGGTTA

AAGAGTCAGA

TTATCAAATT

AACAGTAGAA

TGACCAAAAC

CATTTTCATA

CGGCCACcCCC

GCCTAA-AGTC

AATCAACGGC

TGCTGCAGAC

CGTTGATAAC

GGATAGTGAT

GGATTCAGTT

GAGGCTTGTA

TGTTGTAAGT

AAAGGAGATC

CCAAGTGATT

GATGGCCAAG

CCCCAAAGAT

CCCAGTCCAC

GAATTGAGGG

CAGTGGTTTG

AAATCACAAA

TCAGTTGAGT

GTATATTACC

ATGACAGAGA

TACATGTGGA

GTAGCCATGC

CTCAGAGGTG

GGGTTTTCTG

ACTGATGACA

AGACTTGAAG

ATTGTGTATG

TATCGTGACA

ACAATCCGGA

TGGAAATCTT

CTGACAATGT

TACCCGAAAG

GATGTTTTCC

GGAGCTTACC

AAGGAAACAG

GCTGAAAATC

GATGAGCACG

CTCAAAGAAA

ACAAGTACCA

9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 GGAACGTGAG AGCAGCAA GGGTTTATAG GGTTCCCTCA AGTAATTCGG CAGGACCAAG 169 4 a a.

a a.

l.a a

ACACTGATCA

ATCTCAAGAA

TAAATGAGAT

CTGTCCTGTA

ATAAAGTCCC

GTCAGAAGCT

GAGTAAGGAT

TACCCAGCAC

ACTTTGTAAT

CAATTGTTTC

TGTCCCAATC

AAACAAGGGC

ATGACCGTTA

CTCTTGGCTT

ACAACGACCT

TGAATATGAG

ATCTCAAGAG

CACAACAACC

TTGTATGTGT

TCCATAGTCC

AGGGACTGGC

TCCTGGATCA

AAGGCTTGAT

TGTCCAATTA

GAAATGTCCT

ATATGTGGGC

TCCGGAGAAT

GTACTGCCTT

TTACGGATTG

TGTAAGTGAC

CAATGATCAA

GTGGACCATC

TGCTTCGTTA

ATGGCCCTAC

TCTTAGGCAA

ATCACATTTT

ACT CAAGAGC

AGCATGCAGT

CCTTGCATAT

CACAATCAAT

CTTAATAAGG

CAGGCTGTTT

AATGATTCTC

GGGGGACTCT

CCAGAGCATC

AAACCCAATG

GGCATTCCTC

TAGTGTCACA

TCGAGCCAGC

TGACTATGAA

CATTGACAAA

GAGGCTAGCT

ATGGA.AGCTT

AATTGGAGAT

CCCTCATTTT

CCTCATTGCC

ATCTTCATTA

AGCACCATTC

GTGCALAGGGG

AACCTTAAGA

AGGCTACATG

TTTGTCTATT

ATCGCAAGAT

AATATTGCTA

TCCCTGAACG

TCAACCATGA

ATGGCACTGT

GTCAGAAACA

GCCTCACTAA

TCATTCCTAG

ACTAGACTCC

TTAAAAGGAT

ATGGACAGGC

GGGGCAAGAG

ATGAGGAAGG

CAATTCAGAG

GAGTCATGTT

CGAGGACGGC

ACGAGACAGT

ATGAGACCAT

TCCAGTGGCT

CCCCCGACCT

AGTACCCTAT

CCTATCTATA

ACAATCAGAC

AACGGGAAGC

ATATTGGCCA

CAAAAGGAAT

GTGTATTCTG

CAACAATGGC

TCCTAAAAGT

CCCGGGATGT

TGCCCGCTCC

TCGGTGATCC

TGCCTGAAGA

ACTGGGCTAG

TCAAGAACAT

TATTCCATGA

ATATTATAGT

AGTCTATTGC

GGGGGTT;LAC

CAGGGATGGT

CAGTGCAGCT

CTATTTACGG

CAGTGCATTT

CAGCTTGTTT

GCATAAGAGG

TGACGCCCAT

GGGAGGTATA

CCTGGCTGCT

CATAGCCGTA

TGCTAGAGTA

TCACCTCAAG

ATATTATGAT

GTCAGAGACT

TAAAAGCATC

GATACAGCAA

AGTCATACCC

TATTQGGGGGG

AGTAACATCA

GACCCTCCAT

CGACCCTTAC

AACTGCAAGG

TGACAGTAAA

ACCTAGGGCA

AGGCATGCTG

CTCTCGAGTG

GCTATTGACA

GGCGAGAGCT

CCTTGAGGTC

ATCACGACTG

GCACAGAGGC

CTTGAGACCT

ATCCCGTTAT

GAAGGGTATT

TATGAGAGCG

ACAAAAAGGG

ACTAGAGATT

GCAAATGAGA

GGGCTACTTG

ATAGTTGATG

GAGAGAGGTT

ATTCTGATCT

CTCCTCACAA

ATGAATTATC

TCAATTGCTG

CAAGTAATGA

TCAGCAAATC

TTTGTCCTGA

GAAGAGGACG

GCTCATGA;A

GATACCACAA

ATAACCAGAT

GGAAGAAAGC

CTAAGAAGCC

CCTGATGTAC

11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 170 p r.

P

TAGAATCTAT

GATCAGTCAA

AGGAAACATC

TGAAGCTTGC

CAGTGTACTC

CTAGGCAAAG

CGACTAATTT

CCCTTGTCCG

CAGATA.AGA.A

TTTTAGAA.AC

TTCACGTCGA

CCCGCAAGCT

CTTTAATTGA

AATTTGTTAC

CTATGATTGA

TAGGGGATGA

TCACTATCTA

GACCATCAGG

AAGGAGTGTT

GGCATTGTGG

CAACTGTGTG

AAGAGTTAGA

GATTCGACAA

GGACCTGCCC

ATATCAAGGC

TTGTAGACCA

GCGAGGCCAC

CTACGGATGG

ATCCTTGAGA

CTTCGTAAGA

ATGGGCTTAC

GGCCAATGTG

AGCGCATAGG

AGTGGCGAGG

GGTTGATACT

ATTGTTTCGA

AACAGATTGT

AGAGCTGAGG

CAGAGATGCA

ATGGTCCACA

CCTGGTAACA

CGATATCAAT

CTTGGGCCAG

GAAATATCAG

TAAGGTGCTT

TATTATAGAG

CAACATGGTT

AGAGTTCACA

CATCCAGGCA

ACCAATTCGA

AGAGGCTATG

TTACTCATGC

CTTATTCGGC

TTTTTTGTCC

GTCCCATATA

GCCCCAAGTC

GGTGATGATG

AGCCTGGAGG

TTGAGGGATC

TATACCACA.A

AACTTTATAT

CTCGAGAAAG

TGCGTGATCC

GCAGAGCTAT

ACAAGGCTAT

CCCCAACTAT

AAATTTGAGA

AGTTTCATAA

TGTGCGGCCA

ATGGGTGAGC

GTCAATGCTC

CCTATCCATG

TACACATGCT

TTTCTCTTGT

AAACACTTAT

GGTCTAAGAC

TTATCTCCAG

TCTCTGACTT

GTCATGAGAC

CCTCGGGTTG

TTGGTTCTAC

GATCCTTGCG

ATAGCTCTTG

AGCTAAGGGT

GTAGCACTCA

TCTCCAACGA

ACCAACAAGG

ATACCGGATC

CGATGATAGA

GTACCAACCC

ACACCCAGAG

ATCACATTTT

AGGACCATAT

CTGAGTTTCT

TCAATTGGGC

TGTTGTCATC

TAAGCCACCC

GTCCTTCACT

ATATGACCTA

GTGAAAGCGA

GTGTTCTGGC

CGGTAGAGAA

CAGGATCTTC

ATCTCCGGCG

ATGTGTCATC

CCAACTGGAT

CACTGATGAG

ATCTGCTGTT

GAACGAAGCC

GAT CACT CCC

AGTGAAATAC

CAATCTCTCA

AATGCTTCTA

ATCTAACACG

TCATCCCAGG

ATTGATATAT

CCATAGGAGG

AGCTAAGTCC

GAATGAAATT

GCTCATAGAG

ATTTGATGTA

GTTCCTTTCT

AAAGATCTAC

TGATGCTCAA

CCTCGACCTG

CGAGGATGTA

AGATTTGTAC

ATGTGCAGTT

GTGGAACATA

AGGATCGATC

TGCGAGTGTG

GATATTGACA

AGAACAGACA

AGAATAGCAA

TGGTTGTTGG

ATCTCAACTT

TCAGGTACAT

TTTGTCATAT

GGGTTGGGTG

GTATTACATC

ATACCCAGCT

GATAATGCAC

CACCtTGTGG

ACAGCACTAT

TCAGCTCTCA

CCAAGATTAT

CATTATCATA

AGAATGAGCA

AAGAAATTCT

AACTTGCACA

TTGTTGAATG

GTACCGGACA

TGTCAACCAG

CTAACCGACC

AATCCAATTA

AAACAGATAA

12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 171 0 0. 0 0 0 0* 00 0 0**0 0* 0 0 0 GATTGAGAGT TGATCCAGGA TTCATTTTCG ACGCCCTCGC TGAGGTAAAT GTCAGTCAGC 00*000 0 0 00 0 000 00.

0.

000.

0 00 0 0*

CAA.AGATCGG

ATGATGTTGC

GGGGCAATCT

CTTGCTACAA

ACGGCTTGTT

AACTAAACAA

AATTAGCACC

TTGTCAAAGT

TCAATTTCAT

AGACCTTGCC

TGGCTCTGCT

GGGATTTTGT

TATACCCTAG

AGGCTAACCG

GGACTTCACC

CAATTGTGGG

CTATAGAGCA

AATTGATCCA

TCTACAGGGA

CTTACCCCGT

TCTGGGGGCA

ATCTCAAGTC

CCAAGTCAGA

TAACAGTCAA

CAGCAACAAC

AAAATTGCTC

CGCCAATTAT

AGCTGTTGAG

CTTGGGTGAG

GTGCTTCTAT

CTATCCCTCC

GCTCTTTAAC

AGTTAGTAAT

TGACAAAGAT

CCTGGGCAAA

TCAGGGATTT

ATACAGCAAC

GCTAATGAAT

TGGACTTATA

AGACGCAGTT

GGTGCTGATC

CCATGATGTT

GTTGGCAAGA

ATTGGTAAGT

CATTCTTCTT

CGGCTATCTG

GAAACAGATT

GGAGACCAAA

ATCTCAAATA

AAAGATATCA

GAAATCCATG

ATATCAACAT

GGATCGGGTT

AATAGTGGGG

GAAGTTGGCC

GGGAGGCCCG

ATCCCTACCT

ACTATAGAGA

ATAGGATCAA

ATAAGTTATG

TTCATCTCTA

CCTGAAAAGA

GGTCACATCC

AGTAGAGGTG

AATTGCGGGT

GCCTCAGGGC

TTCAA.AGACA

AGCAGGCAAC

TACTCCGGGA

ATACTAGACT

ATTATGACGG

GAATGGTATA

TGAGCATCAA

ACACAAGCAA

CTTTCCGCAG

TA.ATTAGGAG

CTATGTTGAT

TTTCCGCCAA

TTGTCGAACA

AAGTCACGTG

CTAGTGTGGG

AGCTAGAGGA

TACTGGTGAT

TAGGGTCTCA

CTGAATCTTA

TTAAGCAGCA

TATCCATTAA

ATATCAATCC

TGGCAATTAA

AAGATGGATT

ACCAAAGAAG

GAGAACTTAT

ACAGAAAGTT

TACACCAGAA

GGGGTTTGA

AGTTAGTCGG

GGCTTTCAGA

GCACAATCTT

AATCGGGTTG

ATGCCTTGAG

CACTTATAAG

TTCTAGATCT

CAGAATGGGA

GGTAGGCAGT

GTTTATCCAT

ATTGGCAGCC

TAAGCTTATG

TTATAGAGAA

TTTGGTTATG

GATAATTGAA

GCAACTAAGC

TACTCTGAA

CGGACCTAAG

GCTTAATTCT

TCAACAAGGG

ATCTAGGATC

GATAAATAAG

TATCTTCGTT

ACGTGAGTGG

ATACAGTGCC

CCCCCACACG

CCCATTTCAG

AACTCATCTG

CCAGGGGAGG

GAGATACTTA

GGTCAAAGGG

GTAGGTAATA

GTAGATTGCT

TCAGATATAG

ATCTTATCGA

CCTTTCAGCG

GTGAACCTTG

ACAGATCTCA

TCATCTGTGA

TGCATACAAG

AAACTTACAC

CTGTGCAAAG

ATACTCATCC

ATGTTCCACG

ACCCGCAAAT

TTTATCCAGA

AAGAATCTAT

GTTTTTAAGG

CTGATTAAGG

14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15240 15300 15360 15420 15480 15540 15600 15660 15720 15780 15840 ACTAATTGGT TGAACTCCGG AACCCTAATC CTGCCCTAGG TGGTTAGGCA TTATTTGCAA 172 *TATATTAAAG AAAACTTTGA AAATACGAAG TTTCTATTCC CAGCTTTGTC TGGT 15894 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 2183 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID Met Asp Ser Leu Ser Val Asn Gin Ile Leu Tyr Pro Glu Val His Leu 1 5 1.0 Asp Ser Pro Ile Val Thr Asn Lys Ile Val Ala Ile Leu Glu Tyr Ala 25 *Arg Val Pro His Ala Tyr Ser Leu Giu Asp Pro Thr Leu Cys Gin Asn 40 Ile Lys His Arg Leu Lys Asn Gly Phe Ser Asn Gin Met Ile Ile Asn 55 *Asn Val Giu Val Gly Asn Val Ile Lys Ser Lys Leu Arg Ser Tyr Pro 70 75 Ala His Ser His Ile Pro Tyr Pro Asn Cys Asn Gin Asp Leu Phe Asn 90 Ile Glu Asp Lys Giu Ser Thr Arg Lys Ile Arg Giu Leu Leu Lys Lys 100 105 110 Gly Asn Ser Leu Tyr Ser Lys Val Ser Asp Lys Val Phe Gin Cys Leu *115 120 125 *Arg Asp Thr Asn Ser Arg Leu Gly Leu Gly Ser Giu Leu Arg Giu Asp 130 135 140 Ile Lys Giu Lys Val Ile Asn Leu Gly Val Tyr Met His Ser Ser Gin 145 150 155 160 Trp Phe Giu Pro Phe Leu Phe Trp Phe Thr Val Lys Thr Giu Met Arg 165 170 175 Ser Val Ile Lys Ser Gin Thr His Thr Cys His Arg Arg Arg His Thr 173

S

S

*5S*

S

180 Pro Val Phe Phe Thr Gly Ser Ser Val Glu Leu Leu Ile Ser Leu Phe 225 Thr Arg Gly Ala Leu 305 Phe Ile Phe Asn Leu 385 Arg Ala His Val 210 Glu Glu Val Asn Tyr 290 Asn Ser Phe Arg Val 370 Met Asp Ala Glu 195 Ala Leu Thr Arg Pro 275 Leu His Asp Ile Ser 355 Arg Lye Arg Asp Gin Ile Val Ala Tyr 260 Thr Gin Cys Glu Thr 340 Phe Lye Gly His Thr 420 Cys Ile Leu Met 245 Met Tyr Leu Phe Gly 325 Asp Gly Tyr His Gly 405 Ile Val Ser Met 230 Thr Trp Gin Arg Thr 310 Thr Asp His Met Ala 390 Gly Arg Asp Lye 215 Tyr Ile Lys Ile Asp 295 Glu Tyr Ile Pro Asn 375 Ile Ser Asn Asn 200 Glu Cys Asp Leu Val 280 Ile Ile His His Arg 360 Gin Phe Trp Ala Trp 440 Ser Asp Ala Ile 265 Ala Thr His Glu Leu 345 Leu Pro Cys Pro Gin 425 Lys Gin Val Arg 250 Asp Met Val Asp Leu 330 Thr Glu Lye Gly Pro 410 Ala Ser His Ile 235 Tyr Gly Leu Glu Val 315 Ile Gly Ala Val Ile 395 Leu Ser Phe Val 220 Glu Thr Phe Glu Leu 300 Leu Glu Glu Val Ile 380 Ile Thr Gly Ala 205 Tyr Gly Glu Phe Pro 285 Arg Asp Ala Ile Thr 365 Val Ile Leu 31u Gly 445 Tyr Arg Leu Pro 270 Leu Gly Gin Leu Phe 350 Ala Tyr Asn Pro Gly 430 Val Arg Leu Leu Leu 255 Ala Ser Ala Asn Asp 335 Ser Ala Glu Gly Leu 415 Leu Lye Asp Thr Met 240 Gly Leu Leu Phe Gly 320 Tyr Phe Glu Thr Tyr 400 lis Vhr ?he 435 Gly Cys Phe Met Pro Leu Ser Leu Asp Ser Asp Leu Thr Met Tyr Leu 455 460 174 o o Lys Asp Lys Ala Leu Ala Ala Leu Gin Arg Glu Trj Asp Ser Val Tyr A C: 1 U. -J 470 475 @00.

a.

I..

*0 Pro Arg Val Asn Leu 545 Glu Met Val Val Val 625 Asp Ser Tyr Leu Leu 705 Lys Leu Ile Leu 530 Phe Asn Ala Ser Leu 610 Arg Gin Ala Glu Pro 690 Tyr Glu Val Met 515 Ser Ala Leu Lys Gly 595 Lys Ala Asp Phe Thr 675 Ser Val Phe Asp 500 Tyr Tyr Lys Ile Asp 580 Val Thr Ala Thr Ile 660 Ile Phe Ser Leu 485 Val Val Ser Met Ser 565 Glu Pro Tyr Lys Asp 645 Thr Ser Phe Asp Arg Phe Val Leu Thr 550 Asn His Lys Ser Gly 630 His Thr Leu Gin Pro 710 Tyr Leu Ser Lys 535 Tyr Gly Asp Asp Arg 615 Phe Pro Asp Phe Trp 695 His Asp Asn Gly 520 Glu Lys Ile Leu Leu 600 Ser Ile Glu Leu Ala 680 Leu Cys Pro Asp 505 Ala Lys Met Gly Thr 585 Lys Pro Gly Asn Lye 665 Gin His Pro SPro 490 Ser Tyr Glu Arg Lys 570 Lys Glu Val Phe Met 650 Lys Arg Lys Pro SLys Ser Leu Ile Ala 555 Tyr Ala Ser His Pro 635 Glu Tyr Leu Arg Asp 715 Gly Phe His Lys 540 Cys Phe Leu His Thr 620 Gin Ala Cys Asn Leu 700 Leu SThr Asp Asp 525 Glu Gin Lys His Arg 605 Ser Val Tyr Leu Glu 685 Glu Asp Gly Pro 510 Pro Thr Val Asp Thr 590 Gly Thr lle Glu Asn 670 Ile Thr Ala I Ser 495 Tyr Glu Gly Ile Asn 575 Leu Gly Arg Arg Thr 655 Trp Tyr Ser lis Arg SAsp Phe Arg Ala 560 Gly Ala Pro Asn Gin 640 Val Arg Gly Val Ile 720 Pro Leu Tyr Lys Val Pro Asn Asp Gin Ile Phe Ile Lys Tyr Pro Met 725 730 735 175

S

S.

S.

Gly Pro Leu Ser 785 Arg His Ser Ser Arg 865 Arg Ile Thr Arg Met 945 Ile Thr Asp Gly Tyr Val 770 Thr Asp Leu Lys Ile 850 Al a Gly Gin Arg Met 930 Ser Al a Leu Trp Ile Leu 755 Gin Trp Tyr Lys Gly 835 Ala Ala Tyr Gin Asp 915 Ala Arg Asp His Al a 995 Glu 740 Tyr Gly Pro Phe Al a 820 Ile Arg Cys Asp Ile 900 Val Leu Leu Leu Gin 980 Ser Gly Leu Asp Tyr Vai 805 Asn Tyr Cys S er Arg 885 Leu Val Leu Phe Lys 965 Val Asp Cys Ala Gin 775 Leu Leu Thr Asp Phe 855 Ile Leu Ser Pro Al a 935 Arg Met Thr Tyr Gin Tyr 760 Thr Lys Arg Ile Gly 840 Trp Ala Ala Leu Leu 920 Pro Asn Ile Gin Ser Lys 745 Glu Ile Lys Gin Vai 825 Leu Ser Thr Tyr Giy 905 Leu Ile Ile Leu Gin 985 Ala Trp Gly Val Giu 795 Leu Ser Val Thr Met 875 Leu Thr Asn Gly Asp 955 Ser Gly Leu le Arg 765 Lys Ala Asp Phe Gin 845 Val Lys Val Aen Asp 925 Aen Val Met Ser Cys Ser 750 Ile Arg Arg Ile Phe 830 Ser Asp Ser Leu Ser 910 Leu Tyr Thr Pro Ser 990 Val Thr Al a Val Val Giy 815 Val Leu Giu Ile Lys 895 Thr Leu Leu Ser Glu 975 Phe Ile Ser Pro Thr 800 His Tyr Lye Thr Giu 880 Val1 Met Ile Aen Ser 960 Giu Leu 1000 1005 Ile Thr Arg Leu Leu Lys An Ile Thr Ala Arg Phe Val Leu Ile His 176 1010 1015 1020 .~:Ser Pro Asn Pro Met Leu Lys Gly Leu Phe His Asp Asp Ser Lys Glu *1025 1030 1035 1040 Glu Asp Glu Gly Leu Ala Ala Phe Leu Met Asp Arg His Ile Ile Val 1045 1050 1055 -Pro Arg Ala Ala His Giu Ile Leu Asp His Ser Vai Thr Gly Ala Arg 1060 1065 1070 Glu Ser Ile Ala Gly Met Leu Asp Thr.Thr Lys Gly Leu Ile Arg Ala *1075 1080 1085 Ser Met Arg Lys Gly Gly Leu Thr Ser Arg Val Ile Thr Arg Leu Ser 1090 1095 1100 'Asn TDyr Asp Tyr Glu Gin Phe Arg Ala Gly Met Val Leu Leu Thr Giy 1105 1110 1115 1120 Arg Lys Arg Asn Val Leu Ile Asp Lys Giu Ser Cys Ser Val Gin Leu 1125 1130 1135 Ala Arg Ala Leu Arg Ser His Met Trp Ala Arg Leu Ala Arg Gly Arg 9...*1140 1145 1150 *..Pro Ile Tyr Gly Leu Glu Vai Pro Asp Vai Leu Giu Ser Met Arg Gly *1155 1160 1165 **His Leu Ile Arg Arg His Glu Thr CyB Val Ile Cys Glu Cys Gly Ser *1170 1175 1180 Val Asn Tyr Gly Trp Phe Phe Val Pro Ser Gly Cys Gin Leu Asp Asp :1185 1190 1195 1200 Ile Asp Lys Giu Thr Ser Ser Leu Arg Val Pro Tyr Ile Gly Ser Thr 1205 1210 1215 *Thr Asp Glu Arg Thr Asp Met Lys Leu Ala Phe Val Arg Ala Pro Ser 1220 1225 1230 Arg Ser Leu Arg Ser Ala Val Arg Ile Ala Thr Val Tyr Ser Trp Ala 1235 1240 1245 Tyr Gly Asp Asp Asp Ser Ser Trp Asn Glu Ala Trp Leu Leu Ala Arg 1250 1255 1260 Gin Arg Ala Asn Val Ser Leu Giu Glu Leu Arg Val Ile Thr Pro Ile 1265 1270 1275 1280 Ser Thr Ser Thr Asn Leu Ala His Arg Leu Arg Asp Arg Ser Thr Gin 1285 1290 1295 177 :Val Lys Tyr Ser Gly Thr Ser Leu Val Arg Val Ala Arg Tyr Thr Thr *1300 1305 1310 Sle Ser Asn Asp Asn Leu Ser Phe Val Ile Ser Asp Lys Lys Vai Asp 1315 1320 1325 *Thr Asn Phe Ile Tyr Gin Gin Gly Met Leu Leu Giy Leu Gly Val Leu 1330 1335 1340 Giu Thr Leu Phe Arg Leu Giu Lye Asp Thr Gly Ser Ser Asn Thr Val 1345 1350 1355 1360 Leu His Leu His Val Giu Thr Asp Cys Cys Val Ile Pro Met Ile Asp 1365 1370 1375 His Pro Arg Ile Pro Ser Ser Arg Lye Leu Giu Leu Arg Ala Giu Leu 1380 1385 1390 Cys Thr Asn Pro Leu Ile Tyr Asp Asn Ala Pro Leu Ile Asp Arg Asp 1395 1400 1405 Ala Thr Arg Leu Tyr Thr Gin Ser His Arg Arg His Leu Val Glu Phe 1410 1415 1420 Val Thr Trp Ser Thr Pro Gin Leu Tyr His Ile Leu Ala Lys Ser Thr *1425 1430 1435 1440 Ala Leu Ser Met Ile Asp Leu Val Thr Lye Phe Glu Lye Asp His Met 1445 1450 1455 Asn Giu Ile Ser Ala Leu Ile Gly Asp Asp Asp Ile Asn Ser Phe Ile 1460 1465 1470 *Thr Giu Phe Leu Leu Ile Giu Pro Arg Leu Phe Thr Ile Tyr Leu Gly 1475 1480 1485 Gin Cys Ala Ala Ile Asn Trp Ala Phe Asp Val His Tyr His Arg Pro 1490 1495 1500 Ser Gly Lye Tyr Gin Met Gly Giu Leu Leu Ser Ser Phe Leu Ser Arg 1505 1510 1515 1520 Met Ser Lye Gly Val Phe Lys Val Leu Val Asn Ala Leu Ser His Pro 1525 1530 1535 Lye Ile Tyr Lye Lye Phe Trp His Cys Gly Ile Ile Giu Pro Ile His 1540 1545 1550 Gly Pro Ser Leu Asp Ala Gin Aen Leu His Thr Thr Val Cys Asn Met 1555 1560 1565 178 Val. Tyr Thr Cys Tyr Met Thr Tyr Leu Asp Leu Leu Leu Asn Glu Glu 1570 1575 1580 *Leu Glu Giu Phe Thr Phe Leu Leu Cys Giu Ser Asp Giu Asp Val Vai .1585 1590 1595 1600 Pro Asp Arg Phe Asp Asn Ile Gin Ala Lys His Leu Cys Val *Leu Ala *.1605 1610 1615 Asp Leu Tyr Cys Gin Pro Gly Thr Cys Pro Pro le Arg Gly Leu Arg 1620 1625 1630 *Pro Vai Giu Lys Cys Ala Val Leu Thr Asp His Ile Lys Ala Giu Ala *1635 1640 1645 Met Leu Ser Pro Ala Gly Ser Ser Trp Asn Ile Asn Pro Ile Ile Val *1650 1655 1660 Asp His Tyr Ser Cys Ser Leu Thr Tyr Leu Arg Arg Gly Ser Ile Lys 1665 1670 1675 1680 Gin Ile Arg Leu Arg Val Asp Pro Gly Phe Ile Phe Asp Ala Leu Ala 1685 1690 1695 Glu Val Asn Val Ser Gin Pro Lys Ile Gly Ser Asn Asn Ile Ser Asn 1700 1705 1710 *Met Ser Ile Lys Ala Phe Arg Pro Pro His Asp Asp Val Ala Lys Leu 1715 1720 1725 Leu Lys Asp Ile Asn Thr Ser Lys His Asn Leu Pro Ile Ser Giy Gly 1730 1735 1740 Asn Leu Ala Asn Tyr Giu Ile His Ala Phe Arg Arg Ile Gly Leu Asn 1745 1750 1755 1760 Ser Ser Ala Cys Tyr Lys Ala Val Glu Ile Ser Thr Leu Ile Arg Arg 1765 1770 1775 Cys Leu Giu Pro Gly Giu Asp Gly Leu Phe Leu Gly Glu Gly Ser Gly 1780 1785 1790 Ser Met Leu Ile Thr Tyr LyB Gu Ile Leu Lys Leu Asn Lys Cys Phe 1795 1800 1805 Tyr Asn Ser Gly Val Ser Ala Asn Ser Arg Ser Gly Gin Arg Glu Leu 1810 1815 1820 Ala Pro Tyr Pro Ser Glu Val Gly Leu Val. Glu His Arg Met Gly Val 1825 1830 1835 1840 Gly Asn Ile Val. Lys Val Leu Phe Asn Gly Arg Pro Giu Val Thr Trp 179 1845 1850 1855 Val Gly Ser Val Asp Cys Phe Asn Phe Ile Val Ser Asn Ile Pro Thr 1860 1865 1870 Ser Ser Val Gly Phe Ile His Ser Asp Ile Glu Thr Leu Pro Asp Lys 1875 1880 1885 Asp Thr Ile Glu Lys Leu Glu Glu Leu Ala Ala Ile Leu Ser Met Ala 1890 1895 1900 Leu Leu Leu Gly Lys Ile Gly Ser Ile Leu Val Ile Lys Leu Met Pro 1905 1910 1915 1920 Phe Ser Gly Asp Phe Val Gin Gly Phe Ile Ser Tyr Val Gly Ser His 1925 1930 1935 Tyr Arg Glu Val Asn Leu Val Tyr Pro Arg Tyr Ser Asn Phe Ile Ser 1940 1945 1950 Thr Glu Ser Tyr Leu Val Met Thr Asp Leu Lys Ala Asn Arg Leu Met 1955 1960 1965 Asn Pro Glu Lys Ile Lys Gin Gin Ile Ile Glu Ser Ser Val Arg Thr 1970 1975 1980 Ser Pro Gly Leu Ile Gly His Ile Leu Ser Ile Lys Gin Leu Ser Cys 1985 1990 1995 2000 Ile Gln Ala Ile Val Gly Asp Ala Val Ser Arg Gly Asp Ile Asn Pro 2005 2010 2015 Thr Leu Lys Lys Leu Thr Pro Ile Glu Gin Val Leu Ile Asn Cys Gly 2020 2025 2030 Leu Ala Ile Asn Gly Pro Lys Leu Cys Lys Glu Leu Ile His His Asp 2035 2040 2045 Val Ala Ser Gly Gin Asp Gly Leu Leu Asn Ser Ile Leu Ile Leu Tyr 2050 2055 2060 Arg Glu Leu Ala Arg Phe Lys Asp Asn Gin Arg Ser Gin Gin Gly Met 2065 2070 2075 2080 Phe His Ala Tyr Pro Val Leu Val Ser Ser Arg Gin Arg Glu Leu Ile 2085 2090 2095 Ser Arg Ile Thr Arg Lys Phe Trp Gly His Ile Leu Leu Tyr Ser Gly 2100 2105 2110 Asn Arg Lys Leu Ile Asn Lys Phe Ile Gin Asn Leu Lys Ser Gly Tyr 2115 2120 2125 180

S

S

S. S S *5 5

S@

S

S

S

5.*

S

S.

S

5) Leu Ile Leu Asp Leu His Gin Asn Ile Phe Val Lys Asn Leu Ser Lys 2130 2135 2140 Ser Giu Lys Gin Ile Ile Met Thr Gly Giy Leu Lys Arg Glu Trp Vai 2145 2150 2155 2160 Phe Lys Val Thr Val Lys Giu Thr Lye Glu Trp Tyr Lye Leu Val Gly 2165 2170 2175 Tyr Ser Ala Leu Ile Lye Asp 2180 INFORMATION FOR SEQ ID NO:1i: SEQUENCE CHARACTERISTICS: LENGTH: 15894 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: ACCAAACAAA GTTGGGTAAG GATAGTTCAA TCAATGATCA TCTTCTAGTG CACTTAGGAT S. TCAAGATCCT

TAAGGAGCTT

GTGGAGCCAT

TTACCACTCG

GCGGGCCCAA

GTCAATTGAT

TCCAGAGTGA

ATGAGGCGGA

GATGGTTCGG

TGATTCTGGG

CAGACACGGC

ATTATCAGGG

AGCATTGTTC

CAGAGGAATC

ATCCAGACTT

ACTAACAGGG

TCAGAGGATC

CCAGTCACAA

CCAATACTTT

GAACAAGGAA

TACCATCCTA

AGCTGATTCG

ACAAGAGCAG

AAAAGAAACA

AAACACATTA

CTGGACCGGT

GCACTAATAG

ACCGATGACC

TCTGGCCTTA

TCACATGATG

ATCTCAGATA

GCCCAAATTT

GAGCTAAGAA

GATTAGGGAT ATCCGAGATG

AGGACAAACC

TTATAGTACC

TGGTGAGGTT

GTATATTATC

CTGACGTTAG

CCTTCGCATC

ATCCAATTAG

TTGAAGTGCA

GGGTCTTGCT

GGTGGATAAA

ACCCATTACA

AATCCCTGGA

AATTGGAAAC

CTTATTTGTG

CATAAGGCTG

AAGAGGTACC

TAGTGATCAA

AGACCCTGAG

CGCAAAGGCG

GTACACCCAA

GCCACACTTT

TCAGGATCCG

GATTCCTCAA

CCGGATGTGA

GAGTCTCCAG

TTAGAGGTTG

AACATGGAGG

TCCAGGTTCG

GGATTCAACA

GTTACGGCCC

CAAAGAAGGG

120 180 240 300 360 420 480 540 600 660 720 181. 0* 4~ 44

S

4* 4**4

TAGTTGGTGA

AGGACCTCTC

GAAACAAACC

GATTAGCCAG

GACTGCATGA

AAATGGGGGA

GTGCAGGATC

ACTCCATGGG

GGCAAGAGAT

GTATCACTC

AGATCAGTAG

GTGAGAATGA

GAGAAGCCAG

CCCATCTTCC

CGCAGGACAG

CGGAAGAACA

ACTAGGTGCG

AAAACTTAGG

GAGCCAATGG

CTCAAGGCCG

ATATCAGACA

GGTCTCAGCA

CGCGGTCAGG

AATCTCCAGG

GCGGTTAAGG

ATTTAGATTG

CTTACGCCGA

CAGGATTGCT

TTTTATCCTG

ATTTGCTGGT

AACTGCACCC

ATACCCTCTG

AGGTTTGAAC

GGTAAGGAGG

CGAGGATGCA

AGCGGTTGGA

GCTACCGAGA

GGAGAGCTAC

AACCGGCACA

TCGAAGGTCA

AGGCTCAGAC

AGAGGCCGAG

AACCAGGTCC

CAGAAGAGCA

AGCCCATCGG

ACCCAGGACA

AACCATGCCT

GACCTGGAGA

CATCAAGCAC

GAATCCAAGA

GAGAGAAAAT

TTCATGGTCG

GAAATGATAT

ACTATTAAGT

GAGTTATCCA

TACATGGTAA

CTCTGGAGCT

TTTGGCCGAT

TCAGCTGGA-A

AGGCTTGTTT

CCCAGACAAG

TTGGGGGGCA

AGAGACCG

CCCCTAGACA

GCTGACGCCC

ACGGACACCC

GGCCAGAACA

ACACAGCCGC

GGCACGCCAT

CTCACTGGCC

GGAGCGAGCC

CTCAGCAATT

GAGCGATGAC

TGGGTTACAG

TGCTGACTCT

GGTTGGATGT

CTCTAATCCT

GTGACATTGA

TTGGGATAGA

CACTTGAGTC

TCCTGGAGAA

ATGCCATGGG

CTTACTTTGA

AGGTCAGTTC

CAGAGATTGC

CCCAAGTATC

AGGAAGATAG

GGCCCAGCAG

TTGACACTGC

TGCTTAGGCT

CTATAGTGTA

ACATCCGCCT

CAGCCCATCA

GTCAAAAACG

ATCGAGGAAG

ACCTGCAGGG

GGATCAACTG

GACGCTGAAA

TGTTATTACG

ATCATGGTTC

GGTGAGGAAC

GGATATCAAG

TACATATATC

AACTATGTAT

CTTGATGA-AC

CTCAATTCAG

AGTAGGAGTG

TCCAGCATAT

CACATTGGCA

ALATGCATACT

ATTTCTACAC

GAGGGTCAAA

AGCAAGTGAT

AACGGAGTCC

GCAAGCCATG

CIAATGACAGA

ACCATCCATC

ACCATCCACT

GACTGGAATG

CTATGGCAGC

AAGAGAAGGC

AAGGCGGTGC

CTTTGGGAAT

TTTATGATCA

AATCAGGCCT

AGGATTGCCG

AGAACACCCG

GTAGAGGCAG

CCTGCTCTTG

CTTTACCAGC

AACAAGTTCA

GAACTTGAAA

TTTAGATTAG

TCTGALACTCG

ACTGAGGACA

GGTGATCAAA

CAGAGTCGAG

GCGAGAGCTG

AGCCAAGATC

GCAGGAATCT

AATCTTCTAG

ATTGTTATAA

CCCACGATTG

CATCCGGGCT

ATGGTCAGAA

AGGCAGTTCG

ACCTCGCATC

CCCCCCAAGA

CAGCGGTGAA

TGATGGTGAT

780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 AGCACCCTCT CAGGAGGAGA CAATGALATCT GAAAACAGCG ATGTGGATAT TGGCGAACCT 182 0* a

GATACCGAGG

GCTTCTGATG

AGAGGCAACA

GGTAGGGCCA

TTTGGAACGG

CCCTCGGAAC

GCCGCACTGA

AATAATGAAG

AAAACAGCCT

CTGCTGTTAT

AGCATATCCA

AAGGATCCCA

GGCAGAGATT

CTCCAAGGAA

CTAAAGCCGA

GCATCACGCA

CGTTACCTGA

CAGATGCTGA

CCAGTCGACC

GCCTCCCAAG

AAGGGTCGAT

TCAGAGTCAT

TGCTGGGGGT

TCCTGCCCTT

CTGAGCTTGA

ACAACACCCC

GATATGCTAT

TTGAAACTGC

ACTTTCCGAA

GCACTTCCGG

AGATCGCGTC

CATCAGGGCC

TACAGGAGTG

AAGGGGGAGA

TGGCCAAA-AT

TGAAGGGAGA

CCCTGGAAGG

ACGACCCCAC

CAGGCCGAGC

TGACAAATGG

TCGGGAAAAA

GTGTAATCCG

TGACTCTCCT

TGAAGATAAT

CAACTAGTAC

GTCCACAATG

CGCTCCGATA

AGATCCTGGT

TGTTGAGGAC

AGGTGTTGGC

CATAGTTGTT

ACTAACTCTC

CACTGACCGG

AGA.AGGAGGG

GCTTGGGAAA

GACACCCATT

TTTATTGACA

AGGTGCACCT

GACACCCGAA

CTATTATGAT

ACACGAGGAT

AGTTGAGTCA

ACACCTCTCA

TGCAGATGTC

ACTGGCCGAA

ACGGACCAGT

GATGAGCTCA

CTCCATTATA

TGATGATATC

AATGAAGTAG

IAACCTAAATC

ACAGAGACCT

CAACCCACCA

CTAGGCGACA

AGCGATTCCC

AGATCCACAG

AGACGTACAG

CTCACACCTT

GGATCTGCTC

GAGATCCACG

ACTCTCAATG

AAAAAGGGCA

GGTGGTGCAA

GCGGGGAATG

TCTGGTACCA

GATGAGCTGT

AATCAGAAGA

ATTAAGAAGC

AGCATCATGA

GAAATCAATC

GTTCTCAAGA

TCCAGAGGAC

GCCGTCGGGT

AA.ATCCAGCC

AAAGGAGCCA

CTACAGCTCA

CATTATAAAA

ACGACTTCGA

CCTACAGTGA

GGAAGGATGA

TAGGGCCTCC

CA7LAGCCCGA

CAGGGCTCAA

GGAGAAAGGT

CCATCTCTAT

AGCTCCTGAG

TTCCTCCGCC

CAGACGCGAG

CCCAATGTGC

TCCCCGAGTG

CAATCTCCCC

TCTCTGATGT

TAATCTCCAA

AGATCAACAG

TCGCCATTCC

CCGACTTGAA

KACCCGTTGC

AGCTGCTGAA

TTGTTCCTGA

GGCTAGAGGA

ATGATCTTGC

ACTTACCTGC

AACTTAGGAG

CILAGTCGGCA

TGGCAGGCTG

ATGCTTTATG

AATCGGGCGA

AAAACTCCTC

TGAA.AAACTG

CCTAACAACA

GGGGTTCAGG

ACTCCAATCC

CCCGGACCCC

ATTAGCCTCA

TCGAA.AGTCA

TGTGAGCAAT

GAGATCCCAG

CCAAGATATT

GCTAGAATCA

GCAAAATATC

TGGACTTGGG

ACCCATCATA

CAGCCGACAA

GGAATTTCAG

CACCGGCCCT

GGATCGGAAG

CAAGTTCCAC

CAACCCCATG

CAAAGTGATT

TGGGACATCA

GTGCCCCAGG

TACATGTTTC

GCATTTGGGT

AAAGAGGCCA

GTGTTCTACA

GGGAGTGTCT

2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 183 *0 S 0 00.

0* 5

TCAACGCAA.A

TCCGTGTTGT

GAAGAATGCT

GGATTGACAA

CAACATTTAT

ATTATTGCAA

GCACCAGTCT

GGTTCAAGAA

TCTGGAGGAG

AAGA.ATTCCG

TGTAGACCGT

GCCCGGACAA

GCCGACGGCA

CCACCAGCCA

TGCCCCCGAT

ATTGGAAGGC

GACCGAGGTG

ACTAA.ACAAA

CGGTGCCGCG

CCCCGGTGCC

AATCCAAGAC

GAGGAAGCCC

GGGCCACCAG

ACCCCAGCCC

CGAAGGACCC

CTCCTCCTCT

CCAAGTGTGC

TTATATGAGC

GGAATTCAGA

GGCGATAGGC

GGTCCACATC

AATGAAAATC

TCACATTAGA

GACCTTATGT

CAGATGCAAG

CATTTACGAC

AGTGCCCAGC

AAAAGCCCCC

AGCGCGAACA

CCCCAATCTG

CCAAACCACC

CCCTCCCCCT

ACCCAACCGC

ACTTAGGGCC

CCCCCAACCC

CACAGGCAGG

GGGGGGGCCC

ACCCACCCCA

CTCCCAGACT

CGATCCGGCG

CCGAACCGCA

TCTCGAAGGG

AATGCGGTTA

ATCACCCGTC

TCGGTCAATG

CCTGGGALAGA

GGGAACTTCA

GAAAAGATGG

AGCACAGGCA

TACCCGCTGA

ATAGTAAGALA

GACGTGATCA

AATGCCCGAA

TCCGAAAGAC

CCAGGCGGCC

CATCCTCCTC

AACCGCATCC

CTTCCTCAAC

AGGCATCCGA

ALAGGAACATA

CCGACAACCA

GACACCAACC

CCCCAAAAAA

CACACGACCA

CGGCCATCAC

GGGAGCCACC

AAGGACATCA

ACCAAAAGAT

ATCTGATACC

TTTCGGATAA

CAGTGGCCTT

TCATCGACAA

GGAGAAAGAA

GCCTGGTTTT

AAATGAGCAA

TGGATATCAA

TCCAGGCAGT

TAAATGATGA

AACGACCCCC

TCCACGGACC

CCAGCACAGA

GTGGGACCCC

CCACCACCCC

ACAAGAACTC

CTCCCTAGAC

CACACCCAAC

GAGGGAGCCC

CCCGAACAGA

AGGCCCCCAG

CGGCAACCAA

CCCGCAGAA-A

CAACCCGAAC

GTATCCCACA

CAATCCACCA

GCTCGATACC

CGGGTATTAC

CAACCTGCTG

TACAGAGCAA

GAGTGAAGTC

TGCACTTGGT

GACTCTCCAT

TGAAGACCTT

TTTGCAGCCA

CCAAGGACTA

CTCACAATGA

AAGCGAGAGG

ACAGCCCTGA

CGAGGACCAA

CGGGAAAGAA

CACAACCGAA

AGATCCTCTC

AGAACCCAGA

CCAACCAATC

CCCAGCACCC

GGGCCGACAG

ACCAGAAcCCC

GGAAAGGCCA

CAGCACCCAA

GCCTCTCCAA

CACCCGACGA

CCGCAGAGGT

ACCGTTCCTA

GTGACCCTTA

CTTCCTGAGG

TACTCTGCCG

GGGATAGGGG

GCACAACTCG

AATCGATTAC

TCAGTTCCTC

TTCAALAGTTC

CAGCCAGAAG

CCAGCCAGCA

CACAAGGCCA

CCCCCAAGGC

ACCCCCAGCA

CCGCACAAGC

TCCCCGGCAA

CCCCGGTCCA

CCGCCGGCTC

AACCATCGAC

CCAGCACCGC

AGACCACCCT

CAACCCGCGC

GAGCGATCCC

GTCCCCCGGT

CACTCAACTC

3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 184 0*

CCCACCCCTA

GGTCTCAAGG

ACCGGTCAAA

AGCTACAAAG

ATAACTCTCC

ACAGTTTTGG

CAGAGTGTAG

GCCCTAGGCG

CTGAACTCTC

GAGACAATCA

ATCAATAATG

CTCGGGCTCA

CGGGACCCCA

ATCAATAAGG

AGCGGAGGAA

AGTATAGCCT

GTCTCGTACA

CAAGGGTACC

GTGTGCAGCC

TACACCAAGT

TCACAAGGGA

ACGATCATTA

GTAGTCGAGG

TACTTGCACA

AATCTGGGGA

CAGATATTGA

AAGGAGACAC

TGAACGT CT C

TCCATTGGGG

TTATGACTCG

TCAATA.ACTG

AACCAATTAG

CTTCAAGTAG

TTGCCACAGC

AAGCCATCGA

GACAAGCAGG

AGCTGATACC

AATTGCTCAG

TATCTGCGGA

TGTTAGAAAA

TAAAGGCCCG

ATCCGACGCT

ACATAGGCTC

TTATCTCGAA

AAAATGCCTT

CCTGTGCTCG

ACCTAATAGC

ATCAAGACCC

TGAACGGCGT

GAATTGACCT

ATGCAATTGC

GGAGTATGAA

CGGGAATCCC

TGCCATATTC

CAATCTCTCT

TTCCAGCCAT

CACGAGGGTA

AGATGCACTT

GAGACACAAG

TGCTCAGATA

CAATCTGAGA

GCAGGAGATG

GTCTATGAAC

ATACTATACA

GATATCTATC

GCTCGGATAC

GATAACTCAC

GTCCGAGATT

TCAAGAGTGG

TTTTGATGAG

GTACCCGATG

TACACTCGTA

CAATTGTGCA

TGACAAGATC

GACCATCCAA

CGGTCCTCCC

TAAGTTGGAG

AGGTTTATCG

AGAATCAAGA

ATGGCAGTAC

AAGATAGGGG

CAATCATTAG

GAGATTGCAG

AATGCAATGA

AGATTTGCGG

ACAGCCGGCA

GCGAGCCTGG

ATATTGGCTG

CAACTATCTT

GAAATCCTGT

CAGGCTTTGA

AGTGGAGGTG

GTCGACACAG

AAGGGGGTGA

TATACCACTG

TCATCGTGTA

AGTCCTCTGC

TCCGGGTCTT

TCAATCCTTT

CTAACATACA

GTCGGGAGCA

ATATCAT'TGG

GATGCCAAGG

AGCACTAGCA

CTCATCCAAT

TGTTAACTCT

TGGTAGGAAT

TCATAAILATT

AATACAGGAG

CCCAGALATAT

GAGTAGTCCT

TTGCACTTCA

AAACTACTAA

TTCAGGGTGT

GTGATTTAAT

CATTATTTGG

GCTATGCGCT

ATTTACTGGG

AGTCCTACTT

TTGTCCACCG

TGCCCAAGTA

CTTTCATGCC

TCCAAGAATG

TTGGGAACCG

GCAAGTGTTA

TTGCTGCCGA

GGAGGTATCC

AGAGGTTGGA

AATTGTTGGA

TAGTCTACAT

GTCCATCATG

CCAAACACCC

AGGAAGTGCA

AATGCCCAAT

ACTACTGAGA

AAGACCGGTT

GGCAGGTGCG

CCAGTCCATG

TCAGGCAATT

CCAAGACTAC

CGGCCAGAAG

CCCCAGTTTA

TGGAGGAGAC

CATCTTAGAG

CATTGTCCTC

GCTAGAGGGG

TGTTGCAACC

AGAGGGGACT

CCTCCGGGGG

GTTCATTTTA

CACAACAGGA

TCACTGCCCG

AGACGCTGTG

CGTAGGGACA

GTCATCGGAC

CCTGATTGCA

5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 185 S S

S.

S S

S.

S. S S 5

S

S 5555

S

555*55

S

S 5*

*SS*

5*55

S

S.

I. 55

S

GTGTGTCTTG

AACAAAAAGG

ACATCAAAAT

CACAAGTCTC

TATCTCCGGC

ATCATCCACA

TCCCAAGGGA

TTTGCTGGCT

CATTAGACTT

TCTAGATGTA

AATCATCGGT

AATCTCTGAC

TTGGTGTATC

GGCTGCTGAA

CAATCAGTTC

ATTCTCAAAC

ATCTATAGTC

TAATCTGAGC

AGGTGTTATC

GCAACCAGTC

AGCCCTTTGT

CAGCTTCCAG

CCCCTTATCA

TATCGCTGAC

AATGGAGACA

CGAGTGGGCA

GAGGGTTGAT

GAGAACAAGT

CCTATGTAAG

CTCTTCGTCA

TTCCCTCTGG

ATGTCACCAC

AGTAGGATAG

GTTCTGTTTG

CATCGGGCAG

ACTAACTCALA

GATGAAGTGG

AAGATTAAAT

ILACCCGCCAG

GAGCTCATGA

CTAGCTGTCT

ATGTCGCTGT

ACTATGACAT

AGCAkAAGGT

AGAALATCCGG

AGTAATGATC

CACGGGGAAG

CTCGTCA-AGC

ACGGATGATC

ILATCAAGCAA

TGCTTCCAC

CCATTGAAGG

AGGGATCCCC

TGGTATGTCA

GTCGCTCTGA

TCAAGCAACC

CCGA.ACAATA

AACGAGACCG

TCATTAACAG

TCATGTTTCT

CCATCTACAC

TCGAGCATCA

GCCTGAGGAC

TCCTTAATCC

AGAGA.ATCAA

ATGCATTGGT

CAAAGGGAAA

CCCTGTTAGA

CCCAGGGAAT

CAGAGTTGTC

GTTTGGGGGC

TCAGCAACTG

ATTCTATCAC

TAGGTGTCTG

CAGTGATAGA

AATGGGCTGT

AGGCGTGTAA

ATAACAGGAT

GCTTTAATAT

AGACCAGGCC

TCCTCTACAA

ACCGCACCCA

TCGGTAGTTA

GATAAATGCC

AGAACATCTT

GAGCTTGATC

CGCAGAGATC

GGTCAAGGAC

ACCTCAGAGA

GGATAGGGAG

ATTGGATTAT

GAACTCAACT

CTGCTCAGGG

CTTGTATTTA

GTATGGGGGA

ACAACTGAGC

TCCGGTGTTC

TATGGTGGCT

AATTCCCTAT

GAAATCCCCA

CAGGCTTTAC

CCCGACAAA

GGGTAAAATC

TCCTTCATAC

GTTGCTGCAG

TAAAGCCTGA

CTCTTGAAAC

GCATCAAGCC

ATCAAAACTT

TTCTACAAAG

ATGATTGATA

GGGTTGCTAG

CATAAAAGCC

GTGCTGACAC

TTCACTGACC

TACGACTTCA

GATCAATACT

CTACTGGAGA

CCCACTACAA

GGTCGAGGTT

ACTTACCTAG

ATGTACCGAG

CATATGACAA

TTGGGGGAGC

CAGGGATCAG

ACCGACATGC

CTCTCATCTC

CGAACAGATG

CAAGCACTCT

GGGGTCTTGT

GGGGCGTTGT

TCTTACGGGA

ACAAI-TGTCC

CACCTGAAAT

AGGGTGCAAG

ATAACCCCCA

GACCTTATGT

CCATTGCAGG

TCAGCACCAA

CACTCTTCAA

TAGTGAAATT

GAGATCTCAC

GTGCAGATGT

CCAGAACAAC

TCAGAGGTCA

ACAATGTGTC

TGGAAAAGCC

TGTTTGAAGT

ACTATCTTGA

TCAAACTCGC

GGAALAGGTGT

AATCCTGGGT

ACAGAGGTGT

ACAAGTTGCG

GCGAGAATCC

CTGTTGATCT

7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 186 9 9. 9 9 9* *9 9 9 9 S 9 9. 9 99 9 *9 GAGTCTGACA GTTGAGCTTA AAATCAAAAT TGCTTCGGGA TTCGGGCCAT TGATCACACA 9* 9 5 9*

S

9

S

99 9 9 9 99 9 9 9999 9 9*

CGGTTCAGGG

GCCAATGAAG

GGTTAGTCCC

AACATACCTA

ACCTGGTCAA

TGTGGTTTAT

GCCTATAAAG

CTGGTGCCGT

TGGGATGGTG

ATAGGGCTGC

GTGAA.ATAGA

CGCTATCTGT

ATAAGATAGT

CTACACTGTG

TAAACAATGT

CTCATATTCC

CGAGGAAGAT

AGGTTTTCCA

AGGACATCAA

AGCCCTTTCT

CCCATACTTG

TGCTAATCTC

TGACATTTGA

CCGCTATGAC

AACTGATAGA

ATGGACCTAT

A.ACCTAGCCT

TACCTCTTCA

CCTGCGGAGG

GATCTCCAAT

TACGTTTACA

GGGGTCCCCA

CACTTCTGTG

GGCATGGGAG

TAGTGAACCA

CATCAGAATT

CAACCAGATC

AGCCATCCTG

TCAGAACATC

GGAAGTTGGG

ATATCCAAAT

CCGTGAACTC

ATGCTTAAGG

GGAGAA.AGTT

GTTTTGGTTT

CCATAGGAGG

TCGTGACCTT

ACTGGTTTTG

TATTGATGCT

TGGTTTCTTC

ACAAATCCAA

TAGGTGTAAT

CTGTCCCAAT

TGGATGGTGA

ATGTTTTGGC

GCCCAAGCCG

TCGAATTACA

TGCTTGCGGA

TCAGCTGCAC

ATCACATGAT

AAGAAAAACG

TTATACCCTG

GAGTATGCTC

AAGCACCGCC

AALTGTCATCA

TGTAATCAGG

CTCAAAAAGG

GACACTAACT

ATTAACTTGG

ACAGTCAAGA

AGACACACAC

GTTGCTATAA

ATGTATTGTG

AGGTATACAG

CCTGCACTCG

CCACAACAAT

CAACACATTG

TAAGGAAGCA

TGTCAAACTC

AACCTACGAT

CTCATTTTCT

AGTGGAATGC

CTCAGAATCT

AGTCACCCGG

GTCACCCAGA

TAGGGTCCAA

AAGTTCACCT

GAGTCCCTCA

TAAAAAACGG

AGTCCAAGCT

ATTTATTTAA

GGAATTCGCT

CACGGCTTGG

GAGTTTACAT

CTGAGATGAG

CTGTATTCTT

TCAGTAALAGA

ATGTCATAGA

AGCTTCTAGG

GGAATCCAAC

GTGTATTGGC

GAGTGGATAC

GGCGAAGACT

AGTTCCAATC

ACTTCCAGGG

TACTTTTATC

TTCACATGGG

GGTGGACATA

GAAGATGGAA

CATCAGGCAT

GTGGTTCCCC

AGATAGCCCG

CGCTTACAGC

ATTTTCCAAC

TAGGAGTTAT

CATAGAAGAC

GTACTCCAAA

CCTAGGCTCC

GCACAGCTCC

GTCAGTGATT

CACTGGTAGT

GTCTCAACAT

GGGGAGGTTA

AAGAGTCAGA

TTATCAAATT

TGACTATCCC

CGAGATTCAA

GCCATGCCCC

TGGTGATTCT

TTGAACATGC

CTTTTAGGTT

ACCAAAA.ACT

TCACTCACTC

CCAATCGCAG

ACCCACTAGT

GTTATGGACT

ATAGTTACCA

CTGGAGGACC

CAAATGATTA

CCGGCCCACT

AAAGAGTCAA

GTCAGTGATA

GAATTGAGGG

CAGTGGTTTG

AAATCACAAA

TCAGTTGAGT

GTATATTACC

ATGACAGAGA

TACATGTGGA

GTAGCCATGC

8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 187 S~e a 0 oes0 ease S0.06

TGGAGCCTCT

CTTTCCTTAA

ATGA-AGGTAC

TACATCTGAC

CAGTAACGGC

AGACTCTGAT

GGCACGGAGG

ATGCTCAAGC

TTGCTGGAGT

ACCTAA.AGGA

AGTTCCTGCG

TTAPLTGATTC

TCCATGACCC

GTAGACTTTT

TAATCTCAAA

ATTTGACTAA

GTCACAGGGG

GGAACGTGAG

ACACTGATCA

ATCTCAAGAA

TAAATGAGAT

CTGTCCTGTA

ATAALAGTCCC

GTCAGAAGCT

GAGTAAGGAT

TTCACTTGCT

CCACTGCTTT

TTATCATGAG

AGGGGAGATT

TGCTGAAAAT

GAAAGGTCAT

CAGTTGGCCA

TTCAGGTGA-A

GAAATTTGGC

CAkAGGCACTT

TTACGACCCT

GAGCTTTGAC

TGAGTTCAAC

TGCTAAAATG

CGGGATTGGC

GGCACTCCAC

GGGGCCAGTC

AGCAGCAPAkA

TCCGGAGAAT

GTACTGCCTT

TTACGGATTG

TGTAAGTGAC

CAATGATCAA

GTGGACCATC

TGCTTCGTTA

TACCTGCAGC

ACTGAAATAC

TTAACTGAAG

TTCTCATTTT

GTTAGGAA.AT

GCCATATTTT

C CG CTGAC CC

GGGTTAACAC

TGCTTTATGC

GCTGCTCTCC

CCCAAGGGALA

CCATATGATG

CTGTCTTACA

ACTTACAAA.A

AAATATTTTA

ACTCTAGCTG

TTAAAAACCT

GGGTTTATAG

ATGGAAGCTT

AATTGGAGAT

CCCTCATTTT

CCTCATTGCC

ATCTTCATTA

AGCACCATTC

GTGCAAGGGG

TGAGGGATAT

ATGATGTTCT

CTCTAGATTA

TCAGAAGTTT

ACATGAATCA

GTGGAATCAT

TCCCCCTGCA

ATGAGCAGTG

CTCTTAGCCT

AAAGGGA.ATG

CCGGGTCACG

TGATAATGTA

GCCTGAAAGA

TGAGGGCATG

AGGACA.ATGG

TCTCAGGAGT

ACTCCCGAAG

GGTTCCCTCA

ACGAGACAGT

ATGAGACCAT

TCCAGTGGCT

CCC CCGACCT

AGTACCCTAT

CCTATCTATA

ACAATCAGAC

AACAGTAGAA

TGACCAAAAC

CATTTTCATA

CGGCCACCCC

GCCTAAAGTC

AATCAACGGC

TGCTGCAGAC

CGTTGATAAC

GGATAGTGAT

GGATTCAGTT

GAGGCTTGTA

TGTTGTAAGT

AAAGGAGATC

CCAAGTGATT

GATGGCCAAG

CCCCAAAGAT

CCCAGTCCAC

AGTAATTCGG

CAGTGCATTT

CAGCTTGTTT

GCATAAGAGG

TGACGCCCAT

GGGAGGTATA

CCTGGCTGCT

CATAGCCGTA

CTCAGAGGTG

GGGTTTTCTG

ACTGATGACA

AGACTTGAAG

ATTGTGTATG

TATCGTGACA

ACAATCCGGA

TGGAAATCTT

CTGACA.ATGT

TACCCGAAAG

GATGTTTTCC

GGAGCTTACC

AAGGAAACAG

GCTGAAALATC

GATGAGCACG

CTCAAAGAAA

ACAAGTACCA

CAGGACCAAG

ATCACGACTG

GCACAGAGGC

CTTGAGACCT

ATCCCGTTAT

GAAGGGTATT

TATGAGAGCG

ACAAAAAGGG

10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 TACCCAGCAC ATGGCCCTAC AACCTTAAGA AACGGGAAGC TGCTAGAGTA ACTAGAGATT 188

ESSS

S

6000 S. 05 S S 0 @0 Se S 0

S

00 U. S 0S S S

S.

ACTTTGTAAT TCTTAGGCAA AGGCTACATG ATATTGGCCA TCACCTCAAG

GCAAATGAGA

@0 00 0 Se OCee 5 0050 55005 000.0 !0

S

S

50

S

S

5565

S

S.

S.

0

S.

CAATTGTTTC

TGTCCCAATC

AAACAAGGGC

ATGACCGTTA

CTCTTGGCTT

ACAACGACCT

TGAATATGAG

ATCTCAAGAG

CACAACAACC

TTGTATGTGT

TCCATAGTCC

AGGGACTGGC

TCCTGGATCA

AAGGCTTGAT

TGTCCAATTA

GAAATGTCCT

ATATGTGGGC

TAGAATCTAT

GATCAGTCAA

AGGAAACATC

TGIAAGCTTGC

CAGTGTACTC

CTAGGCAAAG

CGACTAATTT

ACTCILAGAGC

AGCATGCACT

CCTTGCATAT

CACAATCAAT

CTTAATA-AGG

CAGGCTGTTT

AATGATTCTC

GGGGGACTCT

CCAGAGCATC

AAACCCAATG

GGCATTCCTC

TAGTGTCACA

TCGAGCCAGC

TGACTATGAA

CATTGACAAA

GAGGCTAGCT

GCGAGGCCAC

CTACGGATGG

ATCCTTGAGA

CTTCGTAAGA

ATGGGCTTAC

GGCCAATGTG

AGCGCATAGG

ATCGCAAGAT

A-ATATTGCTA

TCCCTGAACG

TCAACCATGA

ATGGCACTGT

GTCAGAAACA

GCCTCACTAA

TCATTCCTAG

ACTAGACTCC

TTAAAAGGAT

ATGGACAGGC

GGGGCAAGAG

ATGAGGAAGG

CAATTCAGAG

GAGTCATGTT

CGAGGACGGC

CTTATTCGGC

TTTTTTGTCC

GTCCCATATA

GCCCCAAGTC

GGTGATGATG

AGCCTGGAGG

TTGAGGGATC

ATCACATTTT

TTTGTCTATT

CAAAAGGAAT

GTGTATTCTG

CAACAATGGC

TCCTAAAAGT

CCCGGGATGT

TGCCCGCTCC

TCGGTGATCC

TGCCTGAAGA

ACTGGGCTAG

TCKAGAACAT

TATTCCATGA

ATATTATAGT

AGTCTATTGC

GGGGGTTAAC

CAGGGATGGT

CAGTGCAGCT

CTATTTACGG

GTCATGAGAC

CCTCGGGTTG

TTGGTTCTAC

GATCCTTGCG

ATAGCTCTTG

AGCTAAGGGT

GTAGCACTCA

ATATTATGAT

GTCAGAGACT

TAAAAGCATC

GATACAGCA

AGTCATACCC

TATTGGGGGG

AGTAACATCA

GACCCTCCAT

CGACCCTTAC

AACTGCAAGG

TGACAGTAAA

ACCTAGGGCA

AGGCATGCTG

CTCTCGAGTG

GCTATTGACA

GGCGAGAGCT

CCTTGAGGTC

ATGTCTCATC

CCAACTGGAT

CACTGATGAG

ATCTGCTGTT

GAACGAAGCC

GATCACTCCC

AGTGAAATAC

GGGCTACTTG

ATAGTTGATG

GAGAGAGGTT

ATTCTGATCT

CTCCTCACAA

ATGAATTATC

TCAATTGCTG

CAAGTAATGA

TCAGCAALATC

TTTGTCCTGA

GAAGAGGACG

GCTCATGAAA

GATACCACAA

ATAACCAGAT

GGAAGAAAGA

CTAAGAAGCC

CCTGATGTAC

TGCGAGTGTG

GATATTGACA

AGAACAGACA

AGAATAGCAA

TGGTTGTTGG

ATCTCAACTT

TCAGGTACAT

11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 CCCTTGTCCG AGTGGCGAGG TATACCACAA TCTCCAACGA CAATCTCTCA

TTTGTCATAT

189

CAGATAAGAA

TTTTAGAAAC

TTCACGTCGA

CCCGCAAGCT

CTTTAATTGA

AATTTGTTAC

CTATGATTGA

TAGGGGATGA

TCACTATCTA

GACCATCAGG

ILAGGAGTGTT

GGCATTGTGG

CAACTGTGTG

AAGAGTTAGA

GATTCGACAA

GGACCTGCCC

ATATCAAGGC

TTGTAGACCA

GATTGAGAGT

CAAAGATCGG

ATGATGTTGC

GGGGCAATCT

CTTGCTACAA

ACGGCTTGTT

AACTAAACAA

AATTAGCACC

e

GGTTGATACT

ATTGTTTCGA

AACAGATTGT

AGAGCTGAGG

CAGAGATGCA

ATGGTCCACA

CCTGGTAACA

CGATATCAAT

CTTGGGCCAG

GAAATATCAG

TAAGGTGCTT

TATTATAGAG

CAACATGGTT

AGAGTTCACA

CATCCAGGCA

ACCAATTCGA

AGAGGCTATG

TTACTCATGC

TGATCCAGGA

CAGCAACAAC

AAAATTGCTC

CGCCAATTAT

AGCTGTTGAG

CTTGGGTGAG

GTGCTTCTAT

CTATCCCTCC

AACTTTATAT

CTCGAGAALAG

TGCGTGATCC

GCAGAGCTAT

ACAAGGCTAT

CCCCA.ACTAT

AAATTTGAGA

AGTTTCATA.A

TGTGCGGCCA

ATGGGTGAGC

GTCAATGCTC

CCTATCCATG

TACACATGCT

TTTCTCTTGT

AALACACTTAT

GGTCTAAGAC

TTATCTCCAG

TCTCTGACTT

TTCATTTTCG

ATCTCAAATA

AAAGATATCA

GAAATCCATG

ATATCAACAT

GGATCGGGTT

AATAGTGGGG

GAAGTTGGCC

ACCAACAAGG

ATACCGGATC

CGATGATAGA

GTACCAACCC

ACACCCAGAG

ATCACATTTT

AGGACCATAT

CTGAGTTTCT

TCAATTGGGC

TGTTLTCATC

TAAGCCACCC

GTCCTTCACT

ATATGACCTA

GTGAAAGCGA

GTGTTCTGGC

CGGTAGAGAA

CAGGATCTTC

ATCTCCGGCG

ACGCCCTCGC

TGAGCATCA

ACACAAGCA

CTTTCCGCAG

TILATTAGGAG

CTATGTTGAT

TTTCCGCCAA

TTGTCGAACA

AATGCTTCTA

ATCTAACACG

TCATCCCAGG

ATTGATATAT

CCATAGGAGG

AGCTAAGTCC

GAATGAAATT

GCTCATAGAG

ATTTGATGTA

GTTCCTTTCT

AAAGATCTAC

TGATGCTCAA

CCTCGACCTG

CGAGGATGTA

AGATTTGTAC

ATGTGCAGTT

GTGGAACATA

AGGATCGATC

TGAGGTAAAT

GGCTTTCAGA

GCACAATCTT

A.ATCGGGTTG

ATGCCTTGAG

CACTTATAIA

TTCTAGATCT

CAGAATGGGA

GGGTTGGGTG

GTATTACATC

ATACCCAGCT

GATAATGCAC

CACCTTGTGG

ACAGCACTAT

TCAGCTCTCA

CCAAGATTAT

CATTATCATA

AGAATGAGCA

AAGAAATTCT

AACTTGCACA

TTGTTGAATG

GTACCGGACA

TGTCAACCAG

CTAACCGACC

AATCCAATTA

AAACAGATAA

GTCAGTCAGC

CCCCCACACG

CCCATTTCAG

AACTCATCTG

CCAGGGGAGG

GAGATACTTA

GGTCAA.AGGG

GTAGGTAATA

13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 190

TTGTCAAAGT

TCAATTTCAT

AGACCTTGCC

TGGCTCTGCT

GGGATTTTGT

TATACCCTAG

AGGCTAACCG

GGACTTCACC

CAATTGTGGG

CTATAGAGCA

AATTGATCCA

TCTACAGGGA

CTTACCCCGT

TCTGGGGGCA

ATCTCAAGTC

CCAAGTCAGA

TAACAGTCAA

ACTAATTGGT

GCTCTTTAAC

AGTTAGTAAT

TGACAAAGAT

CCTGGGCAAA

TCAGGGATTT

ATACAGCAAC

GCTAATGAAT

TGGACTTATA

AGACGCAGTT

GGTGCTGATC

CCATGATGTT

GTTGGCAAGA

ATTGGTAAGT

CATTCTTCTT

CGGCTATCTG

GAAACAGATT

GGAGACCAAA,

TGAACTCCGG

GGGAGGCCCG

ATCCCTACCT

ACTATAGAGA

ATAGGATCAA

ATAAGTTATG

TTCATCTCTA

CCTGAAAAGA

GGTCACATCC

AGTAGAGGTG

AATTGCGGGT

GCCTCAGGGC

TTCAAkGACA

AGCAGGCAAC

TACTCCGGGA

ATACTAGACT

ATTATGACGG

GAATGGTATA

AACCCTAATC

AAGTCACGTG

CTAGTGTGGG

AGCTAGAGGA

TACTGGTGAT

TAGGGTCTCA

CTGAATCTTA

TTAAGCAGCA

TATCCATTAA

ATATCAATCC

TGGCAATTAA

AAGATGGATT

ACCAAAGAAG

GAGAACTTAT

ACAAAAAGTT

TACACCAGAA

GGGGTTTGAA

AGTTAGTCGG

CTGCCCTAGG

TTTCTATTCC

GGTAGGCAGT

GTTTATCCAT

ATTGGCAGCC

TAAGCTTATG

TTATAGAGAA

TTTGGTTATG

GATAATTGAA

GCAACTAAGC

TACTCTGAAA

CGGACCTAAG

GCTTAATTCT

TCAACAAGGG

ATCTAGGATC

GATAAATAAG

TATCTTCGTT

ACGTGAGTGG

ATACAGTGCC

TGGTTAGGCA

C!AGCTTTGTC

GTAGATTGCT

TCAGATATAG

ATCTTATCGA

CCTTTCAGCG

GTGAACCTTG

ACAGATCTA

TCATCTGTGA

TGCATACALAG

AAACTTACAC

CTGTGCAAAG

ATACTCATCC

ATGTTCCACG

ACCCGCAAAT

TTTATCCAGA

AAGAATCTAT

GTTTTTAAGG

CTGATTAAGG

TTATTTGCAA

TGGT

14820 14880 14940 15000 15060 15120 15180 15240 15300 15360 15420 15480 15540 15600 15660 15720 15780 15840 15894 TATATTAAAG AAAACTTTGA AAATACGAAG INFORM4ATION FOR SEQ ID NO:12: SEQUENCE CHARACTERISTICS: LENGTH: 2183 amino acids TYPE: amino acid

STR.ANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: 191 Met Asp Ser Leu Ser Val Asn Gin Ile Leu Tyr Pro Giu Val His Leu 1 5 Asp Arg Ile Asn Aia Ile Gly Arg Ile 145 Trp Ser Pro Leu Phe 225 Thr Ser Vai Lys Vai His Giu Aen Asp 130 Lys Phe Val Vai Vai 210 Glu Glu Pro Pro His Giu S er Asp Ser 115 Thr Glu Giu Ile Phe 195 Ala Leu Thr Ile His Arg Val His Lys 100 Leu Asn Lys Pro Lys 180 Phe Ile Val Al a Val Ala Leu Giy Ile Giu Tyr Ser Val Phe 165 Ser Thr Ile Leu Met 245 Thr Tyr Lye Asn 70 Pro Ser Ser Arg Ile 150 Leu Gin Gly Ser Met 230 Thr Aen Ser Asn 55 Val Tyr Thr Lye Leu 135 Asn Phe Thr Ser Lye 215 Tyr Ile Lys Leu 40 Giy Ile Pro Arg Val1 120 Gly Leu Trp His Ser 200 Giu Cys Asp Ile 25 Giu Phe Lye Asn Lye 105 Ser Leu Gly Phe Thr 185 Val Ser Asp Ala Val Asp Ser Ser Cys 90 Ile Asp Gly Val Thr 170 Cys Glu Gin Val Arg 250 Al a Pro Aen Lye 75 Asn Arg Lye Ser Tyr 155 Val His Leu His Ile 235 Tyr Ile Thr Gin Leu Gin Glu Val Glu 140 Met Lys Arg Leu Val 220 Glu Thr Leu Leu Met Arg Asp Leu Phe 125 Leu His Thr Arg.

Ile 205 Tyr Gly Glu Git Cys Ile Ser Leu Leu 110 Gin Arg Ser Giu Arg 190 Ser ryr Arg Leu Tyr Gin Ile Tyr Phe Lye Cys Glu Ser Met 175 His Arg Leu Leu Leu 255 Al a Asn Asn Pro Asn Lys Leu Asp Gin 160 Arg Thr Asp Thr Met 240 Gly Arg Val Arg Tyr Met Trp Lye Leu Ile Asp Gly Phe Phe Pro Ala Leu 260 7 f; C; 192 Gly Ala Leu 305 Phe Ile Phe Asn Leu 385 Arg Ala His Gly Lys 465 Pro Arg Val Asn Leu Asn Tyr 290 Asn Ser Phe Arg Val 370 Met Asp Ala Glu Cys 450 Asp Lys Leu Ile Leu 530 Phe Pro 275 Leu His Asp Ile Ser 355 Arg Lys Arg Asp Gin 435 Phe Lys Giu Val Met 515 Ser Ala Thr Gin Cys Giu Thr 340 Phe Lys Gly His Thr 420 Cys Met Ala Phe Asp 500 Tyr Tyr Lys Tyr Leu Phe Gly 325 Asp Gly Tyr His Gly 405 Ile Val Pro Leu Leu 485 Val Val Ser Met Gin Arg Thr 310 Thr Asp His Met Ala 390 Gly Arg Asp Leu Ala 470 Arg Phe Val Leu Thr Ile Asp 295 Glu Tyr Ile Pro Asn 375 Ile Ser Asn Asn Ser 455 Ala Tyr Leu Ser Lys 535 Tyr Val 280 Ile Ile His His Arg 360 Gin Phe Trp Al a Trp 440 Leu Leu Asp Asn Gly 520 Glu Lys Al a Thr His Giu Leu 345 Leu Pro Cys Pro Gin 425 Lys Asp Gin Pro Asp 505 Ala Lys Met Met Val Asp Leu 330 Thr Glu Lys Gly Pro 410 Ala S er S er Arg Pro 490 Ser Tyr Giu Arg Leu Glu Val1 315 Thr Gly Ala Val1 Ile 395 Leu Ser Phe Asp Glu 475 Lys Ser Leu Ile Al a Giu Leu 300 Leu Giu Giu Val Ile 380 Ile Thr Gly Ala Leu 460 Trp Gly Phe His Lys 540 Cys Pro Leu 285 Arg Gly Asp Gin Ala Leu Ile Phe 350 Thr Ala 365 Vai Tyr Ile Asn Leu Pro Glu Gly 430 Gly Val 445 Thr Met Asp Ser Thr Gly Asp Pro 510 Asp Pro 525 Glu Thr Gln Val Ser Leu Ala Phe Asn,; Gly 320 Asp Tyr 335 Ser Phe Ala Glu Giu Thr Gly Tyr 400 Leu His 415 Leu Thr Lys Phe Tyr Leu Val Tyr 480 Ser Arg 495 Tyr Asp Glu Phe Gly Arg Ile Ala 193 545 550 555 560 GiU Asn Leu Ile Ser Asn Gly Ile Gly Lys Tyr Phe Lys Asp Asn Gly 565 570 575 Met Ala Lys Asp Glu His Asp Leu Thr Lys Ala Leu His Thr Leu Ala 580 585 590 Val Ser Gly Val Pro Lys Asp Leu Lys Glu Ser His Arg Gly Gly Pro 595 600 605 Val Leu Lys Thr Tyr Ser Arg Ser Pro Val His Thr Ser Thr Arg Asn 610 615 620 Val Arg Ala Ala Lys Gly Phe Ile Gly Phe Pro Gln Val Ile Arg Gin 625 630 635 640 Asp Gin Asp Thr Asp His Pro Giu Asn Met Giu Ala Tyr Giu Thr Vai 645 650 655 Ser Ala Phe Ile Thr Thr Asp Leu Lys Lys Tyr CyS Leu Asn Trp Arg 660 665 670 Tyr Giu Thr Ile Ser Leu Phe Ala Gin Arg Leu Asn Giu Ile Tyr Gly 675 680 685 Leu Pro Ser Phe Phe Gin Trp Leu His Lys Arg Leu Glu Thr Ser Val 690 695 700 Leu Tyr Val Ser Asp Pro His Cys Pro Pro Asp Leu Asp Ala His Ile 71 71 720 Pro Leu Tyr Lys Val Pro Asn Asp Gin Ile Phe Ile Lys Tyr Pro Met 725 730 735 Gly Gly Ile Giu Gly Tyr Cys Gin Lys Leu Trp Thr Ile Ser Thr Ile 740 745 750 Pro Tyr Leu Tyr Leu Ala Ala Tyr Giu Ser Gly Val Arg Ile Ala Ser 755 760 765 Leu Val Gin Gly Asp Asn Gin Thr Ile Ala Val Thr Lys Arg Val Pro 770 775 780 Ser Thr Trp Pro Tyr Asn Leu Lys Lys Arg Giu Ala Ala Arg Val Thr 785 790 795 800 Arg Asp Tyr Phe Vai Ile Leu Arg Gin Arg Leu His Asp Ile Gly His 805 810 815 His Leu Lys Ala Asn Giu Thr Ile Val Ser Ser His Phe Phe Vai Tyr 820 825 830 194 Ser Lys Gly Ile Tyr Tyr Asp Gly Leu Leu Vai Ser Gin Ser Leu Lys 835 845 Ser Ile Ala 850 Arg Ala Ala 865 Arg Giy Tyr Ile Gin Gin Thr Arg Asp 915 Arg Met Aia 930 Met Ser Arg 945 Ile Aia Asp Thr Leu His Asp Trp, Ala 995 Ile Thr Arg 1010 Ser Pro Asn 1025 Giu Asp Giu Pro Arg Ala Giu Ser Ile 1075 Arg Cys Val Phe Trp Ser Giu Thr Ile Vai Asp Giu Thr 855 860 Cys Ser Asn Ile Ala Thr Thr Met Ala Lys Ser Ile Giu 870 875 880 Asp Arg Tyr Leu Ala Tyr Ser Leu Asn Val Leu Lys Vai 885 890 895 Ile Leu Ile Ser Leu Gly Phe Thr Ile Asn Ser Thr Met 900 905 910 Val Vai Ile Pro Leu Leu Thr Asn Asn Asp Leu Leu Ile 920 925 Leu Leu Pro Ala Pro Ile Gly Gly Met Asn Tyr Leu Asn 935 940 Leu Phe Vai Arg Asn Ile Gly Asp Pro Vai Thr Ser Ser 950 955 960 Leu Lys Arg Met Ile Leu Ala Ser Leu Met Pro Giu Giu 965 970 975 Gin Val Met Thr Gin Gin Pro Gly Asp Ser Ser Phe Leu 980 985 990 Ser Asp Pro Tyr Ser Ala Asn Leu Val Cys Val Gin Ser 1000 1005 Leu Leu Lys Asn Ile Thr Aia Arg Phe Val Leu Ile His 1015 1020 Pro Met Leu Lys Gly Leu Phe His Asp Asp Ser Lys Giu 1030 1035 1040 Gly Leu Ala Ala Phe Leu Met Asp Arg His Ile Ile Vai 1045 1050 1055 Ala His Giu Ile Leu Asp His Ser Val Thr Gly Ala Arg 1060 1065 1070 Ala Giy Met Leu Asp Thr Thr Lye Gly Leu Ile Arg Ala 1080 1085 Ser Met Arg Lys Gly Gly Leu Thr Ser Arg Val Ile Thr Arg Leu Ser .L U 1-1 u 1095 1100 195 Asn Tyr Asp Tyr Glu Gin Phe Arg Ala Gly Met Val Leu Leu Thr Gly 1105 1110 1115 1120 Arg Lys Arg Asn Val Leu Ile Asp Lys Giu Ser Cys Ser Val Gin Leu 1125 1130 1135 Ala Arg Ala Leu Arg Ser His Met Trp, Ala Arg Leu Ala Arg Gly Arg 1140 1145 1150 Pro Ile Tyr Gly Leu Glu Vai Pro Asp Vai Leu Giu Ser Met Arg Gly 1155 1160 1165 His Leu Ile Arg Arg His Giu Thr Cys Val Ile Cys Glu Cys Gly Ser 1170 1175 1180 Val Asn Tyr Gly Trp Phe Phe Val Pro Ser Gly Cys Gin Leu Asp Asp 1185 1190 1195 1200 Ile Asp Lys Glu Thr Ser Ser Leu Arg Val Pro Tyr Ile Gly Ser Thr 1205 1210 1215 Thr Asp Giu Arg Thr Asp Met Lys Leu Ala Phe Val Arg Ala Pro Ser 1220 1225 1230 Arg Ser Leu Arg Ser Ala Val Arg Ile Ala Thr Val Tyr Ser Trp Ala 1235 1240 1245 *Tyr Gly Asp Asp Asp Ser Ser Trp Asn Giu Ala Trp Leu Leu Ala Arg 1250 1255 1260 Gin Arg Ala Asn Val Ser Leu Giu Giu Leu Arg Val Ile Thr Pro Ile 1265 1270 1275 1280 Ser Thr Ser Thr Asn Leu Ala His Arg Leu Arg Asp Arg Ser Thr Gin 1285 1290 1295 *Val Lys Tyr Ser Gly Thr Ser Leu Val Arg Val Ala Arg Tyr Thr Thr 1300 1305 1310 Ile Ser Asn Asp Asn Leu Ser Phe Val Ile Ser Asp Lys Lys Val Asp 1315 1320 1325 Thr Asn Phe Ile Tyr Gin Gin Gly Met Leu Leu Gly Leu Gly Val Leu *.*1330 1335 1340 *Glu Thr Leu Phe Arg Leu Giu Lys Asp Thr Gly Ser Ser Asn Thr Val 1345 1350 1355 1360 Leu His Leu His Val Glu Thr Asp Cys Cys Val Ile Pro Met Ile Asp 1365 1370 1375 His Pro Arg Ile Pro Ser Ser Arg Lys Leu Glu Leu Arg Ala Giu Leu 196 1380 1385 1390 Cys Thr Asn Pro Leu Ile Tyr Asp Asn Ala Pro Leu Ile Asp Arg Asp 1395 1400 1405 Ala Thr Arg Leu Tyr Thr Gin Ser His Arg Arg His Leu Val. Giu Phe 1410 1415 1420 Val Thr Trp Ser Thr Pro Gin Leu Tyr His Ile Leu Ala Lys Ser Thr 1425 1430 1435 1440 Ala Leu Ser Met Ile Asp Leu Val Thr Lys Phe Glu Lys Asp His Met 1445 1450 1455 Asn Glu Ile Ser Ala Leu Ile Gly Asp Asp Asp Ile Asn Ser Phe Ile 1460 1465 1470 Thr Glu Phe Leu Leu Ile Glu Pro Arg Leu Phe Thr Ile Tyr Leu Gly 1475 1480 1485 Gin Cys Ala Ala Ile Asn Trp Ala Phe Asp Val His Tyr His Arg Pro 1490 1495 1500 Ser Gly Lys Tyr Gin Met Gly Giu Leu Leu Ser Ser Phe Leu Ser Arg 1505 1510 1515 1520 Met Ser Lys Gly Val Phe Lys Val Leu Val Asn Ala Leu Ser His Pro *1525 1530 1535 Lys Ile Tyr Lys Lys Phe Trp His Cys Gly Ile Ile Glu Pro Ile His 1540 1545 1550 .Gly Pro Ser Leu Asp Ala Gin Asn Leu His Thr Thr Val Cys Asn Met 1555 1560 1565 ***Val Tyr Thr Cys Tyr Met Thr Tyr Leu Asp Leu Leu Leu Asn Giu Giu 1570 1575 1580 Leu Glu Giu Phe Thr Phe Leu Leu Cys Glu Ser Asp Giu Asp Val Val **1585 1590 1595 1600 Pro Asp Arg Phe Asp Asn Ile Gin Ala Lys His Leu Cys Val Leu Ala 1605 1610 1615 Asp Leu Tyr Cys Gin Pro Gly Thr Cys Pro Pro Ile Arg Gly Leu Arg 1620 1625 1630 Pro Val Giu Lys Cys Ala Val Leu Thr Asp His Ile Lys Ala Glu Ala 1635 1640 1645 Met Leu Ser Pro Ala Gly Ser Ser Trp Asn Ile Asn Pro Ile Ile Val 1650 1655 1660 197 Asp His Tyr Ser Cys Ser Leu Thr Tyr Leu Arg Arg Gly Ser Ile Lys 1665 1670 1675 1680 Gin Ile Arg Leu Arg Val Asp Pro Gly Phe Ile Phe Asp Ala Leu Ala 1685 1690 1695 Giu Val Asn Val Ser Gin Pro Lys Ile Gly Ser Asn Asn Ile Ser Asn 1700 1705 1710 Met Ser Ile Lys Ala Phe Arg Pro Pro His Asp Asp Val Ala Lys Leu 1715 1720 1725 Leu Lys Asp Ile Asn Thr Ser Lys His Asn Leu Pro Ile Ser Gly Gly 1730 1735 1740 Asn Leu Ala Asn Tyr Giu Ile His Ala Phe Arg Arg Ile Gly Leu Asn 1745 1750 1755 1760 Ser Ser Ala Cys Tyr Lys Ala Val Giu Ile Ser Thr Leu Ile Arg Arg 1765 1770 1775 Cys Leu Glu Pro Gly Giu Asp Gly Leu Phe Leu Gly Giu Gly Ser Gly 1780 1785 1790 *Ser Met Leu Ile Thr Tyr Lys Gu Ile Leu Lys Leu Aen Lys Cys Phe 1795 1800 1805 *Tyr Aen Ser Gly Val Ser Ala Aen Ser Arg Ser Gly Gin Arg Giu Leu *1810 1815 1820 *.*Ala Pro Tyr Pro Ser Giu Val Gly Leu Val Giu His Arg Met Gly Val 1825 1830 1835 1840 Asn Ile Val Lye Val Leu Phe Asn Gly Arg Pro Giu Val Thr Trp 1845 1850 1855 Val Gly Ser Val Asp Cys Phe Aen Phe Ile Val Ser Asn Ile Pro Thr 1860 1865 1870 0**0Ser Ser Val Gly Phe Ile His Ser Asp Ile Giu Thr Leu Pro Asp Lys 1875 1880 1885 **Asp Thr Ile Glu Lys Leu Giu Giu Leu Ala Ala Ile Leu Ser Met Ala **1890 1895 1900 Leu Leu Leu Gly Lye Ile Gly Ser Ile Leu Val Ile Lye Leu Met Pro 1905 1910 1915 1920 Phe Ser Gly Asp Phe Vai Gin Gly Phe Ile Ser Tyr Val Gly Ser His 1925 1930 1935 198 Tyr Arg Giu Val Asn Leu Val Tyr Pro Arg Tyr Ser Asn Phe Ile Ser 1940 1945 1950 Thr Giu Ser Tyr Leu Val Met Thr Asp Leu Lys Ala Asn Arg Leu Met 1955 1960 1965 Asn Pro Glu Lys Ile Lys Gin Gin Ile Ile Giu Ser Ser Val Arg Thr 1970 1975 1980 Ser Pro Gly Leu Ile Gly His Ile Leu Ser Ile Lys Gin Leu Ser Cys 1985 1990 1995 2000 Ile Gin Ala Ile Val Giy Asp Ala Vai Ser Arg Gly Asp Ile Asn Pro 2005 2010 2015 Thr Leu Lys Lys Leu Thr Pro Ile Giu Gin Val Leu Ile Asn Cys Gly 2020 2025 2030 Leu Ala Ile Asn Gly Pro Lys Leu Cys Lys Giu Leu Ile His His Asp 2035 2040 2045 Val Ala Ser Gly Gin Asp Gly Leu Leu Asn Ser Ile Leu Ile Leu Tyr 2050 2055 2060 Arg Giu Leu Ala Arg Phe Lys Asp Asn Gin Arg Ser Gin Gin Gly Met 2065 2070 2075 2080 Phe His Ala Tyr Pro Val Leu Val Ser Ser Arg Gin Arg Giu Leu Ile 2085 2090 2095 ***Ser Arg Ile Thr Arg Lys Phe Trp Gly His Ile Leu Leu Tyr Ser Gly 2100 2105 2110 Agn Lys Lys Leu Ile Aen Lys Phe Ile Gin Aen Leu Lye Ser Gly Tyr 2115 2120 2125 *Leu Ile Leu Asp Leu His Gin Aen Ile Phe Val Lys Asn Leu Ser Lys 2130 2135 2140 Ser Giu Lys Gin Ile Ile Met Thr Gly Gly Leu Lye Arg Giu Trp Val 2145 2150 2155 2160 Phe Lys Val Thr Val Lye Glu Thr Lye Glu Trp Tyr Lys Leu Val Gly 2165 2170 2175 *Tyr Ser Ala Leu Ile Lye Asp 2180 INFORMATION FOR SEQ ID NO:13: SEQUENCE CHARACTERISTICS: LENGTH: 15894 base pairs 199 TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: ACCAAACAAA GTTGGGTAAG GATAGTTCAA TCAATGATCA TTTTCTAGTG

CACTTAGGAT

U S* U U

U

9. S.

U U flUe S U U.

U*

5 9

U.

TCAAGATCCT

TAAGGAGCTT

GTGGAGCCAT

TTACCACTCG

GCGGGCCCAA

GTCAATTGAT

TCCAGAGTGA

ATGAGGCGGA

GATGGTTCGA

TGATTCTGGG

CAGACACGGC

TAGTTGGTGA

AGGACCTCTC

GAAACAAACC

GATTAGCCAG

GACTGCATGA

AAATGGGGGA

GTGCAGGATC

ACTCCATGGG

GGCAAGAGAT

ATTATCAGGG

AGCATTGTTC

CAGAGGAATC

ATCCAGACTT

ACTAACAGGG

TCAGAGGATC

CCAGTCACAA

CCAATACTTT

GAACAAGGz.A

TACCATCCTA

AGCTGATTCG

ATTTAGATTG

CTTACGCCGA

CAGGATTGCT

TTTTATCCTG

ATTTGCTGGT

AACTGCACCC

ATACCCTCTG

AGGTTTGAAC

GGTAAGGAGG

ACAAGAGCAG

AAAAGAAACA

AAACACATTA

CTGGACCGGT

GCACTAATAG

ACCGATGACC

TCTGGCCTTA

TCACATGATG

ATCTCAGATA

GCTCAAATTT

GAGCTAAGAA

GAGAGAAAAT

TTCATGGTCG

GAAATGATAT

ACTATTAAGT

GAGTTATCCA

TACATGGTAA.

CTCTGGAGCT

TTTGGCCGA.T

TCAGCTGGAA

GATTAAGGAT

AGGACAAACC

TTATAGTACC

TGGTCAGGTT

GTATATTATC

CTGACGTTAG

CCTTCGCATC

ATCCAATTAG

TTGAAGTGCA

GGGTCTTGCT

GGTGGATAA-A

GGTTGGATGT

CTCTAATCCT

GTGACATTGA

TTGGGATAGA

CACTTGAGTC

TCCTGGAGA

ATGCCATGGG

CTTACTTTGA

AGGTCAGTTC

ATCCGAGATG

ACCCATTACA

A.ATCCCTGGA

AATTGGAAAC

CTTATTTGTG

CATILAGGCTG

AAGAGGTACC

TAGTGATCAA

AGACCCTGAG

CGCAA.AGGCG

GTACACCCAA

GGTGAGGAAC

GGATATCAAG

TACATATATC

ILACTATGTAT

CTTGATGAAC

CTCAATTCAG

AGTAGGAGTG

TCCAGCATAT

CACATTGGCA

GCCACACTTT

TCAGGATCCG

GATTCCTCAA

CCGGATGTGA

GAGTCTCCAG

TTAGAGGTTG

AACATGGAGG

TCCAGGTTCG

GGATTCAACA

GTTACGGCCC

CAAAGAAGGG

AGGATTGCCG

AGA.ACACCCG

GTAGAGGCAG

CCTGCTCTTG

CTTTACCAGC

AACAAGTTCA

GAACTTGAAA

TTTAGATTAG

TCTGAACTCG

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260

S

U

9SSUS~

U

U.

U

U.

egg.

S

.5,5 200

GTATCACTGC

AGATCAGTAG

GTGAGAATGA

GAGAAGCCAG

CCCATCTTCC

CGCAGGACAG

CGGAAGAACA

ACTAGGTGCG

APLAACTTAGG

GAGCCGATGG

CTCAAGGCCG

ATATCAGACA

GGTCTCAGCA

CGCGGTCAGG

AATCTCCAGG

GCGGTTAAGG

AGCACCCTCT

GATACCGAGG

GCTTCTGATG

AGAGGCAACA

GGTAGGGCCA

TTTGGAACGG

CCCTCGGAAC

GCCGCACTGA

AATAATGAAG

AAAACAGCCT

CGAGGATGCA

AGCGGTTGGA

GCTACCGAGA

GGAGAGCTAC

AACCGGCACA

TCGAAGGTCA

AGGCTCAGAC

AGAGGCCGAG

AACCAGGTCC

CAGAAGAGCA

AGCCCATCGG

ACCCAGGACA

AACCATGCCT

GACCTGGAGA

CATCAAGCAC

GAATCCAAGA

CAGGAGGAGA

GATATGCTAT

TTGAAACTGC

ACTTTCCGAA

GCACTTCCGG

AGATCGCGTC

CATCAGGGCC

TACAGGAGTG

AAGGGGGAGA

TGGCCAAAAT

AGGCTTGTTT

CCCAGACAAG

TTGGGGGGCA

AGAGAAACCG

CCCCTAGACA

GCTGACGCCC

ACGGACACCC

GGCCAGAACA

ACACAGCCGC

GGCACGCCAT

CTCACTGGCC

GGAGCGAGCC

CTCAGCAATT

GAGCGATGAC

TGGGTTACAG

TGCTGACTCT

CAATGAATCT

CACTGACCGG

AGAAGGAGGG

GCTTGGGAAA

GACACCCATT

TTTATTGACA

AGGTGCACCT

GACACCCGAA

CTATTATGAT

ACACGAGGAT

CAGAGATTGC

CCCAAGTATC

AGGAAGATAG

GGCCCAGCAG

TTGACACTGC

TGCTTAGGCT

CTATAGTGTA

ACATCCGCCT

CAGCCCATCA

GTCAAAAACG

ATCGAGGAAG

ACCTGCAGGG

GGATCAACTG

GACGCTGAALA

TGTTATTATG

ATCATGGTTC

GAAAACAGCG

GGATCTGCTC

GAGATCCACG

ACTCTCAATG

AAAAAGGGCA

GGTGGTGCAA

GCGGGGAATG

TCTGGTACCA

GATGAGCTGT

AATCAGAAGA

AATGCATACT

ATTTCTACAC

GAGGGTCAAA

AGCAAGTGAT

ATCGGAGTCC

GCAAGCCATG

CAATGACAGA

ACCCTCCATC

ACCATCCACT

GACTGGAATG

CTATGGCAGC

AAGAGAAGGC

AAGGCGGTGC

CTTTGGGAAT

TTTATGATCA

AATCAGGCCT

ATGTGGATAT

CCATCTCTAT

AGCTCCTGAG

TTCCTCCGCC

CAGACGCGAG

CCCAATGTGC

TCCCCGAGTG

CAATCTCCCC

TCTCTGATGT

T&ATCTCCAA

ACTGAGGACA

GGTGATCAAA

CAGAGTCGAG

GCGAGAGCTG

AGCCALAGATC

GCAGGAATCT

AATCTTCTAG

ATTGTTATALA

CCCACGATTG

CATCCGGGCT

ATGGTCAGAA

AGGCAGTTCG

ACCTCGCATC

CCCCCCAAGA

CAGCGGTGAA

TGATGGTGAT

TGGCOAACCT

GGGGTTCAGG

ACTCCAATCC

TCCGGACCCC

ATTAGCCTCA

TCGAAAGTCA

TGTGAGCAAT

GAGATCCCAG

CCAAGATATT

GCTAGAATCA

1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 201 I.

CTGCTGTTAT

AGCATATCCA

AAGGATCCCA

GGCAGAGATT

CTCCAAGGAA

CTAAAGCCGA

GCATCACGCA

CGTTACCTGA

CAGATGCTGA

CCAGTCGACC

GCCTCCCAAG

AAGGGTTGAT

TCAGAGTCAT

TGCTGGGGGT

CCCTGCCCTT

CTGAGCTTGA

ACAACACCCC

TCAACGCAAA

TCCGTGTTGT

GAAGAATGCT

GGATTGACA

CAACATTTAT

ATTATTGCAA

GCACCAGTCT

GGTTCAAGAA

TGAAGGGAGA

CCCTGGAAGG

ACGACCCCAC

CAGGCCGAGC

TGACAILATGG

TCGGGAAAAA

GTGTAATCCG

TGACTCTCCT

TGAAGATAAT

CAACTAGTAC

TTCCACAATG

CGCTCCGATA

AGATCCTGGT

TGTTGAGGAC

AGGTGTTGGC

CATAGTTGTT

ACTAACTCTC

CCAAGTGTGC

TTATATGAGC

GGAATTCAGA

GGCGATAGGC

GGTCCACATC

AATGAAAATC

TCACATTAGA

GACCTTATGT

AGTTGAGTCA

ACACCTCTCA

TGCAGATGTC

ACTGGCCGAA

ACGGACCAGT

GATGAGCTCA

CTCCATTATA

TGATGATATC

AATGAAGTAG

AACCTAAATC

ACAGAGATCT

CAACCCACCA

CTAGGCGACA

AGCGATCCCC

AAATCCACAG

AGACGTACAG

CTCACACCTT

AGTGCGGTTA

ATCACCCGTC

TCGGTCAATG

CCTGGGAAGA

GGGAACTTCA

GAAA-AGATGG

AGCACAGGCA

TACCCGCTGA

ATTAAGAAGC AGATCAACAG AGCATCATGA TCGCCATTCC GAAATCAATC CCGACTTGAA GTTCTCAAGA AACCCGTTGC TCCAGAGGAC AGCTGCTGAA GCCGTCGGGT TTGTTCCTGA AAATCCAGCC GGCTAGAGGA AAAGGAGCCA ATGATCTTGC CTACAGCTCA ACTTACCTGC CATTATAAAA AACTTAGGAG ACGACTTCGA CAAGTCGGCA CCTACAGTGA TGGCAGGCTG

GGAAGGATGA

TAGGGCCTCC

CAAAGCCCGA

CAGGGCTCAA

GGAGAAAGGT

ATCTGATACC

TTTCGGATAA

CAGTGGCCTT

TCATCGACAA

GGAGAAAGIA

GCCTGGTTTT

AAATGAGCAA

TAGATATCIA

ATGCTTTATG

AATCGGGCGA

AA.AACTCCTC

TGAAAAACTG

CCTAACAACA

GCTCGATACC

CGGGTATTAC

CAACCTGCTG

TACAGAGCAA

GAGTGAAGTC

TGCACTTGGT

GACTCTCCAT

TGAAGACCTT

GCAAAATATC

TGGACTTGGG

ACCCATCATA

CAGCCGACAA~

GGALATTTCAG

CACCGGCCCT

GGATCGGAAG

CAAGTTCCAC

CAACCCCATG

CAAAGTGATT

TGGGACATCA

GTGCCCCAGG

TACATGTTTC

GCATTTGGGT

AAAGAGGCCA

GTGTTCTACA

GGGAGTGTCT

CCGCAGAGGT

ACCGTTCCTA

GTGACCCTTA

CTTCCTGAGG

TACTCTGCCG

GGGATAGGGG

GCACAACTCG

AATCGATTAC

2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 TCTGGAGGAG CAGATGCAAG ATAGTAAGAA TCCAGGCACT TTTGCAGCCA TCAGTTCCTC 202 C*

AAGAATTCCG

TGTAGACCGT

GCCCGGACA.A

GCCGACGGCA

CCACCAGCCA

TGCCCCCGAT

ATTGGAAGGC

GACCGAGGTG

ACTAAACAAA

CGGCGCCGCG

CCCCGGTGCC

AATCCAAGAC

GAGGAAGCCC

GGGCCACCAG

ACCCCAGCCC

CGAAGGACCC

CTCCTCCCCT

CCCACCCCTA

GGTCTCAAGG

ACCGGTCAAA

AGCTACAALAG

ATAACTCTCC

ACAGTTTTGG

CAGAGTGTAG

GCCCTAGGCG

CTGAACTCTC

CATTTACGAC

AGTGCCCAGC

AAAAGCCCCC

AGCGCGAACA

CCCCAATCTG

CCAAACCACC

CCCTCCCCCT

ACCCAACCGC

ACTTAGGGCC

CCCCCAACCC

CACAGGCAGG

GGGGGGGCcC

ACCCACCCCA

CTCCCAGACT

CGATCCGGCG

CCGAACCGCA

TCTCGAAGGG

APLGGAGACAC

TGAACGTCTC

TCCATTGGGG

TTATGACTCG

TCAATAACTG

ALACCAATTAG

CTTCAAGTAG

TTGCCACAGC

AAGCCATCGA

GACGTGATCA

AATGCCCGAA

TCCGAAAGAC

CCAGGCGGCC

CATCCTCCTC

AACCGCATCC

CTTCCTCAAC

AGGCATCCGA

AAGGAACATA

CCGACAACCA

GACACCAACC

CCCCAAAAAA

CACACGACCA

CGGCCATCAC

GGGAGCCACC

AAGGACATCA

ACCAAAAGAT

CGGGAATCCC

TGCCATATTC

CAATCTCTCT

TTCCAGCCAT

CACGAGGGTA

AGATGCACTT

GAGACACAAG

TGCTCAGATA

CAATCTGAGA

TAAATGATGA

AACGACCCCC

TCCACGGACC

CCAGCACAGA

GTGGGACCCC

CCACCACCCC

ACAAGAACTC

CTCCCTAGAC

CACACCCAAC

GAGGGAGCCC

CCCGAACAGA

AGGCCCCCAG

CGGCAACCAA

CCCGCAGAAA

CAACCCGAAC

GTATCCCACA

CAATCCACCA

AGAATCAAGA

ATGGCAGTAC

AAGATAGGGG

CAATCATTAG

GAGATTGCAG

AATGCAATGA

CCAAGGACTA

CTCACAATGA

AAGCGAGAGG

ACAGCCCTGA

CGAGGACCAA

CGGGAAAGAA

CACAACCGAA

AGATCCTCTC

AGAACCCAGA

CCAACCAATC

CCCAGCACCC

GGGCCGACAG

ACCAGAACCC

GGAAAGGCCA

CAGCACCCAA

GCCTCTCCAA

CACCCGACGA

CTCATCCAAT

TGTTILACTCT

TGGTAGGAAT

TCATAAAATT

AATACAGGAG

CCCAGAATAT

TTCAAAGTTC

CAGCCAGAAG

CCAGCCAGCA

TACAAGGCCA

CCCCCA.AGGC

ACCCCCAGCA

CCGCACAAGC

TCCCCGGCAA

CCCCGGCCCA

CCGCCGGCTC

AACCATCGAC

CCAGCACCGC

AGACCACCCT

CA.ACCCGCGC

GAGCGATCCC

GTCCCCCGGT

CACTCAACTC

GTCCATCATG

CCAAACACCC

AGGAAGTGCA

AATGCCCAAT

ACTACTGAGA

AAGACCGGTT

GGCAGdTGCG

CCAGTCCATG

TCAGGCAATT

4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 AGATTTGCGG GAGTAGTCCT ACAGCCGGCA TTGCACTTCA GCGAGCCTGG AAACTACTAA 203 GAGGCAATCA GACAAGCAGG GCAGGAGATG ATATTGGCTG TTCAGGGTGT CCAAGACTAC

ATCAATAATG

CTCGGGCTCA

CGGGACCCCA

ATCAATAAGG

AGCAGAGGAA

AGTATAGCCT

GTCTCGTACA

CAAGGGTACC

GTGTGCAGCC

TCCACCAAGT

TCACALAGGGA

ACGATCATTA

GTAGTCGAGG

TACTTGCACA

AATCTGGGGA

CAGATATTGA

GTGTGTCTTG

AACAAAAAGG

ACATCAAAAT

CACAAGTCTC

TATCTCCGGC

ATCATCCACA

TCCCAAGGGA

TTTGCTGGCT

CATTAGACTT

AGCTGATACC

AATTGCTCAG

TATCTGCGGA

TGTTAGAAIA

TAA.AGGCCCG

ATCCGACGCT

ACATAGGCTC

TTATCTCGAA

AAAATGCCTT

CCTGTGCTCG

ACCTAATAGC

ATCAAGACCC

TGAACGGCGT

GAATTGACCT

ATGCAATTGC

GGAGTATGAA

GAGGGTTGAT

GAGAACAAGT

CCTATGTAAG

CTCTTCGTCA

TTCCCTCTGG

ATGTCACCAC

AGTAGGATAG

GTTCTGTTTG

CATCGGGCJAG

GTCTATGAAC

ATACTATACA

GATATCTATC

GCTCGGATAC

GATAACTCAC

GTCCGAGATT

TCAAGAGTGG

TTTTGATGAG

GTACCCGATG

TACACTCGTA

CAATTGTGCA

TGACAAGATC

GACCATCCAA

CGGTCCTCCC

TAAGTTGGAG

AGGTTTATCG

AGGGATCCCC

TGGTATGTCA

GTCGCTCTGA

TCAAGCAACC

CCGAACAATA

AACGAGACCG

TCATTAACAG

TCATGTTTCT

CCATCTACAC

CAACTATCTT

GAAATCCTGT

CAGGCTTTGA

AGTGGAGGTG

GTCGACACAG

AAGGGGGTGA

TATACCACTG

TCATCGTGTA

AGTCCTCTGC

TCCGGGTCTT

TCAATCCTTT

CTAACATACA

GTCGGGAGCA

ATATCATTGG

GATGCCAAGG

AGCACTAGCA

GCTTTAATAT

AGACCAGGCC

TCCTCTACAA

ACCGCACCCA

TCGGTAGTTA

GATAALATGCC

AGAACATCTT

GAGCTTGATC

CGCAGAGATC

GTGATTTAAT

CATTATTTGG

GCTATGCGCT

ATTTACTGGG

AGTCCTACTT

TTGTCCACCG

TGCCCAAGTA

CTTTCATGCC

TCCAAGAATG

TTGGGAACCG

GCALAGTGTTA

TTGCTGCCGA

GGAGGTATCC

AGAGGTTGGA

AATTGTTGGA

TAGTCTACAT

GTTGCTGCAG

TAAAGCCTGA

CTCTTGAAAC

GCATCAAG;CC

ATTAAAACTT

TTCTACAAAG

ATGATTGATA

GGGTTGCTAG

CATAAAAGCC

CGGCCAGAAG

CCCCAGCTTA

TGGAGGAGAC

CATCTTAGAG

CATTGTCCTC

GCTAGAGGGG

TGTTGCA.ACC

AGAGGGGACT

CCTCCGGGGG

GTTCATTTTA

CACAACAGGA

TCACTGCCCG

AGATGCTGTG

CGTAGGGACA

GTCATCGGAC

CCTGATTGCA

GGGGCGTTGT

TCTTACGGGA

ACAA.ATGTCC

CACCTGAAAT

AGGGTGCAAG

ATAACCCCCA

GACCTTATGT

CCATTGCAGG

TCAGCACCAA

6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500

C

204 TCTAGATGTA ACTAACTCAA TCGAGCATCA GGTCAAGGAC GTGCTGACAC CACTCTTCAA

AATCATCGGT

CATCTCTGAC

TTGGTGTATC

GGCTGCTGAA

CAATCAGTTC

ATTCTCAAAC

ATCTATAGTC

TAATCTGAGC

AGGTGTTATC

GCAACCAGCC

AGCCCTTTGT

CAGCTTCCAG

CCCCTTATCA

TATCGCTGAC

AATGGAGACA

CGAGTGGGCA

GAGTCTGACA

CGGTTCAGGG

GCCAATGAAG

GGTTAGTCCC

AACATACCTA

ACCTGGTCAA

TGTGGTTTAT

GCCTATAAAG

CTGGTGCCGT

GATGA.AGTGG

AAGATTAA.AT

AACCCGCCAG

GAGCTCATGA

CTAGCTGTCT

ATGTCGCTGT

ACTATGACAT

AGCAAAAGGT

AGAAATCCGG

AGTAATGATC

CACGGGGAAG

CTCGTCAAGC

ACGGATGATC

AATCAAGCAA

TGCTTCCAAC

CCATTGAAGG

GTTGAGCTTA

ATGGACCTAT

AACCTAGCCT

TACCTCTTCA

CCTGCGGAGG

GATCTCCAAT

TACGTTTACA

GGGGTCCCCA

CACTTCTGTG

GCCTGAGGAC

TCCTTAATCC

AGAGAATCAA

ATGCATTGGT

CAAAGGGAAA

CCCTGTTAGA

CCCAGGGAAT

CAGAGTTGTC

GTTTGGGGGC

TCAGCAACTG

ATTCTATCAC

TAGGTGTCTG

CAGTGATAGA

AATGGGCTGT

AGGCGTGTAA

ATAACAGGAT

AA-ATCAAAAT

ACAAATCCAA

TAGGTGTAAT

ATGTCCCAAT

TGGATGGTGA

ATGTTTTGGC

GCCCAGGCCG

TCGAATTACA

TGCTTGCGGA

ACCTCAGAGA

GGATAGGGAG

ATTGGATTAT

GAACTCAACT

CTGCTCAGGG

CTTGTATTTA

GTATGGGGGA

ACAACTGAGC

TCCGGTGTTC

TATGGTGGCT

AATTCCCTAT

GAAATCCCCA

CAGGCTTTAC

CCCGACAZACA

GGGTAAAkATC

TCCTTCATAC

TGCTTCGGGA

CCACAACAAT

CAACACATTG

TAAGGAAGCA

TGTCAAACTC

AACCTACGAT

CTCATTTTCT

AGTGGAATGC

CTCAGAATCT

TTCACTGACC

TACGACTTCA

GATCAATACT

CTACTGGAGA

CCCACTACAA

GGTCGAGGTT

ACTTACCTAG

ATGTACCGAG

CATATGACAA

TTGGGGGAGC

CAGGGATCAG

ACCGACATGC

CTCTCATCTC

CGAACAGATG

CAAGCACTCT

GGGGTCTTGT

TTCGGGCCAT

GTGTATTGGC

GAGTGGATAC

GGCGAAGACT

AGTTCCAATc

ACTTCCAGGG

TACTTTTATC

TTCACATGGG

GGTGGACATA

TAGTGAAATT

GAGATCTCAC

GTGCAGATGT

CCAGAACAAC

TCAGAGGTCA

ACAATGTGTC

TGGAAAAGCC

TGTTTGAAGT

ACTATCTTGA

TCAAACTCGC

GGAAAGGTGT

AATCCTGGGT

ACAGAGGTGT

ACAAGTTGCG

GCGAGAATCC

CTGTTGATCT

TGATCACACA

TGACTATCCC

CGAGATTCAA

GCCATGCCCC

TGGTGATTCT

TTGAACATGC

CTTTTAGGTT

ACCAAAAACT

TCACTCACTC

7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 .99* 205

TGGGATGGTG

ATAGGGCTGC

GTGAAATAGA

CGCTATCTGT

ATAAGATAGT

CTACACTGTG

TAA.ACAATGT

CTCATATTCC

CGAGGAAGAT

AGGTTTTCCA

AGGACATCAA

AGCCCTTTCT

CCCATACTTG

TGCTAATCTC

TGACATTTGA

CCGCTATGAC

AACTGATAGA

TGGAGCCTCT

CTTTCCTTAA

ATGAAGGTAC

TACATCTGAC

CAGTAACGGC

AGACTCTGAT

GGCACGGAGG

ATGCTCAAGC

TTGCTGGAGT

GGCATGGGAG

TAGTGAACCA

CATCAGAATT

CAACCAGATC

AGCCATCCTG

TCAGAACATC

GGAAGTTGGG

ATATCCAAAT

CCGTGAACTC

ATGCTTAAGG

GGAGAAAGTT

GTTTTGGTTT

CCATAGGAGG

TCGTGACCTT

ACTGGTTTTG

TATTGATGCT

TGGTTTCTTC

TTCACTTGCT

CCACTGCTTT

TTATCATGAG

AGGGGAGATT

TGCTGAAAAT

GAAAGGTCAT

CAGTTGGCCA

TTCAGGTGAA

GAAATTTGGC

TCAGCTGCAC

ATCTCATGAT

AAGAAAAACG

TTATACCCTG

GAGTATGCTC

AAGCACCGCC

AATGTCATCA

TGTAATCAGG

CTCAAAAAGG

GACACTAACT

ATTAACTTGG

ACAGTCAAGA

AGACACACAC

GTTGCTATAA

ATGTATTGTG

AGGTATACAG

CCTGCACTCG

TACCTGCAGC

ACTGAA.ATAC

TTAATTGAAG

TTCTCATTTT

GTTAGGAAAT

GCCATATTTT

CCGCTGACCC

GGGTTAACAC

TGCTTTATGC

AGTCACCCGG

GTCACCCAGA

TAGGGTCCAA

AAGTTCACCT

GAGTCCCTCA

TAAAAAACGG

AGTCCAAGCT

ATTTATTTAA

GGAATTCGCT

CACGGCTTGG

GAGTTTACAT

CTGAGATGAG

CTGTATTCTT

TCAGTAAAGA

ATGTCATAGA

AGCTTCTAGG

GGAATCCAAC

TGAGGGATAT

ATGATGTTCT

CTCTAGATTA

TCAGAAGTTT

ACATGAATCA

GTGGAATCAT

TCCCCCTGCA

ATGAGCAGTG

CTCTTAGCCT

GAAGATGGAA

CATCAGGCAT

GTGGTTCCCC

AGATAGCCCG

CGCTTACAGC

ATTTTCCAAC

TAGGAGTTAT

CATAGAAGAC

GTACTCCAAA

CCTAGGCTCC

GCACAGCTCC

GTCAGTGATT

CACTGGTAGT

GTCTCAACAT

GGGGAGGTTA

A.AGAGTCAGA

TTATCAAATT

AACAGTAGAA

TGACCAAAAC

CATTTTCATA

CGGCCACCCC

GCCTAAAGTC

AATCAACGGC

TGCTGCAGAC

CGTTGATAAC

GGATAGTGAT

CCAATCGCAG

ACCCACTAGT

GTTATGGACT

ATAGTTACCA

CTGGAGGACC

CAAATGATTA

CCGGCCCACT

AAAGAGTCAA

GTCAGTGATA

GAATTGAGGG

CAGTGGTTTG

AAATCACAAA

TCAGTTGAGT

GTATATTACC

ATGACAGAGA

TACATGTGGA

GTAGCCATGC

CTCAGAGGTG

GGGTTTTCTG

ACTGATGACA

AGACTTGAAG

ATTGTGTATG

TATCGTGACA

ACAATCCGGA

TGGAAATCTT

CTGACAATGT

9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 206 ACCTAAAGGA CAAGGCACTT AGTTCCTGCG TTACGACCCT TTAATGATTC oGAG CTTTGAC TCCATGACCC TGAGTTCAAC

GTAGACTTTT

TAATCTCAAA

ATTTGACTAA

GTCACAGGGG

GGAACGTGAG

ACACTGATCA

ATCTCAAGAA

TAAATGAGAT

CTGTCCTGTA

ATAAAGTCCC

GTCAGAAGCT

GAGTAAGGAT

TACCCAGCAC

ACTTTGTAAT

CAhTTGTTTC

TGTCCCAATC

AAACAAGGGC

ATGACCGTTA

CTCTTGGCTT

ACAACGACCT

TGAATATGAG

TGCTAAAATG

CGGGATTGGC

GGCACTCCAC

GGGGCCAGTC

AGCAGCAAAA

TCCGGAGAAT

GTACTGCCTT

TTACGGATTG

TGTAAGTGAC

CAATGATCAA

GTGGACCATC

TGCTTCGTTA

ATGGCCCTAC

TCTTAGGCAA

ATCACATTTT

ACTCAAGAGC

AGCATGCAGT

CCTTGCATAT

CACAATCAAT

CTTAATAkGG

CAGGCTGTTT

GCTGCTCTCC

CCCAAGGGAA

CCATATGATG

CTGTCTTACA

ACTTACAAAA

AAATATTTTA

ACTCTAGCTG

TTAAAAACCT

GGGTTTATAG

ATGGAAGCTT

AATTGGAGAT

CCCTCATTTT

CCTCATTGCC

ATCTTCATTA

AGCACCATTC

GTGCAAGGGG

AACCTTAAGA

AGGCTACATG

TTTGTCTATT

ATCGCAAGAT

AATATTGCTA

TCCCTGAACG

TCAACCATGA

ATGGCACTGT

GTCAGAAACA

AAAGGGAATG

CCGGGTCACG

TGATAATGTA

GCCTGAAAGA

TGAGGGCATG

AGGACAATGG

TCTCAGGAGT

ACTCCCGAAG

GGTTCCCTCA

ACGAGACAGT

ATGAGACCAT

TCCAGTGGCT

CCCCCGACCT

AGTACCCTAT

CCTATCTATA

ACAATCAGAC

AACGGGAAGC

GGATTCAGTT

GAGGCTTGTA

TGTTGTAAGT

AAAGGAGATC

CCAAGTGATT

GATGGCCAAG

CCCCAALAGAT

CCCAGTCCAC

AGTAATTCGG

CAGTGCATTT

CAGCTTGTTT

GCATAAGAGG

TGACGCCCAT

GGGAGGTATA

CCTGGCTGCT

CATAGCCGTA

TGCTAGAGTA

TACCCGAAAG

GATGTTTTCC

GGAGCTTACC

AAGGAAACAG

GCTGAAAATC

GATGAGCACG

CTCAAAGAAA

ACAAGTACCA

CAGGACCAAG

ATCACGACTG

GCAC.AGAGGC

CTTGAGACCT

ATCCCGTTAT

GAAGGGTATT

TATGAGAGCG

ACAAAAAGGG

ACTAGAGATT

GCAAATGAGA

GGGCTACTTG

ATAGTTGATG

GAGAGAGGTT

ATTCTGATCT

CTCCTCACAA

ATGAATTATC

TCAATTGCTG

10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 ATATTGGCCA TCACCTCAAG CAAAAGGAAT ATATTATGAT GTGTATTCTG GTCAGAGACT CAACAATGGC TAAkAAGCATC TCCTAAA.AGT GATACAGCAA CCCGGGATGT AGTCATACCC TGCCCGCTCC TATTGGGGGG TCGGTGATCC AGTATACATCA ATCTCAAGAG AATGATTCTC GCCTCACTAA TGCCTGAAGA GACCCTCCAT CAAGTAATGA 207 CACAACAACC GGGGGACTCT TCATTCCTAG ACTGGGCTAG CGACCCTTAC TCAGCAAATC

TTGTATGTGT

TCCATAGTCC

AGGGACTGGC

TCCTGGATCA

AAGGCCTGAT

TGTCCAATTA

GAAATGTCCT

ATATGTGGGC

TAGAATCTAT

GATCAGTCAA

AGGAAACATC

TGAAGCTTGC

CAGTGTACTC

CTAGGCAAAG

CGACTAkTTT

CCCTTGTCCG

CAGATAAGAA

TTTTAGAAAC

TTCACGTCGA

CCCGCAAGCT

CTTTAATTGA

AATTTGTTAC

CTATGATTGA

TAGGGGATGA

TCACTATCTA

CCAGAGCATC

AAACCCAATG

GGCATTCCTC

TAGTGTCACA

TCGAGCCAGC

TGACTATGAA

CATTGACAAA

GAGGCTAGCT

GCGAGGCCAC

CTACGGATGG

ATCCTTGAGA

CTTCGTAAGA

ATGGGCTTAC

GGCCAATGTG

AGCGCATAGG

AGTGGCGAGG

GGTTGATACT

ATTGTTTCGA

AACAGATTGT

AGAGCTGAGG

CAGAGATACA

ATGGTCCACA

CCTGGTAACA

CGATATCAAT

CTTGGGCCAG

ACTAGACTCC

TTAAAAGGAT

ATGGACAGGC

GGGGCAAGAG

ATGAGGAAGG

CAATTCAGAG

GAGTCATGTT

CGAGGACGGC

CTTATTCGGC

TTTTTTGTCC

GTCCCATATA

GCCCCAAGTC

GGTGATGATG

AGCCTGGAGG

TTGAGGGATC

TATACCACAA

AACTTTATAT

CTCGAGAAAG

TGCGTGATCC

GCAGAGCTAT

ACAAGGCTAT

CCCCALACTAT

AAATTTGAGA

AGTTTCATAA

TGTGCGGCCA

TCAAGAACAT

TATTCCATGA

ATATTATAGT

AGTCTATTGC

GGGGGTTAAC

CAGGGATGGT

CAGTGCAGCT

CTATTTACGG

GTCATGAGAC

CCTCGGGTTG

TTGGTTCTAC

GATCCTTGCG

ATAGCTCTTG

AGCTAAGGGT

GTAGCACTCA

TCTCCAACGA

ACCAACAAGG

ATACCGGATC

CGATGATAGA

GTACCAkAccc

ACACCCAGAG

ATCACATTTT

AGGACCATAT

CTGAGTTTCT

TCAATTGGGC

AACTGCAAGG

TGACAGTAAA

ACCTAGGGCA

AGGCATGCTG

CTCTCGAGTG

GCTATTGACA

GGCGAGAGCT

CCTTGAGGTC

ATGTGTCATC

CCAACTGGAT

CACTGATGAG

ATCTGCTGTT

GAACGAAGCC

GATCACTCCC

AGTGAAATAC

CAATCTCTCA

AATGCTTCTA

ATCTAACACG

TCATCCCAGG

ATTGATATAT

CCATAGGAGG

AGCTAAGTCC

GAATGAAATT

GCTCATAGAG

ATTTGATGTA

TTTGTCCTGA

GAAGAGGACG

GCTCATGAAA

GATACCACAA

ATAACCAGAT

GGAAGAILAGA

CTAAGAAGCC

CCTGATGTAC

TGCGAGTGTG

GATATTGACA

AGAACAGACA

AGAATAGCAA

TGGTTGTTGG

ATCTCAACTT

TCAGGTACAT

TTTGTCATAT

GGGTTGGGTG

GTATTACATC

ATACCCAGCT

GATAATGCAC

CACCTTGTGG

ACAGCACTAT

TCAGCTCTCA

CCAAGATTAT

CATTATCATA

12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 208

S

GACCATCAGG

AAGGAGTGTT

GGCATTGTGG

CAACTGTGTG

AAGAGTTAGA

GATTCGACAA

GGACCTGCCC

ATATCAAGC

TTGTAGACCA

GATTGAGAGT

CAAAGATCGG

ATGATGTTGC

GGGGCAATCT

CTTGCTACAA

ACGGCTTGTT

AACTAAACAA

AATTAGCACC

TTGTCAALAGT

TCAATTT CAT

AGACCTTGCC

TGGCTCTGCT

GGGATTTTGT

TATACCCTAG

AGGCTAACCG

GGACTTCACC

GAAATATCAG

TAAGGTGCTT

TATTATAGAG

CAACATGGTT

AGAGTTCACA

CATCCAGGCA

ACCAATTCGA

AGAGGCTAGG

TTACTCATGC

TGATCCAGGA

CAGCAACAAC

AAAATTGCTC

CGCCAATTAT

AGCTGTTGAG

CTTGGGTGAG

GTGCTTCTAT

CTATCCCTCC

GCTCTTTAAC

AGTTAGTAAT

TAACAAAGAT

CCTGGGCAAA

TCAGGGATTT

ATACAGCAAC

GCTAATGAAT

TGGACTTATA

ATGGGTGAGC

GTCAATGCTC

CCTATCCATG

TACACATGCT

TTTCTCTTGT

AAACACTTAT

GGTCTAAGAC

TTATCTCCAG

TCTCTGACTT

TTCATTTTCG

ATCTCAILATA

AAAGATATCA

GAAATCCATG

ATATCAACAT

GGATCGGGTT

AATAGTGGGG

GAAGTTGGCC

GGGAGGCCCG

ATCCCTACCT

ACTATAGAGA

ATAGGATCAA

ATAAGTTATG

TTCATATCTA

CCTGAAAAGA

GGTCACATCC

TGTTGTCATC

TA.AGCCACCC

GTCCTTCACT

ATATGACCTA

GTGAAAGCGA

GTGTTCTGGC

CGGTAGAGAA

CAGGATCTTC

ATCTCCGGCG

ACGCCCTCGC

TGAGCATCAA

ACACAAGCAA

CTTTCCGCAG

TAATTAGGAG

CTATGTTGAT

TTTCCGCC.A

TTGTCGAACA

AAGTCACGTG

CTAGTGTGGG

AGCTAGAGGA

TACTGGTGAT

TAGGGTCCCA

CTGAATCTTA

TTAAGCAGCA

TATCCATTA

GTTCCTTrCT

AAAGATCTAC

TGATGCTCAA

C CTCGACCTG

CGAGGATGTA

AGATTTGTAC

ATGTGCAGTT

GTGGAACATA

AGGATCGATC

TGAGGTAAAT

GGCTTTCAGA

GCACAATCTT

AATCGGGTTG

ATGCCTTGAG

CACTTATAAG

TTCTAGATCT

CAGAATGGGA

GGTAGGCAGT

GTTTATCCAT

ATTGGCAGCC

TAAGCTTATG

TTATAGAGA

TTTGGTTATG

GATAATTGA

GCAACTAAGC

AGAATGAGCA

AAGAAATTCT

AACTTGCACA

TTGTTGAATG

GTACCGGACA

TGTCAACCAG

CTAACCGACC

AATCCAATTA

AAACAGATAA

GTCAGTCAGC

CCCCCACACG

CCCATTTCAG

AACTCATCTG

CCAGGGGAGG

GAGATACTTA

GGTCAAAGGG

GTAGGTAATA

GTAGATTGCT

TCAGATATAG

ATCTTATCGA

CCTTTCAGCG

GTGAACCTTG

ACAGATCTCA

TCATCTGTGA

TGCATACAAG

13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15240 15300 CAATTGTGGG AGACGCAGTT AGTAGAGGTG ATATCAATCC TACTCTGAAA AAACTTACAC 209

CTATAGAGCA

AATTGATCCA

TCTACAGGGA

CTTACCCCGT

TTTGGGGGCA

ATCTCAAGTC

CCAAGTCAGA

TAACAGTCAA

ACTAATTGGT

GGTGCTGATC

CCATGATGTT

GTTGGCAAGA

ATTGGTAAGT

CATTCTTCTT

CGGCTATCTG

GAAACAGATT

GGAGACCAAA

TGAACTCCGG

AATTGCGGGT

GCCTCAGGGC

TTCAAAGACA

AGCAGGCAAC

TACTCCGGGA

ATACTAGACT

ATTATGACGG

GAATGGTATA

AACCCTAATC

TGGCAATTAA

AAGATGGATT

ACCAAAGAAG

GAGAACTTAT

ACAGAAAGTT

TACACCAGAA

GGGGTTTGAA

AGTTAGTCGG

CTGCCCTAGG

CGGACCTAAG

GCTTA-ATTCT

TCAACAAGGG

ATCTAGGATC

GATA.AATAAG

TATCTTCGTT

ACGTGAGTGG

ATACAGTGCC

TGGTTAGGCA

CTGTGCAAAG

ATACTCATCC

ATGTTCCACG

ACCCGCAAAT

TTTATCCAGA

AAGAATCTAT

GTTTTTAAGG

CTGATTAAGG

TTATTTGCAA

15360 15420 15480 15540 15600 15660 15720 15780 15840 15894 TAGATTAAAG AAAACTTTGA AAATACGAAG TTTCTATTCC CAGCTTTGTC TGGT INFORMATION FOR SEQ ID NO:14: SEQUENCE CHARACTERISTICS: LENGTH: 2183 amino acids TYPE: amino acid

STR.ANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) Met 1 Asp SEQUENCE DESCRIPTION: SEQ ID NO:14: Asp Ser Leu Ser Val Asn Gin Ile Leu 5 10 Ser Pro Ile Val Thr Asn Lys Ile Vai Tyr Pro Giu Val His Leu Ala Ile Leu His 25 Glu Arg Val Pro Ile Lys His Ala Tyr Ser Leu 40 Gly Asp Pro Thr Leu Met Giu Tyr Ala Cys Gin Asn Ile Ile Asn Arg Leu Lys Val Asn 55 Val Phe Ser Asn Gin Leu Asn Al a Giu Val Gly Asn 70 Ile Lys Ser Lys 75 Asn.

Arg Ser Tyr Pro Asn His Ser His Ile Pro Tyr Pro Asn Cys Gin Asp Leu Phe 210 Ile Giu Asp Lys Giu Ser Thr Arg Lys Ile Giy Arg Ile 145 Trp Ser Pro Leu Phe 225 Thr Arg Giy Ala Leu 305 Phe Ile Phe Asn Asp 130 Lys Phe Val Val Val 210 Giu Glu Val Asn Tyr 290 Asn Ser Phe Arg Ser 115 Thr Giu Giu Ile Phe 195 Ala Leu Thr Arg Pro 275 Leu HisB Asp Ile Ser 355 100 Lau Asn Lys Pro Lys 180 Phe Ile Val Ala Tyr 260 Thr Gin Cys Giu Thr 340 Phe Ser Arg Ile 150 Leu Gin Gly Ser Met 230 Thr Trp Gin Arg Thr 310 Thr Asp His Lys Leu 135 Asn Phe Thr Ser Lys 215 Tyr Ile Lys Ile Asp 295 Giu Tyr Ile Pro Val 120 Gly Leu Trp His Ser 200 Giu Cys Asp Leu Val 280 Ile Ile His His Arg 360 105 Ser Asp Leu Gly Gly Val Phe Thr 170 Thr Cys 185 Val Glu Ser Gin Asp Val Ala Arg 250 Ile Asp 265 Ala Met Thr Val His Asp Glu Leu 330 Leu Thr 345 Leu Glu Arg Lys Ser Tyr 155 Val1 His Leu His Ile 235 Tyr Gly Leu Glu Val 315 Ile Gly Al a Val1 Giu 140 Met Lys Arg Leu Vai 220 Glu Thr Phe Glu Leu 300 Leu Glu Glu Val Phe 125 Leu His Thr Arg Ile 205 Tyr Gly Giu Phe Pro 285 Arg Asp Ala Ile Thr 365 110 Gin Arg Ser Glu Arg 190 Ser Tyr Arg Leu Pro 270 Leu Gly Gin Leu Phe 350 Al a Glu Leu Leu Lys Cys Giu Ser Met 175 His Arg Leu Leu Leu 255 Ala Ser Al a Asn Asp 335 Ser Al a Lys Leu Asp Gin 160 Arg Thr Asp Thr Met 240 Gly Lau Leu Phe Gly 320 Tyr Phe Glu 211 Asn Val Arg Lys Tyr Met Asn Gin Pro Lys Val Ile Val Tyr Glu Thr 370 375 380 Leu Met Lys Gly His Ala Ile Phe Cys Gly Ile Ile Ile Asn Gly Tyr 385 390 395 400 Arg Asp Arg His Gly Gly Ser Trp Pro Pro Leu Thr Leu Pro Leu His 405 410 415 Ala Ala Asp Thr Ile Arg Asn Ala Gin Ala Ser Gly Glu Gly Leu Thr 420 425 430 His Glu Gin Cys Val Asp Asn Trp Lys Ser Phe Ala Gly Val Lys Phe 435 440 445 Gly Cys Phe Met Pro Leu Ser Leu Asp Ser Asp Leu Thr Met Tyr Leu 450 455 460 *Lys Asp Lys Ala Leu Ala Ala Leu Gin Arg Glu Trp Asp Ser Val Tyr 465 470 475 480 Pro Lys Giu Phe Leu Arg Tyr Asp Pro Pro Lys Gly Thr Gly Ser Arg *485 490 495 Arg Leu Val Asp Val Phe Leu Asn Asp Ser Ser Phe Asp Pro Tyr Asp 500 505 510 Val Ile Met Tyr Val Val Ser Gly Ala Tyr Leu His Asp Pro Glu Phe 515 520 525 **Asn Leu Ser Tyr Ser Leu Lys Giu Lys Giu Ile Lys Giu Thr Gly Arg 530 535 540 Leu Phe Ala Lys Met Thr Tyr Lys Met Arg Ala Cys Gin Val Ile Ala ***545 550 555 560 Giu Asn Leu Ile Ser Asn Gly Ile Gly Lys Tyr Phe Lys Asp Asn Gly 565 570 575 Met Ala Lys Asp Giu His Asp Leu Thr Lys Ala Leu His Thr Leu Ala 580 585 590 Val Ser Gly Val Pro Lys Asp Leu Lys Glu Ser His Arg Gly Gly Pro 595 600 605 Vai Leu Lys Thr Tyr Ser Arg Ser Pro Vai His Thr Ser Thr Arg Asn 610 615 620 Val Arg Ala Ala Lys Giy Phe Ile Gly Phe Pro Gin Vai Ile Arg Gin 625 630 635 640 212 Asp Gin Asp Thr Asp His Pro Glu Asn Met Giu Ala Tyr Giu Thr Val 645 650 655 Ser Tyr Leu Leu 705 Pro Gly Pro Leu Ser 785 Arg Hisa Ser Ser Arg 865 Arg Ile Ala Phe Giu Thr 675 Pro Ser 690 Tyr Vai Leu Tyr Gly Ile Tyr Leu 755 Val Gin 770 Thr Trp Asp Tyr Leu Lys Lys Gly 835 Ile Ala 850 Ala Ala Gly Tyr Gin Gin Ile Thr 660 Ile Ser Phe Phe Ser Asp Lys Val 725 Giu Gly 740 Tyr Leu Gly Asp Pro Tyr Phe Val 805 Ala Asn 820 Ile Tyr Arg Cys Cys Ser Asp Arg 885 Ile Leu Thr Leu Gin Pro 710 Pro Tyr Ala Asn Asn 790 Ile Giu Tyr Val Asn 870 Tyr Ile Asp Phe Trp 695 His Asn Cys Ala Gin 775 Leu Leu Thr Asp Phe 855 Ile Leu Ser Leu Ala 680 Leu Cys Asp Gin Tyr 760 Thr Lys Arg Ile Gly 840 Trp Al a Ala Leu Lys 665 Gin His Pro Gin Lys 745 Giu Ile Lys Gin Val 825 Leu Ser Thr Tyr Gly Lys Arg Lys Pro Ile 730 Leu Ser Ala Arg Arg 810 Ser Leu Glu Thr Ser 890 Phe Tyr Leu Arg Asp 715 Phe Trp Gly Vai Giu 795 Leu Ser Val Thr Met 875 Leu Thr Cys Asn Leu 700 Leu Ile Thr Val Thr 780 Ala His His Ser Ile 860 Al a Asn Ile Leu Giu 685 Giu Asp Lys Ile Arg 765 Lys Al a Asp Phe Gin 845 Val Lys Val Asn Aen 670 Ile Thr Al a Tyr Ser 750 Ile Arg Arg Ile Phe 830 Ser Asp Ser Leu Trp Tyr Ser His Pro 735 Thr Ala Val1 Val Gly 815 Val Leu Giu Ile Lys 895 Arg Giy Val Ile 720 Met Ile Ser Pro Thr 800 His Tyr Lys Thr Giu 880 Val 910 Thr Arg Asp Val-Val Ile Pro Leu Leu Thr Asn Asn Asp Leu Leu Ile 213 915 920 925 Arg Met Ala Leu Leu Pro Ala Pro Ile Gly Gly Met Asn Tyr Leu Asn 930 935 940 Met Ser Arg Leu Phe Val Arg Asn Ile Gly Asp Pro Val Thr Ser Ser 945 950 955 960 Ile Ala Asp Leu Lys Arg Met Ile Leu Ala Ser Leu Met Pro Glu Glu 965 970 975 Thr Leu His Gin Val Met Thr Gin Gin Pro Gly Asp Ser Ser Phe Leu 980 985 990 Asp Trp Ala Ser Asp Pro Tyr Ser Ala Asn Leu Val Cys Val Gin Ser 995 1000 1005 Ile Thr Arg Leu Leu Lys Asn Ile Thr Ala Arg Phe Vai Leu Ile His 1010 1015 1020 Ser Pro Asn Pro Met Leu Lys Gly Leu Phe His Asp Asp Ser Lys Glu 1 025 1030 1035 1040 Glu Asp Giu Giy Leu Ala Ala Phe Leu Met Asp Arg His Ile Ile Val 1045 1050 1055 Pro Arg Ala Ala His Glu Ile Leu Asp His Ser Val Thr Gly Ala Arg 1060 1065 1070 Glu Ser Ile Ala Giy Met Leu Asp Thr Thr Lys Gly Leu Ile Arg Ala 1075 1080 1085 Ser Met Arg Lys Gly Gly Leu Thr Ser Arg Val Ile Thr Arg Leu Ser 1090 1095 1100 ***Asn Tyr Asp Tyr Giu Gin Phe Arg Ala Gly Met Val Leu Leu Thr Giy 1105 1110 1115 1120 Arg Lys Arg Asn Val Leu Ile Asp Lys Glu Ser Cys Ser Val Gin Leu 1125 1130 1135 Ala Arg Ala Leu Arg Ser His Met Trp Ala Arg Leu Ala Arg Gly Arg 1140 1145 1150 Pro Ile Tyr Gly Leu Giu Val Pro Asp Val Leu Giu Ser Met Arg Gly 1155 1160 1165 His Leu Ile Arg Arg His Glu Thr Cys Val Ile Cys Glu Cys Giy Ser 1170 1175 1180 Val Asn Tyr Gly Trp Phe Phe Val Pro Ser Gly Cys Gin Leu Asp Asp 1185 1190 1195 1200 214 Ile Asp Lys Glu Thr Ser Ser Leu Arg Val Pro Tyr Ile Gly Ser Thr 1205 1210 1215 Thr Asp Giu Arg Thr Asp Met Lys Leu Ala Phe Val Arg Ala Pro Ser 1220 1225 1230 Arg Ser Leu Arg Ser Ala Val Arg Ile Ala Thr Val Tyr Ser Trp Ala 1235 1240 1245 Tyr Gly Asp Asp Asp Ser Ser Trp Asn Giu Ala Trp Leu Leu Ala Arg 1250 1255 1260 Gin Arg Ala Asn Val Ser Leu Giu Giu Leu Arg Val Ile Thr Pro Ile 1265 1270 1275 1280 Ser Thr Ser Thr Asn Leu Ala His Arg Leu Arg Asp Arg Ser Thr Gin 1285 1290 1295 .Val Lys Tlyr Ser Gly Thr Ser Leu Val Arg Val Ala Arg Tyr Thr Thr 1300 1305 1310 Sle Ser Asn Asp Asn Leu Ser Phe Val Ile Ser Asp Lys Lys Val Asp 1315 1320 1325 Thr Asn Phe Ile Tyr Gin Gin Gly Met Leu Leu Gly Leu Gly Val Leu 1330 1335 1340 Giu Thr Leu Phe Arg Leu Giu Lys Asp Thr Gly Ser Ser Asn Thr Val 1345 1350 1355 1360 *Leu His Leu His Val Glu Thr Asp Cys Cys Val Ile Pro Met Ile Asp 1365 1370 1375 His Pro Arg Ile Pro Ser Ser Arg Lys Leu Glu Leu Arg Ala Giu Leu 1380 1385 1390 see* Cys Thr Asn Pro Leu Ile Tyr Asp Asn Ala Pro Leu Ile Asp Arg Asp 1395 1400 1405 Thr Thr Arg Leu Tyr Thr Gin Ser His Arg Arg His Leu Val Giu Phe 1410 1415 1420 Val Thr Trp Ser Thr Pro Gin Leu Tyr His Ile Leu Ala Lys Ser Thr 1425 1430 1435 1440 Ala Leu Ser Met Ile Asp Leu Val Thr Lys Phe Glu Lys Asp His Met 1445 1450 1455 Asn Giu Ile Ser Ala Leu Ile Gly Asp Asp Asp Ile Asn Ser Phe Ile 1460 1465 1470 215 Thr Giu Phe Leu Leu Ile Giu Pro Arg Leu Phe Thr Ile Tyr Leu Gly 1475 1480 1485 Gin Cys Ala Ala Ile Asn Trp Ala Phe Asp Vai His Tyr His Arg Pro 1490 1495 1500 Ser Gly Lys Tyr Gin Met Gly Giu Leu Leu Ser Ser Phe Leu Ser Arg 1505 1510 1515 1520 Met Ser Lys Gly Val Phe Lys Val Leu Val Asn Ala Leu Ser His Pro 1525 1530 1535 Lys Ile Tyr Lys Lys Phe Trp His Cys Giy Ile Ile Giu Pro Ile His 1540 1545 1550 Gly Pro Ser Leu Asp Ala Gin Aen Leu His Thr Thr Vai Cys Asn Met 1555 1560 1565 Val Tyr Thr Cys Tyr Met Thr Tyr Leu Asp Leu Leu Leu Asn Giu Giu *1570 1575 1580 *Leu Glu Giu Phe Thr Phe Leu Leu Cys Giu Ser Asp Giu Asp Val Val *1585 1590 1595 1600 Pro Asp Arg Phe Asp ken Ile Gin Ala Lys His Leu Cys Val Leu Ala 1605 1610 1615 Asp Leu Tyr Cys Gin Pro Gly Thr Cys Pro Pro Ile Arg Giy Leu Arg 1620 1625 1630 Pro Val Giu Lys Cys Ala Val Leu Thr Asp His Ile Lys Ala Giu Ala **1635 1640 1645 Arg Leu Ser Pro Ala Gly Ser Ser Trp Asn Ile Aen Pro Ile Ile Val 1650 1655 1660 so.Asp His Tyr Ser Cys Ser Leu Thr Tyr Leu Arg Arg Gly Ser Ile Lys 1665 1670 1675 1680 Gin Ile Arg Leu Arg Val Asp Pro Giy Phe Ile Phe Asp Ala Leu Ala 1685 1690 1695 Glu Val ken Val Ser Gin Pro Lye Ile Gly Ser ken Asn Ile Ser ken 1700 1705 1710 Met Ser Ile Lye Ala Phe Arg Pro Pro His Asp Asp Val Ala Lys Leu 1715 1720 1725 Leu Lys Asp Ile Aen Thr Ser Lye His ken Leu Pro Ile Ser Gly Gly 1730 1735 1740 ken Leu Ala Asn Tyr Giu Ile His Ala Phe Arg Arg Ile Gly Leu ken 216 1745 1750 1755 1760 Ser Ser Ala Cys Tyr Lys Ala Val Glu Ile Ser Thr Leu Ile Arg Arg 1765 1770 1775 Cys Leu Glu Pro Gly Glu Asp Gly Leu Phe Leu Gly Giu Gly Ser Gly 1780 1785 1790 Ser Met Leu Ile Thr Tyr Lys Glu Ile Leu Lys Leu Asn Lys Cys Phe 1795 1800 1805 Tyr Asn Ser Gly Val Ser Ala Asn Ser Arg Ser Gly Gin Arg Giu -Leu 1810 1815 1820 Ala Pro Tyr Pro Ser Glu Val Gly Leu Val Glu His Arg Met Gly Val 1825 1830 1835 1840 V 0. Gly Asn Ile Val Lys Val Leu Phe Asn Gly Arg Pro Giu Val Thr Trp V*Vlp 1845 1850 1855 VlGly Ser Val Asp Cys Phe Aen Phe Ile Val Ser Aen Ile Pro Thr *1860 1865 1870 **Ser Ser Val Gly Phe Ile His Ser Asp Ile Glu Thr Leu Pro Asn Lys Vl1875 1880 1885 0:.:Asp Thr Ile Glu Lye Leu Giu Glu Leu Ala Ala Ile Leu Ser Met Ala 1890 1895 1900 Leu Leu Leu Gly Lye Ile Gly Ser Ile Leu Vai Ile Lye Leu Met Pro 1905 1910 1915 1920 Phe Ser Gly Asp Phe Val Gin Gly Phe Ile Ser Tyr Val Gly Ser His 1925 1930 1935 Tyr Arg Glu Val Aen Leu Val Tyr Pro Arg Tyr Ser Aen Phe Ile Ser 50e1940 1945 1950 Thr Giu Ser Tyr Leu Val Met Thr Asp Leu Lye Ala Asn Arg Leu Met 1955 1960 1965 Asn Pro Glu Lye Ile Lye Gin Gin Ile Ile Giu Ser Ser Val Arg Thr 1970 1975 1980 Ser Pro Gly Leu Ile Gly His Ile Leu Ser Ile Lye Gin Leu Ser Cys 1985 1990 1995 2000 Ile Gin Ala Ile Val Gly Asp Ala Val Ser Arg Gly Asp 1ie Asn Pro 2005 2010 2015 Thr Leu Lye Lye Leu Thr Pro Ile Giu Gin Val. Leu Ile Asn Cys Gly 2020 2025 2030 217 Leu Ala Ile Asn Gly Pro Lys Leu Cys Lys Giu Leu Ile His His Asp 2035 2040 2045 Val Ala Ser Gly Gin Asp Gly Leu Leu Asn Ser Ile Leu Ile Leu Tyr 2050 2055 2060 Arg Giu Leu Ala Arg Phe Lys Asp Asn Gin Arg Ser Gin Gin Gly Met 2065 2070 2075 2080 Phe His Ala Tyr Pro Val Leu Val Ser Ser Arg Gin Arg Giu Leu Ile 2085 2090 2095 Ser Arg Ile Thr Arg Lys Phe Trp Gly His Ile Leu Leu Tyr Ser Gly 2100 2105 2110 Asn Arg Lys Leu Ile Asn Lys Phe Ile Gin Asn Leu Lys Ser Gly Tyr 2115 2120 2125 Leu Ile Leu Asp Leu His Gin Asn Ile Phe Val Lys Asn Leu Ser Lys 2130 2135 2140 *Ser Giu Lys Gin Ile Ile Met Thr Gly Gly Leu Lys Arg Giu Trp Val 2145 2150 2155 2160 *Phe Lys Val Thr Val Lys Giu Thr Lys Glu Trp Tyr Lys Leu Val Gly .2165 2170 2175 Tyr Ser Ala Leu Ile Lys Asp 2180 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 15894 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:lS: ACCAAACAAA GTTGGGTAAG GATAGTTCAA TCAATGATCA TCTTCTAGTG CACTTAGGAT TCAAGATCCT ATTATCAGGG ACAAGAGCAG GATTAGGGAT ATCCGAGATG GCCACACTTT 120 TAAGGAGCTT AGCATTGTTC AAAAGAAACA AGGACAAACC ACCCATTACA TCAGGATCCG 180 218 GTGGAGCCAT CAGAGGAATC AAACACATTA TTATAGTACC AATCCCTGGA GATTCCTCA.A

TTACCACTCG

GCGGGCCCAA

GTCAATTGAT

TCCAGAGTGA

ATGAGGCGGA

GATGGTTCGA

TGATTCTGGG

CAGACACGGC

TAGTTGGTGA

AGGACCTCTC

GAAACAAACC

GATTAGCCAG

GACTGCATGA

AAATGGGGGA

GTGCAGGATC

ACTCCATGGG

GGCAAGAGAT

GTATCACTGC

AGATCAGTAG

GTGAGAATGA

GAGAAGCCAG

CCCATCTTCC

CGCAGGACAG

CGGAAGAACA

ATCCAGACTT

ACTAACAGGG

TCAGAGGATC

CCAGTCACAA

CAAATACTTT

GAACAAGGAA

TACCATCCTA

AGCTGATTCG

ATTTAGATTG

CTTACGCCGA

CAGGATTGCT

TTTTATCCTG

ATTTGCTGGT

AACTGCACCC

ATACCCTCTG

AGGTTTGAAC

GGTAAGGAGG

CGAGGATGCA

AGCGGTTGGA

GCTACCGAGA

GGAGAGCTAC

AACCGGCACA

TCG2LAGGTCA

AGGCTCAGAC

CTGGACCGGT

GCACTA.ATAG

ACCGATGACC

TCTGGCCTTA

TCACATGATG

ATCTCAGATA

GCCCAAATTT

GAGCTAAGAA

GAGAGAAAAT

TTCATGGTCG

GAAATGATAT

ACTATTAAGT

GAGTTATCCA

TACATGGTAA

CTCTGGAGCT

TTTGGCCGAT

TCAGCTGGAA

AGGCTTGTTT

CCCAGACAAG

TTGGGGGGCA

AGAGA.AACCG

CCCCTAGACA

GCTGACGCCC

ACGGACACCC

TGGTCAGGTT

GTATATTATC

CTGACGTTAG

CCTTCGCATC

ATCCAATTAG

TTGAAGTGCA

GGGTCTTGCT

GGTGGATAAA

GGTTGGATGT

CTCTAATCCT

GTGACATTGA

TTGGGATAGA

CACTTGAGTC

TCCTGGAGAA

ATGCCATGGG

CTTACTTTGA

AGGTCAGTTC

CAGAGATTGC

CCCAAGTATC

AGGAAGATAG

GGCCCAGCAG

TTGACACTGC

TGCTTAGGCT

CTATAGTGTA

AATTGGAAAC

CTTATTTGTG

CATAAGGCTG

A.AGAGGTACC

TAGTGATCAA

AGACCCTGAG

CGCAAAGGCG

GTACACCCAA

GGTGAGGAAC

GGATATCAAG

TACATATATC

AACTATGTAT

CTTGATGAAC

CTCAATTCAG

AGTAGGAGTG

TCCAGCATAT

CACATTGGCA

AATGCATACT

ATTTCTACAC

GAGGGTCAAA

AGCAAGTGAT

ATCGGAGTCC

GCAAGCCATG

CAATGACAGA

CCGGATGTGA

GAGTCTCCAG

TTAGAGGTTG

AACATGGAGG

TCCAGGTTCG

GGATTCAACA

GTTACGGCCC

CAAAGAAGGG

AGGATTGCCG

AGAACACCCG

GTAGAGGCAG

CCTGCTCTTG

CTTTACCAGC

AACILAGTTCA

GAACTTGAAA

TTTAGATTAG

TCTGAACTCG

ACTGAGGACA

GGTGATCAAA

CAGAGTCGAG

GCGAGAGCTG

AGCCAAGATC

GCAGGAATCT

AATCTTCTAG

300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 *o ACTAGGTGCG AGAGGCCGAG GACCAGAACA ACATCCGCCT ACCCTCCATC ATTGTTATAA 219 *0 S*

AAA.ACTTAGG

GAGCCGATGG

CTCAAGGCCG

ATATCAGACA

GGTCTCAGCA

CGCGGTCAGG

AATCTCCAGG

GCGGTTAAGG

AGCACCCTAT

GATACCGAGG

GCTTCTGATG

AGAGGCAACA

GGTAGGGCCA

TTTGGAACGG

CCCTCGGAAC

GCCGCACTGA

AATAATGAAG

AAAACAGCCT

CTGCTGTTAT

AGCATATCCA

AAGGATCCCA

GGCAGAGATT

CTCCAAGGAA

CCAAAGCCGA

GCATCACGCA

CGTTACCTGA

AACCAGGTCC

CAGAAGAGCA

AGCCCATCGG

ACCCAGGACA

AACCATGCCT

GACCTGGAGA

CATCAAGCAC

GAATCCAAGA

CAGGAGGAGA

GATATGCTAT

TTGAAACTGC

ACTTTCCGAA

GCACTTCCGG

AGATCGCGTC

CATCAGGGCC

TACAGGAGTG

AAGGGGGAGA

TGGCCAAAAT

TGAAGGGAGA

CCCTGGAAGG

ACGACCCCAC

CAGGCCGAGC

TGACAAATGG

TCGGGAAAAA

GTGTAATCCG

TGACTCTCCT

ACACAGCCGC

GGCACGCCAT

CTCACTGGCC

GGAGCGAGCC

CTCAGCAATT

GAGCGATGAC

TGGGTTACAG

TGCTGACTCT

CAATGAATCT

CACTGACCGG

AGAAGGAGGG

GCTTGGGAAA

GACACCCATT

TTTATTGACA

AGGTGCACCT

GACACCCGAA

CTATTATGAT

ACACGAGGAT

AGTTGAGTCA

ACACCTCTCA

TGCAGATGTC

ACTGGCCGAA

ACGGACCAGT

GATGAGCTCA

CTCCATTATA

TGATGATATC

CAGCCCATCA

GTCAAAAACG

ATCGAGGAAG

ACCTGCAGGG

GGATCAACTG

GACGCTGAAA

TGTTATTATG

ATCATGGTTC

GAAAACAGCG

GGATCTGCTC

GAGATCCACG

ACTCTCAATG

AAAALAGGGCA

GGTGGTGCAA

GCGGGGAATG

TCTGGTACCA

GATGAGCTGT

AATCAGAAGA

ATTAAGAAGC

AGCATCATGA

GAAATCAATC

GTTCTCAAGA

TCCAGAGGAC

GCCGTCGGGT

AAATCCAGCC

AAAGGAGCCA

ACCATCCACT

GACTGGAATG

CTATGGCAGC

AAGAGAAGGC

AAGGCGGTGC

CTTTGGGAAT

TTTATGATCA

AATCAGGCCT

ATGTGGATAT

CCATCTCTAT

AGCTCCTGAG

TTCCTCCGCC

CAGACGCGAG

CCCAATGTGC

TCCCCGAGTA

CAATCTCCCC

TCTCTGATGT

TAATCTCCAA

AGATCAACAG

TCGCCATTCC

CCGACTTGAA

AACCCGTTGC

AGCTGCTGAA

TTGTTCCTGA

GGCTAGAGGA

ATGATCTTGC

CCCACGATTG

CATCCGGGCT

ATGGTCAGAA

AGGCAGTTCG

ACCTCGCATC

CCCCCCAAGA

CAGCGGTGA.A

TGATGGTGAT

TGGCGAACCT

GGGGTTCAGG

ACTCCAATCC

CCCGGACCCC

ATTAGCCTCA

TCGAA.AGTCA

TGTGAGCAAT

GAGATCCCAG

CCAAGATATT

GCTAGAATCA

GCAAAATATC

TGGACTTGGG

ACCCATCATA

CAGCCGACAA

GGAATTTCAG

CACCGGCCCT

GGATCGGAAG

CAAGTTCCAC

1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 C) *C 220 CAGATGCTGA TGAAGATAAT AATGAAGTAG CTACAGCTCA ACTTACCTGC CAACCCCATG 0 00 0 0 0

CCAGTCGACC

GCCTCCCAAG

AkAGGGTCGAT

TCAGAGTCAT

TGCTGGGGGT

CCCTGCCCTT

CTGAGCTTGA

ACAACACCCC

TCAACGCAAA

TCCGTGTTGT

GAAGAATGCT

GGATTGACAA

CAACATTTAT

ATTATTGCA.A

GCACCAGTCT

GGTTCAAGAA

TCTGGAGGAG

AAGAATTCCG

TGTAGACCGT

GCCCGGACAA

GCCGACGGCA

CCACCAGCCA

TGCCCCCGAT

ATTGGAAGGC

GACCGAGGTG

CAACTAGTAC

TTCCACAATG

CGCTCCGATA

AGATCCTGGT

TGTTGAGGAC

AGGTGTTGGC

CATAGTTGTT

ACTAACTCTC

CCAAGTGTGC

TTATATGAGC

GGAATTCAGA

GGCGATAGGC

GGTCCACATC

AATGAAAATC

TCACATTAGA

GACCTTATGT

CAGATGCAAG

CATTTACGAC

AGTGCCCAGC

AAAAGCCCcC

AGCACGAACA

CCCCAATCTG

CCAAACCACC

CCCTCCCCCT

ACCCAACCGC

AACCTAAATC

ACAGAGATCT

CAACCGACCA

CTAGGCGACA

AGCGATCCCC

AGATCCACAG

AGACGTACAG

CTCACACCTT

AATGCGGTTA

ATCACCCGTC

TCGGTCAATG

CCTGGGA-AGA

GGGAACTTCA

GAA.AAGATGG

AGCACAGGCA

TACCCGCTGA

ATAGTAAGAA

GACGTGATCA

AATGCCCGAA

TCCGAALAGAC

CCAGGCGGCC

CAT CCTC CT C

AACCGCATCC

CTTCCTCAAC

AGGCATCCGA

CATTATAAAA

ACGACTTCGA

CCTACAGTGA

GGAAGGATGA

TAGGGCCTCC

CAAAGCCCGA

CAGGGCTCAA

GGAGAA.AGGT

ATCTGATACC

TTTCGGATAA

CAGTGGCCTT

TCATCGACAA

GGAGAAAGAA

GCCTGGTTTT

AAATGAGCAA

TGGATATCAA~

TCCAGGCAGT

TAAATGATGA

AACGACCCCC

TCCACTGACC

CCAGCACAGA

GTGGGACCCC

CCACCACCCC

ACAAGAACTC

CTCCCTAGAC

AACTTAGGAG

CAAGTCGGCA

TGGCAGGCTG

ATGCTTTATG

AATCGGGCGA

AAAACTCCTC

TGAAAAACTG

CCTAACAACA

GCTCGATACC

CGGGTATTAC

CAACCTGCTG

TACAGAGCAA

GAGTGAAGTC

TGCACTTGGT

GACTCTCCAT

TGAAGACCTT

TTTGCAGCCA

CCAAGGACTA

CTCACAATGA

AAGCGAGAGG

ACAGCCCTGA

CGAGGACCAA

CGGGAAAGAA

CACAACCGAA

AGATCCTCTC

CAAAGTGATT

TGGGACATCA

GTGCCCCAGG

TACATGTCTC

GCATTTGGGT

AAAGAGGCCA

GTGTTCTACA

GGGAGTGTCT

CCGCAGAGGT

ACCGTTCCTA

GTGACCCTTA

CTTCCTGAGG

TACTCTGCCG

GGGATAGGGG

GCACAACTCG

AATCGATTAC

TCAGTTCCTC

TTCAAAGTTC

CAGCCAGAAG

CCAGCCAGCA

TACAAGGCCA

CCCCCAAGGC

ACCCCCAGCA

CCGCACAAGC

TCCCCGGCAA

3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 221 ACTAAACAAA ACTTAGGGCC AAGGAACATA CACACCCAAC AGAACCCAGA CCCCGGCCCA

CGGCGCCGCG

CCCCGGTGCC

AATCCILAGAC

GAGGAAGCCC

GGGCCACCAG

ACCCCAGCCC

CGAAGGACCC

CTCCTCCTCT

CCCACCCCTA

GGTCTCAAGG

ACCGGTCAAA

AGCTACAAAG

ATAACTCTCC

ACAGTTTTGG

CAGAGTGTAG

GCCCTAGGCG

CTGAACTCTC

GAGGCAATCA

ATCAATAATG

CTCGGGCTCA

CGGGACCCCA

ATCAATAAGG

AGCAGAGGIA

AGTATAGCCT

GTCTCGTACA

CCCCCAACCC

CACAGGCAGG

GGGGGGGCCC

ACCCACCCCA

CTCCCAGACT

CGATCCGGCG

CCGAACCGCA

TCTCGAAGGG

ILAGGAGACAC

TGAACGTCTC

TCCATTGGGG

TTATGACTCG

TCA-ATAACTG

AACCAATTAG

CTTCAAGTAG

TTGCCACAGC

AAGCCATCGA

GACAAGCAGG

AGCTGATACC

AATTGCTCAG

TATCTGCGGA

TGTTAGAAAA

TAAAGGCCCG

ATCCGACGCT

ACATAGGCTC

CCGACAACCA

GACACCAACC

CC CCAAAAAA

CACACGACCA

CGGCCATCAC

GGGAGCCACC

AAGGACATCA

ACCAAAAGAT

CGGGAATCCC

TGCCATATTC

CAATCTCTCT

TTCCAGCCAT

CACGAGGGTA

AGATGCACTT

GAGACACAAG

TGCTCAGATA

CAATCTGAGA

GCAGGAGATG

GTCTATGAAC

ATACTATACA

GATATCTATC

GCTCGGATAC

GATAACTCAC

GTCCGAGATT

TCAAGAGTGG

GAGGGAGCCC

CCCGAACAGA

AGGCCCCCAG

CGGCAACCAA

CCCGCAGAAA

CAACCCGAAC

GTATCCCACA

CAATCCACCA

AGAATCAAGA

ATGGCAGTAC

AAGATAGGGG

CAATCATTAG

GAGATTGCAG

AATGCAATGA

AGATTTGCGG

ACAGCCGGCA

GCGAGCCTGG

ATATTGGCTG

CAACTATCTT

GAAATCCTGT

CAGGCTTTGA

AGTGGAGGTG

GTCGACACAG

AAGGGGGTGA

TATACCACTG

CCAACCAATC

CCCAGCACCT

GGGCCGACAG

ACCAGAACCC

GGAAAGGCCA

CAGCACCCA-A

GCCTCTCCALA

CACCCGACGA

CTCATCCAAT

TGTTAACTCT

TGGTAGGAAT

TCATAAAATT

AATACAGGAG

CCCAGAATAT

GAGTAGTCCT

TTGCACTTCA

AAACTACTA.A

TTCAGGGTGT

GTGATTTAAT

CATTATTTGO

GCTATGCGCT

ATTTACTGGG

AGTCCTACTT

TTGTCCACCG

TGCCCAAGTA

CCGCCGGCTC

AACCATCGAC

CCAGCACCGC

AGACCACCCT

CAACCCGCGC

GAGCGATCCC

GTCCCCCGGT

CACTCAACTC

GTCCATCATG

CCAAACACCC

AGGAAGTGCA

AATGCCCAAT

ACTACTGAGA

AAGACCGGTT

GGCAGGTGCG

CCAGTCCATG

TCAGGCAATT

CCAAGACTAC

CGGCCAGAAG

CCCCAGCTTA

TGGAGGAGAC

CATCTTAGAG

CATTGTCCTC

GCTAGAGGGG

TGTTGCAACC

4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 222

CAAGGGTACC

GTGTGCAGC

TACACCAAGT

TCACAAGGGA

ACGATCATTA

GTAGTCGAGG

TACTTGCACA

AATCTGGGGA

CAGATATTGA

GTGTGTCTTG

AACAAAAAGG

ACATCAAAAT

CACAAGTCTC

TATCTCCGGC

ATCATCCACA

TCCCAAGGGA

TTTGCTGGCT

CATTAGACTT

TCTAGATGTA

AATCATCGGT

CATCTCTGAC

TTGGTGTATC

GGCTGCTGAA

CAATCAGTTC

ATTCTCALC

ATCTATAGTC

TTATCTCGAA

AAAATGCCTT

CCTGTGCTCG

ACCTAATAGC

ATCAAGACCC

TGAACGGCGT

GAATTGACCT

ATGCAATTGC

GGAGTATGAA

GAGGGTTGAT

GAGAACAAGT

CCTATGTA.AG

CTCTTCGTCA

TTCCCTCTGG

ATGTCACCAC

AGTAGGATAG

GTTCTGTTTG

CATCGGGCAG

ACTAACTCA

GATGAAGTGG

AAGATTAAAT

AACCCGCCAG

GAGCTCATGA

CTAGCTGTCT

ATGTCGCTGT

ACTATGACAT

TTTTGATGAG

GTACCCGATG

TACACTCGTA

CAATTGTGCA

TGACAAGATC

GACCATCCAA

CGGTCCTCCC

TALAGTTGGAG

AGGTTTATCG

AGGGATCCCC

TGGTATGTCA

GTCGCTCTGA

TCAAGCAACC

CCGAACAATA

AACGAGACCG

TCATTAACAG

TCATGTTTCT

CCATCTACAC

TCGAGCATCA

GCCTGAGGAC

TCCTTAATCC

AGAGAATCAA

ATGCATTGGT

CAAAGGGAAA

CCCTGTTAGA

CCCAGGGAAT

TCATCGTGTA

AGTCCTCTGC

TCCGGGTCTT

TCAATCCTTT

CTAACATACA

GTCGGGAGCA

ATATTATTGG

GATGCCAAGG

AGCACTTGCA

GCTTTAATAT

AGACCAGGCC

TCCTCTACAA

ACCGCACCCA

TCGGTAGTTA

GATAAATGCC

AGAACATCTT

GAGCTTGATC

CGCAGAGATC

GGTCAAGGAC

ACCTCAGAGA

GGATAGGGAG

ATTGGATTAT

GAACTCAACT

CTGCTCAGGG

CTTGTATTTA

GTATGGGGGA

CTTTCATGCC

TCCA.AGAATG

TTGGGAACCG

GCAAGTGTTA

TTGCTGCCGA

GGAGGTATCC

AGAGGTTGGA

A.ATTGTTGGA

TAGTCTACAT

GTTGCTGCAG

TAAAGCCTGA

CTCTTGAAAC

GCATCAAGCC

ATTAAAACTT

TTCTACAAAG

ATGATTGATA

GGGTTGCTAG

CATAAAAGCC

GTGCTGACAC

TTCACTGACC

TACGACTTCA

GATCAATACT

CTACTGGAGA

CCCACTACAA

GGTCGAGGTT

ACTTACCTAG

AGAGGGGACT

CCTCCGGGGG

GTTCATTTTA

CACAACAGGA

TAACTGCCCG

AGACGCTGTG

CGTAGGGACA

GTCATCGGAC

CCTGATTGCA

GGGGCGTTGT

TCTTACGGGA

ACAAATGTCC

CACCTGAAAT

AGGGTGCAAG

ATAACCCCCA

GACCTTATGT

CCATTGCAGG

TCAGCACCAA

CACTCTTCAA

TAGTGAALATT

GAGATCTCAC

GTGCAGATGT

CCAGAACAAC

TCAGAGGTCA

ACAATGTGTC

TGGAAAAGCC

6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 223 9 9* 9. 9 9. 9* 9 9 9

TAATCTGAGC

AGGTGTTATC

GCAACCAGTC

AGCCCTTTGT

CAGCTTCCAG

CACCTTATCA

TATCGCTGAC

AATGGAGACA

CGAGTGGGCA

GAGTCTGACA

CGGTTCAGGG

ACCAATGAAG

GGTTAGTCCC

AACATACCTA

ACCTGGTCAA

TGTGGTTTAT

GCCTATAAAG

CTGGTGCCGT

TGGGATGGTG

ATAGGGCTGC

GTGAAATAGA

CGCTATCTGT

ATAAGATAGT

CTACACTGTG

TAAACAATGT

AGCAAAAGGT

AGAAATCCGG

AGTAATGATC

CACCGGGAAG

CTCGTCAAGC

ACGGATGATC

AATCAAGCAA

TGCTTCCAC

CCATTGAAGG

GTTGAGCTTA

ATGGACCTAT

AACCTAGCCT

TACCTCTTCA

CCTGCGGAGG

GATCTCCAAT

TACGTTTACA

GGGGTCCCCA

CACTTCTGTG

GGCATGGGAG

TAGTGAACTA

CATCAGAATT

CAACCAGATC

AGCCATCCTG

TCAGAACATC

GGAAGTTGGG

CAGAGTTGTC

GTTTGGGGGC

TCAGCAACTG

ATTCTATCAC

TAGGTGTCTG

CAGTGATAGA

AATGGGCTGT

AGGCGTGTAA

ATAACAGGAT

AAATCAAAAT

ACAAATCCAA

TAGGTGTAAT

ATGTCCCAAT

TGGATGGTGA

ATGTTTTGGC

GCCCAAGCCG

TCGAATTACA

TGCTTGCGGA

TCAGCTGCAC

ATCTCATGAT

AAGAAAAACG

TTATACCCTG

GAGTATGCTC

AAGCACCGCC

AATGTCATCA

ACAACTGAGC

TCCGGTGTTC

TATGGTGGCT

AATTCCCTAT

GAAATCCCCA

CAGGCTTTAC

CCCGACAACA

GGGTAAAATC

TCCTTCATAC

TGCTTCGGGA

CCACAACAAT

CAACACATTG

TA-AGGAAGCA

TGTCAAACTC

AACCTACGAT

CTCATTTTCT

AGTGGAATGC

CTCAGAATCT

AGTCACCCGG

GTCACCCAGA

TAGGGTCCAA

AAGTTCACCT

GAGTCCCTCA

TAAAAAACGG

AGTCCALAGCT

ATGTACCGAG

CATATGACAA

TTGGGGGAGC

CAGGGATCAG

ACCGACATGC

CTCTCATCTC

CGAACAGArG

C-AAGCACTCT

GGGGTCTTGT

TTCGGGCCAT

GTGTATTGGC

GAGTGGATAC

GGCGAAGACT

AGTTCCAATC

ACTTCCAGGG

TACTTTTATC

TTCACATGGG

GGTGGACATA

GAAGATGGAA

CATCAGGCAT

GTGGTTCCCC

AGATAGCCCG

CGCTTACAGC

ATTTTCCAAC

TAGGAGTTAT

TGTTTGAAGT

ACTATCTTGA

TCAAACTCGC

GGAAAGGTGT

AATCCTGGGT

ACAGAGGTGT

ACAAGTTGCG

GCGAGAATCC

CTGTTGATCT

TGATCACACA

TGACTATCCC

CGAGATTCAA

GCCATGCCCC

TGGTGATTCT

TTGAACATGC

CTTTTAGGTT

ACCAAAAACT

TCACTCACTC

CCAATCGCAG

ACCCACTAGT

GTTATGGACT

ATAGTTACCA

CTGGAGGACC

CAAATGATTA

CCGGCCCACT

8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 CTCATATTCC ATATCCAAAT TGTAATCAGG ATTTATTTAA~ CATAGAAGAC AAAGAGTCAA 224 9* S S

S

CGAGGAAGAT

AGGTTTTCCA

AGGACATCAA

AGCCCTTTCT

CCCATACTTG

TGCTAATCTC

TGACATTTGA

CCGCTATGAC

AkACTGATAGA

TGGAGCCTCT

CTTTCCTTAA

ATGAAGGTAC

TACATCTGAC

CAGTAACGGC

AGACTCTGAT

GGCACGGAGG

ATGCTCAAGC

TTGCTGGAGT

ACCTAAAGGA

AGTTCCTGCG

TTAATGATTC

TCCATGACCC

GTAGACTTTT

TAATCTCAAA

ATTTGACTAA

CCGTGAACTC

ATGCTTAAGG

GGAGAAAGTT

GTTTTGGTTT

CCATAGGAGG

TCGTGACCTT

ACTGGTTTTG

TATTGATGCT

TGGTTTCTTC

TTCACTTGCT

CCACTGCTTT

TTATCATGAG

AGGGGAGATT

TGCTGAAAAT

GAAAGGTCAT

CAGTTGGCCA

TTCAGGTGAA

GAAATTTGGC

CAAGGCACTT

TTACGACCCT

GAGCTTTGAC

TGAGTTCAAC

TGCTAkAATG

CGGGATTGGC

GGCACTCCAC

CTCAAAAAGG

GACACTA.ACT

ATTAACTTGG

ACAGTCAAGA

AGACACACAC

GTTGCTATAA

ATGTATTGTG

AGGTATACAG

CCTGCACTCG

TACCTGCAGC

ACTGAAATAC

TTAATTGAAG

TTCTCATTTT

GTTAGGAAAT

GCCATATTTT

CCGCTGACCC

GGGTTAACAC

TGCTTTATGC

GCTGCTCTCC

CCCAAGGGAA

CCATATGATG

CTGTCTTACA

ACTTACAAAA

AAATATTTTA

ACTCTAGCTG

GGAATTCGCT

CACGGCTTGG

GAGTTTACAT

CTGAGATGAG

CTGTATTCTT

TCAGTAAAGA

ATGTCATAGA

AGCTTCTAGG

GGAATCCAAC

TGAGGGATAT

ATGATGTTCT

CTCTAGATTA

TCAGAAGTTT

ACATGAATCA

GTGGAATCAT

TCCCCCTGCA

ATGAGCAGTG

CTCTTAGCCT

AAAGGGAATG

CCGGGTCACG

TGATAATGTA

GCCTGAAAGA

TGAGGGCATG

AGGACAATGG

TCTCAGGAGT

GTACTCCAAA

CCTAGGCTCC

GCACAGCTCC

GTCAGTGATT

CACTGGTAGT

GTCTCAACAT

GGGGAGGTTA

AAGAGTCAGA

TTATCAKATT

AACAGTAGAA

TGACCAAAAC

CATTTTCATA

CGGCCACCCC

GCCTAAAGTC

AATCAACGGC

TGCTGCAGAC

CGTTGATAAC

GGATAGTGAT

GGATTCAGTT

GAGGCTTGTA

TGTTGTAAGT

AAAGGAGATC

CCAAGTGATT

GATGGCCAAG

CCCCAAAGAT

GTCAGTGATA

GAATTGAGGG

CAGTGGTTTG

AAATCACAAA

TCAGTTGAGT

GTATATTACC

ATGACAGAGA

TACATGTGGA

GTAGCCATGC

CTCAGAGGTG

GGGTTTTCTG

ACTGATGACA

AGACTTGAAG

ATTGTGTATG

TATCGTGACA

ACAATCCGGA

TGGAAATCTT

CTGACAATGT

TACCCGAAAG

GATGTTTTCC

GGAGCTTACC

AAGGAAACAG

GCTGAAAATC

GATGAGCACG

CTCAAAGAAA

9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 GTCACAGGGG GGGGCCAGTC TTAAAAACCT ACTCCCGAAG CCCAGTCCAC ACAAGTACCA 225 GGAACGTGAG AGCAGCAAA-A GGGTTTATAG GGTTCCCTCA AGTAATTCGG CAGGACCAAG

S

S S

S.

SSSS

S

ACACTGATCA

ATCTCAAGA

TAAATGAGAT

CTGTCCTGTA

ATAAAGTCCC

GTCAGAAGCT

GAGTAAGGAT

TACCCAGCAC

ACTTTGTAAT

CAATTGTTTC

TGTCCCAATC

AAACAAGGGC

ATGACCGTTA

CTCTTGGCTT

ACAACGACCT

TGAATATGAG

ATCTCAAGAG

CACAACAACC

TTGTATGTGT

TCCATAGTCC

AGGGACTGGC

TCCTGGATCA

AAGGCCTGAT

TGTCCAATTA

GAAATGTCCT

TCCGGAGAAT

GTACTGCCTT

TTACGGATTG

TGTAAGTGAC

CAATGATCA-A

GTGGACCATC

TGCTTCGTTA

ATGGCCCTAC

TCTTAGGCAA

ATCACATTTT

ACTCAAGAGC

AGCATGCAGT

CCTTGCATAT

CACAATCAAT

CTTAATAAGG

CAGGCTGTTT

AATGATTCTC

GGGGGACTCT

CCAGAGCATC

AAACCCAATG

GGCATTCCTC

TAGTGTCACA

TCGAGCCAGC

TGACTATGAA

CATTGACAA

ATGGAAGCTT

AATTGGAGAT

CCCTCATTTT

CCTCATTGCC

ATCTTCATTA

AGCACCATTC

GTGCAAGGGG

AACCTTAAGA

AGGCTACATG

TTTGTCTATT

ATCGCAAGAT

AATATTGCTA

TCCCTGAACG

TCAACCATGA

ATGGCACTGT

GTCAGAAACA

GCCTCACTAA

TCATTCCTAG

ACTAGACTCC

TTAAAAGGAT

ATGGACAGGC

GGGGCAAGAG

ATGAGGAAGG

CAATTCAGAG

GAGTCATGTT

ACGAGACAGT

ATGAGACCAT

TCCAGTGGCT

CCCCCGACCT

AGTACCCTAT

CCTATCTATA

ACAATCAGAC

AACGGGAAGC

ATATTGGCCA

C.AAAAGGAAT

GTGTATTCTG

CAACAATGGC

TCCTAAAAGT

CCCGGGATGT

TGCCCGCTCC

TCGGTGATCC

TGCCTGAAGA

ACTGGGCTAG

TCAAGAACAT

TATTCCATGA

ATATTATAGT

AGTCTATTGC

GGGGGTTAAC

CAGGGATGGT

CAGTGCAGCT

CAGTGCATTT

CAGCTTGTTT

GCATALAGAGG

TGACGCCCAT

GGGAGGTATA

CCTGGCTGCT

CATAGCCGTA

TGCTAGAGTA

TCACCTCAAG

ATATTATGAT

GTCAGAGACT

TAAAAGCATC

GATACAGCAA

AGTCATACCC

TATTGGGGGG

AGTAACATCA

GACCCTCCAT

CGACCCTTAC

AACTGCAAGG

TGACAGTAAA

ACCTAGGGCA

AGGCATGCTG

CTCTCGAGTG

GCTATTGACA

GGCGAGAGCT

ATCACGACTG

GCACAGAGGC

CTTGAGACCT

ATCCCGTTAT

GAAGGGTATT

TATGAGAGCG

ACAAAAAGGG

ACTAGAGATT

GCAAATGAGA

GGGCTACTTG

ATAGTTGATG

GAGAGAGGTT

ATTCTGATCT

CTCCTCACA-A

ATGAATTATC

TCAATTGCTG

CAAGTAATGA

TCAGCAAATC

TTTGTCCTGA

GA.AGAGGACG

GCTCATGAAA

GATACCACAA

ATAACCAGAT

GGAAGAAAGA

CTAAGAAGCC

11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 226

ATATGTGGGC

TAGAATCTAT

GATCAGTCAA

AGGAAACATC

TGAAGCTTGC

CAGTGTACTC

CTAGGCAAAG

CGACTAATTT

CCCTTGTCCG

CAGATAAGAA

TTTTAGAk.AC

TTCACGTCGA

CCCGCAAGCT

CTTTAATTGA

AATTTGTTAC

CTATGATTGA

TAOGGGATGA

TCACTATCTA

GACCATCAGG

AAGGAGTGTT

GGCATTGTGG

CAACTGTGTG

ALAGAGTTAGA

GATTCGACAA

GGGCCTGCCC

GAGGCTAGCT

GCGAGGCCAC

CTACGGATGG

ATCCTTGAGA

CTTCGTAAGA

ATGGGCTTAC

GGCCAATGTG

AGCGCATAGG

AGTGGCGAGG

GGTTGATACT

ATTGTTTCGA

AACAGATTGT

AGAGCTGAGG

CAGAGATACA

ATGGTCCACA

CCTGGTA.ACA

CGATATCAAT

CTTGGGCCAG

GAAATATCAG

TAAGGTGCTT

TATTATAGAG

CAACATGGTT

AGAGTTCACA

CATCCAGGCA

ACCAATTCGA

CGAGGACGGC

CTTATTCGGC

TTTTTTGTCC

GTCCCATATA

GCCCCAAGTC

GGTGATGATG

AGCCTGGAGG

TTGAGGGATC

TATACCACAA

AACTTTATAT

CTCGAGAAAG

TGCGTGATCC

GCAGAGCTAT

ACAAGGCTAT

CCCCAACTAT

AAATTTGAGA

AGTTTCATkA

TGTGCGGCCA

ATGGGTGAGC

GTCAATGCTC

CCTATCCATG

TACACATGCT

TTTCTCTTGT

AAACACTTAT

GGTCTAAGAC

CTATTTACGG

GTCATGAGAC

CCTCGGGTTG

TTGGTTCTAC

GATCCTTGCG

ATAGCTCTTG

AGCTAAGGGT

GTAGCACTCA

TCTCCA.ACGA

ACCAACAAGG

ATACCGGATC

CGATGATAGA

GTACCAACCC

ACACCCAGAG

ATCACATTTT

AGGACCATAT

CTGAGTTTCT

TCAATTGGGC

TGTTGTCATC

TAAGCCACCC

GTCCTTCACT

ATATGACCTA

GTGAA.AGCGA

GTGTTCTGGC

CGGTAGAGA

CCTTGAGGTC

ATGTGTCATC

CCALACTGGAT

CACTGATGAG

ATCTGCTGTT

GAACGAAGCC

GATCACTCCC

AGTGAAATAC

CAATCTCTCA

AATGCTTCTA

ATCTAACACG

TCATCCCAGG

ATTGATATAT

CCATAGGAGG

AGCTAAGTCC

GAATGAAATT

GCTCATAGAG

ATTTGATGTA

GTTCCTTTCT

AAAGATCTAC

TGATGCTCAA

CCTCGACCTG

CGAGGATGTA

AGATTTGTAC

ATGTGCAGTT

CCTGATGTAC

TGCGAGTGTG

GATATTGACA

AGAACAGACA

AGAATAGCAA

TGGTTGTTGG

ATCTCAACTT

TCAGGTACAT

TTTGTCATAT

GGGTTGGGTG

GTATTACATC

ATACCCAGCT

GATAATGCAC

CACCTTGTGG

ACAGCACTAT

TCAGCTCTCA

CCAAGATTAT

CATTATCATA

AGAATGAGCA

AAGAALATTCT

AACTTGCACA

TTGTTGAATG

GTACCGGACA

TGTCAACCAG

CTAACCGACC

12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 a ATATCAAGGC AGAGGCTAGG TTATCTCCAG CAGGATCTTC GTGGAACATA AATCCAATTA 227 *0 a

TTGTAGACCA

GATTGAGAGT

CAkkAGATCGG

ATGATGTTGC

GGGGCAkATCT

CTTGCTACAA

ACGGCTTGTT

AACTA.AACAA

AATTAGCACC

TTGTCAAAGT

TCAATTTCAT

AGACCTTGCC

TGGCTCTGCT

GGGATTTTGT

TATACCCTAG

AGGCTAACCG

GGACTTCACC

CAkTTGTGGG

CTATAGAGCA

AATTGATCCA

TCTACAGGGA

CTTACCCCGT

TTTGGGGGCA

ATCTCAAGTC

CCAAGTCAGA

TAACAGTCAA

TTACTCATGC

TGATCCAGGA

CAGCAACAAC

AAAATTGCTC

CGCCAATTAT

AGCTGTTGAG

CTTGGGTGAG

GTGCTTCTAT

CTATCCCTCC

GCTCTTTAAC

AGTTAGTAAT

TAACAAAGAT

CCTGGGCAAA

TCAGGGATTT

ATACAGCAAC

GCTAATGAAT

TGGACTTATA

AGACGCAGTT

GGTGCTGATC

CCATGATGTT

GTTGGCAAGA

ATTGGTAAGT

CATTCTTCTT

CGGCTATCTG

GAILACAGATT

GGAGACCAAA

TCTCTGACTT

TTCATTTTCG

ATCTCAAATA

AKAGATATCA

GAA.ATCCATG

ATATCAACAT

GGATCGGGTT

AATAGTGGGG

GAAGTTGGCC

GGGAGGCCCG

ATCCCTACCT

ACTATAGAGA

ATAGGATCAA

ATAAGTTATG

TTCATATCTA

CCTGAAAAGA

GGTCACATCC

AGTAGAGGTG

AATTGCGGGT

GCCTCAGGGC

TTCAAAGACA

AGCAGGCAAC

TACTCCGGGA

ATACTAGACT

ATTATGACGG

GAATGGTATA

ATCTCCGGCG

ACGCCCTCGC

TGAGCATCAA

ACACAAGCA

CTTTCCGCAG

TAATTAGGAG

CTATGTTGAT

TTTCCGCCAA

TTGTCGAACA

A.AGTCACGTG

CTAGTGTGGG

AGCTAGAGGA

TACTGGTGAT

TAGGGTCTTA

CTGAATCTTA

TTAAGCAGCA

TATCCATTA.A

ATATCAATCC

TGGCAATTAA

AAGATGGATT

ACCGAAGAAG

GAGAACTTAT

ACAGAALAGTT

TACACCAGAA

GGGGTTTGAA

AGTTAGTCGG

AGGATCGATC

TGAGGTAAAT

GGCTTTCAGA

GCACAATCTT

AATCGGGTTG

ATGCCTTGAG

CACTTATAAG

TTCTAGATCT

CAGAATGGGA

GGTAGGCAGT

GTTTATCCAT

ATTGGCAGCC

TAAGCTTATG

TTATAGAGAA

TTTGGTTATG

GATAATTGAA

GCAACTAAGC

TACTCTGAAA

CGGACCTAAG

GCTTAATTCT

TCAACAAGGG

ATCTAGGATC

GATAAATAAG

TATCTTCGTT

ACGTGAGTGG

ATACAGTGCC

AAACAGATAA

GTCAGTCAGC

CCCCCACACG

CCCATTTCAG

AACTCATCTG

CCAGGGGAGG

GAGATACTTA

GGTCAAAGGG

GTAGGTAATA

GTAGATTGCT

TCAGATATAG

ATCTTATCGA

CCTTTCAGCG

GTGAACCTTG

ACAGATCTCA

TCATCTGTGA

TGCATACAAG

AAACTTACAC

CTGTGCAAAG

ATACTCATCC

ATGTTCCACG

ACCCGCAAAT

TTTATCCAGA

AAGAATCTAT

GTTTTTAAGG

CTGATTAAGG

14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15240 15300 15360 15420 15480 15540 15600 15660 15720 15780 a a 228 ACTAATTGAT TGAACTCCGG AACCCTAATC CTGCCCTAGG TGGTTAGGCA TTATTTGCAA 15840 TATATTAAAG AAAACTTTGA AAATACGAAG TTTCTATTCC CAGCTTTGTC TGGT 15894 INFORMATION FOR SEQ ID NO:16: SEQUENCE CHARACTERISTICS: LENGTH: 2183 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID, NO:16: Met Asp Ser Leu Ser Val Asn Gin Ile Leu Tyr Pro Giu Val His Leu 1 5 3.0 *Asp Ser Pro Ile Val Thr Asn Lys Ile Val Ala Ile Leu Giu Tyr Ala 25 *p*Arg Val Pro His Ala Tyr Ser Leu Giu Asp Pro Thr Leu Cys Gin Asn 40 Ile Lys His Arg Leu Lys Asn Giy Phe Ser Asn Gin Met Ile Ile Asn 55 Asn Val Giu Vai Gly Asn Val Ile Lys Ser Lys Leu Arg Ser Tyr Pro 70 75 **Aia His Ser His Ile Pro Tyr Pro Asn Cys Asn Gin Asp Leu Phe Asn 90 Ile Glu Asp Lys Giu Ser Thr Arg Lys Ile Arg Glu Leu Leu Lys Lys ***100 105 110 Giy Asn Ser Leu Tyr Ser Lys Vai Ser Asp Lys Vai Phe Gin Cys Leu 115 120 125 Arg Asp Thr Asn Ser Arg Leu Gly Leu Gly Ser Giu Leu Arg Giu Asp 130 135 140 Ile Lys Giu Lys Val Ile Asn Leu Gly Val Tyr Met His Ser Ser Gin 145 150 155 160 Trp Phe Giu Pro Phe Leu Phe Trp Phe Thr Val Lys Thr Giu Met Arg 165 170 175 229 Ser Pro Leu Phe 225 Thr Arg Gly Ala Leu 305 Phe Ile Phe Asn 385 Arg Ala His Val Val Val 210 Glu Glu Val Asn Tyr 290 Asn Ser Phe Arg Val 370 Met Asp Ala Glu Ile Phe 195 Ala Leu Thr Arg Pro 275 Leu His Asp Ile Ser 355 Arg Lys Arg Asp Gin 435 Lys 180 Phe Ile Val Ala Tyr 260 Thr Gin Cys Glu Thr 340 Phe Lys Gly His Thr 420 Cys Ser Thr Ile Leu Met 245 Met Tyr Leu Phe Gly 325 Asp Gly Tyr His Gly 405 Ile Val Gin Gly Ser Met 230 Thr Trp Gin Arg Thr 310 Thr Asp His Met Ala 390 Gly Arg Asp Thr Ser Lys 215 Tyr Ile Lys Ile Asp 295 Glu Tyr Ile Pro Asn 375 Ile Ser Asn Aen His Ser 200 Glu Cys Asp Leu Val 280 Ile Ile His His Arg 360 Gin Phe Trp Ala Trp 440 Thr 185 Val Ser Asp Ala Ile 265 Ala Thr His Glu Leu 345 Leu Pro Cys Pro Gin 425 Lys Cys Glu Gin Val Arg 250 Asp Met Val Asp Leu 330 Thr Glu Lys Gly Pro 410 Ala Ser His Leu His Ile 235 Tyr Gly Leu Glu Val 315 Ile Gly Ala Val Ile 395 Leu Ser Phe Arg Leu Vai 220 Glu Thr Phe Glu Leu 300 Leu Glu Glu Vai Ile 380 Ile Thr Gly Ala Arg Ile 205 Tyr Gly Glu Phe Pro 285 Arg Asp Ala Ile Thr 365 Val Ile Leu Glu Gly 445 Arg 190 Ser Tyr Arg Leu Pro 270 Leu Gly Gin Leu Phe 350 Ala Tyr Asn Pro Gly 430 Val His Arg Leu Leu Leu 255 Ala Ser Ala Asn Asp 335 Ser Ala Glu Gly Leu 415 Leu Lys Thr Asp Thr Met 240 Gly Leu Leu Phe Gly 320 Tyr Phe Glu Thr Tyr 400 His Thr Phe Gly Cys Phe Met Pro Leu Ser Leu Asp Ser Asp Leu Thr Met Tyr Leu 230 450 455 460 Lys Asp Lys Ala Leu Ala Ala Leu Gin Arg Giu Trp Asp Ser Val Tyr 465 470 475 480 Pro Lys Glu Phe Leu Arg Tyr Asp Pro Pro Lys Gly Thr Gly Ser Arg 485 490 495 Arg Leu Val Asp Val Phe Leu Asn Asp Ser Ser Phe Asp Pro Tyr Asp 500 505 510 Val Ile Met Tyr Val Vai Ser Giy Ala Tyr Leu His Asp Pro Glu Phe 515 520 525 Asn Leu Ser Tyr Ser Leu Lys Glu Lys Giu Ile Lys Giu Thr Gly Arg 530 535 540 Leu Phe Ala Lys Met Thr Tyr Lys Met Arg Ala Cys Gin Val Ile Ala 545 550 555 560 *Glu Asn Leu Ile Ser Asn Giy Ile Giy Lys Tyr Phe Lys Asp Asn Giy 565 570 575 Met Ala Lys Asp Glu His Asp Leu Thr Lys Ala Leu His Thr Leu Ala 580 585 590 ***Val Ser Giy Vai Pro Lys Asp Leu Lys Glu Ser His Arg Gly Gly Pro 595 600 605 0 0 0..:Val Leu Lye Thr Tyr Ser Arg Ser Pro Val His Thr Ser Thr Arg Asn 610 615 620 Val Arg Ala Ala Lys Gly Phe Ile Gly Phe Pro Gin Val Ile Arg Gin *625 630 635 640 Asp Gin Asp Thr Asp His Pro Giu Asn Met Giu Ala Tyr Glu Thr Val 645 650 655 .Ser Ala Phe Ile Thr Thr Asp Leu Lys Lys Tyr Cys Leu Asn Trp Arg a..660 665 670 Tyr Giu Thr Ile Ser Leu Phe Ala Gin Arg Leu Asn Giu Ile Tyr Gly 675 680 685 Leu Pro Ser Phe Phe Gin Trp Leu His Lys Arg Leu Giu Thr Ser Val 690 695 700 Leu Tyr Val Ser Asp Pro His Cys Pro Pro Asp Leu Asp Ala His Ile 705 710 715 720 Pro Leu Tyr Lys Val Pro Asn Asp Gin Ile Phe Ile Lys Tyr Pro Met 725 730 735 231 Gly Gly Ile Giu Gly Tyr Cys Gin Lys Leu Trp, Thr Ile Ser Thr Ile 740 745 750 9 .9 9 9.

9* 9 9 9***99 9 9 999w 9*9*99 9 999*99 9* 9 *999 9 *999 Pro Tyr Leu Vai 770 Ser Thr 785 Arg Asp His Leu Ser Lys Ser Ile 850 Arg Ala 865 Arg Giy Ile Gin Thr Arg Arg Met 930 Met Ser 945 Ile -Aia Thr Leu Leu 755 Gin Trp Tyr Lys Giy 835 Aia Ala Tyr Gin Asp 91i5 Ala Arg Asp His Tyr Giy Pro Phe Ala 820 Ile Arg Cys Asp Ile 900 Vai Leu Leu Leu Gin 980 Leu Asp Tyr Vai 805 Asn Tyr Cys Ser Arg 885 Leu Vai Leu Phe Lys 965 Val Al a Asn Asn 790 Ile Giu Tyr Vai Asn 870 Tyr Ile Ile Pro Vai 950 Arg Met Ala Gin 775 Leu Leu Thr Asp Phe 855 Ile Leu Ser Pro Aia 935 Arg Met Thr Tyr 760 Thr Lys Arg Ile Gly 840 Trp Ala Aia Leu Leu 920 Pro Asn Ile Gin Giu Ile Lys Gin Val1 825 Leu Ser Thr Tyr Giy 905 Leu Ile Ile Leu Gin 985 Ser Ala Arg Arg 810 Ser Leu Glu Thr Ser 890 Phe Thr Gly Gly Al a 970 Pro Gly Val Giu 795 Leu Ser Val1 Thr Met 875 Leu Thr Asn Giy Asp 955 Ser Gly Val Thr 780 Al a His His Ser Ile 860 Ala Aen Ile Aen Met 940 Pro Leu Asp Arg 765 Lys Ala Asp Phe Gin 845 Val Lys Val Asn Asp 925 Asn Val Met Ser Ile Arg Arg Ile Phe 830 Ser Asp Ser Leu Ser 910 Leu Tyr Thr Pro Ser 990 Ala Ser Val Pro Val Thr 800 Gly His 815 Val Tyr Leu Lys Giu Thr Ile Giu 880 Lys Val 895 Thr Met Leu Ile Leu Asn Ser Ser 960 Giu Glu 975 Phe Leu Asp Trp Ala Ser Asp Pro Tyr Ser Ala Asn Leu Val Cys Val Gin Ser 995 1000 1005 232 Ile Thr Arg Leu Leu Lys Asn Ile Thr Ala Arg Phe Val Leu Ile His 1010 1015 1020 Ser Pro Asn Pro Met Leu Lys Gly Leu Phe His Asp Asp Ser Lys Glu 1025 1030 1035 1040 Glu Asp Glu Gly Leu Ala Ala Phe Leu Met Asp Arg His Ile Ile Val 1045 1050 1055 Pro Arg Ala Ala His Giu Ile Leu Asp His Ser Val Thr Gly Ala Arg 1060 1065 1070 Glu Ser Ile Ala Gly Met Leu Asp Thr Thr Lys Gly Leu Ile Arg Ala 1075 1080 1085 Ser Met Arg Lys Gly Gly Leu Thr Ser Arg Val Ile Thr Arg Leu Ser 1090 1095 1100 Asn Tyr Asp Tyr Glu Gin Phe Arg Ala Gly Met Val Leu Leu Thr Gly 1105 1110 1115 1120 Arg Lys Arg Asn Val Leu Ile Asp Lys Glu Ser Cys Ser Val Gin Leu *0t1125 1130 1135 SAla Arg Ala Leu Arg Ser His Met Trp Ala Arg Leu Ala Arg Gly Arg *1140 1145 1150 Pro Ile Tyr Gly Leu Giu Val Pro Asp Val Leu Giu Ser Met Arg Gly 1155 1160 1165 0**His Leu Ile Arg Arg His Giu Thr Cys Val Ile Cys Glu Cys Gly Ser 1170 1175 1180 Val Asn Tyr Gly Trp Phe Phe Val Pro Ser Gly Cys Gin Leu Asp Asp **1185 1190 1195 1200 Soso*: Ile Asp Lye Glu Thr Ser Ser Leu Arg Val Pro Tyr Ile Gly Ser Thr 1205 1210 1215 0 a 0 '0064,Thr Asp Glu Arg Thr Asp Met Lys Leu Ala Phe Val Arg Ala Pro Ser 0001220 1225 1230 Arg Ser Leu Arg Ser Ala Val Arg Ile Ala Thr Val Tyr Ser Trp Ala 1235 1240 1245 Tyr Gly Asp Asp Asp Ser Ser Trp Asn Glu Ala Trp Leu Leu Ala Arg 1250 1255 1260 Gin Arg Ala Asn Val Ser Leu Glu Glu Leu Arg Val Ile Thr Pro Ile 1265 1270 1275 1280 Ser Thr Ser Thr Asn Leu Ala His Arg Leu Arg Asp Arg Ser Thr Gin 233 1285 1290 1295 Val Lys Tyr Ser Gly Thr Ser Leu Val Arg Val Ala Arg Tyr Thr Thr 1300 1305 1310 Ile Ser Asn Asp Asn Leu Her Phe Val Ile Ser Asp Lys Lys Val Asp 1315 1320 1325 Thr Asn Phe Ile Tyr Gin Gin Gly Met Leu Leu Gly Leu Gly Val Leu 1330 1335 1340 Giu Thr Leu Phe Arg Leu Giu Lys Asp Thr Gly Her Her Asn Thr Val 1345 1350 1355 1360 Leu His Leu His Val Giu Thr Asp Cys Cys Val Ile Pro Met Ile Asp 1365 1370 1375 His Pro Arg Ile Pro Ser Ser Arg Lys Leu Glu Leu Arg Ala Giu Leu 1380 1385 1390 *Cys Thr Asn Pro Leu Ile Tyr Asp Asn Ala Pro Leu Ile Asp Arg Asp 1395 1400 1405 .seThr Thr Arg Leu Tyr Thr Gin Her His Arg Arg His Leu Val Giu Phe 1 410 1415 1420 *see 0. 0 w.Val Thr Trp Her Thr Pro Gin Leu Tyr His Ile Leu Ala Lys Ser Thr i1425 1430 1435 1440 0Ala Leu Ser Met Ile Asp Leu Val Thr Lys Phe Glu Lys Asp His Met 1445 1450 1455 Asn Glu Ile Ser Ala Leu Ile Gly Asp Asp Asp Ile Asn Her Phe Ile 1460 1465 1470 CThr Giu Phe Leu Leu Ile Giu Pro Arg Leu Phe Thr Ile Tyr Leu Gly 1475 1480 1485 .,*Gin Cys Ala Ala Ile Asn Trp Ala Phe Asp Val His Tyr His Arg Pro 1490 1495 1500 Her Gly Lys Tyr Gin Met Gly Giu Leu Leu Her Her Phe Leu Ser Arg 1505 1510 1515 1520 Met Her Lye Gly Val Phe Lys Val Leu Val Asn Ala Leu Her His Pro 1525 1530 1535 Lys Ile Tyr Lys Lys Phe Trp His Cys Gly Ile Ile Giu Pro Ile His 1540 1545 1550 Gly Pro Her Leu Asp Ala Gin Asn Leu His Thr Thr Val Cys Asn Met 1555 1560 1565 234 Val Tyr Thr Cys Tyr Met Thr Tyr Leu Asp Leu Leu Leu Asn Giu Giu 1570 1575 1580 Leu Giu Giu Phe Thr Phe Leu Leu Cys Giu Ser ASP Giu Asp Val Val 1585 1590 1595 1600 P ro Asp Arg Phe Asp Asn Ile Gin Ala Lys His Leu Cys Val Leu Ala 1605 1610 1615 Asp Leu Tyr Cys Gin Pro Gly Ala Cys Pro Pro Ile Arg Gly Leu Arg 1620 1625 1630 Pro Val Giu Lys Cys Ala Val Leu Thr Asp His Ile Lys Ala Giu Ala 1635 1640 1645 Arg Leu Ser Pro Ala Gly Ser Ser Trp Asn Ile Asn Pro Ile Ile Val 1650 1655 1660 Asp His Tyr Ser Cys Ser Leu Thr Tyr Leu Arg Arg Gly Ser Ile Lys 1665 1670 1675 1680 *Gin Ile Arg Leu Arg Val Asp Pro Gly Phe Ile Phe Asp Ala Leu Ala *1685 1690 1695 .00 0 Giu Val Asn Val Ser Gin Pro Lys Ile Gly Ser Asn Asn Ile Ser Asn o 1700 1705 1710 Met Ser Ile Lys Ala Phe Arg Pro Pro His Asp Asp Val Ala Lys Leu .01715 1720 1725 0 00.. Leu Lys Asp Ile Asn Thr Ser Lys His Asn Leu Pro Ile Ser Gly Gly 1730 1735 1740 o Asn Leu Ala Asn Tyr Glu Ile His Ala Phe Arg Arg Ile Gly Leu Asn *.1745 1750 1755 1760 Ser Ser Ala Cys Tyr Lys Ala Val Glu Ile Ser Thr Leu Ile Arg Arg 1765 1770 1775 000.

Cys Leu Giu Pro Gly Giu Asp Gly Leu Phe Leu Gly Glu Gly Ser Gly 1780 1785 1790 Ser Met Leu Ile Thr Tyr Lys Giu Ile Leu Lye Leu Asn Lys Cys Phe 1795 1800 1805 Tyr Asn Ser Gly Val Ser Ala Asn Ser Arg Ser Gly Gin Arg Giu Leu 1810 1815 1820 Ala Pro Tyr Pro Ser Giu Val Gly Leu Val Glu His Arg Met Gly Val 1825 1830 1835 1840 235 Gly Asn Ile Val Lys Vai Leu Phe Asn Gly Arg Pro Glu Val Thr Trp 1845 1850 1855 Val Gly Ser Val Asp Cys Phe Asn Phe Ile Val Ser Asn Ile Pro Thr 1860 1865 1870 Ser Ser Val Gly Phe Ile His Ser Asp Ile Giu Thr Leu Pro Asn Lys 1875 1880 1885 Asp Thr Ile Giu Lys Leu Giu Giu Leu Ala Ala Ile Leu Ser Met Ala 1890 1895 1900 Leu Leu Leu Gly Lys Ile Gly Ser Ile Leu Val Ile Lys Leu Met Pro 1905 1910 1915 1920 Phe Ser Gly Asp Phe Val Gin Gly Phe Ile Ser Tyr Vai Gly Ser Tyr 1925 1930 1935 Tyr Arg Giu Val Asn Leu Val Tyr Pro Arg Tyr Ser Asn Phe Ile Ser 1940 1945 1950 **.Thr Glu Ser Tyr Leu Val Met Thr Asp Leu Lys Ala Asn Arg Leu Met 1955 1960 1965 Asn Pro Giu Lys Ile Lys Gin Gin Ile Ile Glu Ser Ser Val Arg Thr .1970 1975 1980 Ser Pro Gly Leu Ile Gly His Ile Leu Ser Ile Lys Gin Leu Ser Cys 1985 1990 1995 2000 Ile Gin Ala Ile Val Gly Asp Ala Val Ser Arg Gly Asp Ile Asn Pro 2005 2010 2015 Thr Leu Lys Lys Leu Thr Pro Ile Giu Gin Val Leu Ile Asn Cys Gly 2020 2025 2030 Leu Ala Ile Asn Gly Pro Lys Leu Cys Lys Giu Leu Ile His His Asp **2035 2040 2045 .Val Ala Ser Gly Gin Asp Gly Leu Leu Asn Ser Ile Leu Ile Leu Tyr 2050 2055 2060 Arg Giu Leu Ala Arg Phe Lys Asp Asn Arg Arg Ser Gin Gin Gly Met 2065 2070 2075 2080 Phe His Ala Tyr Pro Val Leu Val Ser Ser Arg Gin Arg Giu Leu Ile 2085 2090 2095 Ser Arg Ile Thr Arg Lys Phe Trp Gly His Ile Leu Leu Tyr Ser Gly 2100 2105 2110 Asn Arg Lys Leu Ile Asn Lye Phe Ile Gin Asn Leu Lys Ser Gly Tyr 236 2115 2120 2125 Leu Ile Leu Asp Leu His Gin Aen Ile Phe Val Lys Asn Leu Ser Lys 2130 2135 2140 Ser Glu Lys Gin Ile Ile Met Thr Gly Gly Leu Lys Arg Giu Trp Val 2145 2150 2155 2160 Phe Lys Val Thr Vai Lys Glu Thr Lys Giu Trp Tyr Lys Leu Vai Gly 2165 2170 2175 Tyr Ser Ala Leu Ile Lye Asp 2180 INFORMATION FOR SEQ ID NO:i7: SEQUENCE CHARACTERISTICS: LENGTH: 15462 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: ACCAAACAAG AGAAGAAACT TGTCTGGGAA TATAAATTTA ACTTTAAATT AACTTAGGAT a. a.

a a a.

a a a

TAAAGACATT

TATTTGATAC

TCATTCCTGG

ATAATGAGAA

AACATGCACA

AGCTCTACCT

AGAAAGATCT

ATGAAAAGAC

TGCAGAACGG

CATGTTTAGG

GACTAGAAGG

ATTTAATGCA

ACAGAAAAAT

AATGACATTA

AAGGGCAGGG

AACAACAAAT

AAAACGGCAA

AACTGATTGG

CAGGAACAAT

AGCTCTTATA

TCAAGAAAAG

CGTAGGCAAG

ACTGTCTCTA

GCTCTTCTAT

TTCTTGGTGT

GGAAGTAATG

AAGTATGGAG

ATATTTGGAA

TCAACAATTG

ATACAGATCT

GGAACTCTAT

AAAACATAAC

TATTCGCCCT

TTCTATCTCA

CTTTATTGTC

CAGATGTCAA

GATTTGTGGT

GTGACCTGGA

AAGACCTTGT

GGATAGTTCT

AATTTCAAAA

AAAATCAGCC

TGGACCGACA

TTCACTAGAT

AATGGCTTAT

GTATGTCATA

TAAGACGAGA

TTATGATCAG

CCACACATTT

GGTCAAAGCT

ATGTTGAGCC

GGTGGAGCTA

ATAACTGATG

AATGAGAAAC

GCCAATCCAG

TACATGATTG

GAGATGATAT

GAAACTATGT

GGGTATCCAT

ATCACTAGTA

120 180 240 300 360 420 480 540 600 660 TCTCAGGGTT AAGAAAAGGC TTTTTCACCC GATTGGAAGC TTTCAGACAA GATGGAACAG 237

S.

S

S*

4* 5 S S

S.

S

TGCAGGCAGG

CTCAACAGAG

ATGACCTCAC

GTCTCGCTTC

CTCTATCCAC

CAAAGGGACC

CACCAGGCAA

GAGCCATGCA

GACALAGCAGT

GAGTGACACA

AGACATCTTT

CAGAACAATT

TTCAATATGC

CTGACAATAT

ACAAGAAGAA

AAATAGATGA

ATCAATAATA

GGTAALATTTA

AAACTATCAA

CTCGGCCCTC

AAACGACACA

CAAACCAACA

GTCATCACAC

GAGAGGACCT

AATCCCCAGA

CAATGAAATT

GCTGGTATTG

CTTGGTAACT

AACCATAGAA

ATTCTTCA.AT

TCTCAGACCA

ACGCGCTCCT

CTATCCTGCC

ACAGTATGTG

AGCACGTGAT

CGAATCTAAA

CCACAAACCG

CGAACATAGA

CTGGGCAGA.A

CAAGACCGAA

ACAAAGCAGT

TCTGTTTA.AC

AATAPLGAAAA

GAGTCTGCTT

ATCATGGATT

AACATCATTG

ATCAACACAA

GAAACAAGTG

GAATGTACAA

GGGAGAAGAA

AGCATCACAG

AGAAAGATGG

AGCGGTGACA

CTTATGGTTG

A.AGAATATAC

ACAATCAGAT

GATATCAATA

TTCATCTGTA

ATATGGAGCT

ACGGGA.AGAT

GCCGAAGCTC

GAA.AGCTTGA

ACAGGTGGAT

GCAGATCAAG

GGAAATAGAA

CAP.CAAAACA

CAACCACCCA

GCATTTGGAA

ACTTAGGATT

GAAACTCAAT

CTTGGGAAGA

AATTCATACT

GAACCCAGCA

AGAAAGATAG

CAGAAGCAAA

GCAGCTCAGA

ATTCTAAAAA

ATAAGGACTC

CAGTGGATCA

AAACATTAAT

AAATTGTTGG

ATGGAATTGA

GATTAAAAGC

TCCTCAGAGA

ATGCAATGGG

CATATCTAGA

AAATGAGCTC

AGAGACATAT

CAGCCATAGA

AACAAAATGG

GCGATGATCA

TCAGAGACAG

CTAATCCCAC

GCAACTAATC

AAAGAATCCT

CAATAGAGAG

GGAATCAAGA

CAGCACCGAC

ACTCAGTGCC

TGGATCAACT

AGATAGAAAT

TAGTAGAGCT

TGGAACCCA

TATTGAGGGG

GATTGGGTCA

AACAATGAAT

CAACTACATA

GACCAGAATG

TTTGATGGAA

TCCTATACAT

GGTGGCAGTT

CATTGATATG

AACACTGGA.A

AAGGAACATA

GATGGCAATA

AGAACCTCAA

GACTGAGCAA

ACTAAACAAG

AAACAGAACA

GAATCAACAT

ATCATACCGG

TTGATGGAAA

GATAAATCAA

CCCCAAGAAG

ACCATCTGTC

GACAAAAATA

ATTGATCAGG

GAGACTGTGG

AACACGGAGG

AAAATGCGAC

ATCATGCGGT

ACCAGCAGAA

AGAGATGCAG

GCAGCTTTGA

CTGTATTTAT

GGTGAGTTCG

GTACAAAATA

TTCCAGCTAG

GATGAACTTG

AACAGTTCAG

GATGAAGAGC

TCATCCATAA

GCTACAGAAT

AGACTCAACG

AACCAGGACG

TTTAATCTAA

AATATAGGGT

GCGATGCTAA

CTAATATCTC

ACTTATCGGA

AACCAGAAAT

GACAGTCCGG

AAACTGTACA

TCTCTGGAGG

ATATTGATCT

AATCTGCAAA

780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280

S.

S S *50S

S

5555 238

S.

S*

S.

S

S

5..

S

TGTTCCAAGC

TGATCATGGA

TACTGCTGCA

AAGTTCTTCA

CTGGTTTALAG

ATCAAKAGGG

AACAGAAATA

CAACAACACC

AACTTATACA

AAATGGAAAG

TCTATTGCAG

ACGAGTTGTA

CCTGGCAGGA

AAATGAA.ATG

GATAGAAAAT

TATGACTGAG

CAAAACAAAA

ACAAGGCATT

CGATGTACAA

AATACCCAAA

TCTCTCACp.A

AGAAGTATCT

CAAAGAAACG

ACACAA.AATC

AGGATTAAAG

CATTCCCAGA

GAGATATCAG

AGAAGCCTGG

ACACCAGATG

ACACATCAAG

AAATCAAAAG

CAGAAGAAAA

CAGACAGAAT

GACCGGAACG

AAAGAATCGA

GAAAGGAAGG

AATCTTGGTG

TGTGTAGCAA

TTAGTCATAG

CTAAACCTCA

CAAAGAGAAC

AGAGGAGGAA

TTGAAAGAAG

GACAAGAATA

GTTAAATCAG

AAAGTGAGCA

AGCACAAAAC

GAATTAATGG

ACACCGAACA

AAGCAGAATG

AATAAATTAA

ATCATCATTC

GAAGTGATGA

AATCTATCAG

ATGAAGAAGA

AAGATGACAA

ATACCGACAA

TCTCAAAGAC

CATCAGAAAC

AACAGACAAG

TCCGAACAAA

ATACAGAAGA

TAATTCALATC

ATGTACTAAA

GGGTTTCAAT

AAGCAGATCT

AACTGTCATT

AGAAAGACCA

AAAAGATCAA

TACCCGATCT

AGATATTAAG

GTACAATGAG

AATCATACAT

ACATGTTCAA

AACAGACAAG

AAACAACAGA

TCCTTGTCCA

TCTGAAAATG

CATATTTACA

TACACCTGAT

AATACTAATG

AAGAATTAAA

CCAGATACCA

AACAACCACC

ACAATCCTCA

CACAACTCCT

CTCTGAATCC

GAGCAATCGA

CACATCAAAA

CAATGTAGAT

GGACAACGAC

AAAGAAAATG

GATCACGTCA

AAATGAATCC

GAAGACCAGG

ATATCGACAT

TTCATACAAT

ATCACTAGTT

AAACGAACTC

TGAAGATGTC

AAACAACAGT

TATCAATCAA

AAATGAGTAT

GTCATATAGA

ACAGAACAAA

ACAAGATCAA

AA.AAATAGTA

AAAGGGGGAA

ACATCAGACT

AACACCGACA

TCATGGAATC

CCAACAACAA

AA.ACCCAAGA

TTTACAGAGA

CTAGATTTAT

ACTGCATCAA

ACAAAATTA

GACGAATCAC

CTAATTTCAA

AATGAGAGAG

TTTGACCCAC

GCAGGAGATA

GAGTCAAATG

GCAGTCATCA

AALACGTTGCA

AACAATTGCC

AGATCAAAAC

TATACAAATA

AACTAACTCT

ACCATTACCA

GTAGAAACAG

TAAGTGTTGT

GGACAAAGAA

AAGGGAAAGA

ACAGATCCAC

CAILAGGGGCA

TCATCATCGA

CTTCCAGATC

CACAAAAGAC

GGGCAATTAC

ATCAAGACAA

AGATAGATTT

CACAGATACA

ATAGAAGATT

ATCTCAAAAT

TATCCATGAT

TTATGGAGGC

CACTAGAGAA

CAACAAGACT

ACAACAGCAA

AAAATGATGA

AATGATCCAA

CTGTCAACAC

AGAAAAACTT

GCAATATACA

CTCAAAGTCA

2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 239

C

CC..

C C *C C

C

C

ATGAACAGAG

ACGGATCCCG

ACAAATACGG

GATCATTACC

CAACCAAACT

CGGTACAAAA

TGTTCGATGC

AATTTAGAGT

CTAAGTCAAT

TAAAAACAGG

AAAAATCACT

ACTCTGTTGA

TAGTTGGAGG

GTCAGCTGGT

ATCTAGTTAT

CTTTACCTGG

AACAATGGAA

AAGGATAATC

TCGCAAGAAT

ACAGAACACC

GAGACCGGCA

AACCATGATC

ATTGGTCAAC

TTTGAGCCTC

ATACAAGAAG

AGATGTGATA

GAAAGCAGTA

GTATTTAGAT

GAGTGTGAAT

AATCGGATTG

GGATATAGAA

TATAAAACCA

CAACAAAGTT

AATCTTCGTG

GGCATCACTA

GGTTCAGACT

GAATTTCATG

ATACTGTAAA

AATCAGTCTT

ATTCAAAAGA

CTGGGCTTCA

CGAGTTCAGA

CTAGTAATCT

AAAAACTTAG

AAGAGAGAAG

AGAACAACAA

ACACAACAAG

ATGGCATCTT

AGTCCCAAAG

ATACCAAAAA

TTATTGGATA

GTAACCAATC

CCCCACATTA

GTCTTCTTAC

GATCTCGACA

GCTAAGTACA

GTGAGAAGAA

GAACTGTACC

GCTCTTGCTC

AATTGTACGG

TCTCTACCCA

GATTCTAALAG

GTCCATCTCG

CAGAAAATCG

CATGTCAATG

GAGATTTGTT

TCAGTAGAGA

TACTATCCTA

CTATTTTAGT

GACAAAAGAG

GGACCAAAAA

AATCAAAACA

CACTGAALCAC

TCTGCCAAAT

GGATGAAGAT

TAGAAGACTC

GACTGATCAT

AAGAATCCAA

GAGTTGCA

TCGGCTTCTT

GTGACCCGAG

CTGGGAATGA

CAGTCAAAGC

CATGGTCCAA

CTCAATGTCT

CAATTGGATC

ACACAATATC

GGATAGTTCA

GATTGATCAA

AGAAAATGAG

CAACTGGGTC

ATCCTTTAAT

TTACAAGAGT

ATATTATTGC

CCGGACGTAT

GTCAATACCA

AGTCAAATAG

TCCAACTCAC

AATGCCA.ACT

AGATATCACA

ATCACAAAAC

TAACTCTTGT

CCCTTTA.TAT

TGAAAACACT

GATCGGAAAT

CGAGATGGAA

TTACAAAGTT

CCAGGAATTG

GAAAGAGATG

TAGACTAAGA

TCCACTAGAT

AATAACCTTG

AATCAATCTG

AATTTTGGAT

AAGAAAAGTA

ATTGATATTT

CATATCAAAA

GGATCTAAAT

GGATGCAATT

AAAAGGAGTT

CTATTAAGCC

ACAACTATTA

GAGAAATCAA

TCAAAACAAA

TCAATACTGC

AAACTACAGC

TTTGAAACAA

GGTGACCAAC

GATGGATTAA

GATCCCAGAA

CCACCAAAAC

CGAATCAAAG

TGTGGCTCTG

TTACAAGCCG

GTTGTTTACA

AAAGGAATGC

AGGAGCATAA

TTCAAAATTC

CAGGTACACA

GAGAAAGGCG

GGCAGAATGT

TCTTTAGGAC

ACACTAGCAA

CCGCATCTCA

TTCCAACCTT

GGGAAAATCA

GAAGCAAATA

GCAGTCACAC

AACAAAAGGT

AATTCCAAAA

TAATTATTAC

ACGTAGGTGT

GATATCTAAT

AGATCAAGCA

GATTACAGAA

CAA.AACGATT

3900 3960 4020 4080 41.40 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 240 CTTTGGAGGG GTAATTGGAA CCATTGCTCT GGGAGTAGCA ACCTCAGCAC AAATTACAGC

C.

a a

C

C a..

a

GGCAGTTGCT

AATTAGGGAC

AGCAATTAAA

AGGTTGTGAA

AACAAACATA

TATAGCATCA

ATATGATATC

CTTGAATGAT

CACTCAGATC

CCCTCTTCCC

ATGTATAGAA

TGAAATAGAG

AGACATTGTT

CACCTGTACA

AATTATAACA

TAAAGAAGGA

ACTTGATCCA

AAAAGAATGG

TAGCACTACA

GATAATTACA

TGACAAGCCA

TATAAAAAAC

CCCAATAGAC

TGCTGGTAAT

AATATACATA

CTGGTTGAAG

ACAILACAAAG

TCAGTCCAGG

GCAGCAGGAC

TTTGGTGATA

TTATACCGCA

TATGATCTGT

TACTCAATCA

TACAAAGTAG

AGCCATATCA

GCATTCAGCA

AGCTGCTTAT

CCAAGATATG

TGCAACGGAA

CATAAAGAAT

ACTCTTGCAT

ATTGACATAT

ATAAGAAGGT

ATCATAATTA

ATTGCAATTA

TATGTACTAA

TTAGGAGTAA

AAATCCAAAT

GAGCTGGAGA

TTATGGACAA

CCAAGCAGGC

CAGTGCAGTC

ATTATGTTAA

TTCA.ATTAGG

ACATAGGATC

CAAATATCAC

TATTTACAGA

CCCTCCAAGT

ATTCCATATC

TGACGAALAGG

GCTATATATG

CAGGAAACAT

CATTTGTCAA

TTGGTAATAG

GTAGTACAAT

TCTATACACC

CAATCGAGCT

CAAATCAAAA

TTTTGATAAT

AGTATTACAG

CAAACAAATA

AGTTACGCAA

TCGAGATGGA

CGTCTATGGC

TAATCCTGGT

AAGATCAGAC

AGTTCAGAGC

CAAAGAAATC

AATTGCATTA

GTTACAAGAA

AGAAATATTC

ATCAATAAAG

CAGACTCCCT

ATATAACATC

GGCATTTCTA

CCCTTCTGAT

ATCCCAATGT

TGGAGGAGTG

AATCAATCAA

AGGTATCAAC

AAATGATATA

CAACAAGGCC

ACTAGATTCT

GATCATTATA

AATTCAAAAG

ACATATCTAC

TCCAACTCTA

ATACTGGAAG

TACTCATGGC

GTTATTATCA

AT CGAAAAA C

TCCATAGGAA

GTGCCATCGA

ACACAGCATT

AAAGGAATAA

ACAACATCAA

GTGAGAGTTA

TTATTAACTA

CAAAACAGAG

GGTGGAGCAG

CCAGGATTTG

CCAAGAACAA

GTTGCAAACT

CCACCTGATC

GGAATGCTGT

ACACTAAACA

AAATCAGATC

ATTGGAAATT

TTGTTTATAA

AGAAATCGAG

AGATCATTAG

CTCATATAAT

CATACCAATC

AACAAGCTCA

ATAGTCTTCA

TCAAAGAAGC

ATTTAATAGT

TTGCGAGGCT

ACTCAGALATT

AATTACAAGG

CAGTTGATAA

TAGATGTTGA

GGCTGCTGAA

AATGGTATAT

ACGTCAA.AGA

TATTAAACCA

CGGTCACATC

GTATA.ACA.AC

AAGGAGTAAA

TCAATACAAA

ATTCTGTTGC

TAGAAGAATC

GGCATCAATC

TTAATATAAC

TGGATCAA;A

ATATTAWAAT

TGAGGAAGGA

ACGGAAAGGA

CTAATAAGAT

TCATAGTGCT

5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 241 A.ATTAATTCC ATCAAAAGTG AAAAGGCCCA CGAATCATTG CTGCAAGACA TAAATAATGA a a a a a a a,

GTTTATGGAA

GTCAGGAGTG

ATCATTGACA

TGATAATCAA

TCCAGATGAT

AAGGTTAATG

AACTCCGTCT

AGGTTGTCAG

CTCAGACTTG

TAGGAAGTCA

CAAAGTTGAT

TGTCAATTAT

TCAACCATAT

AATATTTCTC

AACTGGGTGC

TTCAGATAGG

AAAATTGAAA

ACTTCTACTA

ACAATTAGGA

TAATGTGCTA

ATGTATAACA

ATCTGTCATA

AACCGAAAGA

AACAAGCTGC

TAAAAGCTTA

ATTACAGAAA

AATACAAGGC

CAACAGATGT

GAAGTGCTGC

TTTTGGAGAT

CCAGGGCCGG

TTAGTTATA.A

GATATAGGAA

GTACCTGACT

TGTTCTCTAG

GAAAGATCAG

GATGGTTCAA

GCTGCACTAT

GGGTATGGAG

CCCGGGAAAA

AGGATGGTCA

GTATGGACGA

GGTAACAAGA

ATAATTGATA

TCAAGACCAG

GGAGTATATA

TTAGACTCAC

GTAAACGAGC

ATTACACACT

AACACATTTC

AGATCCAAAT

TTCTTACALAT

CAGATCTTAG

CACAAAGAAT

GCACGTCTGG

GATTATTAGC

ATGATCTGAT

AATCATATCA

TAAATCCTAG

CACTCCTAAA

ATTATGCATC

TCTCAACAAC

ACCCATCTGT

GTCTTGAACA

CACAGAGAGA

ACTCCATCAT

TATCTATGCG

TCTATATATA

TTACTGATTA

GAAACAATGA

CTGATGCATA

AAAA.ATCGAG

TGGCCATCCT

ATAACAAAGG

AACCCATGTT

GGCATCGGAT

TCAGAGTCAT

GAAATTCATT

AACACATGAT

TCTTCCATCT

TATGCCAACG

TTATGCTTAT

AGTCTTACAG

GATCTCTCAT

TACAGATGTA

ATCAGGCATA

AAGATTTAAG

TGGACCAGGG

TCCAATAAAT

CTGTAATCAA

TGTTGTTGAC

ACAAAATTAC

TACAAGATCT

CAGTGATATA

ATGTCCATGG

TCCACTCAAT

AGTGAACCCA

AAACAGAACA

ATATTGTTTT

GTTCAAAACA

AATACCAATG

GTCCAGAATT

AGTGmATTA

GTAGGTATAA

TTAATGAAAA

ACTGTTGATG

ACCTCAA.ATC

ATAGGGATAA

ACCTTTAACA

TATCAACTGT

GAAGATATTG

AATAATAACA

ATATACTACA

GAGAATGTAA

GCGTCTCATA

AAAGGCTTAA

TGGGGGTCAG

ACAAGTTGGC

AGGATAAAAT

GGACATTCAT

CCCACAGGGA

GTCATAACTT

CTCTCAGCTG

CATATAGTAG

GAGATTCCAA

ATCTAATACA

ACATACCAAT

CAATTAGAAA

AACCTTTAAA

CTCCAAAAAT

GCTGTGTTAG

TAATTACTCG

TAACTGTAA-A

TAAATGACAA

GTTCAACTCC

TACTTGATAT

TAAGCTTTGA

AAGGCAAAAT

TCTGCA.ACAC

GTCCATGGTT

ACTCAATTCC

AAGGAAGGTT

ATAGCAAGTT

GGACATGGCA

GTCCAGATGG

GCATTGTGTC

ACTCAACAGC

GATATACAAC

AAATAAATCA

AAAGCTGCAG

7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 '8280 8340 8400 8460 8520 242

C

C

C

TTAATCATAA

ATCAGCAATC

GGGAAATGGA

ACCTTAACTC

CTCAGCCTTA

TTAATAAATT

AAGTGAATGA

TCAAATTATA

GAACATATAG

TAGCCTCAAA

AAGTTCACAC

TCAAGTATGA

AGGATTATALA

TGATATTAGA

ATTGTGACGT

TACAATCTAT

TTATGGGAGA

TTCAAACTCA

AGATGGAATT

TTGATAAAAT

CTTTTTTTAG

GAAAATATAT

TCTTCTGTAC

TGACATTACC

TATCATATGA

TCATAGAGCC

TTAACCATAA

AGACAATAGA

CACTGAATCT

TCCTATCGTT

TGATATGGAT

GGATAAAAGA

CTTAGGAAAA

TATACCTGGT

TCAAATGACT

AAATGATGGA

AACCTATAAA

TATGAGAAGA

CTTGTTAGA.A

TAAACAAAAC

AGTCGAAGGC

GTATCAGAAA

AAAGACATTT

TGATCCTGTT

AATATTTGAA

TTTAGATATA

AACATTTGGG

GTATATTGGA

AATAATAATT

TGATCATGCA

AAATGCTGTT

TCAGTTAGAT

TATGCATCA-A

CAAAAGGGAA

AACAATGGCA

AAAGGTAAAA

GACGACTCAA

CAACGATCTA

TACACATTTA

ATTAACAGTA

GATGGATTA.A

AGCAATTATG

TCAGATAAAT

TTACAAAAAG

GACCAGAAGA

TATAATGGTT

CGATGGAATA

GGTAATAACC

GATGTGATAT

AAACAACTAA

TCTAGAGAAT

TTTAATAAGT

CATCCTCCAT

AAAJCAATTAA

AACGGATATA

CACGAATTCA

GATTATTACC

GAGGATTTGA

TCTATCTATA

ATATAAAkAAA

CTGTATCTGA

TAGCACAATT

TACTAGTTAT

TTAGAAGATT

TCAGATATCC

AAGTGACTGA

GAGATCTATG

ATCTTAATGA

GGTATAATCC

CTCGAAATGA

ATTTCTTATT

ATCTAATTAC

TAAGTGCATG

TGTGGGAAGT

CGTTATTAGA

GAGGAGCTTT

CGATTAAGGA

CTACAAkTAGA

TAGAAGCTAG

AATTTGACAC

GAGAGAGGCA

TCATAA.ATGC

AGAGCTTTAT

CAATTTATAT

ATACAAGTAT

CTTAGGAGCA

CATACTCTAT

ACACACTATT

CACTAGACAG

AA.AATTAATA

AGAA.ATGTCA

ATTATTACTT

GATTAATGTG

AGAAATTAAT

ATTCAAAACA

GATCACTTTT

GATACATCCA

TCCTGAATTA

TGCTAAGTTA

GATAGATAAA

ACCACTTGCA

TTTAAATCAT

ATTTCTGAGT

TGAAATAGCA

TATTGCAGCA

TATTAATAAA

TGGTGGACAG

TTACGGTTCA

AGGAATAAAA

GAAAGATAAA

ATGATAAGTA

AAGCGTGCTC

CCTGAGTGTC

ATGAGTCTAC

AAAATAAAAC

TTAACTGAAA

AAAGAAATGT

AAAGCAGATA

CTATCAAAAT

AATATATCGA

TGGTTTACTA

AATGTTGGGA

GAATTGGTTT

GTATTGATGT

GATCCAAAAT

TTGTTTCCAA

TTATCCTTA

GTGTTATCCG

GTAGATTACA

GAGATTTTCT

GAAAAGGTTA

TGTCATGCTA

TGGCCTCCTG

AACTCTGCGA

TTCAATAAAT

GCATTATCTC

8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 243

S

*5

CAAAAAAATC

CATCCAACGA

ATCAGATATT

CTTATAGTCT

ACAAAATGAG

TCTTTCAAGA

TATCAATATC

ATGACCTTAA

AGAAATTTGA

TCCTAACAAC

TTGGAGAAAC

GTCTTGAAGG

ATATATCATT

TAGAAGGATT

CTGTTAGAAT

TAACCACAAG

ATGTAGTGAG

AATTAAATGA

ATGGGAGAAT

CAGTAATAGA

TTGAGAATGG

AACTATATAT

AGTATTTTAG

GATTCAATTA

CCGCATTGGC

ATAGGATTAT

AAATTGGGAC

ATCACGAAGA

GGATTATGTA

TAAAGAAAAA

AGCTACACA.A

AAATGGGATG

AGGAGTTCCA

AACCTACAAT

ATTCAAGTCA

AGATCTCAAA

TTGCAACCAA

AAGTACAATC

AGAGGATCAC

TTGTCAAAAA

AGGCGTGAGG

AGTACCCAAC

ATTTTTTGAT

AACGATTATA

TCTTCCTCAA

CGAAACAAGA

TTATTCACCT

TGCCCTTGGG

GAATCCAAAT

CATGGCCATG

TGATATTAAA

GAATCAAGAA

ACAGTTTATC

TTAGTTGAAG

GA.ATCTGGGG

GAGATCAAAC

GTTTTATCAG

GTGAAGGGAG

CGGTATAATG

AAAATAAGTA

ACGGATATCT

AAATACTGTC

ATATTTGGAT

TATGTAGGTG

CCTGATTCTG

TTATGGACAC

GTGACTGCAA

AATTATGACT

TCATTAAGAG

AGTAGCAAGA

GCTCTAAA-AG

TCAGCATCTT

GTTCTAGGAT

ATGAATATCA

TGGATGCAAT

TCAAGATGTT

AGATTTATTA

CCAGGTGAGT

CTGCATCTAA

TATTTATAGC

ACTGGTTAGA

AGGAAGGTAG

AGACACTACT

AGATTGAATT

AAGTGTACAA

ATCTTAATTT

ACAATGATGG

TTAATTGGAG

TAAATAAATT

ATCCTTACTG

GTTTTTACGT

TCATATCTAT

TGGTTCAAGG

ACAGAGTTAA

AAGTGATGGA

TGTTCATATA

CATTATCTAG

CAAATTTGGC

ATGCATGCTC

ATCCAACTAT

ATGCCTCTTT

TTGTAAGGAA

AGGCGAATCT

CATCTTTTTT

TTTACTGTAC

AGATAGTAA-A

TGATCCAGAA

ACTCTTTGCA

TGCAAATAAC

ACTTAAGAGA

TAATTCTAAA

GTCTTCTAAT

ATACGAGAC'r

ATATGAATCA

GTTTAATTGG

TCCTCCATCA

TCATAACCCA

AAGTGCAATA

AGACAATCAA

GAAGGAGATA

TGATCTAGGT

TAGCAAAAGA

ATGTGTCTTC

AACATCATTT

AATTTTTAAG

AACACAGAAT

AATACCTGCT

TATTGGTGAT

ATTAGACCGA

GGACTGGGCT

CGTACTAACG

TTTGATCCTC

TTTAATATTT

AAAATGACAT

ATAGGAAA.AT

TTAACAACCA

AGCCATACAG

CAGAAATCAA

GTGAGCTGTT

ACAGCTCTAT

TTACACCCTC

GATAAAGAAC

AGAGGGGGTA

CATCTAGCAG

GCTATAGCTG

GTTTATAAAG

CATGAACTTA

ATCTATTATG

TGGTCAGAGA

GCAAAAGCAA

AACATTCAAC

ATCAGAGATC

AGTGTTGGGG

CCATCAGTTG

AGTGTTCTTT

TCAGATCCAT

10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640

S.

S S S S

SSSS

244

ATTCATGCAA

GGAATGTATT

TAGAAGAAGA

TTGCACATGA

TAGATACGAC

TGTTGAGGA.A

GACTAATTGT

CATTGCGACA

CGCCTGACCC

TATGTTATTC

A.AATAGGATC

CTGATGAAAG

CCGCAATAAG

TGGAAGCCTC

TAACACCGGT

TGAALATTCTC

ACATGTCTAT

TGTTAACAGG

ACCCTATAGT

ATGAACATAT

TTATTTATGA

ACCATTCTTA

CAATATGTAC

AAGAGATAAT

CTCTTGACAT

ACACTCTTTA

TTTACCACAA

ACAAGATTCA

TGAAGAATTA

TATTCTAGAT

AAAATCACTA

AATCAGTAAT

AAGTGATAAA

AAAGATGTGG

ATTAGAATTA

TTCAGATGGC

AGCAGAAACA

ATCTGAAGCA

AATAGCAATG

ACAGATAGCA

AGCTACATCA

CAGTACATCA

CAAAGAAGCT

ATTAAGTGTT

TATGCATCTG

TAATCCAGAG

TAAAGACCCA

CACAATTGAT

TGCA.ATTACA

AGTTATTGCA

ACTTGTATTT

TAGTCTAAAA

TCT CAAAATA

CCAAATCCAT

GCTGAGTTCC

AATTCTCTCA

ATTCGGGTTG

TACGATCTAG

ATCAAGTATG

ATTCATTTAT

CTATCTGGGG

ACA.AAC COAT

GGTATATCGT

CAATTAGGAT

ATATATACAT

CAAACACGTG

ACAA.ATTTAT

TTGATCAGAG

AATGAAACCA

TTCGAATATT

CACATAGAAG

TCTACATTAG

CTCAALAGATG

ATGAATTATT

ATAGCAGATA

AATGATGATG

CTCAAGACAT

ATAGAAGGTA

TAACCACCAT

TATTATCTGG

TGATGGACAG

CAGGA.ATTAG

GCATAAATAG

TACAATATGA

AAGATATGTG

CAGGAGGAAG

TAGTAATAAC

ATACTTGGAT

CATTAAGAGT

ATATCAAGAA

GGGCATTTGG

CAAATTTTAC

CACACAGATT

TCAGCAGATT

AAGATACTAA

TATTTAGATT

ATGAGTGTTG

AATTAATTCG

TGGACTTATC

GGGATGATAC

CTATGTCACA

ATATTAATAG

TTGGTGGATT

GGGATCTCAT

GATAAAAAAT

ATTATTCACA

GAAGGTAATT

AAATGCCATA

AGGAGGACTG

AACACTAAGT

TTCGGTAGAC

GATGATAAGT

AGGATCAGAA

GTATTTACCC

TCCTTATTTT

TCTTAGTAAA

TAATGATGAG

ACTAGATAGT

AAAGGATACT

CATAACAATG

TCTTATTTAT

AAAAGAAACC

TATTAAAGAA

ATATCCTGAA

AAAACTTATG

TGACATCATA

ATTAGATCGA

CTTAATCACT

ATTAGTAAAT

TTGGGATTAT

ATAACAGCAA

AATACAATGA

CTCCCTAGAG

GCTGGAATGT

ACATATAGTT

AGGACTTTGC

CTTGCCATAG

GGACTTGAAA

CATTGTAAAA

GGTAATATCA

GGATCAGTCA

CCTGCAAAAG

ATATCTTGGA

CTCAAAATTT

GCAACTCAGA

TCCAATGATA

CAA.CAAATAA

ACAGGACACA

AGTTTTAATG

AGTAATGAAT

GTTATTAAAG

CATGCAATTT

GATAATTTAA

GAATTTTTGA

CAATTTGCAT

ATAATGAGAA

11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 245 a a.

a.

a a a a a a *aa.

a

CACTGAGAGA

AAGTATTCAA

CTAGTCAAGA

TGAGAGAATG

TTGCAAATGA

CAGAAATTGC

TATTGAAACA

TATCTGGATT

TCAAATATCT

TAGAAGATGA

ATAATAAAGG

TTAAAATCAG

GTGGTTTGAC

TCAACAGCAC

ATAAAGACAA

ATGCCACATT

TTGGTCAACG

GAAATGTGAC

CATGGATAGG

TTGGATTAGT

ATGAACATTA

TTTCCAAAAT

TATATTGGAA

TATATCTAAT

CAAAACTTAA

TACTTCCCAT

GAGGTTCTGG

CCAGATAAkA.

GTTGAATGGT

TAGGAAACAA

ATCTTTCGGA

ATATCTTGAA

ATTAATTAAA

AAGGATTCGC

AAATATGCTG

GAATAAAATT

ATCTATALACA

ACTTCCTCAA

TAGTTGTCTG

GGACAGGCTC

AGGACCTGCA

AGAATTGAAA

ACAGATTCTT

AAATATGGAA

ACATTGTGAT

TAGTGTTATA

TATACCTACA

AGATGTAAGT

TTCGAAAGAT

AAGATTGTCA

TCAATATTAA

GATTGTGGAG

CTTGCCCTAT

GTATCACTTG

GCCTTTATTT

CCTAACCTGT

TTAA.ATATTA

TCGTTCCCAT

GGTATTAGTC

GATAACATTG

AACAATTTCT

AGTGATTCTG

GGAGGGAATT

AAAGCTCTTG

TTCCTGGGAG

GTTAATTATT

ATATTTCCTT

AACAGGGTAA

TGTGAGAGCT

ATGGAAGGAG

AGAATTACAT

ATCACTCCGA

ATAATATCAC

GCATATTGTA

CTCTTGGAAG

AAGTATTATC

TTTTAAACCC

CTATATGTGA

AAATATACAT

CTAGACACCT

TAAACTTAAC

AAGAAGACCC

CAACTGTAAC

CACCTGAGGT

TCAAAACTAT

GGGGACTAGC

ATGATAATGA

ATCTATCGCA

AGTTATCACA

AAGGAGCAGG

ATAATTCAGG

CAGAGGTATC

ALAGTACTGTT

TAATATGGAG

CTATCGGTAA

ACTTGATTGG

ATTGGTCTAG

TCAAAACTTC

CTATAATGGA

AAAATAATCT

TAATGCATTA

TATTTATGGT

ATATTCACTA

TTGTGACAGC

TTCATTTGTT

ATACTTGGAG

TACTCTTAAA

ATACGTAAGA

AATTGATGAT

AAATGATAAC

ACTTA.AGAAC

TAGACTAGAT

TCAATTGAGA

AATTTTAATG

AGCTATGCTA

TTTGAATATA

ATTAGTAGGT

CAATGGGAAT

TGAATTAAAT

ATCAGAAGAA

GGATGATGAT

AATACTTTAT

TAATCCTGCA

ACCTAGTGAA

ATTAAAATGG

TCTCATCCTA

CCTAATACTG

GATCTATTTA

GATATGGAAG

TGTTGTTTAG

AGACTTGATC

TATGTACAAA~

AAGACTGCAA

TGGGATCCGG

TGTAATAAAG

TATCAAGTCC

GCTAATACAA

TTATTCGGAA

AkAGGAAGTCA

GCATGTTATG

ACAGATGTAA

AAAAAATTAG

CCTAATTCAA

GATAAGTCCA

ACTGTTCTAC

GTTGTTTTAG

CTATATAAAT

TCAACAGAAT

ATTGTTTTAT

ATCATTTTAT

13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 CAAAGAAGAG GAATAATGAA TGGTTACATC ATGAAATCA AGA.AGGAGAA AGAGATTATG 246 GAATCATGAG ACCATATCAT ATGGCACTAC AAATCTTTGG ATTTCAAATC AATTTAAATC

ATCTGGCGAA

GTTTTCAGCG

AGAGACATAA

GACTGCTATC

TTACAGGTCG

TAGCTGATAC

GAGAGTGTAT

AATTGATTGG

AGTTATTAGA

TGAAGATATA

TGTAATATAT

AGAATTTTTA

AACAATAAAG

ATTAGGCGGA

GAGAAGACTA

CTTTCCTGAT

TGATTTAGAA

AGGATCAATA

TGGTGCTAAA

AAACTACAAT

TCCTAACCTT

TCAACCCCAG

GATGTTTTAT

AGATATAACA

GTATTAAGTT

GAAAAATTTG

TCATTAAAGT

TCATATTGGT

TTATTAGGAA

CAACATGATG

TATCTTTAAG

ATCTGACTAA

TTGAATGGAT

TATTCCCACT

GGATTTCATT

AACATAGAGC

TATTGTCGAA

TTCTAACCA

TTCCCAGACA

AATTTGATAT

CCTAGGAATA

TATCAACAAT

TAATATA-ACT

GAAAAATAAG

ATCATTATCG

ACAGACTGGA

AAACATCATT

AGA-AGTTAAA

ATATAAAGAA

CGATTAAAAC

GACAAAAAGT

ATAATCCAAA

CATGATGATA

GGAAAGTTAA

ACTCGATTAC

TATGTATCAT

AAGAATTACA

ATACTTATGA

CCCGAAGACC

ATAA.ATACAA

AAGAAAAACA

14820 14880 14940 15000 15060 15120 15180 15240 15300 15360 15420 15462

S

ATATACCAAA. CAGAGTTCTT CTCTTGTTTG GT INFORMATION FOR SEQ ID NO:18: Wi SEQUENCE CHARACTERISTICS: LENGTH: 2233 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID 140:18: Met Asp Thr Glu Ser Asn Asn Gly Thr Val Ser 1 5 10 Glu Cys His Leu Asn Ser Pro Ile Val Lys Gly 25 His Thr Ile Met Ser Leu Pro Gin Pro Tyr Asp 40 Ile Leu Val Ile Thr Arg Gin Lys Ile Lys Leu 55 Asp Ile Leu Tyr Pro Lys Ile Ala Gin Leu Met Asp Asp Asp Ser Asn Lys Leu Asp Lys 247 Arg Asn Glu Leu Arg Gly 145 His Phe Ile Asn Asn 225 S*Asp Pro Ile Ser Val 305 Glu Asp Gin Asp Met Leu Asp 130 Ser Thr Thr Thr Phe 210 Tyr Val Lys Asp Leu 290 Lye Leu Tyr Arg Leu Phe Leu 115 Leu Asn Thr Ile Phe 195 Leu Asn Val Leu Lye 275 Leu Gin Ile Ile Ser Gly Lys 100 Lys Trp Tyr Tyr Lys 180 Asn Leu Gly Glu Gin 260 Leu Glu Leu Phe Asp Ile Lye Leu Ala Ile Asp Lys 165 Tyr Val Ile Tyr Gly 245 Ser Phe Pro Arg Glu 325 Lye Arg 70 Tyr Tyr Asp Asn Leu 150 Ser Asp Gly His Leu 230 Arg Met Pro Leu Gly 310 Ser Ile Arg Thr Ile Arg Val 135 Asn Asp Met Lye Pro 215 Ile Trp Tyr Ile Ala 295 Ala Arg Leu Leu Phe Pro Thr 120 Leu Glu Lye Arg Asp 200 Glu Thr Asn Gin Met 280 Leu Phe Glu Asp Lye Ile Gly 105 Tyr Ser Glu Trp Arg 185 Tyr Leu Pro Ile Lye 265 Gly Ser Leu Ser Ile Ile 75 Tyr Asn Gin Leu Asn 155 Asn Gin Leu Leu Leu 235 Ala Asn Lye Ile His 315 Lye Aen Leu Pro Ser Met Ala 140 Asn Pro Lye Leu Ile 220 Val Cys Asn Thr Gin 300 Val Glu Lye Thr Glu Lye Thr 125 Ser Ile Phe Ala Glu 205 Leu Leu Ala Leu Phe 285 Thr Leu Phe Ser Glu Met Val 110 Asp Lye Ser Lye Arg 190 Asp Asp Met Lye Trp 270 Asp His Ser Leu Thr Lys Ser Thr Gly Asn LyE Thr 175 Asn Gin Lye Tyr Leu 255 Glu Val Asp Glu Ser 335 Ile Vai Lys Glu Leu Asp Val 160 Trp Glu Lye Gin Cys 240 Asp Val Ile Pro Met 320 Val Asp 248 340 345 350 Glu Ile Ala Giu Ile Phe Ser Phe Phe Arg Thr Phe Gly His Pro Pro 355 360 365 Leu Giu Ala Ser Ile Ala Ala Giu Lys Val Arg Lys Tyr Met Tyr Ile 370 375 380 Gly Lys Gln Leu Lys Phe Asp Thr Ile Asn Lye Cys His Ala Ile Phe 385 390 395 400 Cys Thr Ile Ile Ile Asn Giy Tyr Arg Glu Arg His Gly Gly Gin Trp 405 410 415 Pro Pro Val Thr Leu Pro Asp His Ala His Giu Phe Ile Ile Asn Ala 420 425 430 Tyr Gly Ser Asn Ser Ala Ile Ser Tyr Giu Aen Ala Val Asp Tyr Tyr 435 440 445 9Gin Ser Phe Ile Gly Ile Lye Phe Asn LyE; Phe Ile Glu Pro Gin Leu .450 455 460 *99Asp Giu Asp Leu Thr Ile Tyr Met Lye Asp Lys Ala Leu Ser Pro Lye *465 470 475 480 9*9Lye Ser Aen Trp Asp Thr Val Tyr Pro Ala Ser Asn Leu Leu Tyr Arg 485 490 495 Thr Asn Ala Ser Asn Giu Ser Arg Arg Leu Val Giu Val Phe Ile Ala 9...500 505 510 Asp Ser Lye Phe Asp Pro His Gin Ile Leu Asp Tyr Vai Giu Her Gly 515 520 525 99*9Asp Trp Leu Asp Asp Pro Giu Phe Asn Ilie Ser Tyr Her Leu Lys Giu 530 535 540 Lye Giu Ile Lye Gin Giu Giy Arg Leu Phe Ala Lys Met Thr Tyr Lys 545 550 555 560 Met Arg Ala Thr Gin Val Leu Ser Glu Thr Leu Leu Ala Aen Aen Ile 565 570 575 Gly Lye Phe Phe Gin Giu Asn Giy Met Val Lye Gly Giu Ile Giu Leu 580 585 590 Leu Lye Arg Leu Thr Thr Ile Her Ile Ser Giy Val Pro Arg Tyr Asn 595 600 605 Giu Vai Tyr Aen Asn Ser Lye Ser His Thr Asp Asp Leu Lye Thr Tyr 610 615 620 249 Asn 625 Phe Ser Tyr Leu Ile 705 Ser Gly .Ser *9 Met 999*** Asn 785 995999 Val 9 Glu Ser Ala Arg 865 Asn Lys Glu Cys Glu Asn 690 Tyr Leu Gly Ala Val 770 Asn Arg Leu Lys Leu 850 Ser Gly Ile Phe Phe Ser 675 Lys Val Glu Ile Ile 755 Gin Tyr Phe Lye Arg 835 Ser Ala Tyr Ser Lye Leu 660 Thr Leu Gly Asp Glu 740 His Gly Asp Phe Leu 820 Ile Arg Ser Ser Asn Ser 645 Thr Ala Phe Asp His 725 Gly Leu Asp Tyr Asp 805 Asn Tyr Cys Ser Pro 885 Leu 630 Thr Thr Leu Asn Pro 710 Pro Phe Ala Asn Arg 790 Ser Glu Tyr Val Asn 870 Val Asn Asp Asp Phe Trp 695 Tyr Asp Cys Ala Gin 775 Val Leu Thr Asp Phe 855 Leu Leu Leu Ile Leu Gly 680 Leu Cys Ser Gin Val 760 Ala Lys Arg Ile Gly 840 Trp Ala Gly Ser Tyr Lys 665 Glu His Pro Gly Lye 745 Arg Ile Lys Glu Ile 825 Arg Ser Thr Tyr Ser Asn 650 Lye Thr Pro Pro Phe 730 Leu Ile Ala Glu Val 810 Ser Ile Glu Ser Ala 890 Asn 635 Asp Tyr Cys Arg Ser 715 Tyr Trp Gly Vai Ile 795 Met Ser Leu Thr Phe 875 eye Gin Gly Cys Asn Leu 700 Asp Val Thr Val Thr 780 Val Asp Lye Pro Val 860 Ala Ser Lye Tyr Leu Gin 685 Glu Lye His Leu Arg 765 Thr Tyr Asp Met Gin 845 Ile Lys Ile Ser Glu Asn 670 Ile Gly Glu Asn Ile 750 Val Arg Lye Leu Phe 830 Ala Asp Ala Phe Lye Thr 655 Trp Phe Ser His Pro 735 Ser Thr Val Asp Gly 815 Ile Leu Glu Ile Lye 895 Lye 640 Val Arg Gly Thr Ile 720 Arg Ile Ala Pro Val 800 His Tyr Lye Thr Glu 880 Asn 250 Ile Gin Gin Leu Tyr Ile Ala Leu Gly Met Asn Ile Asn Pro Thr Ile 900 905 910 Thr Gin Asn Ile Arg Asp Gin Tyr Phe Arg Asn Pro Asn Trp Met Gin 915 920 925 Tyr Ala Ser Leu Ile Pro Ala Ser Val Gly Gly Phe Asn Tyr Met Ala 930 935 940 Met Ser Arg Cys Phe Val Arg Asn Ile Gly Asp Pro Ser Val Ala Ala 945 950 955 960 Leu Ala Asp Ile Lys Arg Phe Ile Lys Ala Asn Leu Leu Asp Arg Ser 965 970 975 Val Leu Tyr Arg Ile Met Asn Gin Giu Pro Gly Glu Ser Ser Phe Leu 980 985 990 Asp Trp Ala Ser Asp Pro Tyr Ser Cys Asn Leu Pro Gin Ser Gin Asn ease 995 1000 1005 000Ile Thr Thr Met Ile Lys Asn Ile Thr Ala Arg Asn Val Leu Gin Asp :001010 loi5 1020 ***Ser Pro Asn Pro Leu Leu Ser Gly Leu Phe Thr Asn Thr Met Ile Glu *1025 1030 1035 1040 Glu Asp Giu Giu Leu Ala Glu Phe Leu Met Asp Arg Lys Val Ile Leu 1045 1050 1 055 .Pro Arg Vai Ala His Asp Ile Leu Asp Asn Ser Leu Thr Gly Ile Arg 1060 1065 1070 Asn Ala Ile Ala Gly Met Leu Asp Thr Thr Lys Ser Leu Ile Arg Val 1075 1080 1085 Gly Ile Asn Arg Gly Gly Leu Thr Tyr Ser Leu Leu Arg Lys Ile Ser @.1090 1095 1100 *Asn Tyr Asp Leu Val Gin Tyr Giu Thr Leu Ser Arg Thr Leu Arg Leu 1105 1110 1115 1120 Ile Val Ser Asp Lys Ile Lys Tyr Giu Asp Met Cys Ser Val Asp Leu 1125 1130 1135 Ala Ile Ala Leu Arg Gin Lys Met Trp Ile His Leu Ser Gly Gly Arg 1140 1145 1150 Met Ile Ser Gly Leu Giu Thr Pro Asp Pro Leu Giu Leu Leu Ser Gly 1155 1160 1165 Vai Val Ile Thr Gly Ser Glu His Cys Lys Ile Cys Tyr Ser Ser Asp 251 1170 1175 1180 Gly Thr Asn Pro Tyr Thr Trp Met Tyr Leu Pro Gly Asn Ile Lys Ile 1185 1190 1195 1200 Gly Ser Ala Giu Thr Giy Ile Ser Ser Leu Arg Val Pro Tyr Phe Gly 1205 1210 1215 Ser Val Thr Asp Giu Arg Ser Giu Ala Gin Leu Gly Tyr Ile Lys Asn 1220 1225 1230 Leu Ser Lys Pro Ala Lys Ala Ala Ile Arg Ile Ala Met Ile Tyr Thr 1235 1240 1245 Trp Ala Phe Gly Asn Asp Giu Ile Ser Trp, Met Glu Ala Ser Gin Ile 1250 1255 1260 Ala Gin Thr Arg Ala Asn Phe Thr Leu Asp Ser Leu Lys Ile Leu Thr 1265 1270 1275 1280 Pro Val Ala Thr Ser Thr Asn Leu Ser His Arg Leu Lys Asp Thr Ala 1285 1290 1295 *Thr Gin Met Lys Phe Ser Ser Thr Ser Leu Ile Arg Val Ser Arg Phe *1300 1305 1310 Soo le Thr Met Ser Asn Asp Asn Met Ser Ile Lys Glu Ala Asn Giu Thr 1315 1320 1325 Lys Asp Thr Asn Leu Ile Tyr Gin Gin Ile Met Leu Thr Gly Leu Ser 1330 1335 1340 Phe Giu Tyr Leu Phe Arg Leu Lys Glu Thr Thr Gly His Asn Pro 1345 1350 1355 1360 Ile Val Met His Leu His Ile Giu Asp Glu Cys Cys Ile Lys Giu Ser 1365 1370 1375 Phe Asn Asp Giu His Ile Asn Pro Giu Ser Thr Leu Giu Leu Ile Arg 1380 1385 1390 Tyr Pro Glu Ser Asn Glu Phe Ile Tyr Asp Lys Asp Pro Leu Lys Asp 1395 1400 1405 Val Asp Leu Ser Lys Leu Met Val Ile Lys Asp His Ser Tyr Thr Ile 1410 1415 1420 Asp Met Asn Tyr Trp Asp Asp Thr Asp Ile Ile His Ala le 'Ser Ile 1425 1430 1435 1440 Cys Thr Ala Ile Thr Ile Ala Asp Thr Met Ser Gin Leu Asp Arg Asp 1445 1450 1455 252 Aen Leu Lys Glu Ile Ile Val Ile Ala Asn Asp Asp Asp Ile Asn Ser 1460 1465 1470 Leu Ile Thr Giu Phe Leu Thr Leu Asp Ile Leu Val Phe Leu Lys Thr 1475 1480 1485 Phe Gly Gly Leu Leu Val Asn Gin Phe Ala Tyr Thr Leu Tyr Ser Leu 1490 1495 1500 Lys Ile Glu Gly Arg Asp Leu Ile Trp Asp Tyr Ile Met Arg Thr Leu 1505 1510 1515 1520 Arg Asp Thr Ser His Ser Ile Leu Lys Val Leu Ser Asn Ala Leu Ser 1525 1530 1535 His Pro Lys Val Phe Lys Arg Phe Trp Asp Cys Gly Val Leu Asn Pro 1540 1545 1550 Ile Tyr Gly Pro Asn Thr Ala Ser Gin Asp Gin Ile Lys Leu Ala Leu 1555 1560 1565 *Ser Ile Cys Glu Tyr Ser Leu Asp Leu Phe Met Arg Giu Trp Leu Aen :1570 1575 1580 Gly Val Ser Leu Giu Ile Tyr Ile Cys Asp Ser Asp Met Glu Val Ala *1585 1590 1595 1600 *Asn Asp Arg Lys Gin Ala Phe Ile Ser Arg His Leu Ser Phe Val Cys 1605 1610 1615 **Cys Leu Ala Glu Ile Ala Ser Phe Gly Pro Asn Leu Leu Aen Leu Thr 1620 1625 1630 Tyr Leu Glu Arg Leu Asp Leu Leu Lys Gin Tyr Leu Glu Leu Asn Ile 1635 1640 1645 *Lye Glu Asp Pro Thr Leu Lye Tyr Val Gin Ile Ser Gly Leu Leu Ile 1650 1655 1660 Lys Ser Phe Pro Ser Thr Val Thr Tyr Val Arg Lye Thr Ala Ile Lye 1665 1670 1675 1680 Tyr-Leu Arg Ile Arg Gly Ile Ser Pro Pro Glu Val Ile Asp Asp Trp, 1685 1690 1695 Asp Pro Val Giu Asp Glu Asn Met Leu Asp As Ile Val Lye Thr Ile 1700 1705 1710 Aen Asp Asn Cys Asn Lye Asp Asn Lye Gly Aen Lye Ile Asn Asn Phe 1715 1720 1725 253 Trp Gly Leu Ala Leu Lys Asn Tyr Gin Val Leu Lys Ile Arg Ser Ile 1730 1735 1740 Thr Ser Asp Ser Asp Asp Asn Asp Arg Leu Asp Ala Asn Thr Ser Gly 1745 1750 1755 1760 Leu Thr Leu Pro Gin Gly Gly Asn Tyr Leu Ser His Gin Leu Arg Leu 1765 1770 1775 Phe Gly Ile Asn Ser Thr Ser Cys Leu Lys Ala Leu Glu Leu Ser Gin 1780 1785 1790 Ile Leu Met Lys Giu Val Asn Lys Asp Lys Asp Arg Leu Phe Leu Gly 1795 1800 1805 Giu Gly Ala Gly Ala Met Leu Ala Cys Tyr Asp Ala Thr Leu Gly Pro 1810 1815 1820 Ala Val Asn Tyr Tyr Asn Ser Gly Leu Asn Ile Thr Asp Val Ile Gly 1825 1830 1835 1840 Gin Arg Glu Leu Lys Ile Phe Pro Ser Glu Val Ser Leu Val Giy Lys 1845 1850 1855 Lys Leu Gly Asn Val Thr Gin Ile Leu Asn Arg Val Lys Val Leu Phe 1860 1865 1870 *Asn Gly Asn Pro Asn Ser Thr Trp Ile Gly Asn Met Giu Cys Glu Ser *1875 1880 1885 Leu Ile Trp Ser Giu Leu Asn Asp Lys Ser Ile Gly Leu Val His Cys **1890 1895 1900 Asp Met Giu Gly Ala Ile Gly Lys Ser Giu Giu Thr Val Leu His Glu 1905 1910 1915 1920 His Tyr Ser Val Ile Arg Ile Thr Tyr Leu Ile Gly Asp Asp Asp Val *1925 1930 1935 *Val Leu Val Ser Lys Ile Ile Pro Thr Ile Thr Pro Asn Trp Ser Arg *1940 1945 1950 Ile Leu Tyr Leu Tyr Lys Leu Tyr Trp Lys Asp Val Ser Ile Ile Ser 1955 1960 1965 Leu Lys Thr Ser Asn Pro Ala Ser Thr Giu Leu Tyr Leu Ile Ser Lys 1970 1975 1980 Asp Ala Tyr Cys Thr Ile Met Glu Pro Ser Glu Ile Val Leu Ser Lys 1985 1990 1995 2000 Leu Lys Arg Leu Ser Lau Leu Glu Giu Asn Asn Leu Leu Lys Trp Ile 254 2005 2010 2015 Ile Leu Ser Lys Lys Arg Asn Asn Giu Trp Leu His His Giu Ile Lys 2020 2025 2030 Glu Gly Giu Arg Asp Tyr Gly Ile Met Arg Pro Tyr His Met Ala Leu 2035 2040 2045 Gin Ile Phe Gly Phe Gin Ile Asn Leu Asn His Leu Ala Lys Giu Phe 2050 2055 2060 Leu Ser Thr Pro Asp Leu Thr Asn Ile Asn Asn Ile Ile Gin Ser Phe 2065 2070 2075 2080 Gin Arg Thr Ile Lys Asp Val Leu Phe Glu Trp Ile Asn Ile Thr His 2085 2090 2095 Asp Asp Lys Arg His Lys Leu Gly Giy Arg Tyr Asn Ile Phe Pro Leu 2100 2105 2110 Lys Asn Lys Giy Lys Leu Arg Leu Leu Ser Arg Arg Leu Val Leu Ser 2115 2120 2125 Trp Ile Ser Leu Ser Leu Ser Thr Arg Leu Leu Thr Giy Arg Phe Pro 2130 2135 2140 *Asp Giu Lys Phe Giu His Arg Ala Gin Thr Gly Tyr Val Ser Leu Ala 2145 2150 2155 2160 Asp Thr Asp Leu Giu Ser Leu Lys Leu Leu Ser Lys Asn Ile Ile Lys *2165 2170 2175 Asn Tyr Arg Glu Cys Ile Gly Ser Ilie Ser Tyr Trp Phe Leu Thr Lys 2180 2185 2190 Giu Val Lys Ile Leu Met Lys Leu Ile Gly Gly Ala Lys Leu Leu Gly 2195 2200 2205 Ile Pro Arg Gin Tyr Lys Glu Pro Giu Asp Gin Leu Leu Glu Asn Tyr 2210 2215 2220 Asn Gin His Asp Giu Phe Asp Ile Asp 2225 2230 INFORMATION FOR SEQ ID NO:19: SEQUENCE CHARACTERISTICS: LENGTH: 15462 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear 255 (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: ACCAAACAAG AGAAGAAACT TGCTTGGTA. TATAAATTTA ACTTAAAATT AACTTAGGAT 0* *0 0

C

C C

C

TTAAGACATT

TATTTGATAC

TCATTCCTGG

ATAATGAGAA

AACATGCACA

AGCTCTACCT

AGAAAGATCT

ATGAAAAGAC

TGCAGAACGG

CATGTTTAGG

TCTCAGGGTT

TGCAGGCAGG

CTCAACAGAG

ATGACCTCAC

GTCTCGCTTC

CTCTATCCAC

CAAAGGGACC

CACCAGGCAA

GAGCCATGCA

GACAAGCAGT

GAGTGACACA

AGACATCTTT

GACTAGAAGG

ATTTAATGCA

ACAGAAAAAT

AATGACATTA

A.AGGGCAGGG

AACAACAAAT

AAAACGGCAA

AACTGATTGG

CAGGAACAAT

AGCTCTTATA

AAGAAAAGGC

GCTGGTATTG

CTTGGTAACT

AACCATAGAA

ATTCTTCAAT

TCTCAGACCA

ACGCGCTCCT

CTATCCTGCC

ACAGTATGTG

AGCACGTGAT

CGAAGCTAAA

CCACAAACCG

TCAAGAA.AAG

CGTAGGCAAG

ACTGTCTCTA

GCTCTTCTAT

TTCTTGGTGT

GGAAGTAATG

AAGTATGGAG

ATATTTGGAA

TCAACAATTG

ATACAGATCT

TTTTTCACCC

AGCGGTGACA

CTTATGGTTG

AAGAATATAC

ACAATCAGAT

GATATCAATA

TTCATCTGTA

ATATGGAGCT

ACGGGAAGAT

GCCGAAGCTC

GAAAGCTTGA

ACAGGTGGAT

GGAACTCTAT

AAAACATAAC

TATTCGCCCT

TTCTATCTCA

CTTTATTGTC

CAGATGCCAA

GATTTGTGGT

GTGACCTGGA

AAGACCTTGT

GGATAGTTCT

GATTGGAAGC

CAGTGGATCA

AAACATTAAT

AAATTGTTGG

ATGGAATTGA

GATTAAAAGC

TCCTCAGAGA

ATGCAATGGG

CATATCTAGA

AAATGAGCTC

AGAGACATAT

CAGCCATAGA

AATTTCAAAA

AAAATCAGCC

TGGACCGACA

TTCACTAGAT

AATGGCTTAT

GTATGTCATA

TAAGACGAGA

TTATGATCAG

CCACACATTT

GGTCAAAGCT

TTTCAGACAA

GATTGGGTCA

AACAATGAAT

CAACTACATA

GACCAGAATG

TTTGATGGAA

TCCTATACAT

GGTGGCAGTT

CATTGATATG

AACACTGGAA

AAGGAACATA

GATGGCAATA

ATGTTGAGCC

GGTGGAGCTA

ATAACTGATG

AATGAGAAAC

GCCAATCCAG

TACATGATTG

GAGATGATAT

GAAACTATGT

GGGTATCCAT

ATCACTAGTA

GATGGAACAG

ATCATGCGGT

ACCAGCAGAA

AGAGATGCAG

GCAGCTTTGA

CTGTATTTAT

GGTGAGTTCG

GTACAAAATA

TTCCAGCTAG

GATGAACTTG

AACAGTTCAG

GATGAAGAGC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 256 CAGAACAATT CGAACATAGA GCAGATCAAG AACAAAATGG AGAACCTCAA TCATCCATAA

TTCAATATGC

CTGACAATAT

ACA.AGA.AGAA

AAATAGATGA

ATCAATAATA

GGTA.AATTTA

AAACTATCAA

CTCGGCCCTC

AAACGACACA

CAAACCAACA

GTCATCACAC

GAGAGGACCT

AATCCCCAGA

CAATGAAATT

TGTTCCAAGC

TGATCATGGA

TACTGCTGCA

AAGTTCTTCA

CTGGTTTAAG

ATCAAAAGGG

AACAGAAATA

CAACAACACC

AACTTATACA

AAATGGAAAG

CTGGGCAGALA

CAAGACCGAA

ACAAAGCAGT

TCTGTTTALAC

AATAAGAAAA

GAGTCTGCTT

ATCATGGATT

AACATCATTG

ATCAACACAA

GAAACAAGTG

GAATGTACAA

GGGAGAAGAA

AGCATCACAG

AGAAAGATGG

GAGATATCAG

AGAAGCCTGG

ACACCAGATG

ACACATCAAG

AAATCAAAAG

CAGAAGAAAA

CAGACAGAAT

GACCGGAACG

AAAGAATCGA

GAAAGGAAGG

GGAILATAGALA

CAACAAAACA

CAACCACCCA

GCATTTGGA.A

ACTTAGGATT

GAA.ACTCAAT

CTTGGGAAGA

AATTCATACT

GA.ACCCAGCA

AGAAAGATAG

CAGAAGCAAA

GCAGCTCAGA

ATTCTAAAAA

ATAAGGACTC

GAAGTGATGA

AATCTATCAG

ATGAAGA.AGA

AAGATGACAA

ATACCGACAA

TCTCAALAGAC

CATCAGAAAC

AACAGACAAG

TCCGAACAAA

ATACAGAAGA

GCGATGATCA

TCAGAGACAG

CTA.ATCCCAC

GCAACTAATC

AAAGAATCCT

CAATAGAGAG

GGA.ATCAAGA

CAGCACCGAC

ACTCAGTGCC

TGGATCAACT

AGATAGAALAC

TAGTAGAGCT

TGGAACCCAA

TATTGAGGGG

CATATTTACA

TACACCTGAT

AATACTAATG

AAGAATTAAA

CCAGATACCA

AACAACCACC

ACAATCCTCA

CACAACTCCT

CTCTGAATCC

GAGCAATCGA

GACTGAGCAA

ACTAAACAAG

AAACAGAACA

GAATCAACAT

ATCATACCGG

TTGATGGAAA

GATAAATCAA

CCCCAAGAAG

ACCATCTGTC

GACAAAAATA

ATTGATCAGG

GAGACTGTGG

AACACGGAGG

AAAATGCGAC

ACAGAACAA

ACAAGATCAA

AAAAATAGTA

AA.AGGGGGAA

ACATCAGACT

AACACCGACA

TCATGGAATC

CCAACAACAA

AAACCCAAGA

TTTACAGAGA

GCTACAGAAT

AGACTCAACG

AACCAGGACG

TTTAATCTAA

AATATAGGGT

GCGATGCTAA

CTAATATCTC

ACTTATCGGA

AACCAGAAAT

GACAGTCTGG

AAACTGTACA

TCTCTGGAGG

ATATTGATCT

AATCTGCAAA

GTAGAAACAG

TAAGTGTTGT

GGACAAAGAA

AAGGGAAAGA

ACAGATCCAC

CAAAGGGGCA

TCATCATCGA

CTTCCAGATC

CACAAAAGAC

GGGCAATTAC

1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 TCTATTGCAG AATCTTGGTG TAATTCAATC CACATCAAALA CTAGATTTAT ATCAAGACAA 257

ACGAGTTGTA

CCTGGCAGGA

AAATGAAATG

GATAGAAAAT

TATGACTGAG

CAAAACAAAA

ACAAGGCATT

CGATGTACAA

AATACCCAAA

TCTCTCACAA

AGAAGTATCT

CAAAGAAACG

ACACAAAATC

AGGATTAAAG

CATTCCCAGA

ATGAACAGAG

ACGGATCCCG

ACAAATACGG

GATCATTACC

CAACCAAACT

CGGTACAAAA

TGTTCGATGC

AATTTAGAGT

CTAAGTCA.AT

TAAAAACAGG

AAAAATCACT

TGTGTAGCAA

TTAGTCATAG

CTAAACCTCA

CAAAGAGAAC

AGAGGAGGAA

TTGAAAGAAG

GACAAGAATA

GTTAAATCAG

AAAGTGAGCA

AGCACAAAAC

GAATTAATGG

ACACCGAACA

AAGCAGAATG

AATAAATTAA

ATCATCATTC

GAAAGCAGTA

GTATTTAGAT

GAGTGTGAAT

AATCGGATTG

GGATATAGAA

TATAAILACCA

CAACAAAGTT

AATCTTCGTG

GGCATCACTA

GGTTCAGACT

GAATTTCATG

ATGTACTAAA

GGGTTTCAAT

AAGCAGATCT

AACTGTCATT

AGAAAGACCA

AAAAGATCAA

TACCCGATCT

AGATATTAAG

GTACAATGAG

AATCATACAT

ACATGTTCAA

AACAGACAAG

AAACAACAGA

TCCTTGTCCA

TCTGAAAATG

CCCCACATTA

GTCTTCTTAC

GATCTCGACA

GCTAAGTACA

GTGAGAAGAA

GAACTGTACC

GCTCTTGCTC

APLTTGTACGG

TCTCTAACCA

GATTCTAAAG

GTCCATCTCG

CAATGTAGAT

GGACAACGAC

AAAGAAAATG

GATCACGTCA

AAATGIAATCC

GAAGACCAGG

ATATCGACAT

TTCATACAAT

ATCACTAGTT

AAACGA.ACTC

TGAAGATGTC

AAACAACAGT

TATCAATCAA

A7LATGAGTAT

GTCATATAGA

GAGTTGCCAA

TCGGCTTCTT

GTGACCCGAG

CTGGGAATGA

CAGTCAAAGC

CATGGTCCAA

CTCAATGTCT

CAATTGGATC

ACACAATATC

GGATAGTTCA

GATTGATCAA

ACTGCATCAA

ACAAAATTAA

GACGAATCAC

CTAATTTCAA

AATGAGAGAG

TTTGACCCAC

GCAGGAGATA

GAGTCAAATG

GCAGTCATCA

AAACGTTGCA

AACAATTGCC

AGATCAAAAC

TATACAAATA

AACTAACTCT

ACCATTACCA

GATCGGAAAT

CGAGATGGAA

TTACAAAGTT

CCAGGAATTG

GAAAGAGATG

TAGACTAAGA

TCCACTAGAT

AATAACCTTG

AATCAATCTG

AATTTTGGAT

AAGAAAAGTA

AGATAGATTT

CACAGATACA

ATAGAAGATT

ATCTCAAAAT

TATCCATGAT

TTATGGAGGC

CACTAGAGAA

CAACAAGACT

ACAACAGCAA

AAAATGATGA

AATGATCCAA

CTGTCAACAC

AGAAAALACTT

GCAATATACA

CTCAAAGTCA

CCACCAAAAC

CGAATCA.AAG

TGTGGCTCTG

TTACAAGCCG

GTTGTTTACA

AAAGGAATGC

AGGAGCALTAA

TTCAAAATTC

CAGGTACACA

GAGAAAGGCG

GGCAGAATGT

3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 258

ACTCTGTTGA

TAGTTGGAGG

GTCAGCTGGT

ATCTAGTTAT

CTTTACCTGG

AACAATGGAA

AAGGATAATC

TCGCAAGAAT

ACAGAACACC

GAGACCGGCA

AACCATGATC

ATTGGTCAAC

TTTGAGCCTC

ATACAAGAAG

AGATGTGATA

CTTTGGAGGG

GGCAGTTGCT

AATTAGGGAC

AGCAATTAAA

AGGTTGTGAA

AACAAACATA

TATAGCATCA

ATATGATATC

CTTGAATGAT

CACTCAGATC

CCCTCTTCCC

ATACTGTAA

ATTCAAAAGA

CTGGGCTTCA

CGAGTTCAGA

CTAGTALATCT

AAAA.ACTTAG

AAGAGAGAAG

AGAACAACAA

ACACAACAAG

ATGGCATCTT

AGTCCCAAAG

ATACCAAAAA

TTATTGGATA

GTAACCAATC

GTAATTGGAA

CTGGTTGAAG

ACAkAATAAAG

TCAGTCCAGG

GCAGCAGGAC

TTTGGTGATA

TTATACCGCA

TATGATCTGT

TACTCAATCA

TACAAAGTAG

AGCCATATCA

CAGAAAATCG

CATGTCAATG

GAGATTTGTT

TCAGTAGAGA

TACTATCCTA

CTATTTTAGT

GACAAAAGAG

GGACCAA.AAA

AATCAAAACA

CACTGAACAC

TCTGCCAAAT

GGATGAAGAT

TAGAAGACTC

-GACTGATCAT

AAGAATCCAA

CCATTGCTCT

CCAAGCAGGC

CAGTGCAGTC

ATTATGTTAA

TTCAATTAGG

ACATAGGATC

CAAATATCAC

TATTTACAGA

CCCTCCAAGT

ATTCCATATC

TGACGAALAGG

AGAAAATGAG

CAACTGGGTC

ATCCTTTAAT

TTACAAGAGT

ATATTATTGC

CCGGACGTAT

GTCAATACCA

AGTCAAATAG

TCCAACTCAC

AATGCCAACT

AGATATCACA

ATCACAAAAC

TAACTCTTGT

CCCTTTATAT

TGAAAACACT

GGGAGTAGCA

AAGATCAGAC

AGTTCAGAGC

CAAAGAAATC

AATTGCATTA

GTTACAAGAA

AGAAkATATTC

ATCAATAAAG

CAGACTCCCT

ATATAACATC

GGCATTTCTA

ATTGATATTT

CATATCAAAA

GGATCTAAAT

GGATGCAATT

AAAAGGAGTT

CTATTAAGCC

ACAACTATTA

GAGAAATCAA

TCAAAACAAA

TCAATACTGC

AAACTACAGC

TTTGALACAA

GGTGACCAAC

GATGGATTAA

GATCCCAGAA

ACCTCAGCAC

ATCGAAAAAC

TCCATAGGAA

GTGCCATCGA

ACACAGCATT

AAAGGAATAA

ACAACATCAA

GTGAGAGTTA

TTATTAACTA

CAA.AACAGAG

GGTGGAGCAG

TCTTTAGGAC

ACACTAGCAA

CCGCATCTCA

TTCCAACCTT

GGGAAAATCA

GAAGCAAATA

GCAGTCACAC

AA.CAAAAGGT

AATTCCAAAA

TA.ATTATTAC

ACGTAGGTGT

GATATCTAAT

AGATCAAGCA

GATTACAGAA

CAAAACGATT

AAATTACAGC

TCAAAGAAGC

ATTTAATAGT

TTGCGAGGCT

ACTCAGAATT

AATTACAAGG

CAGTTGATAA

TAGATGTTGA

GGCTGCTGAA

AATGGTATAT

ACGTCAAAGA

4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 259

U

U

U

U

ATGTATAGAA

TGAAATAGAG

AGACATTGTT

CACCTGTACA

AATTATAACA

TAAAGAAGGA

ACTTGATCCA

A.AAAGAATGG

TAGCACTACA

GATAATTACA

TGACAAGCCA

TATAAAAAAC

CCCAATAGAC

TGCTGGCAAT

AATATACATA

AATTAATTCC

GTTTATGGA

GTCAGGAGTG

ATCATTGACA

TGATAATCAA

TCCAGATGAT

AAGGTTAATG

AACTCCGTCT

AGGTTGTCAG

CTCAGACTTG

TAGGAAGTCA

GCATTCAGCA

AGCTGCTTAT

CCAAGATATG

TGCAACGGAA

CATAAAGAAT

ACT CTTGCAT

ATTGACATAT

ATAAGAAGGT

ATCATAATTA

ATTGCAATTA

TATGTACTAA

TTAGGAGTAA

AAATCCAAAT

GAGCTGGAGA

TTATGGACAA

ATCAAALAGTG

ATTACAGAAA

AATACA.AGGC

CAACAGATGT

GAAGTGCTGC

TTTTGGAGAT

CCAGGGCCGG

TTAGTTATAA

GATATAGGAA

GTACCTGACT

TGTTCTCTAG

GCTATATATG

CAGGAAACAT

CATTTGTCAA

TTGGTAATAG

GTAGTACAGT

TCTATACACC

CAATCGAGCT

CA.AATCAAAA

TTTTGATAAT

AGTATTACAG

CAAACA.AATA

AGTTACGCAA

TCGAGATGGA

CGTCTATGGC

TAATCCTGGT

AAAAGGCCCA

AGATCCAAAT

TTCTTACAAT

CAGATCTTAG

CACAAAGAAT

GCACGTCTGG

GATTATTAGC

ATGATCTGAT

AATCATATCA

TAAATCCTAG

CACTCCTAAA

CCCTTCTGAT

ATCCCAATGT

TGGAGGAGTG

AATCALATCAA

AGGTATCILAC

AAATGATATA

CAACAAGGCC

ACTAGATTCT

GATCATTATA

AATTCAAAAG

ACATATCTAC

TCCAACTCTA

ATACTGGAAG

TACTCATGGC

GTTATTATCA

CGAATCATTG

GGCATCGGAT

TCAGAGTCAT

GAAATTCATT

AACACATGAT

TCTTCCATCT

TATGCCAACG

TTATGCTTAT

AGTCTTACAG

GATCTCTCAT

TACAGATGTA

CCAGGATTTG

CCAAGAACAA

GTTGCAAACT

CCACCTGATC

GGAATGCTGT

ACACTAAACA

AAATCAGATC

ATTGGAAATT

TTGTTTATAA

AGAAATCGAG

AGATCATTAG

CTCATATAAT

CATACCAATC

AACAAGCTCA

ATAGTCTTCA

CTGCAAGACA

A.ATACCAATG

GTCCAGAATT

AGTGAAATTA

GTAGGTATAA

TTAATGAkA

ACTGTTGATG

ACCTCAAATC

ATAGGGATA.A

ACCTTTAACA

TATCAACTGT

TATTAAACCA

CGGTCACATC

GTATAACAAC

AAGGAGTAAA

TCAATACAAA

ATTCTGTTAC

TAGALAGAATC

GGCATCAATC

TTAATATAAC

TGGATCAAAA

ATATTAAA.AT

TGAGGAAGGA

ACGGAAAGGA

CTAATA.AGAT

TCATAGTGCT

TAA.ATAATGA

ATCTAATACA

ACATACCAAT

CAATTAGAAA

AACCTTTAAA

CTCCAAAAAT

GCTGTGTTAG

TAATTACTCG

TAACTGTAAA

TAAATGACAA

GTTCAACTCC

6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620

U.

260 et S.

S *5 5

S

t be

*SESSS

5 *.a

S

.555 5,5.55

S

5* S S

S*

CAAAGTTGAT

TGTCAATTAT

TCAACCATAT

AATATTTCTC

AACTGGGTGC

TTCAGATAGG

AA.AATTGAAA

ACTTCTACTA

ACAATTAGGA

TAATGTGCTA

ATGTATAACA

ATCTGTCATA

AACCGAAAGA

AACAAGCTGC

TAA.AAGCTTA

TTAATCATAA

ATCAGCAPLTC

GGGAAATGGA

ACCTTAACTC

CTCAGCCTTA

TTAATAAATT

AAGTGAATGA

TCAA.ATTATA

GAACATATAG

TAGCCTCAA)

AAGTTCACAC

GAAAGATCAG

GATGGTTCAA

GCTGCACTAT

GGGTATGGAG

CCCGGGAAAA

AGGATGGTCA

GTATGGACGA

GGTAACAAGA

ATAATTGATA

TCAAGACCAG

GGAGTATATA

TTAGACTCAC

GTAAACGAGC

ATTACACACT

AACACATTTC

TTAACCATAA

AGACAATAGA

CACTGAATCT

TCCTATCGTT

TGATATGGAT

GGATAAAAGA

CTTAGGAAAA

TATACCTGG7 1TCAAATGAC7

LAAATGATGG.A

'AACCTATAAP

ATTATGCATC

TCTCAACAAC

ACCCATCTGT

GTCTTGAACA

CACAGAGAGA

ACTCCATCAT

TATCTATGCG

TCTATATATA

TTACTGATTA

GAAACAATGA

CTGATGCATA

AAAA.ATCGAG

TGGCCATCCT

ATAACAAAGG

AACCCATGTT

TATGCATCAA

CAAAAGGGAA

AACAATGGCA

AALAGGTAAAA

GACGACTCAA

CAACGATCTA

*TACACATTTA

ATTAAiCAGTA

*GATGGATTAA

AGCAATTATC

LTCAGATAAAI

ATCAGGCATA

AAGATTTAAG

TGGACCAGGG

TCCAATAAAT

CTGTAATCAA

TGTTGCTGAC

ACAAAATTAC

TACAAGATCT

CAGTGATATA

ATGTCCATGG

TCCACTCAAT

AGTGAACCCA

AAACAGAACA

ATATTGTTTT

GTTCAAAACA

TCTATCTATA

ATATAAAAAA

CTGTATCTGA

TAGCACAATT

TACTAGTTAT

TTAGAAGATT

TCAGATATCC

'AAGTGACTGA

GAGATCTATG

IATCTTAATGA

GGTATAATCC

GAAGATATTG

AATAATAACA

ATATACTACA

GAGAATGTAA

GCGTCTCATA

AAAGGCTTAA

TGGGGGTCAG

ACAAGTTGGC

AGGATAAAAT

GGACATT CAT

CCCACAGGGA

GTCATAACTT

CTCTCAGCTG

CATATAGTAG

GAGATTCCAA

ATACAAGTAT

CTTAGGAGCA

CATACTCTAT

ACACACTATT

CACTAGACAG

AAAATTAATA

AGAAATGTCA

ATTATTACTT

GATTAATGTG

AGAAATTAAT

ATTCAAAACA

TACTTGATAT

TAAGCTTTGA

AAGGCAAAAT

TCTGCAACAC

GTCCATGGTT

PCTCAATTCC

AAGGAAGGTT

ATAGCAAGTT

GGACATGGCA

GTCCAGATGG

GCATTGTGTC

ACTCAACAGC

GATATACAAC

AAATAAATCA

AAAGCTGCAG

ATGATAAGTA

AAGCGTGCTC

CCTGAGTGTC

ATGAGTCTAC

AAAATAAAAC

TTAACTGAAA

AAAGAAATGT

AAAGCAGATA

CTATCAAAAT

AATATATCGA

TGGTTTACTA

7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 261

S

TCAAGTATGA

AGGATTATAA

TGATATTAGA

ATTGTGACGT

TACAATCTAT

TTATGGGAGA

TTCAAACTCA

AGATGGAATT

TTGATAAAAT

CTTTTTTTAG

GAAAATATAT

TCTTCTGTAC

TGACATTACC

TATCATATGA

TCATAGAGCC

CAAAAAAATC

CATCCAACGA

ATCAGATATT

CTTATAGTCT

ACAAAATGAG

TCTTTCAAGA

TATCAATATC

ATGACCTTAA

AGAAATTTGA

TCCTAACAAC

TTGGAGAAAC

TATGAGAAGA

CTTGTTAGAA

TAAACAAAAC

AGTCGAAGGC

GTATCAGAAA

AAAGACATTT

TGATCCTGTT

AATATTTGAA

TTTAGATATA

AACATTTGGG

GTATATTGGA

AATAATAATT

TGATCATGCA

GAATGCTGTT

TCAGTTAGAT

AAATTGGGAC

ATCACGAAGA

GGATTATGTA

TAAAGAAAAA

AGCTACACAA

AAATGGGATG

AGGAGTTCCA

AACCTACAAT

ATTCAAGTCA

AGATCTCAAA

TTGCAACCAA

TTACAAA.AAG

GACCAGAAGA

TACAATGGTT

CGATGGAATA

GGTAATAACC

GATGTGATAT

AAACAACTAA

TCTAGAGAAT

TTTAATAAGT

CATCCTCCAT

AAACAATTAA

AACGGATATA

CACGAATTCA

GATTATTACC

GAGGATTTGA

ACAGTTTATC

TTAGTTGAAG

GAATCTGGGG

GAGATCAAAC

GTTTTATCAG

GTGAAGGGAG

CGGTATAATG

AAAATAAGTA

ACGGATATCT

AAATACTGTC

ATATTTGGAT

CTCGAAATGA

ATTTCTTATT

ATCTAATTAC

TAAGTGCATG

TGTGGGAAGT

CGTTATTAGA

GAGGAGCTTT

CGATTAAGGA

CTACAATAGA

TAGAAGCTAG

AATTTGACAC

GAGAGAGGCA

TCATAAATGC

AGAGCTTTAT

CAATTTATAT

CTGCATCTAA

TATTTATAGC

ACTGGTTAGA

AGGAAGGTAG

AGACACTACT

AGATTGAATT

AAGTGTACAA

ATCTTAATTT

ACAATGATGG

TTAATTGGAG

TAAATAAATT

GATCACTTTT

GATACATCCA

TCCTGAATTA

TGCTAAGTTA

GATAGATAAA

ACCACTTGCA

TTTAAATCAT

ATTTCTGAGT

TGAAATAGCA

TATTGCAGCA

TATTAATAAA

TGGTGGACAG

TTACGGTTCA

AGGAATAAAA

GAAAGATAAA

TTTACTGTAC

AGATAGTAA.A

TGATCCAGAA

ACTCTTTGCA

TGCAAATAAC

ACTTAAGAGA

TAATTCTAAA

GTCTTCTAAT

ATACGAGACT

ATATGIAATCA

GTTTAATTGG

AATGTTGGGA

GAATTGGTTT

GTATTGATGT

GATCCAAAAT

TTGTTTCCAA

TTATCCTTAA

GTGTTATCCG

GTAGATTACA

GAGATTTTCT

GAAAAGGTTA

TGTCATGCTA

TGGCCTCCTG

AACTCTGCGA

TTCAATAAAT

GCATTATCTC

CGTACTAACG

TTTGATCCTC

TTTAATATTT

AAAATGACAT

ATAGGAAAAT

TTAACAACCA

AGCCATACAG

CAGAAATCAA

GTGAGCTGTT

ACAGCTCTAT

TTACACCCTC

9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 262

GTCTTGA.AGG

ATATATCATT

TAGA.AGGATT

CTGTTAGAAT

TAACCACAAG

ATGTAGTGAG

AATTAAATGA

ATGGGAGAAT

CAGTAATAGA

TTGAGAATGG

AACTATATAT

AGTATTTTAG

GATTCAATCA

CCGCATTGGC

ATAGGATTAT

ATTCATGCAA

GGAATGTATT

TAGAAGAAGA

TTGCACATGA

TAGATACGAC

TGTTGAGGAA

GACTAATTGT

CATTGCGACA

CGCCTGACCC

TATGTTATTC

AAATAGGATC

AAGTACAATC

AGAGGATCAC

TTGTCAAAAA

AGGCGTGAGG

AGTACCCAAC

ATTTTTTGAT

AACGATTATA

TCTTCCTCAA

CGAAACAAGA

TTATTCACCT

TGCCCTTGGG

GAATCCAAAT

CATGGCCATG

TGATATTAAA

GAATCAAGAA

TTTACCACAA

ACAAGATTCA

TGAAGAATTA

TATTCTAGAT

AAAATCACTA

AATCAGTAAT

AAGTGATAAA

AAAGATGTGG

ATTAGAATTA

TTCAGATGGC

AGCAGAAACA

TATGTAGGTG

CCTGATTCTG

TTATGGACAC

GTGACTGCAA

AATTATGACT

TCATTAAGAG

AGTAGCAAGA

GCTCTAAZAAG

TCAGCATCTT

GTTCTAGGAT

ATGAATATCA

TGGATGCAAT

TCAAGATGTT

AGATTTATTA

CCAGGTGAGT

TCTCAAA.ATA

CCAAATCCAT

GCTGAGTTCC

AATTCTCTCA

ATTCGGGTTG

TACGATCTAG

ATCAAGTATG

ATTCATTTAT

CTATCTGGGG

ACAA.ACCCAT

GGTATATCGT

ATCCTTACTG

GTTTTTACGT

TCATATCTAT

TGGTTCAAGG

ACAGAGTTAA

A.AGTGATGGA

TGTTCATATA

CATTATCTAG

CAAATTTGGC

ATGCATGCTC

ATCCAACTAT

ATGCCTCTTT

TTGTAAGGAA

AGGCGAATCT

CATCTTTTTT

TAACCACCAT

TATTATCTGG

TGATGGACAG

CAGGAATTAG

GCATAAATAG

TACAATATGA

AAGATATGTG

CAGGAGGAAG

TAGTAATAAC

ATACTTGGAT

CATTAAGAGT

TCCTCCATCA

TCATAACCCA

AAGTGCAATA

AGACAATCAA

GAAGGAGATA

TGATCTAGGT

TAGCAAAAGA

ATGTGTCTTC

AACATCATTT

AATTTTTAAG

AACACAGAAT

AATACCTGCT

TATTGGTGAT

ATTAGACCGA

TGACTGGGCT

GATAAAAAAT

ATTATTCACA

GAAGGTAATT

AAATGCCATA

AGGAGGACTG

AACACTAAGT

TTCGGTAGAC

GATGATAAGT

AGGATCAGAA

GTATTTACCC

TCCTTATTTT

GATAAAGAAC

AGAGGGGGTA

CATCTAGCAG

GCTATAGCTG

GTTTATAAAG

CATGAACTTA

ATCTATTATG

TGGTCAGAGA

GCAAAAGCAA

AACATTCAAC

ATCAGAGATC

AGTGTTGGGG

CCATCAGTTG

AGTGTTCTTT

TCAGATCCAT

ATAACAGCAA

AATACAATGA

CTCCCTAGAG

GCTGGAATGT

ACATATAGTT

AGGACTTTGC

CTTGCCATAG

GGACTTGAAA

CATTGTAAAA

GGTAATATCA

GGATCAGTCA

10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 263 a. a.

a a a a a. a a a a *0

C

CTGATGAAAG

CCGCAATAAG

TGGAAGCCTC

TAACACCGGT

TGAAATTCTC

ACATGTCTAT

TGTTAACAGG

ACCCTATAGT

ATGAACATAT

TTATTTATGA

ACCATTCTTA

CAATATGTAC

AAGAGATIAT

CTCTTGACAT

ACACTCTTTA

CACTGAGAGA

AAGTATTCAA

CTAGTCAAGA

TGAGAGA.ATG

TTGCAAATGA

CAGAALATTGC

TATTGAAACA

TATCTGGATT

TCAAATATCT

TAGAAGATGA

ATAATAAAGG

AT CTGAAG CA

AATAGCAATG

ACAGATAGCA

AGCTACATCA

CAGTACATCA

CAA.AGAAGCT

ATTAAGTGTT

TATGCATCTG

TAATCCAGAG

TAAAGACCCA

CACAATTGAT

TGCAATTACA

AGTTATTGCA

ACTTGTATTT

TAGTCTAAAA

TACTTCCCAT

GAGGTTCTGG

CCAGATAAAA

GTTGAATGGT

TAGGAAACAA

ATCTTTCGGA

ATATCTTGAA

ATTAATTAAA

AAGGATTCGC

AAATATGCTG

GAATArT

CAATTAGGAT

ATATATACAT

CAAACACGTG

ACAAATTTAT

TTGATCAGAG

AATGAAACCA

TTCGAATATT

CACATAGAAG

TCTACATTAG

CTCAAAGATG

ATGAATTATT

ATAGCAGATA

AATGATGATG

CTCAAGACAT

ATAGAAGGTA

TCALATATTAA

GATTGTGGAG

CTTGCCCTAT

GTATCACTTG

GCCTTTATTT

CCTAACCTGT

TTAAATATTA

TCGTTCCCAT

GGTATTAGTC

GATAACATTG

AACAATTTCT

ATATCAAGAA

GGGCATTTGG

CAAATTTTAC

CACACAGATT

TCAGCAGATT

AAGATACTAA

TATTTAGATT

ATGAGTGTTG

AATTAATTCG

TGGACTTATC

GGGATGATAC

CTATGTCACA

ATATTAATAG

TTGGTGGATT

GGGATCTCAT

AAGTATTATC

TTTTAAACCC

CTATATGTGA

AALATATACAT

CTAGACACCT

TAA.ACTTAAC

A~AGAGACCC

CAACTGTAAC

CACCTGAGGT

rCAA.AACTAT

GGGGACTAGC

TCTTAGT)AJA

TAATGATGAG

ACTAGATAGT

AAAGGATACT

TATAACAATG

TCTTATTTAT

AAAAGAAACC

TATTAXAGAA~

ATATCCTGAA

AAAACTTATG

TGACATCATA

ATTAGATCGA

CTTAATCACT

ATTAGTAAAT

TTGGGATTAT

TAATGCATTA

TATTTATGGT

ATATTCACTA

TTGTGACAGC

TTCATTTGTT

ATACTTGGAG

TACTCTTAAA

ATACGTAAGA

AATTGATGAT

AAATGATAAC

ACTTAAGAAC

CCTGCAAA-AG

ATATCTTGGA

CTCAAAATTT

GCAACTCAGA

TCCAATGATA

CA.ACA2LATAA

ACAGGACACA

AGTTTTAATG

AGTAATGAAT

GTTATTAAAG

CATGCAATTT

GATAATTTAA

GAATTTTTGA

CAATTTGCAT

ATAATGAGAA

TCTCATCCTA

CCTAATATTG

GATCTATTTA

GATATGGAAG

rGTTGTTTAG kGACTTGATC 1ATGTACAAA kAGACTGCAA

LGGGATCCGG

rGTAATAAAG rATCAAGTCC 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 264

S

TTAAAATCAG

GTGGTTTGAC

TCAACAGCAC

ATAAAGACAA

ATGCCACATT

TTGGTCAACG

GAAATGTGAC

CATGGATAGG

TTGGATTAGT

ATGAACATTA

TTTCCAAAAT

TATATTGGAA

TATATCTAAT

CAAAACTTAA

CAAAGAAGAG

GAATCATGAG

ATCTGGCGAA

GTTTTCAGCG

AGAGACATAA

GACTGCTATC

TTACAGGTCG

TAGCTGATAC

GAGAGTGTAT

AATTGATTGG

AGTTATTAGA

TGAAGATATA

ATCTATAACA

ACTTCCTCAA

TAGTTGTCTG

GGACAGGCTC

AGGACCTGCA

AGAATTGAAA

ACAGATTCTT

AALATATGGAA

ACATTGTGAT

TAGTGTTATA

TATACCTACA

AGATGTAAGT

TTCGAALAGAT

AAGATTGTCA

GAATAATGAA

ACCATATCAT

AGAATTTTTA

AACAATAAAG

ATTAGGCGGA

GAGAAGACTA

CTTTCCTGAT

TGATTTAGAA

AGGATCAATA

TGGTGCTAAA

AAACTACAAT

TCCTAACCTT

AGTGATTCTG

GGAGGGAATT

AAAGCTCTTG

TTCCTGGGAG

GTTAATTATT

ATATTTCCTT

AACAGGGTAA

TGTGAGAGCT

ATGGAAGGAG

AGAATTACAT

ATCACTCCGA

ATAATATCAC

GCATATTGTA

CTCTTGGAAG

TGGTTACATC

ATGGCACTAC

TCAACCCCAG

GATGTTTTAT

AGATATAACA

GTATTAAGTT

GAAAA.ATTTG

TCATTAAAGT

TCATATTGGT

TTATTAGGAA

CAACATGATG

TATCTTTAAG

ATGATAATGA

ATCTATCGCA

AGTTATCACA

AAGGAGCAGG

ATAATTCAGG

CAGAGGTATC

AAGTACTGTT

TALATATGGAG

CTATCGGTAA

ACTTGATTGG

ATTGGTCTAG

TCAAAACTTC

CTATAATGGA

AAAATAATCT

ATGAAJATCA-A

AAATCTTTGG

ATCTGACTAA

TTGAATGGAT

TATTCCCACT

GGATTTCATT

AACATAGAGC

TATTGTCGAA

TTCTAACCAA

TTCCCAGACA

AATTTGATAT

CCTAGGAATA

TAGACTAGAT

TCAATTGAGA

AATTTTAATG

AGCTATGCTA

TTTGAATATA

ATTAGTAGGT

C-AATGGGAAT

TGAATTA.AAT

ATCAGAAGAA

GGATGATGAT

AATACTTTAT

TAATCCTGCA

ACCTAGTGAA

ATTAAAATGG

AGAAGGAGAA

ATTTCAAATC

TATCAACAAT

TAATATAACT

GAAAAATAAG

ATCATTATCG

ACAGACTGGA

AAACATCATT

AGAAGTTAAA

ATATAAAGAA

CGATTAAAAC

GACAAAAAGT

GCTALATACAA

TTATTCGGAA

AAGGAAGTCA

GCATGTTATG

ACAGATGTAA

AAAAAATTAG

CCTAATTCAA

GATAAGTCCA

ACTGTTCTAC

GTTGTTTTAG

CTATATAAAT

TCAACAGAAT

ATTGTTTTAT

ATCATTTTAT

AGAGATTATG

AATTTAAATC

ATAATCCA.AA

CATGATGATA

GGAAAGTTAA

ACTCGATTAC

TATGTATCAT

AAGALATTACA

ATACTTATGA

CCCGALAGACC

ATAAATACAA

AAGAAAAACA

13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15240 15300 15360 15420 6 265 TGTAATATAT ATATACCAAA CAGAGTTCTT CTCTTGTTTG GT INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 2233 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID 15462 Met Asp Thr Giu Ser Asn Asn Gly Thr Val Ser Asp Ile Leu Tyr Pro 0000.

0 .so.

Giu His Ile Arg Asn Glu Leu Arg Gly 145 His Cys Thr Leu Gin Asp Met Leu Asp 130 Ser Thr His Ile Val Arg Leu Phe Leu 115 Leu Asn Thr Leu Met Ile Ser Gly Lys 100 Lys Trp Tyr Tyr Asn Ser Thr Ile Lys Leu Ala Ile Asp Lys 165 Ser Leu Arg Arg 70 Tyr Tyr Asp Asn Leu I50 Ser Pro Pro Gin 55 Arg Thr Ile Arg Val 135 Afin Asp Ile Gin 40 Lys Leu Phe Pro Thr 120 Leu Giu Lys Val 25 Pro Ile Lys Ile Gly 105 Tyr Ser Giu Trp Lys Tyr Lys Leu Arg 90 le Ser Lys Ile Tyr Gly Asp Leu Ile 75 Tyr Asn Gin Leu Asn 155 Asn Lys Met Asn Leu Pro Ser Met Ala 140 Asn Pro Ile Asp Lys Thr Giu Lys Thr 125 Ser Ile Phe Ala Asp Leu Giu Met Val 110 Asp Lys Ser Lys Gin Asp Asp Lys Ser Thr Gly Asn Lys Leu Ser Lys Val Lys Giu Leu Asp Val 160 Trp 170 175 Phe Thr Ile Lys Tyr Asp Met Arg Arg Leu Gin Lys Ala Arg Asn Giu 266 Ile Asn Asn 225 Asp Pro Ile Ser Val Glu .Asp Glu Leu Gly 385 Cys Pro Tyr Thr Phe 195 Phe Leu 210 Tyr Asn Val Val Lys Leu Asp Lys 275 Leu Leu 290 Lys Gin Leu Ile Tyr Ile Ile Ala 355 Giu Ala 370 Lys Gin Thr Ile Pro Vai Giy Ser 435 180 Asn Leu Gly Giu Gin 260 Leu Giu Leu Phe Asp 340 Giu Ser Leu Ile Thr 420 Asn Val Gly Lys Asp Ile Tyr Giy 245 Ser Phe Pro Arg Giu 325 Lys Ile Ile Lys Ile 405 Leu Ser His Leu 230 Arg Met Pro Leu Gly 310 Ser Ile Phe Ala Phe 390 Asn Pro Ala Pro 215 Ile Trp Tyr Ile Al a 295 Ala Arg Leu Ser Ala 375 Asp Gly Asp Ile Glu Thr Asn Gin Met 280 Leu Phe Giu Asp Phe 360 Glu Thr Tyr His Ser 440 185 Tyr Leu Pro Ile Lys 265 Gly Ser Leu Ser Ile 345 Phe Lys Ile Arg Ala 425 Tyr 190 Asn Leu Leu Glu Asp Gin Lys 205 Vai Giu Ser 250 Gly Glu Leu Asn Ile 330 Phe Arg Val Asn Giu 410 His Giu Leu Leu 235 Al a Asn Lys Ile His 315 Lys Asn Thr Arg Lys 395 Arg Giu Asn Ile Leu 220 Val Leu Cys Ala Asn Leu Thr Phe 285 Gin Thr 300 Val Leu Giu Phe Lys Ser Phe Gly 365 Lys Tyr 380 Cys His His Gly Phe Ile Ala Val 445 Asp Lys Gln Met Tyr Cys 240 Lys Leu Asp 255 Trp Giu Val 270 Asp Val Ile His Asp Pro Ser Glu Met 320 Leu Ser Val 335 Thr Ile Asp 350 His Pro Pro Met Tyr Ile Ala Ile Phe 400 Gly Gin Trp 415 Ile Asn Ala 430 Asp Tyr Tyr Gin Ser 450 Phe Ile Gly Ile Lys 455 Phe Asn Lys Phe Ile 460 Giu Pro Gin Leu 267 Asp 465 Lys Thr Asp Asp Lys 545 Met Gly Leu Glu Asn 625 Phe Ser Tyr Leu Ile 705 Giu Asp Leu Thr Ile Tyr Met Lye Asp Lys Ala Leu Ser Pro Lys 470 475 9.

C

9 Ser Asn Ser Trp 530 Glu Arg Lys Lys Val 610 Lys Glu Cys Giu Asn 690 Tyr Asn Ala Lys 515 Leu Ile Al a Phe Arg 595 Tyr Ile Phe Phe Ser 675 Lys Val Trp Ser 500 Phe Asp Lys Thr Phe 580 Leu Asn Ser Lys Leu 660 Thr Leu Gly Asp 485 Asn Asp Asp Gin Gin 565 Gin Thr Asn Asn Ser 645 Thr Ala Phe Asp His 725 Thr Giu Pro Pro Giu 550 Val Giu Thr Ser Leu 630 Thr Thr Leu Asn Pro 710 Val Ser His Glu 535 Gly Leu Asn Ile Lys 615 Asn Asp Asp Phe Trp 695 Tyr Pro Arg 505 Ile Asn Leu Glu Met 585 Ile His Ser Tyr Lys 665 Glu His Pro Al a 490 Leu Leu Ile Phe Thr 570 Val1 Ser Thr Ser Asn 650 Lys Thr Pro Pro Phe 730 Ser Val Asp Ser Al a 555 Leu Lys Gly Asp Asn 635 Asp Tyr, Cys Arg Ser 715 Asn Glu Tyr Tyr 540 Lys Leu Gly Val Asp 620 Gln Gly Cys Asn Leu 700 Asp Leu Val Val 525 Ser Met Al a Glu Pro 605 Leu Lys Tyr Leu Gin 685 Glu Lys Leu Phe 510 Glu Leu Thr Asn Ile 590 Arg Lys Ser Glu Asn 670 Ile Gly Glu Tyr 495 Ile Ser Lys Tyr Asn 575 Glu Tyr Thr Lys Thr 655 Trp Phe Ser His 480 Arg Ala Gly Glu Lye 560 Ile Leu Asn Tyr Lys 640 Val1 Arg Gly Thr Ile 720 Ser Leu Giu Asp Pro Asp Ser Gly Tyr Val His Asn Pro Arg 735 268 Gly Gly Ile Giu Gly Phe Cys Gin

V.

V

V. V V

C

1 740 Ser Ala Ile His 755 Met Val Gin Gly 770 Asn Aen Tyr Asp 785 Val Arg Phe Phe Giu Leu Lys Leu 820 Ser Lys Arg Ile 835 Ala Leu Ser Arg 850 Arg Ser Ala Ser 865 ksn Gly Tyr Ser Ile Gin Gin Leu 900 ['hr Gin Asn Ile 915 ['yr Ala Ser Leu 930 'let Ser Arg Cys 945 eu Ala Asp Ile Pal Leu Tyr Arg 980 ~sp Trp Ala Ser 995 Leu Asp Tyr Asp 805 Asn Tyr Cys Ser Pro 885 Tyr Arg Ile Phe Lys 965 Ile Asp Ala Asn Arg 790 Ser Glu Tyr Val Asn 870 Val Ile Asp Pro Vai 950 Arg Met Pro Ala Gin 775 Val Leu Thr Asp Phe 855 Leu Leu Ala Gin Al a 935 Arg Phe Asn Tyr Val 760 Ala Lys Arg Ile Gly 840 Trp Ala Gly Leu Tyr 920 Ser Asn Ile Gin Ser 1000 Lys 745 Arg Ile Lye Giu Ile 825 Arg Ser Thr Tyr Gly 905 Phe V.al Ile Lys G1u 985 Cys Leu Ile Ala Glu Val 810 Ser Ile Glu S er Ala 890 Met Arg Gly Gly Ala 970 Pro Asn Trp Gly Val Ile 795 Met Ser Leu Thr Phe 875 Cys Aen Aen Gly Asp 955 Asn Gly Leu Thr Val Thr 780 Val1 Asp Lys Pro Val 860 Al a Ser Ile Pro Phe 940 Pro Leu Giu Pro Leu Arg 765 Thr Tyr Asp Met Gin 845 Ile Lys Ile Asn Aen 925 Aen Ser Leu Ser Gin Ile 750 Val Arg Lys Leu Phe 830 Ala Asp Ala Phe Pro 910 Trp His Val Asp Ser 990 Ser Ser Thr Val Asp Gly 815 Ile Leu Giu Ile Lys 895 Thr Met Met Ala Arg 975 Phe Ile Al a Pro Val 800 His Tyr Lys Thr Giu 880 Asn Ile Gin Ala Ala 960 Ser Phe 1005 Ile Thr Thr Met Ile Lye An Ile Thr Ala Arg Asn Val Leu Gin Asp 269 1010 1015 1020 Ser Pro Asn Pro Leu Leu Ser Gly Leu Phe Thr Asn Thr Met Ile Giu 1025 1030 1035 1040 Glu Asp Giu Giu Leu Ala Giu Phe Leu Met Asp Arg Lys Val Ile Leu 1045 1050 1055 Pro Arg Val Ala His Asp Ile Leu Asp Asn Ser Leu Thr Gly Ile Arg 1060 1065 1070 Asn Ala Ile Ala Gly Met Leu Asp Thr Thr Lys Ser Leu Ile Arg Val 1075 1080 1085 Gly Ile Asn Arg Gly Gly Leu Thr Tyr Ser Leu Leu Arg Lys Ile Ser 1090 1095 1100 Asn Tyr Asp Leu Val Gin Tyr Giu Thr Leu Ser Arg Thr Leu Arg Leu 1105 1110 1115 1120 Ile Val Ser Asp Lys Ile Lys Tyr Glu Asp Met Cys Ser Val Asp Leu 1125 1130 1135 Ala Ile Ala Leu Arg Gin Lys Met Trp Ile His Leu Ser Gly Gly Arg 1140 1145 1150 Met Ile Ser Gly Leu Giu Thr Pro Asp Pro Leu Glu Leu Leu Ser Gly 1155 1160 1165 Val Val Ile Thr Gly Ser Glu His Cys Lys Ile Cys Tyr Ser Ser Asp 1170 1175 1180 Gly Thr Asn Pro Tyr Thr Trp Met Tyr Leu Pro Gly Asn Ile Lys Ile 1185 1190 1195 1200 Gly Ser Ala Giu Thr Gly Ile Ser Ser Leu Arg Val Pro Tyr Phe Gly 1205 1210 1215 Ser Val Thr Asp Glu Arg Ser Glu Ala Gin Leu Gly Tyr Ile Lys Asn 1220 1225 1230 Leu Ser Lys Pro Ala Lys Ala Ala Ile Arg Ile Ala Met Ile Tyr Thr a1235 1240 1245 Trp Ala Phe Gly Asn Asp Giu Ile Ser Trp Met Giu Ala Ser Gin Ile 1250 1255 1260 Ala Gin Thr Arg Ala Asn Phe Thr Leu Asp Ser Leu Lye Ile Leu Thr 1265 1270 1275 1280 Pro Val Ala Thr Ser Thr Asn Leu Ser His Arg Leu Lys Asp Thr Ala 1285 1290 1295 270 Thr Gin Met Lys Phe Ser Ser Thr Ser Leu Ile Arg Val Ser Arg Phe 1300 1305 1310 Ile Thr Met Ser Asn Asp Asn Met Ser Ile Lys Giu Ala Asn Giu Thr 1315 1320 1325 Lys Asp Thr Asn Leu Ile Tyr Gin Gin Ile Met Leu Thr Gly Leu Ser 1330 1335 1340 Vai Phe Giu Tyr Leu Phe Arg Leu Lys Giu Thr Thr Gly His Asn Pro 1345 1350 1355 1360 Ile Val Met His Leu His Ile Giu Asp Giu Cys Cys Ile Lys Giu Ser 1365 1370 1375 Phe Asn Asp Giu His Ile Asn Pro Giu Ser Thr Leu Giu Leu Ile Arg 1380 1385 1390 Tyr Pro Giu Ser Asn Giu Phe Ile Tyr Asp Lys Asp Pro Leu Lys Asp 1395 1400 1405 Vai Asp Leu Ser Lys Leu Met Vai Ilie Lys Asp His Ser Tyr Thr Ile 1410 1415 1420 Asp Met Asn Tyr Trp Asp Asp Thr Asp Ile Ile His Ala Ile Ser Ile *1425 1430 1435 1440 V Cys Thr Ala Ile Thr Ile Ala Asp Thr Met Ser Gin Leu Asp Arg Asp 1445 1450 1455 .Asn Leu Lys Gu Ile Ile Val Ile Ala Asn Asp Asp Asp Ile Asn Ser 1460 1465 1470 *.Leu Ile Thr Giu Phe Leu Thr Leu Asp Ile Leu Val Phe Leu Lys Thr 1475 1.480 1485 Phe Gly Gly Leu Leu Val Asn Gin Phe Ala Tyr Thr Leu Tyr Ser Leu 1490 1495 1500 *Lys Ile Giu Gly Arg Asp Leu Ile Trp Asp Tyr Ile Met Arg Thr Leu 1505 1510 1515 1520 *Arg Asp Thr Ser His Ser Ile Leu Lys Val Leu Ser Asn Ala Leu Ser *1525 1530 1535 His Pro Lys Val Phe Lys Arg Phe Trp Asp Cys Giy Val Leu Asn Pro 1540 1545 1550 Ile Tyr Gly Pro Asn Ile Ala Ser Gin Asp Gin Ile Lys Leu Ala Leu 1555 1560 1565 271 Ser Ile Cys Glu Tyr Ser Leu Asp Leu Phe Met Arg Glu Trp Leu Asn 1570 1575 1580 Gly Val Ser Leu Glu Ile Tyr Ile Cys Asp Ser Asp Met Giu Val Ala 1585 1590 1595 1600 Asn Asp Arg Lys Gin Ala Phe Ile Ser Arg His Leu Ser Phe Vai Cys 1605 1610 1615 Cys Leu Ala Glu Ile Ala Ser Phe Gly Pro Asn Leu Leu Asn Leu Thr 1620 1625 1630 Tyr Leu Giu Arg Leu Asp Leu Leu Lys Gin Tyr Leu Giu Leu Asn Ile 1635 1640 1645 Lys Giu Asp Pro Thr Leu Lys Tyr Val Gin Ile Ser Gly Leu Leu Ile 1650 1655 1660 Lys Ser Phe Pro Ser Thr Val Thr Tyr Val Arg Lys Thr Ala Ile Lys 1665 1670 1675 1680 Tyr Leu Arg Ile Arg Gly Ile Ser Pro Pro Giu Val Ile Asp Asp Trp 1685 1690 1695 Asp Pro Val Glu Asp Giu Asn Met Leu Asp Asn Ile Val Lys Thr Ile *1700 1705 1710 *Asn Asp Asn Cys Asn Lys Asp Asn Lys Gly Asn Lys Ile Asn Asn Phe *1715 1720 1725 .00 Trp Gly Leu Ala Leu Lys Asn Tyr Gin Val Leu Lys Ile Arg Ser Ile *1730 1735 1740 Thr Ser Asp Ser Asp Asp Asn Asp Arg Leu Asp Ala Asn Thr Ser Gly *.1745 1750 1755 1760 Leu Thr Leu Pro Gin Gly Giy Asn Tyr Leu Ser His Gin Leu Arg Leu 1765 1770 1775 Phe Gly Ile Asn Ser Thr Ser Cys Leu Lys Ala Leu Giu Leu Ser Gin **1780 1785 1790 0. *le Leu Met Lys Glu Val Asn Lys Asp Lys Asp Arg Leu Phe Leu Gly .1795 1800 1805 Giu Gly Ala Gly Ala Met Leu Ala Cys Tyr Asp Ala Thr Leu Gly Pro 1810 1815 1820 Ala Val Asn Tyr Tyr Asn Ser Gly Leu Asn Ile Thr Asp Val Ile Gly 1825 1830 1835 1840 Gin Arg Glu Leu Lys Ile Phe Pro Ser Glu Val Ser Leu Val Gly Lys 272 1845 1850 1855 Lys Leu Gly Asn Val Thr Gin Ile Leu Asn Arg Val Lye Val Leu Phe 1860 1865 1870 Asn Gly Aen Pro Asn Ser Thr Trp Ile Gly Asn Met Giu Cys Giu Ser 1875 1880 1885 Leu Ile Trp Ser Glu Leu Asn Asp Lys Ser Ile Gly Leu Val His Cys 1890 1895 1900 Asp Met Giu Gly Ala Ile Gly Lys Ser Giu Glu Thr Val Leu His Giu 1905 1910 1915 1920 His Tyr Ser Val Ile Arg Ile Thr Tyr Leu Ile Gly Asp Asp Asp Val 1925 1930 1935 Val Leu Val Ser Lys Ile Ile Pro Thr Ile Thr Pro Asn Trp Ser Arg 1940 1945 1950 Ile Leu Tyr Leu Tyr Lye Leu Tyr Trp Lys Asp Vai Ser Ile Ile Ser 1955 1960 1965 Leu Lys Thr Ser Asn Pro Ala Ser Thr Glu Leu Tyr Leu Ile Ser Lys 1§70 1975 1980 .Asp Ala Tyr Cys Thr Ile Met Giu Pro Ser Glu Ile Val Leu Ser Lye *1985 1990 1995 2000 Leu Lye Arg Leu Ser Leu Leu Glu Giu Asn Asn Leu Leu Lye Trp Ile 2005 2010 2015 Ile Leu Ser Lye Lye Arg Asn Asn Giu Trp Leu His His Glu Ile Lye 2020 2025 2030 Clu Giy Giu Arg Asp Tyr Gly Ile Met Arg Pro Tyr His Met Ala Leu 2035 2040 2045 Gin Ile Phe Gly Phe Gin Ile Aen Leu Aen His Leu Ala Lye Glu Phe *.2050 2055 2060 Leu Ser Thr Pro Asp Leu Thr Asn Ile Asn Asn Ile Ile Gin Ser Phe 2065 2070 2075 2080 Gin Arg Thr Ile Lye Asp Val Leu Phe Giu Trp Ile Asn Ile Thr His 2085 2090 2095 Asp Asp Lye Arg His Lye Leu Gly Gly Arg Tyr Asn Ile Ph6 Pro Leu 2100 2105 2110 Lye Asn Lye Gly Lye Leu Arg Leu Leu Ser Arg Arg Leu Val Leu Ser 2115 2120 2125 273 Trp Ile Ser Leu Ser Leu Ser Thr Arg Leu Leu Thr Gly Arg Phe Pro 2130 2135 2140 Asp Giu Lys Phe Giu His Arg Ala Gin Thr Gly Tyr Vai Ser Leu Ala 2145 2150 2155 2160 Asp Thr Asp Leu Glu Ser Leu Lys Leu Leu Ser Lys Asn Ile Ile Lys 2165 2170 2175 Asn Tyr Arg Glu Cys Ile Gly Ser Ile Ser Tyr Trp Phe Leu Thr Lys 2180 2185 2190 Glu Val Lys Ile Leu Met Lys Leu Ile Gly Gly Ala Lys Leu Leu Gly 2195 2200 2205 Ile Pro Arg Gin Tyr Lys Glu Pro Giu Asp Gin Leu Leu Glu Asn Tyr 2210 2215 2220 Asn Gin His Asp Giu Phe Asp Ile Asp 2225 2230 INFORMATION FOR SEQ ID NO:21: SEQUENCE CHARACTERISTICS: LENGTH: 15462 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: ACCAAACAAG AGAAGAAACT TGCTTGGTAA TATAAATTTA

ACTTAAAATT

TTAAGACATT GACTAGAAGG TCAAGAAAAG GGAACTCTAT AATTTCAAAA TATTTGATAC ATTTAATGCA CGTAGGCAAG AAAACATAAC

AAAATCAGCC

TCATTCCTGG ACAGAAAAAT ACTGTCTCTA TATTCGCCCT

TGGACCGACA

ATAATGAGAA AATGACATTA GCTCTTCTAT TTCTATCTCA

TTCACTAGAT

AACATGCACA AAGGGCAGGG TTCTTGGTGT CTTTATTGTC AATGGCTTAT AGCTCTACCT AACAACAA.AT GGAAGTAATG CAGATGCCAA

GTATGTCATA

AGAAAGATCT AAAACGGCAA AAGTATGGAG GATTTGTGGT TAAGACGAGA

AACTTAGGAT

ATGTTGAGCC

GGTGGAGCTA

ATAACTGATG

AATGAGAAAC

GCCAATCCAG

TACATGATTG

GAGATGATAT

120 180 240 300 360 420 480 274 ATGAAAAGAC AACTGATTGG ATATTTGGAA GTGACCTGGA TTATGATCAG GA.AACTATGT

TGCAGA.ACGG

CATGTTTAGG

TCTCAGGGTT

TGCAGGCAGG

CTCAACAGAG

ATGACCTCAC

GTCTCGCTTC

CTCTATCCAC

CAXAGGGACC

CACCAGGCAA

GAGCCATGCA

GACAAGCAGT

GAGTGACACA

AGACATCTTT

CAGAACAATT

TTCAATATGC

CTGACAATAT

ACAAGAAGAA

AAATAGATGA

ATCAATAATA

GGTAAATTTA

AAACTATCAA

CTCGGCCCTC

AAACGACACA

CAAACCAACA

CAGGAACALAT

AGCTCTTATA

AAGAAAAGGC

GCTGGTATTG

CTTGGTAACT

AACCATAGAA

ATTCTTCAkAT

TCTCAGACCA

ACGCGCTCCT

CTATCCTGCC

ACAGTATGTG

AGCACGTGAT

CGAAGCTAAA

CCACAAACCG

CGAACATAGA

CTGGGCAGAA

CAAGACCGAA

ACAAAGCAGT

TCTGTTTAAC

AATAAGAAAA

GAGTCTGCTT

ATCATGGATT

AACATCATTG

ATCAACACAA

GAAACAAGTG

TCAACAATTG

ATACAGATCT

TTTTTCACCC

AGCGGTGACA

CTTATGGTTG

AAGAATATAC

ACAATCAGAT

GATATCAATA

TTCATCTGTA

ATATGGAGCT

ACGGGAAGAT

GCCGAAGCTC

GAAAGCTTGA

ACAGGTGGAT

GCAGATCAAG

GGAAATAGAA

CAACAAAACA

CAACCACCCA

GCATTTGGAA

ACTTAGGATT

GAAACTCAAT

CTTGGGAAGA

AATTCATACT

GAACCCAGCA

AGAAAGATAG

AAGACCTTGT

GGATAGTTCT

GATTGGAAGC

CAGTGGATCA

AALACATTAAT

AAATTGTTGG

ATGGAATTGA

GATTAAAAGC

TCCTCAGAGA

ATGCAATGGG

CATATCTAGA

AAATGAGCTC

AGAGACATAT

CAGCCATAGA

AACAAAATGG

GCGATGATCA

TCAGAGACAG

CTAATCCCAC

GCAACTAATC

AAAGAATCCT

CAATAGAGAG

GGAATCAAGA

CAGCACCGAC

ACTCAGTGCC

TGGATCAACT

CCACACATTT

GGTCAAAGCT

TTTCAGACAA

GATTGGGTCA

AACAATGAAT

CAACTACATA

GACCAGAATG

TTTGATGGAA

TCCTATACAT

GGTGGCAGTT

CATTGATATG

AACACTGGAA

AAGGAACATA

GATGGCA.ATA

AG;AACCTCAA

GACTGAGCAA

ACTAAACAAG

AAACAGAACA

GAATCAACAT

ATCATACCGG

TTGATGGAAA

GATAAATCAA

CCCCAAGAAG

ACCATCTGTC

GACAAAAATA

GGGTATCCAT

ATCACTAGTA

GATGGILACAG

ATCATGCGGT

ACCAGCAGA.A

AGAGATGCAG

GCAGCTTTGA

CTGTATTTAT

GGTGAGTTCG

GTACAAAATA

TTCCAGCTAG

GATGAACTTG

AACAGTTCAG

GATGAAGAGC

TCATCCATAA

GCTACAGAAT

AGACTCAACG

AACCAGGACG

TTTAATCTAA

AATATAGGGT

GCGATGCTA.A

CTAATATCTC

ACTTATCGGA

AACCAGAAAT

GACAGTCTG

600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 275 GTCATCACAC GAATGTACAA CAGAAGCAAA AGATAGAAAC ATTGATCAGG AAACTGTACA

GAGAGGACCT

AATCCCCAGA

CAATGAAATT

TGTTCCAAGC

TGATCATGGA

TACTGCTGCA

AAGTTCTTCA

CTGGTTTAAG

ATCAAAAGGG

AACAGAAATA

CAACAACACC

AACTTATACA

AAATGGAAAG

TCTATTGCAG

ACGAGTTGTA

CCTGGCAGGA

AAATGAAATG

GATAGAAAAT

TATGACTGAG

CAAAACAAAA

ACAAGGCATT

CGATGTACAA

AATACCCAAA

TCTCTCACAA

AGAAGTATCT

GGGAGAAGAA

AGCATCACAG

AGAAAGATGG

GAGATATCAG

AGAAGCCTGG

ACACCAGATG

ACACATCAAG

AAATCAAAAG

CAGAAGAAAA

CAGACAGAAT

GACCGGAACG

AAAGAATCGA

GAAAGGAAGG

AATCTTGGTG

TGTGTAGCAA

TTAGTCATAG

CTAAACCTCA

CAAAGAGAAC

AGAGGAGGAA

TTGAAAGAAG

GACAAGAATA

GTTAAATCAG

AAAGTGAGCA

AGCACAAAAC

GAATTAATGG

GCAGCTCAGA

ATTCTAAAAA

ATAAGGACTC

GAAGTGATGA

AATCTATCAG

ATGAAGA.AGA

AAGATGACAA

ATACCGACAA

TCTCAAAGAC

CATCAGAAAC

AACAGACAAG

TCCGAACAAA

ATACAGAAGA

TAATTCAATC

ATGTACTAAA

GGGTTTCAAT

AAGCAGATCT

AACTGTCATT

AGAAAGACCA

AAAAGATCAA

TACCCGATCT

AGATATTAAG

GTACAATGAG

AATCATACAT

ACATGTTCAA

TAGTAGAGCT

TGGAACCCAA

TATTGAGGGG

CATATTTACA

TACACCTGAT

AATACTAATG

AAGAATTA.AA

CCAGATACCA

AACAACCACC

ACAATCCTCA

CACAACTCCT

CTCTGAATCC

GAGCAATCGA

CACATCAAAA

CAATGTAGAT

GGACAACGAC

AAAGAAAATG

GATCACGTCA

AAATGAATCC

GAAGACCAGG

ATATCGACAT

TTCATACAAT

ATCACTAGTT

A;ACGAACTC

TGAAGATGTC

GAGACTGTGG

AACACGGAGG

AAAATGCGAC

ACAGAACAAA

ACAAGATCAA

AAAAATAGTA

AAAGGGGGAA

ACATCAGACT

AACACCGACA

TCATGGAATC

CCAACAACAA

AAACCCAAGA

TTTACAGAGA

CTAGATTTAT

ACTGCATCAA

ACAAAATTAA

GACGAATCAC

CTILATTTCAA

ILATGAGAGAG

TTTGACCCAC

GCAGGAGATA

GAGTCAAATG

GCAGTCATCA

AAACCTTGCA

AACA.ATTGCC

TCTCTGGAGG

ATATTGATCT

A.ATCTGCAAA

GTAGAAACAG

TAAGTGTTGT

GGACAAAGAA

XAGGGAAAGA

ACAGATCCAC

CAALAGGGGCA

TCATCATCGA

CTTCCAGATC

CACAAAAGAC

GGGCAATTAC

ATCAAGACAA

AGATAGATTT

CACAGATACA

ATAGAAGATT

ATCTCAAAAT

TATCCATGAT

TTATGGAGGC

CACTAGAGAA

CAACAAGACT

ACAACAGCA

AAAATGATGA

AATGATCCAA

2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 276

V.

V 9 *9 99 V V

V

9**V V V V. V V V

V.

V

V

CAAAGAAACG

ACACAAAATC

AGGATTAAAG

CATTCCCAGA

ATGAACAGAG

ACGGATCCCG

ACAAATACGG

GATCATTACC

CAACCAAACT

CGGTACAAAA

TGTTCGATGC

AATTTAGAGT

CTAAGTCAAT

TAAAAACAGG

AAAAATCACT

ACTCTGTTGA

TAGTTGGAGG

GTCAGCTGGT

ATCTAGTTAT

CTTTACCTGG

AACAATGGAA

AAGGATAATC

TCGCAAGAAT

ACAGAACACC

GAGACCGGCA

ACACCGALACA

AAGCAGAATG

AATAAkATTAA

ATCATCATTC

GAAAGCAGTA

GTATTTAGAT

GAGTGTGAkAT

AATCGGATTG

GGATATAGAA

TATAAAACCA

CAACAAAGTT

AATCTTCGTG

GGCATCACTA

GGTTCAGACT

GAATTTCATG

ATACTGTAAA

AATCAGTCTT

ATTCAAAAGA

CTGGGCTTCA

CGAGTTCAGA

CTAGTAATCT

AAAAACTTAG

AAGAGAGAAG

AGAACAACAA

ACACAACAAG

A.ACAGACAAG

AAACAACAGA

TCCTTGTCCA

TCTGAAAATG

CCCCACATTA

GTCTTCTTAC

GATCTCGACA

GCTALAGTACA

GTGAGAAGAA

GAACTGTACC

GCTCTTGCTC

AATTGTACGG

TCTCTALACCA

GATTCTAAAG

GTCCATCTCG

CAGAAAATCG

CATGTCAATG

GAGATTTGTT

TCAGTAGAGA

TACTATCCTA

CTATTTTAGT

GACAAAAGAG

GGACCAAAAA.

AATCAAAACA

CACTGAACAC

AAACAACAGI

TAT CAAT CAA

AAATGAGTAT

GTCATATAGA

GAGTTGCCAA

TCGGCTTCTT

GTGACCCGAG

CTGGGAATGA

CAGTCAAAGC

CATGGTCCAA

CTCAATGTCT

CAATTGGATC

ACACAATATC

GGATAGTTCA

GATTGATCAA

AGAAAATGAG

CAACTGGGTC

ATCCTTTAAT

TTACAAGAGT

ATATTATTGC

CCGGACGTAT

GTCAATACCA

AGTCAAATAG

TCCAACTCAC

P.ATGCCAA~CT

AGATCAAAAC

TATACAAATA

AACTAACTCT

ACCATTACCA

GATCGGAAAT

CGAGATGGAA

TTACAAAGTT

CCAGGAATTG

GAAAGAGATG

TAGACTAAGA

TCCACTAGAT

AATAACCTTG

AATCAATCTG

AATTTTGGAT

AAGAAAAGTA

ATTGATATTT

CATATCAAAA

GGATCTAAAT

GGATGCAATT

AAAAGGAGTT

CTATTAAGCC

ACAACTATTA

GAGAAATCAA

TCAAAACAAA

TCAATACTGC

CTGTCAACAC

AGAAAAACTT

GCA.ATATACA

CTCAALAGTCA

CCACCAA.AAC

CGAATCAAAG

TGTGGCTCTG

TTACAAGCCG

GTTGTTTACA

AAAGGAATGC

AGGAGCATAA

TTCAAAATTC

CAGGTACACA

GAGAILAGGCG

GGCAGAATGT

TCTTTAGGAC

ACACTAGCAA

CCGCATCTCA

TTCCAACCTT

GGGAAAATCA

GAAGCAAATA

GCAGTCACAC

AACAAAAGGT

A.ATTCCAAAA

TAATTATTAC

3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 9V

V.

V

AACCATGATC ATGGCATCTT TCTGCCAAAT AGATATCACA AAACTACAGC ACGTAGGTGT 5160 277 Ge.' c Oe SI C C

C

CS SC C 9

I

See.

S S le 0

S.

S C Ce eel...

S

*59@

S

0 eel...

S

S

CS

S C

S.

5605

C

See.

ATTGGTCAAC

TTTGAGCCTC

ATACAAGAAG

AGATGTGATA

CTTTGGAGGG

GGCAGTTGCT

AATTAGGGAC

AGCAATTAAA

AGGTTGTGAA

AACAAACATA

TATAGCATCA

ATATGATATC

CTTGAATGAT

CACTCAGATC

CCCTCTTCCC

ATGTATAGA.A

TGAAATAGAG

AGACATTGTT

CACCTGTACA

AATTATAACA

TAAAGAAGGA

ACTTGATCCA

AAAAGAATGG

TAGCACTACA

GATAATTACA

TGACAAGCCA

AGTCCCAAAG

ATACCAAAA

TTATTGGATA

GTAACCAATC

GTAATTGGAA

CTGGTTGAAG

ACAAATAAAG

TCAGTCCAGG

GCAGCAGGAC

TTTGGTGATA

TTATACCGCA

TATGATCTGT

TACTCAATCA

TACAkAGTAG

AGCCATATCA

GCATTCAGCA

AGCTGCTTAT

CCAAGATATG

TGCAACGGALA

CATAAAGAAT

ACTCTTGCAT

ATTGACATAT

ATAAGAAGGT

ATCATAATTA

ATTGCAATTA

TATGTACTA

GGATGAAGAT

TAGAAGACTC

GACTGATCAT

AAGAATCCAA

CCATTGCTCT

CCAA.GCAGGC

CAGTGCAGTC

ATTATGTTA.A

TTCAATTAGG

ACATAGGATC

CAA.ATATCAC

TATTTACAGA

CCCTCCAAGT

ATTCCATATC

TGACGAAAGG

GCTATATATG

CAGGAAACAT

CATTTGTCAA

TTGGTAATAG

GTAGTACAGT

TCTATACACC

CAATCGAGCT

CAA.ATCAAAA

TTTTGATAAT

AGTATTACAG

CA.AACAAATA

ATCACAAAAC

TAACTCTTGT

CCCTTTATAT

TGAAAACACT

GGGAGTAGCA

ALAGATCAGAC

AGTTCAGAGC

CAAAGAAATC

AATTGCATTA

GTTACAAGAA

AGAAATATTC

ATCAATAAAG

CAGACTCCCT

ATATAACATC

GGCATTTCTA

CCCTTCTGAT

ATCCCAATGT

TGGAGGAGTG

AATCAATCAA

AGGTATCAA~C

AAATGATATA

CAACAAGGCC

ACTAGATTCT

GATCATTATA

AATTCAAAAG

ACATATCTAC

TTTGAAACAA

GGTGACCAAC

GATGGATTAA

GATCCCAGAA

ACCTCAGCAC

ATCGAAAAAC

TCCATAGGAA

GTGCCATCGA

ACACAGCATT

AAAGGALATIA

ACAACATCAA

GTGAGAGTTA

TTATTAACTA

CAAAACAGAG

GGTGGAGCAG

CCAGGATTTG

CCAAGAACAA

GTTGCAAACT

CCACCTGATC

GGAATGCTGT

ACACTAAACA

AAATCAGATC

ATTGGAAATT

TTGTTTATAA

AGAAATCGAG

AGATCATTAG

GATATCTAAT

AGATCAAGCA

GATTACAGAA

CAAAACGATT

AAATTACAGC

TCAAAGAAGC

ATTTAATAGT

TTGCGAGGCT

ACTCAGAATT

AATTACAAGG

CAGTTGATAA

TAGATGTTGA

GGCTGCTGAA

AATGGTATAT

ACGTCAAAGA

TATTAAACCA

CGGTCACATC

GTATAACAAC

AAGGAGTAAA

TCAATACAAA

ATTCTGTTAC

TAGAAGAATC

GGCATCAATC

TTAATATAAC

TGGATCAAAA

ATATTAAAAT

5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 278 TATAAAAAAC TTAGGAGTAA AGTTACGCAA TCCAACTCTA CTCATATAAT TGAGGA-AGGA

S

S. S.

S. 55 S S

S

SS

S S

S.

CCCAATAGAC

TGCTGGCA.AT

AATATACATA

AATTAATTCC

GTTTATGGAA

GTCAGGAGTG

ATCATTGACA

TGATAATCAA

TCCAGATGAT

AAGGTTAATG

AACTCCGTCT

AGGTTGTCAG

CTCAGACTTG

TAGGAAGTCA

CAAAGTTGAT

TGTCAATTAT

TCAACCATAT

AATATTTCTC

AACTGGGTGC

TTCAGATAGG

AAAATTGAAA

ACTTCTACTA

ACAATTAGGA

TAATGTGCTA

ATGTATAACA

AAATCCAAAT

GAGCTGGAGA

TTATGGACAA

ATCAAAAGTG

ATTACAGAAA

AATACAAGGC

CAACAGATGT

GAAGTGCTGC

TTTTGGAGAT

CCAGGGCCGG

TTAGTTATAA

GATATAGGA.A

GTACCTGACT

TGTTCTCTAG

GAAAGATCAG

GATGGTTCAA

GCTGCACTAT

GGGTATGGAG

CCCGGGAAAA

AGGATGGTCA

GTATGGACGA

GGTAACAAGA

ATAATTGATA

TCAAGACCAG

GGAGTATATA

TCGAGATGGA

CGTCTATGGC

TA.ATCCTGGT

AAAAGGCCCA

AGATCCAAAT

TTCTTACA.AT

CAGATCTTAG

CACAAPLGAAT

GCACGTCTGG

GATTATTAGC

ATGATCTGAT

AATCATATCA

TAALATCCTAG

CACTCCTAAA

ATTATGCATC

TCTCAACAAC

ACCCATCTGT

GTCTTGA.ACA

CACAGAGAGA

ACTCCATCAT

TATCTATGCG

TCTATATATA

TTACTGATTA

GAAACAATGA

CTGATGCATA

ATACTGGAAG

TACTCATGGC

GTTATTATCA

CGAATCATTG

GGCATCGGAT

TCAGAGTCAT

GAAATTCATT

AACACATGAT

TCTTCCATCT

TATGCCAACG

TTATGCTTAT

AGTCTTACAG

GATCTCTCAT

TACAGATGTA

ATCAGGCATA

AAGATTTAAG

TGGACCAGGG

TCCAATAAAT

CTGTAATCAA

TGTTGCTGAC

ACAAAATTAC

TACAAGATCT

CAGTGATATA

ATGTCCATGG

TCCACTCAAT

CATACCAATC

AACAAGCTCA

ATAGTCTTCA

CTGCAAGACA

ILATACCAATG

GTCCAGAATT

AGTGAAATTA

GTAGGTATAA

TTAATGAAAA

ACTGTTGATG

ACCTCAAATC

ATAGGGATAA

ACCTTTAACA

TATCA.ACTGT

GAAGATATTG

AATAATAACA

ATATACTACA

GAGAA.TGTAA

GCGTCTCATA

AAAGGCTTAA

TGGGGGTCAG

ACAAGTTGGC

AGGATAAAAT

GGACATTCAT

CCCACAGGGA

ACGGAAAGGA

CTAATAAGAT

TCATAGTGCT

TAAATAATGA

ATCTALATACA

ACATACCAAT

CAATTAGAA-A

AACCTTTAAA

CTCCAAAAAT

GCTGTGTTAG

TAATTACTCG

TAACTGTAA

TAAATGACAA

GTTCA-ACTCC

TACTTGATAT

TAAGCTTTGA

AAGGCAAAAT

TCTGCAACAC

GTCCATGGTT

ACTCAATTCC

AAGGAAGGTT

ATAGCAAGTT

GGACATGGCA

GTCCAGATGG

GCATTGTGTC

6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 279 o S. 0* 0 0* .0.*e0

S

005 5 S

S

ATCTGTCATA

AACCGAAAGA

AACAAGCTGC

TAAA.AGCTTA

TTAATCATAA

ATCAGCAkATC

GGGAAATGGA

ACCTTAACTC

CTCAGCCTTA

TTAATA.AATT

AAGTGAATGA

TCAAATTATA

GAACATATAG

TAGCCTCAAA

AAGTTCACAC

TCAAGTATGA

AGGATTATAA

TGATATTAGA

ATTGTGACGT

TACAATCTAT

TTATGGGAGA

TTCAAACTCA

AGATGGAATT

TTGATAAAAT

CTTTTTTTAG

TTAGACTCAC

GTAAACGAGC

ATTACACACT

AACACATTTC

TTAACCATAA

AGACAATAGA

CACTGAATCT

TCCTATCGTT

TGATATGGAT

GGATAAAAGA

CTTAGGAAAA

TATACCTGGT

TCAAATGACT

AA.ATGATGGA

AACCTATAkA

TATGAGAAGA

CTTGTTAGAA

TAAACAAAC

AGTCGAAGGC

GTATCAGAA

AAAGACATTT

TGATCCTGTT

AATATTTGAA

TTTAGATATA

AACATTTGGG

AAAA.ATC GAG

TGGCCATCCT

ATAACAAAGG

AACCCATGTT

TATGCATCAA

CAAAAGGGAA

AACAATGGCA

AAAGGTAAAA

GACGACTCAA

CAACGATCTA

TACACATTTA

ATTAACAGTA

GATGGATTAA

AGCAATTATG

TCAGATAAAT

TTACAAAAAG

GACCAGAAGA

TACAATGGTT

CGATGGAATA

GGTAATAACC

GATGTGATAT

AAACAACTAA

TCTAGAGAAT

TTTAATAAGT

CATCCTCCAT

AGTGAACCCA

AAACAGAACA

ATATTGTTTT

GTTCAAAACA

TCTATCTATA

ATATAAAAAA

CTGTATCTGA

TAGCACAATT

TACTAGTTAT

TTAGA.AGATT

TCAGATATCC

AAGTGACTGA

GAGATCTATG

ATCTTAATGA

GGTATAATCC

CTCGAAATGA

ATTTCTTATT

ATCTA.ATTAC

TAAGTGCATG

TGTGGGAAGT

CGTTATTAGA

GAGGAGCTTT

CGATTAAGGA

CTACAATAGA

TAGAAGCTAG

GTCATAACTT

CTCTCAGCTG

CATATAGTAG

GAGATTCCAA

ATACA.AGTAT

CTTAGGAGCA

CATACTCTAT

ACACACTATT

CACTAGACAG

AA.AATTAATA

AGAAATGTCA

ATTATTACTT

GATTAATGTG

AGAAATTAAT

ATTCAAAACA

GATCACTTTT

GATACATCCA

TCCTGAATTA

TGCTAAGTTA

GATAGATAAA

ACCACTTGCA

TTTAAATCAT

ATTTCTGAGT

TGAAATAGCA

TATTGCAGCA

ACTCAACAGC

GATATACAAC

AAATAAATCA

AA.AGCTGCAG

ATGATAAGTA

AAGCGTGCTC

CCTGAGTGTC

ATGAGTCTAC

AAAATAAAAC

TTAACTGAAA

A.AAGAAATGT

AAAGCAGATA

CTATCAAAAT

AATATATCGA

TGGTTTACTA

AATGTTGGGA

GAATTGGTTT

GTATTGATGT

GATCCAAAAT

TTGTTTCCAA

TTATCCTTAA

GTGTTATCCG

GTAGATTACA

GAGATtTTCT

GAAAAGGTTA

8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 GAAAATATAT GTATATTGGA AAACAATTAA AATTTGACAC TATTAATAAA TGTCATGCTA 280

TCTTCTGTAC

TGACATTACC

TATCATATGA

TCATAGAGCC

CAAAAAAATC

CATCCAACGA

ATCAGATATT

CTTATAGTCT

ACAAAATGAG

TCTTTCAAGA

TATCAATATC

ATGACCTTAA

AGAAATTTGA

TCCTAACAAC

TTGGAGAAAC

GTCTTGAAGG

ATATATCATT

TAGAAGGATT

CTGTTAGAAT

TAACCACAAG

ATGTAGTGAG

AATTAAATGA

ATGGGAGAAT

CAGTAATAGA

TTGAGkATGG

AACTATATAT

AATA-ATAATT

TGATCATGCA

GAATGCTGTT

TCAGTTAGAT

AAATTGGGAC

ATCACGAAGA

GGATTATGTA

TAAAGAAAAA

AGCTACACALA

AAATGGGATG

AGGAGTTCCA

AACCTACAAT

ATTCA-AGTCA

AGATCTCA7A

TTGCAACCAA

AAGTACAATC

AGAGGATCAC

TTGTCAAAAA

AGGCGTGAGG

AGTACCCAAC

ATTTTTTGAT

AACGATTATA

TCTTCCTCAA

CGAAACAAGA

TTATTCACCT

TGCCCTTGGG

AACGGATATA

CACGA.ATTCA

GATTATTACC

GAGGATTTGA

ACAGTTTATC

TTAGTTGAAG

GAATCTGGGG

GAGATCAAAC

GTTTTATCAG

GTGAAGGGAG

CGGTATAATG

AAAAJTAAGTA

ACGGATATC2

AILATACTGTC

ATATTTGGAT

TATGTAGGTG

CCTGATTCTG

TTATGGACAC

GTGACTGCAA

AATTATGACT

TCATTAAGAG

AGTAGCAAGA

GCTCTAkAAAG

TCAGCATCTT

GTTCTAGGAT

ATGAATATCA

GAGAGAGGCA

TCATAAATGC

AGAGCTTTAT

CAATTTATAT

CTGCATCTAA

TATTTATAGC

ACTGGTTAGA

AGGAAGGTAG

AGACACTACT

AGATTGAATT

AAGTGTACIA

ATCTTAATTT

ACAATGATGG

TTAATTGGAG

TAAATAAATT

ATCCTTACTG

GTTTTTACGT

TCATATCTAT

TGGTTCAAGG

ACAGAGTTAA

AAGTGATGGA

TGTTCATATA

CATTATCTAG

CAAATTTGGC

ATGCATGCTC

ATCCAACTAT

TGGTGGACAG

TTACGGTTCA

AGGAATAAAA

GAAAGATAAA

TTTACTGTAC

AGATAGTAAA

TGATCCAGA-A

ACTCTTTGCA

TGCAAATAAC

ACTTAAGAGA

TAATTCTAIA

GTCTTCTAAT

ATACGAGACT

ATATGAATCA

GTTTAATTGG

TCCTCCATCA

TCATAACCCA

AAGTGCkATA

AGACAATCAA

GAAGGAGATA

TGATCTAGGT

TAGCAAAAGA

ATGTGTCTTC

AACATCATTT

AATTTTTAAG

AACACAGAAT

TGGCCTCCTG

A.ACTCTGCGA

TTCAATAAAT

GCATTATCTC

CGTACTAACG

TTTGATCCTC

TTTAATATTT

AAAATGACAT

ATAGGAAAAT

TTAACAACCA

AGCCATACAG

CAGAAATCAA

GTGAGCTGTT

ACAGCTCTAT

TTACACCCTC

GATAAAGAAC

AGAGGGGGTA

CATCTAGCAG

GCTATAGCTG

GTTTATAAAG

CATGAACTTA

ATCTATTATG

TGGTCAGAGA

GCAAAAGCAA

AACATTCAAC

ATCAGAGATC

9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 281

AGTATTTTAG

GATTCAATCA

CCGCATTGGC

ATAGGATTAT

ATTCATGCAA

GGAATGTATT

TAGAAGAAGA

TTGCACATGA

TAGATACGAC

TGTTGAGGAA

GACTAATTGT

CATTGCGACA

CGCCTGACCC

TATGTTATTC

AAATAGGATC

CTGATGAAAG

CCGCAATAAG

TGGAAGCCTC

TAACACCGGT

TGAALATTCTC

ACATGTCTAT

TGTTAACAGG

ACCCTATAGT

ATGAACATAT

TTATTTATGA

ACCATTCTTA

GAATCCAAAT

CATGGCCATG

TGATATTAAA

GAATCAAGAA

TTTACCACAA

ACAAGATTCA

TGAAGAATTA

TATTCTAGAT

AAAATCACTA

AATCAGTAAT

AAGTGATAAA

AAAGATGTGG

ATTAGAATTA

TTCAGATGGC

AGCAGAAACA

ATCTGAAGCA

AATAGCAATG

ACAGATAGCA

AGCTACATCA

CAGTACATCA

CAAAGAAGCT

ATTAAGTGTT

TATGCATCTG

TAATCCAGAG

TAAAGACCCA

CACAATTGAT

TGGATGCAAT

TCAAGATGTT

AGATTTATTA

CCAGGTGAGT

TCTCAAAATA

C CAAAT CCAT

GCTGAGTTCC

AATTCTCTCA

ATTCGGGTTG

TACGATCTAG

ATCAAGTATG

ATTCATTTAT

CTATCTGGGG

ACAAACCCAT

GGTATATCGT

CAATTAGGAT

ATATATACAT

CAA.ACACGTG

ACAAATTTAT

TTGATCAGAG

AATGAAACCA

TTCGAATATT

CACATAGAAG

TCTACATTAG

CTCAAAGATG

ATGAATTATT

ATGCCTCTTT

TTGTAAGGAA

AGGCGAATCT

CATCTTTTTT

TAACCACCAT

TATTATCTGG

TGATGGACAG

CAGGAATTAG

GCATAAATAG

TACAATATGA

AAGATATGTG

CAGGAGGALAG

TAGTAATAAC

ATACTTGGAT

CATTAAGAGT

ATATCAAGIA

GGGCATTTGG

CAAATTTTAC

CACACAGATT

TCAGCAGATT

AAGATACTAA

TATTTAGATT

ATGAGTGTTG

AATTAATTCG

TGGACTTATC

GGGATGATAC

AATACCTGCT

TATTGGTGAT

ATTAGACCGA

TGACTGGGCT

GATAAAAAAT

ATTATTCACA

GALAGGTAATT

AAATGCCATA

AGGAGGACTG

AACACTAAGT

TTCGGTAGAC

GATGATALAGT

AGGATCAGAA

GTATTTACCC

TCCTTATTTT

TCTTAGTAAA

TAATGATGAG

ACTAGATAGT

TAAGGATACT

TATALACA.ATG

TCTTATTTAT

AAAAGAAACC

TATTAAAGAA

ATATCCTGAA

AAAACTTATG

TGACATCATA

AGTGTTGGGG

CCATCAGTTG

AGTGTTCTTT

TCAGATCCAT

ATAACAGCAA

AATACAATGA

CTCCCTAGAG

GCTGGAATGT

ACATATAGTT

AGGACTTTGC

CTTGCCATAG

GGACTTGAAA

CATTGTAAAA

GGTAATATCA

GGATCAGTCA

CCTGCAAAAG

ATATCTTGGA

CTCAAAATTT

GCAACTCAGA

TCCAATGATA

CAACAAATAA

ACAGGACACA

AGTTTTAATG

AGTAATGAAT

GTTATTAAAG

CATGCAATTT

11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 282 CAATATGTAC TGCAATTACA ATAGCAGATA CTATGTCACA ATTAGATCGA GATAATTTAA 9

AAGAGATAAT

CTCTTGACAT

ACACTCTTTA

CACTGAGAGA

AAGTATTCAA

CTAGTCAAGA

TGAGAGA.ATG

TTGCAAATGA

CAGAAATTGC

TATTGAAACA

TATCTGGATT

TCAAATATCT

TAGAAGATGA

ATAATAAAGG

TTAAAATCAG

GTGGTTTGAC

TCAACAGCAC

ATAAAGACAA

ATGCCACATT

TTGGTCAACG

GAALATGTGAC

CATGGATAGG

TTGGATTAGT

ATGAACATTA

TTTCCAAAAT

AGTTATTGCA

ACTTGTATTT

TAGTCTAAAA

TACTTCCCAT

GAGGTTCTGG

CCAGATAAAA

GTTGAATGGT

TAGGAAACAA

ATCTTTCGGA

ATATCTTGAA

ATTAATTAAA

AAGGATTCGC

AAATATGCTG

GAATAAAATT

ATCTATAACA

ACTTCCTCAA

TAGTTGTCTG

GGACAGGCTC

AGGACCTGCA

AGAATTGAAA

ACAGATTCTT

AAATATGGAA

ACATTGTGAT

TAGTGTTATA

TATACCTACA

AATGATGATG

CTCKAGACAT

ATAGALAGGTA

TCAATATTAA

GATTGTGGAG

CTTGCCCTAT

GTATCACTTG

GCCTTTATTT

CCTAACCTGT

TTAAATATTA

TCGTTCCCAT

GGTATTAGTC

GATAACATTG

ALACALATTTCT

AGTGATTCTG

GGAGGGAATT

AAAGCTCTTG

TTCCTGGGAG

GTTAATTATT

ATATTTCCTT

AACAGGGTAA

TGTGAGAGCT

ATGGAAGGAG

AGAATTACAT

ATCACTCCGA

ATATTAATAG

TTGGTGGATT

GGGATCTCAT

AAGTATTATC

TTTTAkACCC

CTATATGTGA

AAATATACAT

CTAGACACCT

TAAACTTAAC

AAGA.AGACCC

CAACTGTAAC

CACCTGAGGT

TCAAAACTAT

GGGGACTAGC

ATGATAATGA

ATCTATCGCA

AGTTATCACA

AAGGAGCAGG

ATAATTCACG

CAGAGGTATC

AAGTACTGTT

TAPLTATGGAG

CTATCGGTA

ACTTGATTGG

ATTGGTCTAG

CTTAATCACT

ATTAGTAA-AT

TTGGGATTAT

TAATGCATTA

TATTTATGGT

ATATTCACTA

TTGTGACAGC

TTCATTTGTT

ATACTTGGAG

TACTCTTAAA

ATACGTAAGA

AATTGATGAT

AAATGATAAC

ACTTAAGAAC

TAGACTAGAT

TCAATTGAGA

AATTTTAATG

AGCTATGCTA

TTTGAATATA

ATTAGTAGGT

CAATGGGAAT

TGAATTAAAT

ATCAGAAGAA

GGATGATGAT

AATACTTTAT

GAATTTTTGA

CAATTTGCAT

ATILATGAGAA

TCTCATCCTA

CCTAATATTG

GATCTATTTA

GATATGGAAG

TGTTGTTTAG

AGACTTGATC

TATGTACAAA

AAGACTGCAA

TGGGATCCGG

TGTAATAAAG

TATCAAGTCC

GCTAATACAA

TTATTCGGAA

AAGGAAGTCA

GCATGTTATG

ACAGATGTAA

OAAAAAATTAG

CCTAATTCAA

GATAAGTCCA

ACTGTTCTAC

GTTGTTTTAG

CTATATA;AAT

13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 9 283

TATATTGGAA

TATATCTAAT

CAAAACTTAA

AGATGTAAGT

TTCGAAAGAT

AAGATTGTCA

CAAAGAAGAG

GAATAATGAJA

GAATCATGAG

ATCTGGCGAA

GTTTTCAGCG

AGAGACATAA

GACTGCTATC

TTACAGGTCG

TAGCTGATAC

GAGAGTGTAT

AATTGATTGG

AGTTATTAGA

TGAAGATATA.

TGTAATATAT

ACCATATCAT

AGAATTTTTA

AACAATAAAG

ATTAGGCGGA

GAGAAGACTA

CTTTCCTGAT

TGATTTAGAA

AGGATCAATA

TGGTGCTAAA

AAACTACAAT

TCCTAACCTT

ATAATATCAC

GCATATTGTA

CTCTTGGAAG

TGGTTACATC

ATGGCACTAC

TCAACCCCAG

GATGTTTTAT

AGATATAACA

GTATTAAGTT

GAAAAATTTG

TCATTAAAGT

TCATATTGGT

TTATTAGGAA

CAACATGATG

TATCTTTAAG

TCAAAACTTC

CTATAATGGA

AAAATAATCT

ATGAAATCAA

AAATCTTTGG

ATCTGACTAA

TTGAATGGAT

TATTCCCACT

GGATTTCATT

AACATAGAGC

TATTGTCGAA

TTCTAACCAA

TTCCCAGACA

AATTTGATAT

CCTAGGAATA

CTCTTGTTTG

TAATCCTGCA

ACCTAGTGAA

ATTAAAATGG

AGAAGGAGAA

ATTTCAAATC

TATCA.ACAAT

TAATATAACT

GAAAKATAAG

ATCATTATCG

ACAGACTGGA

AAACATCATT

AGAAGTTAAA

ATATA&AGAA

CGATTAAAAC

GACAAAAAGT

GT

TCAACAGAAT

ATTGTTTTAT

ATCATTTTAT

AGAGATTATG

AATTTAAATC

ATAATCCAAA

CATGATGATA

GGAAAGTTAA

ACTCGATTAC

TATGTATCAT

AAGAATTACA

ATACTTATGA

CCCGAAGACC

ATAAATACAA

AAGAAAAACA

14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15240 15300 15360 15420 15462 ATATACCA

CAGAGTTCTT

INFORMATION FOR SEQ ID NO:22: Wi SEQUENCE

CHARACTERISTICS:

LENGTH: 2233 amino acids TYPE: amino acid STRANflEDNESS: TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) Met 1 Glu SEQUENCE DESCRIPTION: SEQ ID NO:22: Asp Thr Glu Ser Asn Asn Gly Thr Val Ser Asp Ile Leu Tyr Pro 5 10 Cys His Leu Asn Ser Pro Ile Val Lys Gly Lys Ile Ala Gin Leu 284 His Ile Arg Asn Glu Leu Arg Gly 145 His Phe Ile *Asn Asn 225 Asp Pro Ile Ser Thr Leu Gin Asp Met Leu Asp 130 Ser Thr Thr Thr Phe 210 Tyr Val Lys Asp Leu 290 Ile Val Arg Leu Phe Leu 115 Leu Asn Thr Ile Phe 195 Leu Asn Val Leu Lys 275 Leu Met Ile Ser Gly Lys 100 Lys Trp Tyr Tyr Lys 180 Asn Leu Gly Glu Gin 260 Leu Glu Ser Thr Ile Lys Leu Ala Ile Asp Lys 165 Tyr Val Ile Tyr Gly 245 Ser Phe Pro Leu Arg Arg 70 Tyr Tyr Asp Asn Leu 150 Ser Asp Gly His Leu 230 Arg Met Pro Leu Pro Gin 55 Arg Thr Ile Arg Val 135 Asn Asp Met Lys Pro 215 Ile Trp Tyr Ile Ala 295 Gin 40 Lys Leu Phe Pro Thr 120 Leu Glu Lys Arg Asp 200 Glu Thr Asn Gin Met 280 Leu 25 Pro Ile Lys Ile Gly 105 Tyr Ser Glu Trp Arg 185 Tyr Leu Pro Ile Lys 265 Gly Ser Tyr Lys Leu Arg 90 Ile Ser Lys Ile Tyr 170 Leu Asn Val Glu Ser 250 Gly Glu Leu Asp Leu Ile 75 Tyr Asn Gin Leu Asn 155 Asn Gin Leu Leu Leu 235 Ala Asn Lys Ile Met Asn Leu Pro Ser Met Ala 140 Asn Pro Lys Leu Ile 220 Val Cys Asn Thr Gin 300 Asp Lys Thr Glu Lys Thr 125 Ser Ile Phe Ala Glu 205 Leu Leu Ala Leu Phe 285 Thr Asp Leu Glu Met Val 110 Asp Lys Ser Lys Arg 190 Asp Asp Met Lys Trp 270 Asp His Asp Asp Lys Ser Thr Gly Asn Lys Thr 175 Asn Gin Lys Tyr Leu 255 Glu Val Asp Ser Lys Val Lys Glu Leu Asp Val 160 Trp Glu Lys Gin Cys 240 Asp Val Ile Pro 285 Val Lys Gin Leu Arg Giy Ala Phe Leu Asn His Val Leu Ser Giu Met 305 310 315 320 Glu Leu Ile Phe Glu Ser Arg Giu Ser Ile Lys Giu Phe Leu Her Vai 325 330 335 Asp Tyr Ile Asp Lye Ile Leu Asp Ile Phe Asn Lys Ser Thr Ile Asp 340 345 350 Glu Ile Ala Giu Ile Phe Ser Phe Phe Arg Thr Phe Gly His Pro Pro 355 360 365 Leu Giu Ala Ser Ile Ala Ala Giu Lys Vai Arg Lys Tyr Met Tyr Ile 370 375 380 Gly Lys Gin Leu Lys Phe Asp Thr Ile Asn Lys Cys His Ala Ile Phe 385 390 395 400 Cys Thr Ile Ile Ile Asn Gly Tyr Arg Giu Arg His Gly Gly Gin Trp 405 410 415 Pro Pro Vai Thr Leu Pro Asp His Ala His Giu Phe Ile Ile Asn Ala 420 425 430 Tyr Gly Ser Asn Her Ala Ile Ser Tyr Giu Aen Ala Val Asp Tyr Tyr *..435 440 445 Gin Ser Phe Ile Gly Ile Lye Phe Asn Lys Phe Ile Giu Pro Gin Leu 450 455 460 *.Asp Glu Asp Leu Thr Ile Tyr Met Lys Asp Lys Ala Leu Her.Pro Lye 465 470 475 480 Lys Ser Aen Trp Asp Thr Val Tyr Pro Ala Ser Aen Leu Leu Tyr Arg **485 490 495 Thr Asn Ala Ser Asn Glu Ser Arg Arg Leu Val Giu Val Phe Ile Ala 500 505 510 Asp Ser Lys Phe Asp Pro His Gin Ile Leu Asp Tyr Val Glu Her Gly 515 520 525 Asp Trp Leu Asp Asp Pro Glu Phe Asn Ile Ser Tyr Her Leu Lye Giu 530 535 540 Lys Giu Ile Lye Gin Glu Gly Arg Leu Phe Ala Lye Met Thr Tyr Lys 545 550 555 560 Met Arg Ala Thr Gin Val Leu Her Giu Thr Leu Leu Ala Aen Aen Ile 565 570 575 286 Gly Leu Glu Asn 625 Phe Ser Tyr *.Ile 705 Ser Gly Ser Met 785 Val Giu Ser Lys Lys Val1 610 Lys Giu Cys Giu Asn 690 Tyr Leu Gly Ala Val 770 Asn Arg Leu Lys Phe Arg 595 Tyr Ile Phe Phe Ser 675 Lys Val Giu Ile Ile 755 Gin Tyr Phe Lys Arg 835 Phe 580 Leu Asn Ser Lys Leu 660 Thr Leu Giy Asp Giu 740 His Giy Asp Phe Leu 820 Ile Gin Thr Asn Asn Ser 645 Thr Ala Phe Asp His 725 Giy Leu Asp Tyr Asp 805 Asn Tyr Giu Thr Ser Leu 630 Thr Thr Leu Asn Pro 710 Pro Phe Ala Asn Arg 790 Ser Giu Tyr Asn Ile Lys Aen Asp Asp Phe Trp 695 Tyr Asp Cys Al a Gin 775 Val Leu Thr Asp Gly Met 585 Ser Ile 600 Ser His Leu Ser Ile Tyr Leu Lys 665 Giy Giu 680 Leu His Cys Pro Ser Gly Gin Lys 745 Vai Arg 760 Ala Ile Lys Lys Arg Giu Ile Ile 825 Gly Arg 840 Val Lye Giy Giu Ile Glu Leu 590 Ser Thr Ser Asn 650 Lys Thr Pro Pro Phe 730 Leu Ile Al a Giu Val 810 Ser Ile Gly Asp Aen 635 Asp Tyr eye Arg Ser 715 Tyr Trp Gly Vai Ile 795 Met Ser Leu Val1 Asp 620 Gin Gly eye Asn Leu 700 Asp Vai Thr Val Thr 780 Val Asp Lys Pro Pro 605 Leu Lys Tyr Leu Gin 685 Giu Lye His Leu Arg 765 Thr Tyr Asp Met Gin Arg Lys Ser Glu Asn 670 Ile Giy Glu Aen Ile 750 Val Arg Lye Leu Phe 830 Ala Tyr Thr Lye Thr 655 Trp Phe Ser His Pro 735 Ser Thr Val Asp Giy 815 Ile Leu Asn Tyr Lye 640 Vali Arg Giy Thr Ile 720 Arg Ile Al a Pro Val 800 His Tyr Lys 845 Ala Leu Ser Arg eye Vai Phe Trp Ser Giu Thr Val Ile Asp Giu Thr 287 850 855 860 Arg Ser Ala Ser Ser Asn Leu Ala Thr Ser Phe Ala Lys Ala Ile Glu 865 870 875 880 Asn Gly Tyr Ser Pro Val Leu Gly Tyr Ala Cys Ser Ile Phe Lys Asn 885 890 895 Ile Gin Gln Leu Tyr Ile Ala Leu Gly Met Asn Ile Asn Pro Thr Ile 900 905 910 Thr Gln Asn Ile Arg Asp Gin Tyr Phe Arg Asn Pro Asn Trp Met Gin 915 920 925 Tyr Ala Ser Leu Ile Pro Ala Ser Val Gly Gly Phe Asn His Met Ala 930 935 940 Met Ser Arg Cys Phe Val Arg Asn Ile Gly Asp Pro Ser Vai Ala Ala 945 950 955 960 Leu Ala Asp Ile Lys Arg Phe Ile Lys Ala Asn Leu Leu Asp Arg Ser 965 970 975 Vai Leu Tyr Arg Ile Met Asn Gin Glu Pro Gly Giu Ser Ser Phe Phe *980 985 990 *Asp Trp Ala Ser Asp Pro Tyr Ser Cys Asn Leu Pro Gin Ser Gin Asn .*.995 1000 1005 Ile Thr Thr Met Ile Lys Asn Ile Thr Ala Arg Asn Vai Leu Gin Asp 1010 loi5 1020 Ser Pro Asn Pro Leu Leu Ser Gly Leu Phe Thr Asn Thr Met Ile Giu 1025 1030 1035 1040 Glu Asp Giu Giu Leu Ala Giu Phe Leu Met Asp Arg Lys Val Ile Leu 0: :1045 1050 1055 Pro Arg Val Ala His Asp Ile Leu Asp Asn Ser Leu Thr Gly Ile Arg **1060 1065 1070 *see Asn Ala Ile Ala Gly Met Leu Asp Thr Thr Lys Ser Leu Ile Arg Val 1075 1080 1085 Gly Ile Asn Arg Gly Gly Leu Thr Tyr Ser Leu Leu Arg Lys Ile Ser 1090 1095 1100 Asn Tyr Asp Leu Val Gin Tyr Giu Thr Leu Ser Arg Thr Leu Arg Leu 1105 1110 1115 1120 Ile Val Ser Asp Lys Ile Lys Tyr Giu Asp Met Cys Ser Val Asp Leu 1125 1130 1135 288 Ala Ile Ala Leu Arg Gin Lys Met Trp Ile His Leu Ser Gly Gly Arg 1140 1145 1150 Met Ile Ser Gly Leu Giu Thr Pro Asp Pro Leu Glu Leu Leu Ser Gly 1155 1160 1165 Val Val Ile Thr Gly Ser Glu His Cys Lys Ile Cys Tyr Ser Ser Asp 1170 1175 1180 Gly Thr Asn Pro Tyr Thr Trp Met Tyr Leu Pro Gly Asn Ile Lys Ile 1185 1190 1195 1200 Gly Ser Ala Glu Thr Gly Ile Ser Ser Leu Arg Val Pro Tyr Phe Gly 1205 1210 1215 Ser Val Thr Asp Giu Arg Ser Giu Ala Gin Leu Gly Tyr Ile Lys Asn 1220 1225 1230 Leu Ser Lys Pro Ala Lys Ala Ala Ile Arg Ile Ala Met Ile Tyr Thr 1235 1240 1245 Trp Ala Phe Gly Asn Asp Giu Ile Ser Trp Met Glu Ala Ser Gin Ile *..1250 1255 1260 .Ala Gin Thr Arg Ala Asn Phe Thr Leu Asp Ser Leu Lys Ile Leu Thr *1265 1270 1275 1280 Pro Val Ala Thr Ser Thr Asn Leu Ser His Arg Phe Lys Asp Thr Ala 1285 1290 1295 **Thr Gin Met Lys Phe Ser Ser Thr Ser Leu Ile Arg Val Ser Arg Phe 1300 1305 1310 Ile Thr Met Ser Asn Asp Asn Met Ser Ile Lys Glu Ala Asn Glu Thr **1315 1320 1325 Lys Asp Thr Asn Leu Ile Tyr Gin Gin Ile Met Leu Thr Gly Leu Ser 1330 1335 1340 Val Phe Giu Tyr Leu Phe Arg Leu Lys Giu Thr Thr Gly His Asn Pro 1345 1350 1355 1360 Ile Val Met His Leu His Ile Giu Asp Glu Cys Cys Ile Lys Giu Ser 1365 1370 1375 Phe Asn Asp Giu His Ile Asn Pro Giu Ser Thr Leu Giu Leu Ile Arg 1380 1385 1390 Tyr Pro Giu Ser Asn Giu Phe Ile Tyr Asp Lys Asp Pro Leu Lys Asp 1395 1400 1405 289 Val Asp Leu Ser Lys Leu Met Val Ile Lys Asp His Ser Tyr Thr Ile 1410 1415 1420 Asp Met Asn Tyr Trp Asp Asp Thr Asp Ile Ile His Ala Ile Ser Ile 1425 1430 1435 1440 Cys Thr Ala Ile Thr Ile Ala Asp Thr Met Ser Gin Leu Asp Arg Asp 1445 1450 1455 Asn Leu Lys Giu Ile Ile Val Ile Ala Asn Asp Asp Asp Ile Asn Ser 1460 1465 1470 Leu Ile Thr Giu Phe Leu Thr Leu Asp Ile Leu Val Phe Leu Lys Thr 1475 1480 1485 Phe Gly Gly Leu Leu Val Asn Gin Phe Ala Tyr Thr Leu Tyr Ser Leu 1490 1495 1500 Lys Ile Giu Giy Arg Asp Leu Ile Trp Asp Tyr Ile Met Arg Thr Leu 1505 1510 1515 1520 *Arg Asp Thr Ser His Ser Ile Leu Lys Val Leu Ser Asn Ala Leu Ser 1525 1530 1535 *His Pro Lys Val Phe Lys Arg Phe Trp Asp Cys Gly Val Leu Asn Pro *1540 1545 1550 I *le Tyr Gly Pro Asn Ile Ala Ser Gin Asp Gin Ile Lys Leu Ala Leu 1555 1560 1565 Ser Ile Cys Giu Tyr Ser Leu Asp Leu Phe Met Arg Glu Trp Leu Asn 1570 1575 1580 Gly Val Ser Leu Giu Ile Tyr Ile Cys Asp Ser Asp Met Giu Val Ala 1585 1590 1595 1600 Asn Asp Arg Lys Gin Ala Phe Ile Ser Arg His Leu Ser Phe Val Cys 1605 1610 1615 *Cys Leu Ala Giu Ile Ala Ser Phe Gly Pro Asn Leu Leu Asn Leu Thr 1620 1625 1630 Tyr Leu Giu Arg Leu Asp Leu Leu Lys Gin Tyr Leu Giu Leu Asn Ile 1635 1640 1645 Lys Giu Asp Pro Thr Leu Lys Tyr Val Gin Ile Ser Gly Leu Leu Ile 1650 1655 1660 Lys Ser Phe Pro Ser Thr Val Thr Tyr Val Arg Lys Thr Ala Ile Lys 1665 1670 1675 1680 Tyr Leu Arg Ile Arg Gly Ile Ser Pro Pro Giu Val Ile Asp Asp Trp 290 1685 1690 1695 Asp Pro Val Glu Asp Glu Asn Met Leu Asp Asn Ile Val Lys Thr Ile 1700 1705 1710 Asn Asp Asn Cys Asn Lys Asp Asn Lys Gly Asn Lys Ile Asn Asn Phe 1715 1720 1725 Trp Gly Leu Ala Leu Lys Asn Tyr Gin Val Leu Lys Ile Arg Ser Ile 1730 1735 1740 Thr Ser Asp Ser Asp Asp Asn Asp Arg Leu Asp Ala Asn Thr Ser Gly 1745 1750 1755 1760 Leu Thr Leu Pro Gin Gly Giy Asn Tyr Leu Ser His Gin Leu Arg Leu 1765 1770 1775 Phe Gly Ile Asn Ser Thr Ser Cys Leu Lys Ala Leu Giu Leu Ser Gin 1780 1785 1790 Ile Leu Met Lys Giu Val Asn Lys Asp Lys Asp Arg Leu Phe Leu Gly *1795 1800 1805 *.,Glu Gly Ala Gly Ala Met Leu Ala Cys Tyr Asp Ala Thr Leu Gly Pro *1810 1815 1820 **.Ala Val Asn Tyr Tyr Asn Ser Gly Leu Asn Ile Thr Asp Val Ile Gly **1825 1830 1835 1840 Gln Arg Glu Leu Lys Ile Phe Pro Ser Giu Val Ser Leu Val Gly Lys 1845 1850 1855 *Lys Leu Gly Aen Val Thr Gin Ile Leu Asn Arg Val Lys Val Leu Phe 1860 1865 1870 *.Asn Gly Asn Pro Asn Ser Thr Trp Ile Gly Asn Met Glu Cys Giu Ser 1875 1880 1885 Leu Ile Trp Ser Glu Leu Asn Asp Lys Ser Ile Gly Leu Val His Cys 0* *1890 1895 1900 ASP Met Giu Gly Ala Ile Gly Lys Ser Giu Glu Thr Val Leu His Glu 1905 1910 1915 1920 His Tyr Ser Val Ile Arg Ile Thr Tyr Leu Ile Gly Asp Asp Asp Val 1925 1930 1935 Val Leu Val Ser Lye Ile Ile Pro Thr Ile Thr Pro Asn Trp Ser Arg 1940 1945 1950 Ile Leu Tyr Leu Tyr Lys Leu Tyr Trp Lys Asp Val Ser Ile Ile Ser 1955 1960 1965 291 Leu Lys Thr Ser Asn Pro Ala Ser Thr Glu Leu Tyr Leu Ile Ser Lys 1970 1975 1980 Asp Ala Tyr Cys Thr Ile Met Giu Pro Ser Glu Ile Val Leu Ser Lys 1985 1990 1995 2000 Leu Lys Arg Leu Ser Leu Leu Glu Glu Asn Asn Leu Leu Lys Trp Ile 2005 2010 2015 Ile Leu Ser Lys Lys Arg Asn Asn Giu Trp Leu His His Giu Ile Lys 2020 2025 2030 Giu Gly Giu Arg Asp Tyr Gly Ile Met Arg Pro Tyr His Met Ala Leu 2035 2040 2045 Gin Ile Phe Gly Phe Gin Ile Asn Leu Asn His Leu Ala Lys Giu Phe 2050 2055 2060 Leu Ser Thr Pro Asp Leu Thr Asn Ile Asn Asn Ile Ile Gin Ser Phe 2065 2070 2075 2080 $*so 000. ,Gin Arg Thr Ile Lys Asp Val Leu Phe Giu Trp Ile Asn Ile Thr His *2085 2090 2095 Asp Asp Lys Arg His Lys Leu Gly Gly Arg Tyr Asn Ile Phe Pro Leu 2100 2105 2110 .Lys Asn Lys Gly Lys Leu Arg Leu Leu Ser Arg Arg Leu Val Leu Ser 2115 2120 2125 coos*: Trp Ile Ser Leu Ser Leu Ser Thr Arg Leu Leu Thr Giy Arg Phe Pro 2130 2135 2140 see**:Asp Glu Lys Phe Giu His Arg Ala Gin Thr Giy Tyr Val Ser Leu Ala 2145 2150 2155 2160 Asp Thr Asp Leu Glu Ser Leu Lys Leu Leu Ser Lys Asn Ile Ile Lys 2165 2170 2175 Asn Tyr Arg Giu Cys Ile Gly Ser Ile Ser Tyr Trp Phe Leu Thr Lys 2180 2185 2190 Giu Val Lys Ile Leu Met Lys Leu Ile Gly Gly Ala Lys Leu Leu Gly 2195 2200 2205 Ile Pro Arg Gin Tyr Lys Giu Pro Giu Asp Gin Leu Leu Giu Asn Tyr 2210 2215 2220 Asn Gin His Asp Glu Phe Asp Ile Asp 2225 2230 292 INFORMATION FOR SEQ ID NO:23: SEQUENCE CHARACTERISTICS: LENGTH: 13218 base pairs TYPE: nucleic acid STRA1NDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: ACGCGAAAAA ATGCGTACTA CAA.ACTTGCA CATTCGAAAA AAATGGGGCA AATAAGAACT

TGATAAGTGC

TGATAAAGGT

CATGTTATAC

CAATTAAATT

ATAACAATAT

ACATATGGGA

ATTGTGAAAT

AAATATCTGA

AGACATGTGT

ATAAACTCAC

ATTGATGATC

AGAAATCATC

TGATGAAAGA

AGTAGGGAGT

CATGCCTATA

ACACACTOCT

CCAACCAAAC

ATTTTAGTAA

TATTTAAGTC

TAGATTACAA

TGATAAATTA

AAACGGCATA

TGTAGTGAAA

ATTGATTGAG

CAAATTTTCT

CTTACTTGGG

TTATTACCAT

CTAATCAATC

ACAGACATGA

ACACACAAAT

CAAGCTACAT

ACCAAATACA

TTTATCAATC

ATAATATACA

CAAACTATTC

TTAAAAATL

TAACCTTTTC

AATTTATTTG

ATTCTTCTGA

GTTTTTATAC

TCTAACTTTA

TTGACACACT

AAAAGACTAA

CTTGATCTCA

TTTAGTTAAT

AAACCATGAG

GACCCCTGTC

TCATATACTT

TTACATTCTT

AAAAATACAC

ACGGCGGGTT

AATATGACCT

CTCAAACAAC

A.AGTAAAGCC

AATCAGAAAT

ACAATGACGA

CCAATGCATT

ATGTTATAAC

CAACAATGCC

GCTCTCILATT

GTGACTCAGT

ATTCATGAAT

ATAAAAACTC

CACTACAAAT

AATGGATTCA

GATAAACAAT

AGTCAATTAT

TGAATATAAT

TCTAGAATGT

CAACCCGTGA

AGTGCTCAAT

AATAACATAA,

GGGGTGCAAT

AGTAGCATTG

AGCCAAAGCA

AAGCAGTGAA

AATACTACAA

AAACGGTTTA

AATGACTAAT

TATGTTTAGT

ATCAALAGGGA

GACAACACTA

ATAATAACAT

GAATGTATTG

GAGATGAAGC

ACAAAATATG

ATTGGCATTA

ATTCCAACAA

AGTTAAGAAG

ATTGGGGCAA

TCACTGAGCA

TTAAAAATAA

GCAATACATA

GTGTGCCCTG

AATGGAGGAT

ATGGATGATA

TATATGAATC

CTAATTCAAT

AATGGGGCAA

CTATGCAAAG

CTCTTACCAA

TAAGAAAACT

TACTGCACAA

GCACTTTCCC

AGCCTACAAA

AAAAACCAAC

GAGCTAATCC

ATACAAAGAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 293 GGCTCTTAGC AAAGTCAAGT TGAATGATAC ATTAAATAAG GATCAGCTGC TGTCATCCAG

CAAATACACT

AAAACACCTA

CACAGGATTA

GATACTTAAA

TCAAGATATA

AGAAATALCA.A

GATGGGAGAA

GTGTATAGCT

AGTAATTAGG

ACCAAAGGAT

TGTTTTCGTG

AATCTTTGCA

AGTTTTAGCC

GGAGCAAGTT

CCATATATTG

AAGTGTGGTC

AAGAAACCAG

AGTAATAAAC

ACTCAACCCC

GTCAACATGG

AALATTCCTAG

AGCATAATAT

GGCACCAACA

TACCCAAGAA

ATTCAACGTA

AACAAACTAT

ATAGGTATGT

GATGCTGGAT

AATGGAAAGG

GTCAATATTG

GTGGCTCCAG

GCACTTGTGA

AGGGCAAACA

ATAGCTAACA

CACTTTGGCA

GGATTGTTTA

AAATCTGTAA

GTGGAAGTCT

AACAATCCAA

CTAGGCAATG

GATCTTTATG

TACAGTGTAT

AAIAGAAGATG

AGAAGTTTGC

AATCAATAAA

CTGTTAACTC

TCATCAATCC

AACCCCTAGT

GTACAGGAGA

GTGGTATGCT

TATATGCTAT

ATCATGTTAA

AAATGAAATT

AGATAGAATC

AATATAGGCA

TAACCAAATT

ATGTCTTAAA

GTTTTTATGA

TTGCACAATC

TGAATGCCTA

AAAATATCAT

ATGAGTATGC

AAGCATCATT

CAGCAGGTCT

ATGCAGCTAA

TAGACTTAAC

ATGTAGAGCT

ACCTGAATTT

GGGCAAGTTC

AATAGATATA

AACAAGTGAA

AAGCTTCAAA

TAATATTGAC

ATTAATCACT

GTCCAGGTTA

AGCTAATGGA

CGAAGTATTA

TAGAAAGTCC

TGATTCTCCA

AGCAGCAGGA

AAACGAAATA

AGTGTTTGAA

ATCCACAAGA

TGGTTCAGGG

GCTAGGACAT

ACAGAAGTTG

GCTGTCATTA

AGGCATAATG

AGCATATGCA

AGCAGALAGAA~

TTAAGTTAC

CATGGAGAAG

GCATCATCCA

GAAGTAACTA

GCCGACAGTA

GAAGATCTCA

ACTCCCAATT

GAAGATGCAA

GGAAGGGAAG

GTAGATATAA

ACATTATCAA

TACAAAAAAA

GACTGTGGGA

GACAGATCAG

AAACGATACA

AAACACCCTC

GGGGGTAGTA

CAAGTAATGC

GCTAGTGTCC

GGAGGAGALAG

ACTCAATTTC

GGAGAGTATA

GAGCAACTCA

TTGGAAGCCA

AAA.AAATACG

ATGCAAATAA

AAGATCCTAA

AAGAGAGCCC

CCCCAGAALAC

CCCCAAGTGA

ATGATGTGCA

ATCATAAATT

ACACTATAAA

CAACATATCG

GCTTGACATC

TGCTAAA.AGA

TGATAATACT

GTCTTACAGC

AGGGCCTCAT

ATCTTATAGA

GAGTTGAAGG

TAAGATGGGG

AGGCAGAAAT

CTGGATTCTA

CCAACTTCTC

GAGGTACACC

AAGAAAATGG

TAAAGCATCA

GGGCAAATAA

CAAAGCTACC

GAAGAAAGAT

GATAACATCT

AAAAGCCAAC

CAACCCTTTT

1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 a to TCTAAGTTGT ACAAGGAC AATAGAAACA TTTGATAACA ATGAAGAAGA ATCTAGCTAC 294 TCATATGA-AG AGATAAATGA TCAAACAAAT GACAACATTA CAGCAAGACT AGATAGAATT .e

GATGAAAAAT

CCCACTTCAG

GAAAAAATAA

AGGA.ATGAGG

ACTTCCAAAA

GATGATTTTT

CILATCCATTG

CAATCAATCA

AAAGAACAAG

TACACAGCAG

ATATGGGTGC

AGCATCAATA

ATTAACTCAA

GTATCATTAG

GCATGCAGTC

ATGAAGACAT

ACATCAAAAA

CTGAACTCAC

ATTATTCCTT

AAATATATCA

AGCATATATT

CTAGAGGATT

CACACTATAT

CACTCAAAAT

AATAAAACCA

TAAGTGAAAT

CTCGCGATGG

GAGCGGAAGC

AAAGCGAAAA

AATTGAGTGA

GATCAGCGAT

AATCAACTGC

ACCAATTGAT

ATGGGGCAAA

CTGTTCAGTA

CTATGTTCCA

TACTAGTGAA

GAAGTGCTGT

ATGAAAGAAG

TAACATGCTT

TCAACCCCAC

GAGTAATAAT

TAGAAAATAT

ATGCAGGATT

AACCACAGAG

ATGTGACTAC

AAACTTAATT

CCAAACATCA

CCAAAATCAC

AAATATGGGG

ATTAGGAATG

AATAAGAGAT

ATTAATGACC

AATGGCAAAA

CTTGTTGGAA

CAACTCACTC

CAGACCGAAC

CAATCAGCAA

TATGGAAACA

CAATGTTCTA

GTCATCTGTG

GCAGATCTCT

GCTGGCTCAA

CAAATTAGCA

AAAAGTAAAA

TCATGAGATC

ACCAACCTAT

AGCAACCACC

AGTGTTAGTT

TCAATTTATA

TAATTGGAAG

ATCAACACTG

TAAACATCTA

TACCAGCCAC

TAAATAGACA

CTCCATACAT

GCTATGGTTG

AATGATAGGT

GACACCTCAG

GACAACGATA

AGCAATCAAC

AAACAAACGT

CCCGACAAAA

TACGTGAACA

GAAAAAGATG

CCAGCAGACT

ACGCCCAAAG

ATGCCTAGTA

TATGATGTAA

AGTATGTTAA

ATTGCTCTAT

CTAAGATCAA

GAATTCAAAA

ATCACAGTTA

GTAGATCTTG

CATACAGCTA

AATGACAGGT

CACTACACAC

TATCTGCTAG

TTAGTTAGAG

TAGTAGTTGC

GTCTAAGAGA

TAGAGGCTAT

ATGAAGTGTC

GTGACAATGA

AACATCAATA

CCATCAGTAG

TTAACAATAT

AGCTTCACGA

ATGATCCTGC

TGCTCATAAA

GACCTTCACT

ATTTCATCAT

CTACACCTTG

CTACAGTCAA

GTGAATTTGA

TTAGTGTCAA

ATGCTATCAC

CTGACAATAA

GTGCCTACCT

CACGTTTTTC

CCACATATAT

TTCATCACAC

ACCTAGAGTG

TTCAATCAAT

AAGTGCAGGA

AGAGATGATA

GGCAAGACTT

TCTTAATCCA

TCTATCACTT

AAACAGACAT

AACCACCAAC

AGTAACAAAA

AGGCTCCACA

ATCACTAACA

AGAACTTGCA

ACGAGTCACG

AAGCGCAAAT

TGAAATCAAA

AGATCTTACC

AAATATTATG

GAACAAGGAT

CAATGCAAAA

AGGAGCATTC

AGAAAAAGAG

AATCAAACCA

CCTCAAACTA

AAACCAATCC

CGAATAGGTA

CTTAACAACC

2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 295 o

ATTTATACCG

CAATAGAATT

TAATCTTTTT

ATAAAGCATT

GTTCTACCAT

TTCTCACAGA

ATTTAAAAAT

ATGCAACCAT

ATACTCTTAA

TAGCACAA.AT

CCATAATATT

CAATAAAAAA

GGGTTAGTTC

CATCACCCAA

CCACTTCAAC

AAGATGATTA

AACTTTGCAA

TCAAACCCAC

CCAAAACGAC

CAGAAAGAGA

CAGTCCAACA

CACCCACAGC

AGTTATTCAA

AACCTGGGGC

CTTGCTATTA

TCGACATGTA

CCA.ATTCAAC

CACAAGCAAA

ACTAATTATA

CTGTAACAAA

TATGCTGTGT

GTCATGGTGT

TAACATAATG

GTCCAAACAC

TCATCTAATT

AGCACTATCA

CATCATCTCT

CCACACTGAA

ATCCAAGCAA

TACAAAATCA

ACAGACCAAC

CCATTTTGAA

ATCCATCTGC

AAACAAACCA

GAAAAAAGAA

CACCAGCACC

GCAATCCCTC

ATCCGAGCCC

AAACTACATC

AAATAACCAT

ATGCATTGTA

GTGCAGTTAG

ACATATACTA

TTTTGGCCCT

ATCACTATTA

ACTCTTGAAC

CAAATTATAA

CGCAAAACCA

ATGAATTGTT

AAGAATCAAC

GTAATATCCT

GTTTTGGCAA

GCCAATCACA

AAAAACATCA

CCCACAACCA

GAkAACACACC

AAGCCAAGCA

GTGTTCAACT

AAAACAATAC

ACCACCAAAA

ACTACCACCA

TCACAATCCA

CTCTCA.ACCA

TCCACACCAA

TTAGCAGAGA

GGAGTTGATG

CCTCACCTCA

CAGAGGTTAT

TAAATCTTAA

ATTTTACACT

TGATTGCAAT

TAGGACAGAT

TCCTGTATAT

CGCTAACTAT

AGTATGAGAT

GCACTGCCAG

CTTGTTTATA

TGATAATCTC

AAGTTACACT

CCACCTACCC

CATCACCAAT

ATACAACAGC

CAAAACCACG

TCGTTCCCTG

CAAGCAACAA

CCACAAACAA

ACCCAACAAA

CTGCACTCGA

CCCCCGAAAA

ACTCCACCCA

ACCGTGATCT

ATCCACAAGT

AGTCAGAACA

TTTAGTGCTT

AATGGGAAAT

AATACATATG

ACTAAATAAG

GTATCAAATC

ATAAACAAAC

CATGGTAGCA

CAAAAACAAC

GACTCTAGAA

CAGATTAAAT

AACCTCTCTC

AACAACGGTC

TACTCAAGTC

CCACACAAGT

ACAAACCAAA

TCCAAAAAAT

CAGTATATGT

ACCAAAGAAG

AAGAGACCCA

AAAACTAACC

CACAACCACA

CACACCCAAC

AAAAACCCAG

ATCAAGCAAG

CAAGTGCAAT

TAACTGAGGA

TAAGAACAGG

ACATCCATCA

ATCTTAACTC

CTALAGTGAAC

AACACATAGA

AAATCCAATC

TAGAGTAGTT

ATTGGGGCAA

AAGACCTGGG

TTAAAATCTA

ATAATTGCAG

ACAGTTCAA-A

TCACCAGAAA

TCAGCTACAA

GGCAGAACCA

CCACCAAAAA

GGCAACAATC

AAACCAACCA

AAAACACCAG

CTCAAGACCA

TTAAAACACA

TCCACACAAA

CCACATGCTT

AACGAALATTA

CTTCCTAACT

GTTTTACCAA

TTGGTATACT

4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 296

S

S.

5* S. S 5,

S.

AGTGTCATAA

AAAGTAAAAC

CTACTTATGC

ATGAACTACA

CGALAGATTTC

TCAAAAGTTC

AACAAAGCTG

CTCAAGAATT

TCCAACATTG

AGAGAATTTA

AGTGAGTTAC

TCAAGCAATG

GAAGTCCTTG

AA.ATTGCACA

ACAAGGACTG

GCTGACACTT

TTACCAAGTG

ATTATGACAT

TCATGCTATG

TTTTCTAATG

ACTTTATACT

ATAAATTACT

GTCAATGAkLA

AATGTAAATA

ATTGTAGTAT

ACACCAGTTA

CAATAGAATT

TTATGAAACA

AAAACACACC

CAATCAATAC

TAGGCTTCTT

TACACCTTGA

TAGTCAGTTT

ACATAAATAA

AAACAGTTAT

GTGTCAATGC

TATCATTAAT

TTCAGATAGT

CATATGTTGT

CATCGCCTCT

ATAGAGGATG

GTAALAGTACA

AAGTCAGCCT

CAAAA.ACAGA

GTAAAACTAA

GTTGTGACTA

ATGTAAACAA

ATGACCCTCT

AAATCAATCA

CTGGCAAATC

TGTTATCATT

CACTAAGCAA

AAGTAATATA

AGAATTAGAT

AGCTGTCAAC

CACTAAAAAC

GTTAGGTGTG

AGGAGAAGTG

ATCAAATGGG

CCAATTATTA

AGAATTCCAG

AGGTGTAACA

CAATGATATG

AAGGCAACAA

ACAGCTGCCT

ATGCACTACC

GTATTGTGAT

GTCCALATCGA

TTGTAACACT

CATAAGCAGC

ATGCACTGCA

TGTGTCAAAC

GCTGGAAGGC

AGTGTTTCCT

AAGTTTAGCT

TACTACAAAT

AATAGCTATT

AGACCAACTA

A.AAGAAACCA

AAGTATAAGA

A.ACCGGGCCA

CTAAATGTAT

GGATCTGCAA

AACAAGATCA

GTCAGTGTTT

CCCATAGTAA

CAGAAGAACA

ACACCTTTAA

CCTATALACAA

AGTTATTCCA

ATCTATGGTG

A.ACATCAAAG

AATGCAGGAT

GTATTTTGTG

GACATATTCA

TCAGTAATTA

TCCAACAAAA

AAAGGAGTAG

AAGAACCTTT

TCTGATGAGT

TTTATTCGTA

ATTATGATAA~

GGTTTACTGT

AGTGGAATCA

AATGCAATGG

ATGCAGTAAC

GAAGAGAAGC

CAATAAGCAA

TAGCAAGTGG

AA.AATGCTTT

TAACCAGCAA

ATCAACAGAG

GCAGATTGTT

GCACTTACAT

ATGATCAGAA

TCATGTCTAT

TAATAGATAC

AAGGATCAAA

CAGTATCCTT

ACACTATGA.A

ATTCCAAGTA

CTTCTCTTGG

ATCGTGGGAT

ATACTGTGTC

ATGTAAAAGG

TTGATGCATC

GATCTGATGA

CTACAATTAT

TGTATTGTAA

ATAATATTGC

AACTGACACT

AGA.ATTACAG

ACCACAGTAT

GAAGAGGAIA

TATAGCTGTA

GTTGTCTACA

AGTGTTAGAT

CTGTCGCATC

GGAAATCACC

GTTGACAAAC

AAAATTAATG

AATA.AAGGAA

ACCTTGCTGG

TATTTGTTTA

CTTTCCACAG

CAGTTTGACA

TGACTGCAAA

AGCTATAGTG

TATAAAGACA

AGTGGGCAAC

GGAACCTATA

AATATCTCAA

ATTACTACAT

TATAGTAATC

AGCCAAAAAC

ATTCAGCAAA

5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 0.

297 0*

TAGACAAAAA

AACTTACAAC

ACCCACATAA

TCAACCACTA

GAAATCCTTG

GTCATAATTA

ACAAGATACT

CTGAACTGGA

TAGGATCTAT

TTGAGATCAA

AGATAAGAGT

AAACCATCCA

CATTAGATAT

AAAATGACCA

ATATTGATCT

AACCATAACT

TGGACACCTA

GAAGATATAT

CATCCAACCA

GAAACTCTGC

AGTGTAATGC

ACTTAATTAG

CACAGTCATT

TCCAGTCATT

ACTTACTTAA

TCTTGAATAA

ACCACCTGAT

AALATATTTCA

CTAAGCTAGA

AATCAACACA

TAAkATTTGAG

CTTTGAATGG

CAAGTCAATG

TAGAACAGAA

AAACAACATA

TAGTGATGAC

GTACAATACT

TCTGCTCALAG

CCACAAAAGC

AACCAAAAAT

CAAGTGAAAG

ATTTGGATAA

AAAACTTATT

ATACAGTATA

TAAAACTATT

TAATGTGTAT

TTTAGGGAGT

TAGACAAAGC

AATATCTAGA

ACTTATGACA

AAAAATAATA

ACTAGGATTA

CATGTTTCAA

ACATCACAGT

TCCTTAACTT

TCATTCACAA

ATTAGAGGTC

CCTCCTCATG

GACAAAAGCA

GAATATGCTC

ACAAAACAAT

ATTAAAAAGC

GTTATATCAT

AGACTACCAG

ATAACCATAA

AATGATATTA

CATGGTTGCT

CCACCAGCGT

AGATGCCACT

TATATTAGTG

TTGATAAGGT

CTAACTGATA

TATCTTTTTA

CCACTACTAG

TATCATAAAG

TATAAAAGTA

CGAAGAGCCA

AAGGAAAAGG

CAACAATCTG

ACAGGCTGAA

ATAGTTACAT

AATTAACAGC

ATTGCTTGAA

CATTACTAGT

TAGACACTTT

TTGGTATAGT

CAGCATGTGT

TTAGAGATAA

ACATTGAGAG

CAGACGTGCT

GCAATCCAAA

CCGGATAA.AT

ACATTCAATC

TTATTAA.ATC

CAACAATTTC

TCATAATGCT

TATGGGACAA

GTTATTTAAA

ACGGCCCTTA

AGCATATGAA

GTGAACTGAA

TGTCCTCGTC

TAGAAATAAG

ACAGAGTTAA

CTGACCACCA

TCATTTCCTC

AAAAACCTCA

TGGGGC.AAAT

TGGTAGAAGA

GAGGCAAAAC

GTCTGAAATA

TGGAGTGCTA

TGCTATGAGT

TGAAGA.ACCC

CAATAGAAAA

GAAGAAGACA

AGAGTCAACT

ATCCTTGTAG

ATAAAAACAT

ATATATTTGA

TCCAACATCT

TGACCATAAC

AATGGATCCC

AGGTGTTATC

TCTTAAAAAT

TCTTAAAAAA

ATTAGAAGALA

TGAACAAATT

TGATGTAAAG

GCCCAACAAT

AT C CCAAAT C

ACATCATGCT

AGTATCACAA

ATGTCGCGAA

TGTCACTACA

TTCATGTTAA

AGTGGAGCTG

GAGAGTTACA

AAACTTCTTA

AATTCACCTA

AACAACAAGC

ATAAAGAACA

GTGAATGATC

TATATCATCC

ATTACAATTT

TGAAATTCAT

TAACATCCCT

GACTCTATGT

ATTATTAATG

TCTTTTTCAG

GATTACACCA

CTAACTATAA

CCAACTTATT

GCTACAACTA

GTGTACGCCA

AATTCAGGTG

7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 298

C

ATGAAAACTC

ATCAATCATA

CAACACTCTT

GGTTCAATTT

AA.AGTCATGG

ATCAATATGG

ATCAATTTTT

GGATAAGTAA

ATGTTGTGTT

AAGGCTTCTA

CAGAAGAAGA

CAGCTATTAA

CAGTGTCTGA

TGATTAAGCT

GAATCTTTGG

GTAATGAAAC

ATAGAATCAT

TTGTCCTACC

AAATCACAGA

TGCCTAAAAA

ATCTAATATG

AACATGAAAA

TGAGAGATAA

TCAACAACTC

GAATGTTTGC

TAGCTGAAAA

AGTACTTACA

TACAAATTCA

GAAAAAATTG

ATATACAAA-A

GTTTATATTA

TTGTATCGTT

GACATGGAAA

TTGTTTAAAT

ATCACAATTA

CATAATAAAA

TCAATTTAGG

GGCTCAAAAG

TAATATCATA

TGCAGGTGAT

ACATCCAATG

TALAGTTCTAC

AAAAGGGTTT

TCTAAGATGG

AAATGATTTG

AGTGGATCTT

GACTAGTTTT

GTTGAAGTTC

TAAATTCAAT

TAATCACGTG

TATGCAACCA

TATTTTACAA

ACCATAATTA

GACAAAAGTC

ATGTGTTCAA

TTAAATAACA

ATAGATAATC

TATCATAAAG

GACATCAGCC

ACATTAAACA

TTTCTTTATG

GAAGTAGAGG

AAACGATTTT

GACCTACTAT

AATGGTA.AT

AATAATCTCA

GTCGATGAAA

TTATTAAGTA

GTAAATACCT

TTAAACTACT

ATTATTTTAT

GAAATGATAA

CCTAGAAATT

TCTGAAAGCG

GAATGCGATC

GTATCACTAA

GGTATGTTTA

TTCTTCCCTG

AAGATGATAT

ACTCAGTAAA

TGCAACATCC

TATTAACACA

AAACTTTAAG

GACTCAAAALA

TTAGCAGATT

AAAGCTTAGG

GAGATTGTAT

GATTTATTAT

ATAATAGCAT

CA.AGAGTATG

GGATAATCCT

ATAACTTGAG

GACAAGCAAT

GTCTAAGTAC

ACAACAGATG

ATAAACTTAA

CAGGATTGCG

TAAATGACAA

ACATGCCATC

ACAGATCGAG

TATACAATTG

CTGGTAAAGA

GGCAAATCCA

AGAGTTTGAC

ACTTTCGGCT

TCAAA.ATATC

TCCATCATGG

ATATCGATCA

TGGTTTTCAG

AATCACAACT

AAATGTTTGC

GCTGAGATGT

ACTGAAATTA

GTCTTTAATT

GCTAAATAAC

TCACACTTTA

ATTAAGTAAA

TGAGCTATAT

GGATTCTGTA

ATTAAGAGGT

GCCCACCTTA

TACTTATCCA

GTTCTATCGT

AGCCATTTCA

ACATATACAA

AAGAGTACTA

TGTAGTCAAT

AAGAGAGCTC

AATCTTAGCA

AAGATATGGT

GTGGAAAACA

ACTATCAAAA

TTAATACACT

AATGAGGTAA

TTTATTTTAA

ACTACTTACA

TTAATTACTT

GGATTCAATA

TTTCATAATG

CTAAACATA-A

ATCACAGATG

TTAGACAAGA

TTTCTTAAAT

TTTCTCTTCA

AGAATTAACT

GCTTTCATTT

AGGAATGCTA

TCTCTACTTG

GAGTTTCATC

CCTCCAA.AG

AATTATATAG

GAGTATTACT

CAAAGCTATC

AGTGTAGGTA

GAGAAAATGA

GATCTAGAGC

9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 299 TTCAAAAGAT ATTAGAATTA AAAGCAGGAA TAAGCAACAA GTCAAATCGT TATAATGATA *0 S S

S.

ACTACALACAA

CATTTAGATA

AATCTCTGTT

GACATGCACC

GTGGATTATA

TTGAAGCTAT

TGATAALATGG

AGACCCATGC

AGTATGCAGG

AGTTCATGAG

TCCTGAGAGT

CTATAGGCAG

TATTTAGGIA

GTAACAATAA

ATCTTGATAG

GTGGTGATCC

AAGCTATAGT

AGCTCCAGGA

ATAAAAATCC

AAAGGCAAGC

TAGCCCCAAA

TAAATGACAT

AAAGTTTACC

TAACTAATAT

ATATGATGAG

TTATATCAGT

TGAAACATCA

CTCTTGGTTG

TCCTTTCATA

CAGATATCAT

ATCATTATTA

TGATAATCAG

ACAAGCAGAT

TATAGGCCAT

CAAAACAATC

AGGTCCATGG

CTTAACACAG

CATTTGGTTA

GCTATATTTA

CATTGATATG

TAATTTGTTA

ACATTCAGTG

TCTTCCAGAT

CAATGCCGAG

TAAAATTACT

CAAAATATTT

TATGCAAAAT

TTTTTATAAA

ACTTGAAAAA

GAAAAATATA

AAATGTTCTA

TGTATCTGCA

CATTTA.ACA.A

AAGGATCATG

ATGGGTGGTA

GATCTAATAT

TCAATTGATA

TATTTGTTAG

AAGCTTAAGG

CAGCACAATG

ATAAACACGA

GAGTTAGA.AT

TACAATCAAA

GATATATTGA

GCTTTATCAT

TATCGAAGCT

TTTGTGTTGA

GATAGACTGA

TTTGTAACAT

AGTGAGATTA

TCTAAAAGTG

ATAGAACCAA

GCAGAAAAAA

ACATCAGCAA

ACTTACTTA

TCATTACAGA

GTGATGTATT

TACCTCTTGT

TTGTTAATCT

TTGAGGGCTG

CTCTCAAAGG

TAAGCAAACC

CATTAAATAG

GAACAGAGAC

GAGTGTACTA

TACTTGATGA

ACAGAGGAGA

TTGCTTTGCA

AAGTATTAAA

TGTATATGAA

TTTATAGGAG

GCTATTATAC

ACAAATTCTT

TGATGAGGGA

ATAGATTAGC

CACAACATTA

CTTACCCTCA

TAGTTAATCT

TAGATACAC

TAAGGATACT

TCTTAGCAAA

AGATGILACTG

CACAATAATA

TAATGAGGTT

GTGTCAAAAA

GAAATTCTCT

AGTTAGACTT

CCTTAAATTG

CTATATATCC

TCCAGCCAGT

TTTTAAAGTT

AAGCTTATTA

ACTCCGAAAT

ACACTTAAAA

TTTGCCTATG

AACTCCAGAC

TGGTCACGAT

GACATGTGTC

TCCACAGGCT

AGTAACAGAA

TACTACCACT

TGGATTAAGA

TATATCAGGA

TGATATTAAT

TCCACTAGAT

TTCAATCAGG

CATGGAGTAC

TGTACATATA

GATGAACAAA

CTGTGGACCA

ATCACAGCTC

ATAGAGGGTC

TTATATAAAG

CGAGATATGC

ATCAAAAAAG

AGTTTAGAAT

TGCAGTTTAA

CATGCATTAT

ACTTTTTTTA

CTGTTTGGTG

TTCCTTACAG

TTACAAGATA

ATCACATTTG

TTAGGGTCTG

GTCTTAAGTA

GAGATTGATC

GTTGTTTATG

ACAAAATCCA

AGGGCTACTG

TGTAACAAAG

10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 300 S S

SS

S

S

S.

S

S

S

a S

*SSS

S.

ACAAAAGAGA

GAGAAAGATC

CAATGGACAT

ATGTTAATAG

CGCAGGAGA-A

ACCAAATAGA

AATTCATGGA

TGTTTCCACA

GTGAATTCCC

CTATCAATCA

ATTGCATAAG

CTAATAGAAT

TTACAGGAGA

TACCAGATAA

AATCTGGATC

ATAATGCTTA

TGAAAGATTC

TGTTCATTAA

AAGGTTATGG

TGGAGTTAAT

TCATAAAATA

TTAAGTTGTG

TTAACATAGA

GAATGGGGTT

AATTTTACAC

GTTATTAAGT

TTGGTCATTA

TAAATATACA

TTTAACTCGT

AAAAACAATG

TTTATTAGCA

AGAACTGAGT

ATATCTAAGT

TGCATCAATA

TGTATTALACA

TTTTGGTCTT

TATTCTCATA

TGTTGATATC

AATAAGTTTA

TCACATCAAC

TATTTTAAGT

AAAAGGTATT

TTTGAATGTT

TAAAGCAAAA

AGACAGTAGC

CATAGTCAAT

GTTTTTAAAA

TTATCACCCA

AATAAATGTA

ATCAAATCTC

TTAGAAAATC

TCCAATATAG

ACTAGCACTA

GGTGAAAGAG

CCAGTGTACA

AAATTAGACT

ACTGGA.ACAC

GTCAATTATT

CCAGCTTATA

GAAAAGTATG

AGCCTGATGT

CCGAAGCTGA

ATCAAGTTGA

ACCCAATATG

TCTAATTTAA

ACTAATTTAG

TTTGAAAAAG

TTCTTTAATG

TTAGAATGTG

TACTGGAAAT

CAAGACACAA

CGCCTTAATA

ACACACATGA

GATAAATTAA

TTTTACATTA

TTAGTATAAC

TAGGAGTAAC

TAGCCAGTGG

GACCCACCA

ACAGACAAGT

GGGTATATGC

TTGGACTGTC

TACACCGTTT

GAACAACAAA

GAGATGAAGA

CGGTTGTGGA

ATGAGATACA

AGC.AAGTGAT

TAGAATTATT

TATTAGTACA

CTGGACATTG

ATTGGGGAGA

CTTATAAGAC

ATATGAACAC

CTATGTCTAA

GTTTGCGTAG

ATGCTAAATT

AAGCTATATT

CCATTAAAAA

GTTATAACTT

TGAATTA-AGC

ATCGCCAAGT

TATA.ATAATA

GCCATGGGTA

TTTAACCAAA

ATCCATAGAC

ATATGAAAAA

AACAGTCAGT

TTATCATTTT

TATCGACATT

ACA.ATTCACA

TTTGATGA

ACAAAAGCAG

CTTAAGTAAC

TAAAATGTCT

GATTCTGATT

GGGGTACATA

TTATTTGCTA

TTCAGATCTT

AGTTTTCCTA

AATAAAAGGC

TACCGTATGC

ATCTTACATA

TAAAALACAAA

TTCAGACAAC

AAGTATGTAA

ATTATGTTCA

GAAAAATATA

GGCTCATCCA

AAGCAA.AGAG

AACAAAGATG

GCCAAAAAGT

AGTAGACCAT

GATACTAGTC

GTGTTTCAAA

AACATATGTC

CCTCCTATAT

CACATGTTCC

AAAGCACTTA

GATTATTTTC

ATTCAACTTA

ACTGATCATA

TGTTTTCATA

CTTTGTGTTT

GAACAAAAAG

TGTCACAGTT

CCTTGGGTTG

GATTTAGTTA

TTCAATGATG

ACTCATTTGC

12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 TAACAAAACA AATAAGAATT GCTAATTCAG AATTAGAAGA TAATTATAAC AAACTATATC 301

ACCCAACCCC

ACAAACCTZA

GTAAAATGCA

TGTACAATTT

CAAAATCTAA

CATCACTTTA

CCACAGGATG

GTTGTATAGC

TTCATCCAGA

CTATTGAATT

CCATTCCTGC

CAGAkACCTAT

AAATTATAAT

GATGCATTTT

TTACTATATT

TAATCCTTAC

AATTGACACT

TCGATGCAA.A

TTAAGACTTC

TAGCTGGACG

TAAAATGGCT

ACATGATAGA

AGCTCAAGAA

AGTTTAAAAT

AGTTATTAAA

TTTAGTCTTA

AGAAACTTTA

ATTTTGTATA

TATTAAATCT

ATTTCCAATT

CCAACTTTAC

TTGCATGCTT

CAAGATCAGT

ATTCATAGGT

CATAAGATAC

TCTAAGGTTA

TACAGATGCA

TAGCATCTTT

TGAATGGAGT

AATTGCAAAA

AAAAACTTAC

IAATAGGCCCT

TTCAAGAACT

TATTAAALAGC

ATTGTCAAAA

TAATGAAGTA

AGATCATGTT

GTCCACATAT

GCTGATTAAA

ATCATTAACA

AAATATACAA

AGGGGTTAAA

GAAAATATGT

AGTGGAAATA

TCCACTGTTA

GTTGTGATAG

ACCACCACTT

CCTTGGCATC

ATAGAGTATA

GAAGGAGCTG

ATTTACAGA-A

TACALACGGGC

ACTAATAACA

GTCTGCGATG

AAGCATGTAA

TATCATGCTC

GTGTGCCTAG

GCAAATATAC

AAAA.ATTTCA

TTAATACCTT

TTGAAGAGTG

TTCAGCAACA

TTAAATTTTA

CCTTACTTAA

ATAACAGGTA

AGTTTGGTCA

ACTTTTCAAT

TAAAAGTCTA

CATTAATTCC

CCGAATCTAT

CCACAAGATT

ACA.AGATTAT

CACATCAGAC

ATGTCAATAG

TTTTAAAAGA

GTAACTTATT

GTTTAAAAGA

ATATAXACAT

TTCATTGGTC

CTGAATTACC

GAAAGTGCAA

AAGATGACAT

GTAGCAAGTT

TTCCTGTTTT

TTATGCCTAA

TCCTTTGTTA

TAGTTAATGG

AGCTTATAAA

GATCAGCTGA

GTGAATTGTT

GTGTGCTATA

AATTTAGATG

AATTTAGCAT

AAACTAACAA

TGTTAAAAGT

GATGATGTCA

CAATTATAGC

AGATCATTCA

ATCTTTAGTA

ATTTAACTTT

TCTTAAGATT

ATTACGTACG

TTGCAATGAT

AGATTATGGT

TTATTTACAT

TGTTACACC

GTACTGTTCT

TGATTTCAAA

AAAAGGATCT

TGATGTTGTA

AAAAACTGAC

CCCTATAACA

AGATATATTA

CCACAAGCAT

ACTTAATTAC

AAATAGTTTA

CAACCTTCCC

CTAACACATC

ATTGATTCCA

TTATACATGT

AA.TAATAGTA

ACATTCTCTA

AAACAAGACT

GGTAATACAG

AGGA.ATAGTG

GTATTTAGTT

AAGGACCCCA

GTAGTAGA-AC

CATAGTTTAC

GAGAATTTAA

ATAAAATTTG

AATTGGAGTA

TCTGTAAATA

TTAGATAACA

GAAGTTTACT

CAAAATGCTA

AAGGAATCTA

AAAAAAGGAA

TCATATTCTA

ATGAATATCC

AATCATTTAT

ACAACCAATG

AACGAACAGT

ATTATATTAT

AA-ATTATCAT

GCATTCACAA

13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 302 CACAACGAGA CATTAGTTTT TGACACTTTT TTTCTCGT 15218 INFORMATION FOR SEQ ID NO:24: SEQUENCE CHARACTERISTICS: LENGTH: 2166 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: Met Asp Pro Ile Ile Asn Gly Asn Ser Ala Asn Val Tyr Leu Thr Asp 1 5 10 Ser Tyr Leu Lys Giy Val Ile Ser Phe Ser Glu Cys Asn Ala Leu Gly 25 Ser Tyr Leu Phe Asn Gly Pro Tyr Leu Lys Aen Asp Tyr Thr Asn Leu 40 Sle Ser Arg Gin Ser Pro Leu Leu Glu His Met Asn Leu Lys Lys Leu 50 55 Thr Ile Thr Gin Ser Leu Ile Ser Arg Tyr His Lys Gly Glu Leu Lys 70 75 Leu Giu Giu Pro Thr Tyr Phe Gin Ser Leu Leu Met Thr Tyr Lys Ser 90 Met Ser Ser Ser Giu Gin Ile Ala Thr Thr Asn Leu Leu Lys Lys Ile *.100 105 110 Ile Arg Arg Ala Ile Giu Ile Ser Asp Val Lys Val Tyr Ala Ile Leu 115 120 125 Asn Lys Leu Gly Leu Lys Giu Lys Asp Arg Vai Lys Pro Asn Asn Asn 130 135 140 Ser Gly Asp Glu Asn Ser Val Leu Thr Thr Ile Ile Lys Asp Asp Ile 145 150 155 160 Leu Ser Ala Val Glu Asn Asn Gin Ser Tyr Thr Asn Ser Asp Lys Ser 165 170 175 His Ser Val Asn Gin Asn Ile Thr Ile Lys Thr Thr Leu Leu Lys Lys 303 180 Leu Met Cys Ser Met Gin His Pro S. S S

S

S

S

S

S

S*

S

S.

S

.5* Asn Giu 225 Gly Gly Lys Ser Phe 305 Leu Gly Arg Ile Asp 385 Leu Asn Met Leu 210 Val1 Phe Leu Asp Asn 290 Asn Lys Phe Lys Lys 370 Lys Ser Asn Val 195 Tyr Lys Gin Lys Ile 275 Cys Asn Leu Ile Arg 355 Ala Thr Lys Leu Asp 435 Thr S er Phe Lys 260 Ser Leu Val Phe Met 340 Phe Gin Val Phe Ser 420 Glu Lys His Ile 245 Ile Leu Asn Val His 325 Ser Tyr Lys Ser Leu 405 Giu Arg Leu Giy 230 Leu Thr Ser Thr Leu 310 Asn Leu Asn Asp Asp 390 Lys Leu Gin Asn 215 Phe Asn Thr Arg Leu 295 Ser Giu Ile Ser Leu 375 Aen Leu Tyr Ala 200 Asn Ile Gin Thr Leu 280 Aen Gin Gly Leu Met 360 Leu Ile Ile Phe Met 440 185 Pro Ile Leu Tyr Thr 265 Aen Lye Leu Phe Asn 345 Leu Ser Ile Lye Leu 425 Asp Ser Leu Ile Gly 250 Tyr Val Ser Phe Tyr 330 Ile Asn Arg Asn Leu 410 Phe Ser Trp Thr Asp 235 Cys Asn Cys Le u Leu 315 Ile Thr As n Val Gly 395 Aila Arg Val1 Leu Gin 220 Aen Ile Gin Leu Gly 300 Tyr Ile Giu Ile Cys 380 Lye Giy Ile Arg Ile 205 Tyr Gin Val Phe Ile 285 Leu Gly Lys Giu Thr 365 His Trp Asp Phe Ile 445 190 His Arg Thr Tyr Leu 270 Thr Arg Asp Glu Asp 350 Asp Thr Ile Asn Gly 430 Asn Trp Ser Leu His 255 Thr Trp Cys Cys Val 335 Gin Ala Leu Ile Asn 415 His Cys Phe Aen Ser 240 Lye Trp Ile Gly Ile 320 Glu Phe Al a Leu Leu 400 Leu Pro Asn Giu Thr Lye Phe Tyr Leu Leu Ser Ser Leu Ser Thr Leu Arg Gly Ala 450 455 460 304 Phe Ile Tyr Arg Ile Ile Lye Gly Phe Val Asn Thr Tyr Asn Arg Trp 465 470 475 480 a. a.

a a a.

a a Pro Tyr Leu Lys Pro 545 His Asp Asn Asn Val 625 Ile Giu Leu Asn Asn 705 Asp Thr Lys Ile Lys 530 Lys Ile Arg Giu Ser 610 Gly Leu Ser Lys Asn 690 Gin Giu Leu Leu Ile Val Asp Gin S er Cys 595 Asn Arg Ala Leu Ala 675 Tyr Ala Leu Arg Asn 500 Leu Asp Leu Asn Arg 580 Asp His Met Giu Thr 660 Gly Ile Phe His Asn 485 Thr Ser Leu Ile Tyr 565 Arg Leu Vai Phe Lys 645 Arg Ile Ser Arg Gly 725 Al a Tyr Giy Giu Trp 550 Ile Vai Tyr Val Ala 630 Met Tyr Ser Lys Tyr 710 Val Ile Pro Leu Met 535 Thr Giu Leu Aen Ser 615 Met Ile Gly Aen Cys 695 Giu Gin Val Ser Arg 520 Ile Ser His Giu Cys 600 Leu Gin Ala Asp Lys 680 Ser Thr S er Leu Leu 505 Phe Ile Phe Giu Tyr 585 Val Thr Pro Giu Leu 665 Ser Ile Ser Leu Pro 490 Leu Tyr Asn Pro Lye 570 Tyr Val1 Gly Gly Asn 650 Giu Asn Ile eye Phe 730 Leu Glu Arg Asp Arg 555 Leu Leu Asn Lys Met 635 Ile Leu Arg Thr Ile 715 Ser Arg Ile Giu Lye 540 Aen Lye Arg Gin Giu 620 Phe Leu Gin Tyr Asp 700 Cys Trp Trp Thr Phe 525 Al a Tyr Phe Asp Ser 605 Arg Arg Gin Lye Asn 685 Leu Ser Leu Leu Giu 510 His Ile Met Ser Asn 590 Tyr Giu Gin Phe Ile 670 Asp Ser Asp His Asn Tyr 495 Aen Asp Leu Pro Ser Pro Pro Ser 560 Giu Ser 575 Lye Phe Leu Asn Leu Ser Ile Gin 640 Phe Pro 655 Leu Giu Aen Tyr Lye Phe Val Leu 720 Leu Thr 735 305 Ile Pro Leu Val Thr Ile Ile Cys

S

*S0.

S*

9 9 *9*9 Ile Leu Trp 785 Lye Ile Asp Ala Asp 865 Pro Ile Gin Arg Ala 945 His Leu Leu Lye Asp 755 Tyr Arg 770 Thr Ile Phe Ser Ser Lys Tyr Leu 835 Gly Ile 850 Met Gin Ala Ser Leu Asp Glu Leu 915 Asn Ile 930 Leu Cys Leu Lye Tyr Met Tyr Arg 995 His Val Tyr His Glu Ala Ile Thr 805 Pro Val 820 Leu Ala Gly His Phe Met Ile Lys 885 Asp Phe 900 Glu Tyr Trp Leu Asn Asn Thr Phe 965 Asn Leu 980 Ser Phe Val Met Ile 790 Ala Arg Leu Lye Ser 870 Lye Lys Arg Tyr Lye 950 Phe Pro Tyr Asn Gly 775 Ser Leu Leu Asn Leu 855 Lys Val Val Gly Asn 935 Leu Asn Met Arg Leu 760 Gly Leu Ile Ile Ser 840 Lye Thr Leu Ser Glu 920 Gin Tyr Leu Leu Arg 1000 Thr 745 Asn Ile Leu Asn Glu 825 Leu Gly Ile Arg Leu 905 Ser Ile Leu Asp Phe 985 rhr Tyr Glu Glu Asp Gly 810 Gly Lye Thr Gin Vai 890 Glu Leu Ala Asp Ser 970 Gly Pro Arg Val Gly Leu 795 Asp Gin Leu Glu His 875 Gly Ser Leu Leu Ile 955 Ile Gly Asp His Asp Trp 780 Ile Asn Thr Leu Thr 860 Asn Pro Ile Cys Gin 940 Leu Asp Gly Phe Ala Glu 765 Cys Ser Gin His Tyr 845 Tyr Gly Trp Gly Ser 925 Leu Lys Met Asp Leu Pro 750 Gin Gin Leu Ser Ala 830 Lye Ile Vai Ile Ser 910 Leu Arg Val Ala Pro 990 Thr Pro Ser Lye Lye Ile 815 Gin Glu Ser Tyr Asn 895 Leu Ile Asn Leu Leu 975 Asn Glu Phe Gly Leu Gly 800 Asp Ala Tyr Arg Tyr 880 Thr Thr Phe His Lys 960 Ser Leu Ala 1005 Ile Val His Ser Val Phe Val Leu Ser Tyr Tyr Thr Gly His Asp Leu 306 1010 1015 1020 Gin Asp Lys Leu Gin Asp Leu Pro Asp Asp Arg Leu Asn Lys Phe Leu 1025 1030 1035 1040 Thr Cys Vai Ile Thr Phe Asp Lys Asn Pro Asn Ala Giu Phe Val Thr 1045 .1050 1055 Leu Met Arg Asp Pro Gin Ala Leu Gly Ser Giu Arg Gin Ala Lys Ile 1060 1065 1070 Thr Ser Giu Ile Asn Arg Leu Ala Val Thr Glu Val Leu Ser Ile Ala 1075 1080 1085 Pro Asn Lys Ile Phe Ser Lys Ser Ala Gin His Tyr Thr Thr Thr Giu 1090 1095 1100 Ile Asp Leu Asn Asp Ile Met Gin Asn Ile Glu Pro Thr Tyr Pro His 1105 1110 1115 1120 Gly Leu Arg Val Val Tyr Giu Ser Leu Pro Phe Tyr Lys Ala Glu Lys 1125 1130 1135 Sle Val Asn Leu Ile Ser Giy Thr Lys Ser Ile Thr Asn Ile Leu Giu 1140 1145 1150 Lys Thr Ser Ala Ile Asp Thr Thr Asp Ile Asn Arg Ala Thr Asp Met 1155 1160 1165 Met Arg Lys Asn Ile Thr Leu Leu Ile Arg Ile Leu Pro Leu Asp Cys 1170 1175 1180 Asn Lys Asp Lys Arg Glu Leu Leu Ser Leu Glu Asn Leu Ser Ile Thr 1185 1190 1195 1200 Giu Leu Ser Lys Tyr Val Arg Giu Arg Ser Trp Ser Leu Ser Asn Ile 1205 1210 1215 **Val Gly Val Thr Ser Pro Ser Ile Met Phe Thr Met Asp Ile Lys Tyr 1220 1225 1230 Thr Thr Ser Thr Ile Ala Ser Gly Ile Ile Ile Glu Lys Tyr Asn Val 1235 1240 1245 Asn Ser Leu Thr Arg Gly Glu Arg Gly Pro Thr Lys Pro Trp Val Giy 1250 1255 1260 Ser Ser Thr Gin Giu Lys Lys Thr Met Pro Val Tyr Asn Arg Gin Val 1265 1270 1275 1280 Leu Thr Lys Lys Gin Arg Asp Gin Ile Asp Leu Leu Ala Lys Leu Asp 1285 1290 1295 307 Trp Val Tyr Ala Ser Ile Asp Asn Lys Asp Giu Phe Met Giu Giu Leu 1300 1305 1310 Ser Thr Gly Thr Leu Gly Leu Ser Tyr Giu Lys Ala Lys Lys Leu Phe 1315 1320 1325 Pro Gin Tyr Leu Ser Vai Asn Tyr Leu His Arg Leu Thr Val Ser Ser 1330 1335 1340 Arg Pro Cys Giu Phe Pro Ala Ser Ile Pro Ala Tyr Arg Thr Thr Asn 1345 1350 1355 1360 Tyr His Phe Asp Thr Ser Pro Ile Asn His Val Leu Thr Giu Lys Tyr 1365 1370 1375 Giy Asp Giu Asp Ile Asp Ile Val Phe Gin Asn Cys Ile Ser Phe Gly 1380 1385 1390 Leu Ser Leu Met Ser Val Val Giu Gin Phe Thr Asn Ile Cys Pro Asn 1395 1400 1405 Arg Ile Ile Leu Ile Pro Lys Leu Asn Giu Ile His Leu Met Lys Pro 1410 1415 1420 .Pro Ile Phe Thr Gly Asp Val Asp Ile Ile Lys Leu Lys Gin Val Ile *1425 1430 1435 1440 Gin Lys Gin His Met Phe Leu Pro Asp Lys Ile Ser Leu Thr Gin Tyr .1445 1450 1455 Vai Glu Leu Phe Leu Ser Asn Lys Ala Leu Lys Ser Gly Ser His Ile 1460 1465 1470 Asn Ser Asn Leu Ile Leu Val His Lys Met Ser Asp Tyr Phe His Asn 1475 1480 1485 *Ala Tyr Ile Leu Ser Thr Asn Leu Ala Gly His Trp Ile Leu Ile Ile *1490 1495 1500 Gin Leu Met Lys Asp Ser Lys Gly Ile Phe Giu Lys Asp Trp Gly Giu 9**1505 1510 1515 1520 Gly Tyr Ile Thr Asp His Met Phe Ile Asn Leu Asn Val Phe Phe Asn 1525 1530 1535 Ala Tyr Lys Thr Tyr Leu Leu Cys Phe His Lys Giy Tyr Gly Lys Ala 1540 1545 1550 Lys Leu Glu Cys Asp Met Asn Thr Ser Asp Leu Leu Cys Val Leu GiU 1555 1560 1565 308 Leu Ile Asp Ser Ser Tyr Trp Lys Ser Met Ser Lys Val Phe Leu Glu 1570 1575 1580 Gin Lys Val Ile Lys Tyr Ile Val Asn Gin Asp Thr Ser Leu Arg Arg 1585 1590 1595 1600 Ile Lys Gly 0 ys His Ser Phe Lys Leu Trp Phe Leu Lys Arg Leu Asn 1605 1610 1615 Asn Ala Lys Phe Thr Val Cys Pro Trp Val Val Asn Ile Asp Tyr His 1620 1625 1630 Pro Thr His Met Lys Ala Ile Leu Ser Tyr Ile Asp Leu Val Arg Met 1635 1640 1645 Gly Leu Ile Asn Val Asp Lys Leu Thr Ile Lys Asn Lys Asn Lys Phe 1650 1655 1660 Asn Asp Glu Phe Tyr Thr Ser Asn Leu Phe Tyr Ile Ser Tyr Asn Phe 1665 1670 1675 1680 Ser Asp Asn Thr His Leu Leu Thr Lys Gin Ile Arg Ile Ala Asn Ser 1685 1690 1695 Giu Leu Glu Asp Asn Tyr Asn Lys Leu Tyr His Pro Thr Pro Glu Thr *991700 1705 1710 9Leu Glu Asn Met Ser Leu Ile Pro Val Lys Ser Asn Asn Ser Asn Lys *1715 1720 1725 *Pro Lys Phe Cys Ile Ser Gly Asn Thr Glu Ser Met Met Met Ser Thr 1730 1735 1740 *9Phe Ser Ser Lys Met His Ile Lys Ser Ser Thr Val Thr Thr Arg Phe 1745 1750 1755 1760 Asn Tyr Ser Lys Gin Asp Leu Tyr Asn Leu Phe Pro Ile Val Val Ile *.1765 1770 1775 Asp Lys Ile Ile Asp His Ser Gly Asn Thr Ala Lys Ser Asn Gin Leu 1780 1785 1790 999Tyr Thr Thr Thr Ser His Gin Thr Ser Leu Val Arg Asn Ser Ala Ser 1795 1800 1805 Leu Tyr Cys Met Leu Pro Trp His His Val Asri Arg Phe Asn Phe Val 1810 1815 1820 Phe Ser Ser Thr Gly Cys Lys Ile Ser Ile Glu Tyr Ile Leu Lys Asp 1825 1830 1835 1840 Leu Lys Ile Lys Asp Pro Ser Cys Ile Ala Phe Ile Gly Glu Gly Ala 309 1845 1850 1855 Gly Asn Leu Leu Leu Arg Thr Val Val Glu Leu His Pro Asp Ile Arg 1860 1865 1870 Tyr Ile Tyr Arg Ser Leu Lys Asp Cys Asn Asp His Ser Leu Pro Ile 1875 1880 1885 Glu Phe Leu Arg Leu Tyr Asn Gly His Ile Asn Ile Asp Tyr Gly Glu 1890 1895 1900 Asn Leu Thr Ile Pro Ala Thr Asp Ala.Thr Asn Asn Ile His Trp Ser 1905 1910 1915 1920 Tyr Leu His Ile Lys Phe Ala Glu Pro Ile Ser Ile Phe Val Cys Asp 1925 1930 1935 Ala Glu Leu Pro Val Thr Ala Asn Trp Ser Lys Ile Ile Ile Glu Trp 1940 1945 1950 Ser Lys His Val Arg Lys Cys Lys Tyr Cys Ser Ser Val Asn Arg Cys 1955 1960 1965 Ile Leu Ile Ala Lys Tyr His Ala Gin Asp Asp Ile Asp Phe Lys Leu 1970 1975 1980 Asp Asn Ile Thr Ile Leu Lys Thr Tyr Val Cys Leu Gly Ser Lys Leu 0 1985 1990 1995 2000 Lys Gly Ser Glu Val Tyr Leu Ile Leu Thr Ile Gly Pro Ala Asn Ile 2005 2010 2015 Leu Pro Val Phe Asp Val Val Gin Asn Ala Lys Leu Thr Leu Ser Arg 2020 2025 2030 Thr Lys Asn Phe Ile Met Pro Lys Lys Thr Asp Lys Glu Ser Ile Asp 2035 2040 2045 Ala Asn Ile Lys Ser Leu Ile Pro Phe Leu Cys Tyr Pro Ile Thr Lys 2050 2055 2060 Lys Gly Ile Lys Thr Ser Leu Ser Lys Leu Lys Ser Val Val Asn Gly o.o. 2065 2070 2075 2080 Asp Ile Leu Ser Tyr Ser Ile Ala Gly Arg Asn Glu Val Phe Ser Asn 2085 2090 2095 Lys Leu Ile Asn His Lys His Met Asn Ile Leu Lys Trp Leu Asp His 2100 2105 2110 Val Leu Asn Phe Arg Ser Ala Glu Leu Asn Tyr Asn His Leu Tyr Met 2115 2120 2125 310 Ile Giu Ser Thr Tyr Pro Tyr Leu Ser Giu Leu Leu Asn Ser Leu Thr 2130 2135 2140 Thr Asn Glu Leu Lys Lys Leu Ile Lys Ile Thr Gly Ser Vai Leu Tyr 2145 2150 2155 2160 Asn Leu Pro Asn Giu Gin 2165 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 15229 base pairs TYPE: nucleic acid STRA1NDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID ACGCGAAAAA ATGCGTACTA CAAACTTGCA CATTCGGAAA AAATGGGGCA AATAAGAATT 4* TGATAAGTGC

TGATAAAGGT

CATGTTATAC

CAATTAAATT

ACAACAATAT

ACATATGGGA

ATTGTGAAAT

AAATATCTGA

AGACATGTGT

ATAAACTCAC

ATTGATGATC

AGAAATCATA

TGATGAA.AGA

TATTTAAATC

TAGATTACAA

TGACAAATTA

AAACGGCATA

TGTAGTGAAA

ATTGATTGAG

CAAATTTTCT

TTTACTTGGG

TTATCACCAT

CTAATCAGTC

ACAGACATGA

ACACACAAAT

CAAGCTACAT

TAACCTTTTC

AATTTATTTG

ATTCTTCTGA

GTTTTTATAC

TCTAACTTTA

TTGACACACT

AAAAGACTAA

CTTGATCTCA

TTTAGTTAAT

AAACCATGAG

GACCCCTGTC

TCATATACTT

TTACATTCTT

AATCAGAKAT

ACAATGACGA

CCAATGCATT

ATGTTATAAC

CAACAATGCC

GCTCTCAATC

GTGACTCAGT

ATTCATGAAT

ATAAAACCTC

CACTACAAAT

GATGGAATCA

GATAAACAAT

AGTCAATTAT

GGGGTGCAAT

AGTAGCATTG

AGCCAAAGCA

AAGCAGTGAA

AATATTACAA

AAATGGTCTA

AATGACTAAT

TATGTTTAGT

ATCAAAGGGA

GACAACACTA

ATAATAACAT

GAATGTATTG

GAGATGAAGC

TCACTGAGCA

TTAAAAATAA

GTAATACATA

GTGTGCCCTG

AACGGAGGAT

ATGGATGATA

TATATGAATC

CTAATTTA.AT

AATGGGGCAA

CTATGCAAAG

CTCTCACCAA

TAAGAAAACT

TATTGCACAA

120 180 240 300 360 420 480 540 600 660 720 780 840 311 a.

a. a a a a.

a a a a a.

AGTAGGGAGT

CATGCCTATA

ACACACTCCT

CATCCAAACT

TTTTAGTAAT

GCTCTTAGCA

AALATACACTA

AALACACCTAA

ACAGGATTAA

ATACTTAAAG

CAAGATATAA

GAAATACAAG

ATGGGAGAAG

TGTATAGCTG

GTAATTAGGA

CCAAAGGATA

GTTTTTGTGC

ATCTTTGCAG

GTTCTAGCCA

GAACAAGTTG

CATATATTGA

AGTGTGGTCC

AGAAACCAAG

GTAATAAACT

CTCAACCCCA

ACCAAATACA

TTTATCAATC

ATAATATACA

AAGCTATTCC

TAAAAATAAA

AAGTCAAGTT

TTCAACGTAG

ACAAACTATG

TAGGTATGTT

ATGCTGGATA

ACGGAA.AGGA

TCAATATTGA

TGGCTCCAGA

CACTTGTAAT

GGGCAAACAA

TAGCTAACAG

ACTTTGGCAT

GATTATTTAT

AATCTGTAAA

TGGAAGTTTA

ACAATCCAAA

TAGGCAATGC

ATCTATATGA

ACAGTGTATT

AAGAAGATGA

AGAAATACAC

ATGACGGGTT

AATATGACCT

TCAAACAACA

GGCAGAGCCA

AALATGATACA

TACAGGAGAT

TGGTATGCTA

ATATGCTATG

TCATGTTAAA

AATGAAATTC

GATAGAATCT

ATATAGGCAT

AACCAAGTTA

TGTCTTAAAA

TTTTTATGAA

TGCACAATCA

GAATGCCTAT

AAATATCATG

TGAGTATGCA

AGCATCATTG

AGCAGGTCTA

TGCAGCCAAA

AGACTTAACA

TGTAGAGCTT

TGAATATAAT

TCTAGAATGT

CAACCCGTAA

GTGCTCAACA

ATAACATAAA

TTAAATAAGG

TTAATCACTG

TCCAGGTTAG

GCTAATGGAG

GAAGTATTIA

AGAAAGTCCT

GATTCTCCAG

GCAGCAGGAG

AACGAAATAA

GTGTTTGAAA

TCCACAAGAG

GGTTCAGGGC

CTAGGACATG

CAGAAGTTGG

CTGTCATTAA

GGCATAATGG

GCATATGCAG

GCAGAAGAAT

TAAGTTAACA

ACAAAATATG

ATTGGCATTA

ATTCCAACAA

GTTAAGAAGG

TTGGGGCAA.A

ATCAGCTGCT

CTCCCAATTA

AAGATGCAAA

GAAGGGAAGA

TAGATATAAC

CATTATCAAG

ACAAAAAAAT

ACTGTGGGAT

ATAGATCAGG

AACGCTACIA

AACACCCTCA

GGGGTAGTAG

AAGTAATGCT

CTAGTGTCCA

GAGGAGAAGC

CTCAATTTCC

GAGAGTATAG

AGCAACTCAA

TGGAAGCCAT

AAAAATACGG

GCACTTTCCC

AGCCTACAAA

AAAACTAACC

AGCTAATCCA

TACAAAGATG

GTCATCCAGC

TGATGTGCAA

TCATAAATTC

CACTATAAAG

ALACATATCGT

CTTGACATCA

GCTAAAAGAG

GATAATACTG

TCTTACAGCA

GGGCCTCATA

TCTTATAGAT

AGTTGAAGGA

AAGATGGGGA

GGCAGAAATG

TGGATTCTAC

TAACTTCTCA

AGGTACACCA

AGAAAATGGA

AAAGCATCAA

GGCAAATAAG

900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 TCAACATGGA GAAGTTTGCA CCTGAATTTC ATGGAGAAGA TGCAAACAAC AAAGCTACCA 312 q

AATTCCTAGA

GCATAATATC

GCACCAACAT

ACCCAAGAAA

CTAAGTTGTA

CATATGAAGA

ATGAAAAATT

CCACCTCAGC

AAAAAATAAG

GGAATGAGGA

CTTCCAAA;A

ATGATTTTTG

AATCCATTGA

AATCAATCAA

AAGAACAAGA

ACACAGCAGC

TATGGGTGCC

GCATCAACAT

TTAACTCAAG

TATCATTAGA

CATGCAGTCT

TGAAAACATT

CATCAAAAAG

TGAACTCACT

TTATTCCCTA

AATATATCAA

ATCAATAAAG

TGTTAACTCA

CATCKATCCA

ACCCCTAGTA

CAAAGAAACA

AATAAATGAT

ALAGTGAAATA

TCGCGATGGA

AGCGGAAGCA

AAGCGAAAAA

ATTGAGTAAT

ATCAGTGATC

ATCAACTGCC

CCAATTGATC

TGGGGCA.AT

TGTTCAGTAC

TATGTTCCAG

ACTAGTGAAG

AAGTGCTGTG

TGAAAGAAGC

AACATGCTTA

CAATCCCACT

AGTAATAATA

AGAAAATATA

TGCAGGATTA

GCCACAGAGT

GGCAAGTTTG

ATAGATATAG

ATAAGTGAAG

AGCTTCAALAG

ATAGAAACAT

CAAACAAATG

TTAGGAATGC

ATAAGAGATG

TTA.ATGACCA

ATGGCAAAAG

TTGTTGGA.AG

AACTCACTCA

AGACTGAACA

AATCAGCGAC

ATGGAAACAT

AATGTTCTAG

TCATCTGTGC

CAGATCTCCA

CTGGCACAAA

AAATTAGCAT

AAAGTAAAAA

CATGAGATTA

CCAACCTATC

GCAACCACCG

GTATTAGTTA

CAATTTATAG

CATCATCCAJA

AAGTALACTAA

CTGATAGTAC

AAGATCTCAC

TTGATAACAA

ACAACATTAC

TCCATACATT

CTATGGTTGG

ATGATAGGTT

ACACCTCAGA

ACAACGATAG

GCAATCAACA

CACAAACGTC

CTAACAAAAT

ACGTGAACAA

AAAAAGATGA

CAGCAGACTT

CGCCCAAAGG

TGCCTAGTAG

ATGATGTAAC

GTATGTTAAC

TTGCTCTATG

TAAGATCAAT

AATTCAAAA.A

TCACAGTTAC

TAGATCTTGG

AGATCCTAAG

AGAGAGCCCG

CCCAGAAGCT

CCCAAGTGAC

TGAAGAAGAA

AGCAAGACTA

AGTAGTTGCA

TCTAAGAGAA

AGAGGCTATG

TGAAGTGTCT

TGACAATGAT

ACATCAATGA

CATCAGCAGA

TA.ACAATATA

GCTTCACGAG

TGATCCTGCA

GCTCATAAAA

ACCTTCACTA

TTTTATCATA

TACACCTTGT

TACAGTCAA.A

TGAATTTGAA

TAGTGTCAAA

TGCTATCACC

TGACAATAAA

GGCCTACCTA

AAGAAAGATA

ATAACATCTG

AAAGCCAACT

A-ACCCCTTTT

TCTAGCTACT

GATAGAATTG

AGTGCAGGAC

GAA.ATGATAG

GCAAGACTTA

CTTAATCCAA

CTATCACTTG

AACAGACATC

ACTACCAACC

GTAAC.AAAAA

GGCTCCACAT

TCACTAACAA

GAACTTGCAA

CGAGTCACGA

AGTGCAAATG

GAAATCAAAG

GATCTTACCA

AATATTATGA

AACAAGGACC

kLATGCGAAAA

GGAGCATTCA

GAAAAAGAGA

2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 0 313 GCATATATTA TGTGACTACA AATTGGAAGC ATACAGCTAC ACGTTTTTCA ATCAAACCAC S. ~1

TAGAGGATTA

ACATTATATC

CATTTAAAAT

AATAAAACCA

ATTTATACCG

CAATAGAATT

TAATCTCTTT

ATAAA.ACATT

GTTCTACCAT

TTCTCACAGA

ATTTAAAAAT

ATGCAGCCAT

ATACTCTTAA

TAGCACAAAT

CCATAATATT

CAATAAAAAA

GGGTCAA.CTC

TATCACCAAA

CCACTTCAAC

AACCAMAAGA

ATAATCAACT

CAACCATCAA

CACCAGCCAA

AGACCACAGA

AATACACAAT

AACTTAATTA

CAAACATCAT

CCAAAATTAC

AAATATGGGG

CCAATTCAGT

CACAAGCAAA

ACTALATTATA

CTGCAACAALA

TATGCTGTGT

GTCATGGTGG

TAACATAATG

GTCCAAGCAC

TCATCTAATT

AGCACTGTCA

CATCATCTCT

CCACACTGAA

ATCCAAACAA

TACAAAATCA

ACAGACCAAC

TGATTACCAT

CTGCAAATCC

ACCCACAAAC

AATGCCAAAA

AAGAGACACC

CCAACAGCAA

TCAACACTAA

GAGCATTTAC

TTCCAGCTAT

TAAATAGACA

ACATATACTA

TTTTGGCCTT

ATCACTATTA

ACTCTTGAAC

CAAATTATAA

CGCAAAACCA

ATGAATTATT

AAGAATCGGC

GTAATATCCT

GTTTTGGCAA

GCCAATCACA

AAAAACATCT

CCCACAACCA

GAAACACACC

AAGCCAAGCA

TTTGAAGTGT

ATCTGCAAA-A

AAACCAACCA

AAAGAAATCA

AGCATTTCAC

TCCCTCCACT

ATGACAGGTC

ACTACACACT

CATCTGTTAG

TTAGTTAGAG

TAAATCTCAA

ATTTTACACT

TGATTGCAAT

TAGGACAGAT

TCTTGTATAT

CGCCAACCAT

GGTATGAGAT

GCACTGCCGG

CTTGTTTATA

TGATAATCTC

AAGTTACACT

CCACCTACCT

CATCACCAAT

ATACAACAGC

CAAAATCACG

TCAATTTTGT

CAATACCAAG

CCAA.AACCAC

TCACCAACCC

AATCCACCGT

CAACCACCTC

TTTACCATAT

ACCTAGAGTG

TTCAATCAAT

AATGGGAAAT

AATACATATG

ACTAAATAAG

GTATCAAATC

ATA.AACAAAC

CATGATAGCA

CAGGAACAAC

GACTCTAGAA

CAGATTAAAT

AACCTCTCTC

AACAACGGTT

TACTCAAGTC

CCACACAAAT

ACAAACCAAA~

TTCAAAAAAT

TCCCTGTAGT

CAACAALACCA

AALACAAAAGA

AGCAAAAAA

GCTCGACACA

CGAAAACACA

AAATCAATCT

CGAATAGGTA

CT CAACAAC C

ACATCCATCA

ATCTTAACTC

CTAAGTGAAC

AACACATAGT

AAATCCAATC

TAGAGTAGTT

ATTGGGGCAA

AGGACCTGGG

TTAAAATCTA

ATAATTGCAG

ACAGTTCAA6A

CCACCAGAAA

TCAGCCACAA

GGCAGAATCA

CCACCAAAAA

ATATGTGGTA

AAGAAAAAAC

GACCCCAAAA

CCAACCCTCA

ATCACTCCAA

CCCAGCTCCA

CACATATATC TTCAAACTAT 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 314

C.

CACAAATACC

ATGCTTAGTT

AAATTAAACC

CTAACTCTTG

TACCAATCGA

TATACCAGTG

GACACTAAAG

TTACAGCTAC

CAGTACATGA

AGGAAACGAA

GCTGTATCCA

TCTACAI.ACA

TTAGATCTCA

CGCATCTCCA

ATCACCAGAG

ACAAACAGTG

TTAATGTCAA

AAGGAAGAAG

TGCTGGAAAT

TGTTTAACAA

CCACAGGCTG

TTAACATTAC

TGCAAAATTA

ATAGTGTCAT

AAGACATTTT

GGCAACACTT

CACAGCATCC

ATTCAAAA-AC

TGGGGCAAAT

CTGTTAATGC

CATGTAGTGC

TCATAACAAT

TAAAACTTAT

TTATGCAAAA

ACTACACAAT

GATTTCTGGG

AAGTTTTACA

AAGCTGTAGT

AGAATTACAT

ACATTGAAAC

AATTTAGTGT

AGTTACTATC

GCAATGTTCA

TCCTTGCATA

TACACACATC

GGACTGATAG

ATACTTGCAA

CAAGTGAAGT

TGACATCAAA

GCTATGGAAA

CTAATGGTTG

TATACTATGT

GAGCCCTCCA

TACATCTTAG

AACCATGGAG

ATTGTACCTC

AGTTAGCAGA

AGAATTAAGT

AAAACAAGAA

CACGCCAGCT

CAATACCACA

CTTCTTGTTA

CCTTGAAGGA

CAGTCTATCA

AAATAkCCGA

AGTTATAGAA

TAATGCAGGT

ATTGATCAAT

GATAGTAAGG

TGTTGTACAG

ACCTCTATGC

AGGATGGTAT

AGTACAGTCC

CAGCCTTTGT

AACAGACATA

AACTAAATGC

TGACTATGTG

AAACAAGCTG

CATTAAATCC

CAGAGAACCG

TTGCTGATCC

ACCTCAAGTC

GGTTATTTTA

AATATAAAAG

TTAGATAAGT

GCCAACAACC

AAAAACCTAA

GGTGTAGGAT

GAAGTGAACA

AATGGGGTCA

ATATTACCCA

TTCCAGCAGA

GTAACAACAC

GATATGCCTA

CAACAAAGTT

CTACCTATCT

ACCACCAACA

TGTGATAATG

AATCGAGTAT

AACACTGACA

AGCAGCTCAG

ACTGCATCCA

TCAAACAAAG

GAAGGCAA

TAATTAAAAA

TGATCTATCA

ACAGGTCAAG

AGAACATAAC

GTGCTTTAAG

AAACCAAATG

ATAAGAATGC

GGGCCAGAAG

ATGTATCAAT

CTGCAATAGC

AAATCAAAAA

GTGTTTTAAC

TAGTAALATCA

AGAATAGCAG

CTTTAAGCAC

TAACAAATGA

ATTCTATCAT

ATGGTGTAAT

TCAAAGAAGG

CAGGATCAGT

TTTGTGACAC

TATTCAATTC

TAATTACTTC

ATAAAAATCG

GAGTAGATAC

ACCTTTATGT

ACCTAGTCAC

AGCAAGAACA

TGCAATCTTC

TGAGGAGTTT

AACAGGTTGG

CAATGGAACT

AGTAACAGAA

AGAAGCACCA

AAGCAAGAAA

AAGTGGTATA

TGCTTTGTTG

CAGCAAAGTG

ACAGAGCTGT

ATTGTTGGAA

TTACATGTTA

CCAGAAAAAA

GTCTATAATA

AGATACACCT

ATCAAATATT

ATCCTTCTTC

TATGAACAGT

CAAGTATGAC

TCTTGGAGCT

TGGGATTATA

TGTGTCAGTG

AAAAGGGGAA

5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 315 CCTATAATAA ATTACTATGA TCCTCTAGTG TTTCCTTCTG ATGAGTTTGA TGCATCA.ATA TCTCAAGTCA ATGAAAAXAT

S

CTACATAATG

GTAATCATTG

AAAAACACAC

AGCAAATAGA

CAAATCAACT

TCATGCTACC

ATCACAATCA

TCGCGAAGAA

CACTACAGTC

ATGTTAAACA

GGAGCTGCTG

AGTTACATAG

CTTCTTATTG

TCGCCTAAGA

AACAAGCAAA

AAGAACACAT

AATGATCAAA

ATCATCCATA

ACAATTTAAC

AATTCATTGG

CATCCCTGAA

TTTATATCAT

ATTAATGGAA

TTTTCAGAAT

TAAATACTGG

TAGTATTGTT

CAGTTACACT

CAAAAAACTA

TAACAACAAA

TACACAACTA

AACACTAAAT

ATCCTTGTAA

ATAATTATTT

AGATACTTAA

AACTGGATAG

GATCAPLTAAA

AGATCAPLCAG

TAAGAGTGTA

CCATCCATCT

TAGATATCCA

ATGACCAAAC

TTGATTTCAA

CATAACCATT

ACACCTAAAA

GATATATAT)A

TCAACCATA.A

ACTCTGCCAA

GTAATGCTT!I

CAATCAAAGT

CAAATCTACT

ATCATTAATA

AAGCAAAGAC

CTTAATCATG

TATTTCAACA

AGCTAGATCT

CGACACATCA

ATTTGAGATT

TGAATGGCCT

GTCAATGGAC

AACAGAAGAA

CAACATAACA

TGATGACATT

CAATACTGTT

GCTCAAAAGA

CAAAAGCATA

CAAAAATAAT

GTGAAAGCAT

TGGATAACCA

ACTTATTAGA

CAGTATATAT

AACAACCTTA

*TGTGTATCTA

*AGGGAGTTAC

TTAGCTTTTA

ACAAATATTA

GCTATTGGTT

CAACTAAGTG

TTTCAACAAC

TCATAGCACA

TCAACTCATA

TTCACAAAAT

AGAGGTCATT

CCTCATGCAT

AAAAGCATAG

TATGCTCTTG

AAACAATCAG

AAAAAACTGA

ATATCATACA

CTACCAGCAG

ACCATAAGCA

GATATTACCG

GATTGCTACA

CCAGTGTTTA

TGCCACTCAA

ATTAGTGTCA

*ATAAGGTTAT

*ACTGATAGTT

CTTTTTAACG

TTCGTAGATC

TGATA.ACTAC

TACTGTTGTA

GAATCAATAA

AATCTGCTGA

GGCTGAATCA

GTTACATAAA

TAACAACTGG

GCTTGAATGG

TACTAGTGAG

ACACTTTGTC

GTATAGTTGG

CATGTGTTGC

GAGATAACGA

TTGAGAGCAA

ACGTGCTGAA

ACTCAAAAGA

GATAAATATC

TTCAATCATA

TTAAATCATA

CAATTTCTCC

TAATGCTTGA

GGGACAAAAT

ATCTAAAAGG

GCCCCTATCT

TGATGAATTA

AATTATTATA

TTGCAAAGCC

TATTGCATTC

CCACCAATCC

TTTCCTCATA

AACCCCALAGT

GGCAAATATG

TAGAAGATGT

GCAAALACTTC

GGAAATAAGT

AGTGCTAGAG

TATGAGTAAA

AGAACCCAAT

TAGAAAAAAC

GAAGACAATA

GTCAACCGTG

CTTGTAGTAT

AAAACATATT

TATTTGATGA

AACATCTTAA

CCATAACAAT

GGATCCCATT

TGTTATCTCT

TAA.AAATGAT

7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640

S

316 TACACCAACT TAATTAGTAG ACAAAGCCCA CTACTAGAGC ATATGAATCT

AAAAAAACTA

ACTATAACAC AGTCATTAAT ATCTAGATAT CATAAAGGTG AACTGAAGTT

AGAAGAACCA

ACTTATTTCC AGTCATTACT

TATOACATAT

ACAACTAATT

TACGCCATCT

TCAGGTGATG

GAAAACAATC

ATCAAAACAA

ATACACTGGT

GAGGTAAAAA

TACTTAAAAA

TGAATAAACT

AAAACTCAGT

AATCATATAC

CACTCTTGAA

TCAATTTATA

GTCATGGGTT

AATAATACGA

GGGACTAAAG

TCTTACAACC

AALATTCAGAC

AAAATTGATG

TACAAA.ATTA

TATATTAATA

AAALAGTATGT

AGAGCTATAG

GAAAAGGACA

ATAATCAAAG

AAA.AATCATT

TGTTCAATGC

AATAACATAT

GATAATCA;A

CCTCGTCTGA

AAATAAGTGA

GAGTTAAGCC

ATGATATACT

CAGTAAATCA

AACATCCTCC

TAACACAATA

CTTTAAGTGA

AC

TC

cl

T

A

4*e**c ATTTTAAATC AATATGGTTG TATCGTTTAT CATAAAGGAC

TCAAAAAAAT

ACTTACAATC AATTTTTGAC

A

ATTACTTGGA TAAGTAATTG

I

TTCAATAATG TTGTGTTATC

I

CATAATGAAG GCTTCTACAT AACATAACAG AAGAAGATCA ACAGATGCAG

CTATTAAGGC

GACAAGACAG

TGTCTGATAA

CTTAAATTGA

TTAAGCTTGC

CTCTTCAGAA

TCTTTGGACA

ATTAACTGTA

ATGAAACCAA

TTCATTTATA GAATCATAAA AATGCTATTG

TTCTACCTCT

CTACTTGAALA TCACAGAGAA TTTCATCTGC CTAAAAAAGT CCAAAAGATT TAATATGGAC

LTGGAAAGAC

TTAAATACA

~CAACTATTT

kATAAAAGAA kTTTAGGAA.A

TCAAAAAAAC

TATCATAKAT

AGGTGATAAiT

TCCAATGGTC

GTTCTACTTA

GGGGTTTGTA

AAGATGGTTC

AGATTTGATJ

GGATCTTGA)

TAGTTTTCC'

ATCAGCCTTA GCAGATTAAA T TTAAATAAAA

GCTTAGGGCT

CTTTATGGAG

ATTGTATACT

GTAGAGGGAT TTATTATGTC

I

CGATTTTATA

ATAGCATGCT

CTACTATCAA

GAGTATGTCAC

GGTAAATGGA

TKATCCTATT

AATCTCAILTA

ACTTGAGTGA

GATGAAAGAC

AAGCAATGGA

TTAAGTAATC TAAGTACGTT AATACCTACA

ACAGATGGCC

AACTATTATA

AA.CTTAATAC

ATTTTATCAG GATTGCGGTT ~ATGATAATAA

ATGACAAAGC

r AGAAATTACA TGCCATCACA

AAATTGCT

;TAAAGGTG

M.CAATAAT

LCAGCTGTG

kATATCACT rCATGGTTA

CGATCAAAT

TTTCAGTTT

ACAACTACT

GTTTGCTTA

,AGATGTGGA

,AAATTATTC

~TTAATTCTA

U ATAACATC

MACTTTATTA

A.AGTAAATTT

GCTTTATTTT

TGCTGTAAGA

AAGAGGTGCT

CACTTTAAGG

TTATCCATCT

CTATCGTGAG

CATTTCACCT

TATACAAAAT

8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 317 0 0 0

TATATAGAAC

TATTACTTGA

AGCTATCTCA

GTAGGTAGA.A

AAAATGATAG

CTAGAGCTTC

AATGATAACT

AATCAAGCAT

GGAGTACAAT

ACATATAGAC

GAACAAAGTG

TGGACCATTG

ACAGCTCTA.A

GAGGGTCAGA

TATAAAGAGT

GATATGCAAT

AAAAAAGTCC

TTAGAATCTA

AGTTTAATAT

GCATTATGTC

TTTTTTAATC

TTTGGTGGTG

CTTACAGAAG

CAAGATAAGC

ACGTTTGATA

GGGTCTGAAA

ATGAAAAGTT

GAGATAATAA

ACAACTCTAA

TGTTTGCTAT

CCGAAAATAT

AAAAGATATT

ACAACAATTA

TTAGATATGA

CTCTGTTCTC

ATGCACCTCC

GATTATACAG

AAGCTATATC

TAAATGGTGA

CCCATGCTCA

ATGCGGGCAT

TCATGAGCAA

TGAGAGTAGG

TAGGTAGCTT

TTAGGAACAT

ACAATAAGCT

TTGATAGTAT

GTGATCCTAA

CTATAGTACA

TCCAGGATCT

AAAATCCCAA

GGCAAGCAAA

GAAGTTCTCT

ATTCAATGAA

CCATGTGGTA

GCAACCAGGT

TTTACAATTC

AGAATTAAAA

TATCAGTAAA

AACATCATGT

TTGGTTGCAT

TTTTATAAAG

ATATCATATG

ATTATTAGAT

TAATCAGTCA

AGCAGATTAT

AGGCCACAAG

AACAATCCAG

TCCATGGATA

AACACAGGAG

TTGGTTATAC

ATATTTAGAT

TGATATGGCT

TTTGTTATAT

TTCAGTGTTT

TCCAGATGAT

TGCCGAGTTT

AATTACTAGT

GAAAGTGACA

TGCGATCTAT

TCACTAACTG

ATGTTTAGGC

TTCCCTGAGA

GCAGGAATAA

TGTTCTATCA

ATCTGCAGTG

TTAACAATAC

GATCATGTTG

GGTGGTATTG

CTAATATCTC

ATTGATATAA

TTGTTAGCAT

CTCAAGGGAA

CACAATGGAG

AATACAATAC

TTAGAATATA

AATCAAATTG

ATATTGAAG

TTAACATTGT

CGAAGCTTTT

GTGTTGAGCT

AGACTGAACA

GTAACATTGA

GAGATTAATA

GATCAAGAAG

ACAATTGTGT

GTAAAGAAAG

AAATTCAAAT

GTTTGACAAG

GCAACAAGTC

TTACAGACCT

ATGTATTAGA

CTCTTGTCAC

TTAATCTTA.A

AAGGCTGGTG

TCAAAGGGAA

GTAAIACCAGT

TAAATAGCCT

CAGAGACCTA

TGTACTATCC

TTGATGATTT

GAGGAGAGAG

CTTTGCAACT

TATTAAAACA

ATATGAATTT

ATAGGALGAAC

ATTATACTGG

AATTCTTGAC

AGTACTAGAG

GGTCAATCAA

AGAGCTCAGT

CTTAGCAGAG

ATATGGTGAT

AAATCGTTAT

TAGCAAATTC

TGAACTGCAT

ALATAATATGT

TAAAGTTGAT

TCAAAAACTG

ATTCTCTATC

TAGACTTATA

TAAATTGCTA

TATATCCCGA

AGCCAGTATC

TAAAGTTAGT

CTTATTATGC

CCGAAATCAT

CTTAAAAACT

GCCTATGCTG

TCCAGACTTC

TCACGATTTA

ATGTATCATC

10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 TGAGAGATCC ACAGGCTTTA GATTAGCAGT GACAGAAGTC

I

318 TTAAGTATAG CTCCAAACAA ILATATTTTCT AAAAGTGCAC AACATTATAC TACCACTGAG b

ATTGATCTAA

GTTTATGAAA

AAATCCATAA

GCTACTGATA

AACAAAGACA

TATGTAAGAG

ATGTTCACAA

AAATATA.ATG

TCATCTACGC

CAAAGAGACC

AAAGATGAAT

AAAAAATTGT

AGACCATGTG

ACTAGTCCTA

TTTCAAAATT

ATATGTCCTA

CCTATATTTA

ATGTTCCTAC

GCACTTAAT

TATTTTCATA

CAACTTATGA

GATCATATGT

TTTCATAAAG

TGTGTTTTGG

CAAAAAGTCA

ATGATATTAT

GTTTACCTTT

CTAATATACT

TGATGAGGAA

AAAGAGAGTT

AAAGATCTTG

TGGACATTAA

TTAATAGTTT

AGGAGAAAAA

AAATAGATTT

TCATGGAAGA

TTCCACAATA

AATTCCCTGC

TCAACCATGT

GCATAAGTTT

ATAGAATTAT

CAGGAGATGT

CAGATAAAAT

CTGGATCTCA

ATGCTTATAT

AGGATTCAAA

TCATTAATTT

GTTATGGTAA

AGCTAATAGA

TAAAATACAT

GCAAAATATA

TTATAAAGCA

TGAAAAAACA

AA.ATATAACT

ATTAAGTTTA

GTCGTTATCC

ATATACAACT

ALACTCGTGGT

AACAATGCCA

ATTAGCAA;A

ACTGAGTACT

TCTA.AGTGTC

ATCAATACCA

ATTA-ACAGAA

TGGTCTTAGC

TCTCATACCG

TGATATCATC

AAGTTTAACC

CATCAACTCT

TTTAAGTACT

AGGTATTTTT

GAATGTTTTC

AGCAAAATTA

CAGTAGCTAC

AATCAATCAA

GAACCAACTT

GAAAAAATAG

TCAGCAATAG

TTACTTATAA

GAAAATCTTA

AATATAGTAG

AGCACTATAG

GAA.AGAGGAC

GTGTACAATA

TTAGACTGGG

GGAACACTTG

AATTATTTAC

GCTTATAGAA

AAGTATGGAG

TTAATGTCGG

AAGCTGAATG

AAGTTGAAGC

CAATATGTAG

ILATTTAATAT

AATTTAGCTG

GAAAA.AGATT

TTTAATGCTT

GAATGTGATA

TGGAAATCTA

GACACAJAGTT

ACCCTCATGG

TTAATCTTAT

ATTCAACTGA

GGATACTTCC

GTATAACTGA

GAGTAACATC

CCAGTGGTAT

CTACTAAGCC

GACAAGTTTT

TATATGCATC

GACTGTCATA

ACCGCTTAAC

CAACAAATTA

PLTGAAGATAT

TTGTGGAACA

AGATACATTT

AAGTGATACA

AATTATTCCT

TAGTACATAA

GACATTGGAT

GGGGAGAGGG

ATAAGACTTA

TGAACACTTC

TGTCTmAGT

TGCATAGAAT

ATTAAGAGTT

ATCAGGAACA

TATTAATAGG

ACTAGATTGT

ATTA.AGCAAG

GCCAAGTATT

AATTATAGAA

ATGGGTAGGT

AACCAAAAAG

CATAGACAAC

TGAGA7LAGCC

AGTCAGTAGT

TCATTTCGAT

CGACATTGTG

ATTCACAAAC

GATGAAACCT

AAAACAGCAC

AAGTAACAAA

AATGTCTGAT

TCTGATTATT

GTATATAACT

TTTGCTATGT

AGATCTTCTT

TTTCCTAGAA

AAAAGGTTGT

11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 319

CATAGTTTTA

TGGGTTGTTA

TTAGTTAGAA

AATGATGAkAT

CATTTGCTAA

CTATATCACC

AATAGTAATA

TTCTCCAATA

CA.AGACTTGT

AATACAGCAA

AATAGTGCAT

TTTAGTTCCA

GACCCCAGTT

GTAGAACTTC

AGTTTACCTA

AATTTAACCA

AAATTTGCAG

TGGAGTAAAA

GTAA.ATAGAT

GATAACATTA

GTTTACTTAG

AATGCTAAAT

GAATCTATCG

AAAGGAATTA

TATTCTATAG

AATATCCTAA

AGTTATGGTT

ACATAGATTA

TGGGGTTAAT

TTTACACATC

CAAAACAAAT

CAACCCCAGA

AACCTAAATT

AAACGCATAT

ACAATTTATT

AATCTAACCA

CACTTTATTG

CAGGATGCAA

GTATAGCATT

ATCCAGACAT

TTGAATTTCT

TTCCTGCTAC

AACCTATTAG

TTATAATTGA

GCATTTTAAT

CTATATTAAA

TCCTTACAAT

TGATTCTTTC

ATGCAALATAT

AGACTTCATT

CTGGACGTAA

AATGGCTAGA

TTTAAAACGC

TCACCCAACA

AA.ATGTAGAT

AAATCTCTTT

AAGAATTGCT

AACTTTAGALA

TGGTATAAGT

TAAATCTTCC

TCCAATTGTC

ACTCTACACT

CATGCTTCCT

GATCAGTATA

CATAGGTGALA

AAGATACATT

AAGGTTATAC

AGATGCAACT

CATTTTTGTC

ATGGAGTAAG

TGCAAAATAT

ALACTTACGTG

AGGCCCTGCA

AAGGACTAAA

TAAAAG CT TA

GTCAAAATTG

TGAAGTATTC

TCATGTTTTA

CTTALATAATG

CACATGAAAG

AAATTAACCA

TACATTAGTT

AATTCAGAAT

AATATGTCAT

GGAAATACCG

GCTGTTATTA

GTGATAGACA

ACCACTTCAC

TGGCATCATG

GAGTATATTT

GGAGCTGGTA

TACAGAAGTT

AACGGGCATA

AATAACATTC

TGCGATGCTG

CATGTAAGAA

CATGCCCAAG

TGCCTAGGTA

AATATACTTC

AATTTCATTA

ATACCTTTCC

AALGAGTGTAG

AGCAACAAGC

AACTTTAGAT

CTAAATTTAC

CTATATTATC

TTAAAAATAA

ATAACTTTTC

TAGAAAATAA

TAATTCCTGT

A.ATCTATGAT

CAAGATTCA.A

GGATTATAGA

ATCAGACATC

TCAATAGATT

TAAAAGATCT

ACTTATTATT

TAAAAGATTG

TAAACATAGA

ATTGGTCTTA

AATTACCTGT

AGTGCAAGTA

ATGATATTGA

GCAAGTTAAA

CTGTTTTTAA

TGCCTAAAAA

TTTGTTACCC

TTAGTGGAGA

TTATAAACCA

CAGCTGAACT

CGTATGCCCT

TTACATAGAT

AAATAAATTC

AGATALACACT

TTATAACAA.A

CAAAAGTAAT

GACGTCAACA

TTATAGTAAA

TCATTCAGGT

TTTAGTAAGG

TAACTTTGTA

TAAGATTAAA

ACGTACAGTA

CAATGATCAT

TTATGGTGAG

TTTACATATA

TACAGCCAAT

CTGTTCCTCT

TTTCAAATTA

AGGATCTGAA

TGTTGTGCAA

AACTGACAAA

TATAACAAAA

TATATTATCA

CAAGCATALTG

TAATTACAAT

13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 320 CATTTATATA TGATAGAGTC CACATATCCT TACTTAAGTG ACCAATGAGC TCAAGAAGCT GATTAAAATA ACAGGTAGTG GAACAGTAAC TTAAAACATC ATTAACAAGT TTGATCAAAT ATATTATAGT TATTAAAAAA TATATATGCA

AACTTTTCAA

AAAGTTATCA TTTTGGTCTT AAGGGGTTGA

ATAAAAATCT

TGCATTTACA ACACAACGAG0 ACATTAGTTT TTGACACTTT INFORMATION FOR SEQ ID NO:26: SEQUENCE CHARACTERISTICS: LENGTH: 2166 amino acids TYPE: amino acid

STRAN'DEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein AATTGTTAAA CAGTTTAACA TACTATACAA CCTTCCCAAC TTAGATGCTA ACACATCATA TAATTTAGCA TATTGATTCC AA-AACTAACA ATTATACATG

TTTTCTCGT

14940 15000 15060 15120 15180 15229 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: Met Asp Pro Ile Ile Asn Gly Asn Ser Ala Asn Val Tyr Leu 1 Ser Tyr Leu Ser Tyr Leu 35 Ile Ser Arg Thr Asp Lys 20 Phe Gly Val Ile Ser Phe 25 Ser Glu Cys Asn Asn Gly Pro Leu Lys Asn Asp Tyr Leu Ala Leu Gly Thr Asn Leu Lys Lys Leu Gin Ser Pro Thr Ile Leu 55 Ile Leu Giu His Met Asn Lys Thr Gin Ser Leu Leu 70 Ser Arg Tyr His 75 Gly Glu Leu Lys Glu Giu Pro Thr Glu Tyr Phe Gin Ser Leu 90 Thr Leu Met Thr Tyr Lys Ser Lys Ile Met Ser Ser Ser 100 Gin Ile Ala Thr 105 Asn Leu Leu Lys 110 Ile Arg Arg Aia Ile Giu Ile Ser 120 Asp Val Lys Val Tyr Ala Ile Leu 125 321 Asn Lys Leu Gly Leu Lys 130

C.

C.

C

C

C.

C,

Ser 145 Leu His Leu Asn Giu 225 Asp Giy Lys Ser Phe 305 Leu Gly Arg Ile Asp 385 Gly Ser Ser Met Leu 210 Val Phe Leu Asp Asn 290 Asn Lys Phe Lys Lys 370 Lys Asp Al a Val Cys 195 Tyr Lys Gin Lys Ile 275 Cys Aen Leu Ile Arg 355 Aia Thr Glu Val Asn 180 Ser Thr Ser Phe Lys 260 Ser Leu Vai Phe Met 340 Phe Gin Val Asn Ser 150 Giu Asn 165 Gin Asn Met Gin Lys Leu His Gly 230 Ile Leu 245 Ile Thr Leu Ser Asn Thr Val Leu 310 His Asn 325 Ser Leu Tyr Asn Lys Aen Ser Asp 390 Giu Lys Asp 135 Val Leu Thr Asn Gin Ser Ile Thr Ile 185 His Pro Pro 200 Asn Asn Ile 215 Phe Ile Leu Asn Gin Tyr Thr Thr Thr 265 Arg Leu Asn 280 Leu Aen Lys 295 Ser Gin Leu Giu Gly Phe Ile Leu Aen 345 Ser Met Leu 360 Leu Leu Ser 375 Asn Ile Ile Arg Val Thr Ile 155 Tyr Thr 170 Lys Thr Ser Trp Leu Thr Ile Asp 235 Gly Cys 250 Tyr Aen Val Cys Ser Leu Phe Leu 315 Tyr Ile 330 Ile Thr Asn Asn Arg Val Asn Gly 395 Lys 140 Ile Asn Thr Leu Gin 220 Asn Ile Gin Leu Gly 300 Tyr Ile Giu Ile Cys 380 Lys Pro Lys Ser Leu Ile 205 Tyr Gin Val Phe Ile 285 Leu Gly Lys Giu Thr 365 His Trp Asn Asp Asp Leu 190 His Arg Thr Tyr Leu 270 Thr Arg Asp Giu Asp 350 Asp Thr Ile *Asn Asp Lys 175 Lys Trp Ser Leu His 255 Thr Trp Cys Cys Val 335 Gin Ala Leu Ile Asn Ile 160 Asn Lye Phe Asn Ser 240 Lys Trp Ile Gly Ile 320 Giu Phe Al a Eaeu Leu 400 Leu Ser Lye Phe Leu Lye Leu Ile Lye Leu Ala Gly Asp Asn Aen Leu 322 405 410 Asn Asn Leu Ser Giu Leu Tyr Phe Leu Phe Met Giu Phe 465 Pro Tyr Leu Lys Pro 545 His Asp Asn Asn Val 625 Ile Glu Val1 Thr 450 Ile Thr Lys Ile Lys 530 Lys Ile Arg Glu Ser 610 Gly Leu Ser Asp 435 Lys Tyr Leu Leu Ile 515 Val Asp Gin Ser Cys 595 Asn Arg Al a Leu Arg Tyr Ile Asn 485 Thr Ser Leu Ile Tyr 565 Arg Leu Val Phe Lys 645 Arg Gin Leu Ile 470 Aila Tyr Giy Giu Trp 550 Ile Val Tyr Val Ala 630 Met Tyr Ala Leu 455 Lye Ile Pro Leu Met 535 Thr Glu Leu Asn Ser 615 Met Ile Gly Met 440 Ser Gly Val S er Arg 520 Ile Ser His Giu Cys 600 Leu Gin Al a Asp 425 Asp Asn Phe Leu Leu 505 Phe Ile Phe Glu Tyr 585 Val Thr Pro Glu Leu 665 Ala Leu Val Pro 490 Leu Tyr Asn Pro Lye 570 Tyr Val Gly Gly Asn 650 Glu Arg Val1 Ser Asn 475 Leu Glu Arg Asp Arg 555 Leu Leu Asn Lys Met 635 Ile Leu Ile Arg Thr 460 Thr Arg Ile Giu Lye 540 Asn Lye Arg Gin Giu 620 Phe Leu Gin Phe Ile 445 Leu Tyr Trp Thr Phe 525 Ala Tyr Phe Asp Ser 605 Arg Arg Gin Lys Gly 430 Asn Arg Asn Leu Glu 510 His le Met Ser Asn 590 Tyr Giu Gin Phe le 670 His Cys Gly Arg Asn 495 Lye Leu Ser Pro Glu 575 Lys Leu Leu Ile Phe 655 Leu Pro Aen Ala Trp 480 Tyr Asp Pro Pro Ser 560 Ser Phe Aen Ser Gin 640 Pro Glu Lou Lye Ala Gly Ile Ser Aen Lye Ser Asn Arg Tyr Asn Asp Aen Tyr 675 680 685 323 Asn Asn Tyr Ile Ser Lys Cys Ser Ile Ile Thr Asp Leu Ser Lys Phe 690 695 700 Asn Gin Ala Phe Arg Tyr Giu Thr Ser Cys Ile Cys Ser Asp Val Leu 705 710 715 720 Asp Giu Leu His Gly Val Gin Ser Leu Phe Ser Trp Leu His Leu Thr 725 730 735 Ile Pro Leu Val Thr Ile Ile Cys Thr Tyr Arg His Ala Pro Pro Phe 740 745, 750 Ile Lys Asp His Val Val Asn Leu Asn Lys Vai Asp Giu Gin Ser Giy 755 760 765 Leu Tyr Arg Tyr His Met Giy Gly Ile Glu Giy Trp Cys Gin Lys Leu 770 775 780 Trp Thr Ile Giu Aia Ile Ser Leu Leu Asp Leu Ile Ser Leu Lys Giy *785 790 795 800 .Lys Phe Ser Ile Thr Aia Leu Ile Asn Giy Asp Asn Gin Ser Ile Asp .*.805 810 815 Ile Ser Lys Pro Vai Arg Leu Ile Giu Gly Gin Thr His Aia Gin Aia 820 825 830 .eo Asp Tyr Leu Leu Ala Leu Asn Ser Leu Lys Leu Leu Tyr Lys Glu Tyr 835 840 845 Ala Giy Ile Gly His Lys Leu Lys Gly Thr Giu Thr Tyr Ile Ser Arg **850 855 860 Asp Met Gin Phe Met Ser Lys Thr Ile Gin His Asn Gly Val Tyr Tyr 865 870 875 880 o .6 Pro Ala Ser Ile Lys Lys Val Leu Arg Val Gly Pro Trp Ile Asn Thr 885 890 895 Ile Leu Asp Asp Phe Lys Vai Ser Leu Giu Ser Ile Gly Ser Leu Thr 900 905 910 Gin Giu Leu Giu Tyr Arg Gly Glu Ser Leu Leu Cys Ser Leu Ile Phe 915 920 925 Arg Asn Ile Trp Leu Tyr Asn Gin Ile Ala Leu Gin Leu Arg Asn His 930 935 940 Aia Leu Cys His Asn Lye Leu Tyr Leu Asp Ilie Leu Lys Vai Leu Lys 945 950 955 960 324 His Leu Lys Thr Phe Phe Asn Leu Asp Ser Ile Asp Met Ala Leu Thr 965 970 975 Leu Tyr Met Asn Leu Pro Met Leu Phe Gly Gly Gly Asp Pro Asn Leu 980 985 990 Leu Tyr Arg Ser Phe Tyr Arg Arg Thr Pro Asp Phe Leu Thr Giu Ala 995 1000 1005 Ile Val His Ser Val Phe Val Leu Ser Tyr Tyr Thr Gly His Asp Leu 1010 1015 1020 Gin Asp Lys Leu Gin Asp Leu Pro Asp Asp Arg Leu Asn Lys Phe Leu 1025 1030 1035 1040 Thr Cys Ile Ile Thr Phe Asp Lys Asn Pro Asn Ala Giu Phe Val Thr 1045 1050 1055 *Leu Met Arg Asp Pro Gin Ala Leu Gly Ser Glu Arg Gin Ala Lys Ile 1060 1065 1070 .Thr Ser Giu Ile Asn Arg Leu Ala Val Thr Giu Vai Leu Ser Ile Ala 1075 1080 1085 Pro Asn Lys Ile Phe Ser Lys Ser Ala Gin His Tyr Thr Thr Thr Glu 1090 1095 1100 Ile Asp Leu Asn Asp Ile Met Gin Asn Ile Glu Pro Thr Tyr Pro His 1105 1110 1115 1120 Gly Leu Arg Val Vai Tyr Glu Ser Leu Pro Phe Tyr Lys Ala Glu Lys 1125 1130 1135 Ile Val Asn Leu Ile Ser Gly Thr Lys Ser Ile Thr Asn Ile Leu Glu 1140 1145 1150 *Lys Thr Ser Ala Ile Asp Ser Thr Asp Ile Asn Arg Ala Thr Asp Met 1155 1160 1165 Met Arg Lys Asn Ile Thr Leu Leu Ile Arg Ile Leu Pro Leu Asp Cys 1170 1175 1180 Asn Lys Asp Lys Arg Giu Leu Leu Ser Leu Glu Asn Leu Ser Ile Thr 1185 1190 1195 1200 Giu Leu Ser Lys Tyr Val Arg Glu Arg Ser Trp Ser Leu Ser Asn Ile 1205 1210 1215 Val Gly Val Thr Ser Pro Ser Ile Met Phe Thr Met Asp Ile Lys Tyr 1220 1225 1230 Thr Thr Ser Thr Ile Ala Ser Gly Ile Ile Ile Giu Lys Tyr Asn Val 325 1235 1240 1245 Asn Ser Leu Thr Arg Gly Giu Arg Gly Pro Thr Lys Pro Trp Val Gly 1250 1255 1260 Ser Ser Thr Gin Giu Lys Lys Thr Met Pro Val Tyr Asn Arg Gin Vai 1265 1270 1275 1280 Leu Thr Lys Lys Gin Arg Asp Gin Ile Asp Leu Leu Ala Lys Leu Asp 1285 1290 1295 Trp Val Tyr Ala Ser Ile Asp Asn Lys Asp Giu Phe Met Giu Giu Leu 1300 1305 1310 Ser Thr Gly Thr Leu Gly Leu Ser Tyr Glu Lys Ala Lys Lys Leu Phe 1315 1320 1325 Pro Gin Tyr Leu Ser Val Asn Tyr Leu His Arg Leu Thr Val Ser Ser 1330 1335 1340 6Arg Pro Cys Giu Phe Pro Ala Ser Ile Pro Ala Tyr Arg Thr Thr Asn *1345 1350 1355 1360 *Tyr His Phe Asp Thr Ser Pro Ile Asn His Val Leu Thr Glu Lys Tyr **1365 1370 1375 Gly Asp Glu Asp Ile Asp Ile Val Phe Gin Asn Cys Ile Ser Phe Gly 1380 1385 1390 Leu Ser Leu Met Ser Val Vai Giu Gin Phe Thr Asn Ile Cye Pro Aen 1395 1400 1405 Arg Ile Ile Leu Ile Pro Lys Leu Asn Giu Ile His Leu Met Lys Pro 1410 1415 1420 Pro Ile Phe Thr Gly Asp Val Asp Ile Ile Lys Leu Lys Gin Val Ile ***1425 143014540 0*eGin Lye Gin His Met Phe Leu Pro Asp Lye Ile Ser Leu Thr Gin Tyr 1445 1450 1455 Vai Giu Leu Phe Leu Ser Asn Lye Ala Leu Lys Ser Gly Ser His Ile 1460 1465 1470 Aen Ser Aen Leu Ile Leu Val His Lye Met Ser Asp Tyr Phe His Asn 1475 1480 1485 Ala Tyr Ile Leu Ser Thr Aen Leu Ala Gly His Trp Ile Leu Ile Ile 1490 1495 1500 Gin Leu Met Lye Asp Ser Lye Gly Ile Phe Giu Lye Asp Trp Gly Glu 1505 1510 1515 1520 326 Gly Tyr Ile Thr Asp His Met Phe Ile Aen Leu Asn Val Phe Phe Asn 1525 1530 1535 Ala Tyr Lys Thr Tyr Leu Leu Cys Phe His Lys Gly Tyr Gly Lys Ala 1540 1545 1550 Lys Leu Giu Cys Asp Met Asn Thr Ser Asp Leu Leu Cys Val Leu Giu 1555 1560 1565 Leu Ile Asp Ser Ser Tyr Trp Lys Ser Met Ser Lys Vai Phe Leu Giu 1570 1575 1580 Gin Lys Val Ile Lys Tyr Ile Ile Asn Gin Asp Thr Ser Leu His Arg 1585 1590 1595 1600 Ile Lye Gly Cys His Ser Phe Lys Leu Trp Phe Leu Lys Arg Leu Asn 1605 1610 1615 Aen Ala Lye Phe Thr Val Cys Pro Trp Val Val Asn Ile Asp Tyr His *1620 1625 1630 *Pro Thr His Met Lye Ala Ile Leu Ser Tyr Ile Asp Leu Val Arg Met *1635 1640 1645 .Gly Leu Ile Asn Val Asp Lye Leu Thr Ile Lye Asn Lye Aen Lye Phe 1650 1655 1660 Asn Asp Giu Phe Tyr Thr Ser Asn Leu Phe Tyr Ile Ser Tyr Aen Phe *.1665 1670 1675 1680 Ser Asp Asn Thr His Leu Leu Thr Lye Gin Ile Arg Ile Ala Asn Ser **1685 1690 1695 Glu Leu Glu Asn Asn Tyr Aen Lye Leu Tyr His Pro Thr Pro Glu Thr 1700 1705 1710 Leu Giu Asn Met Ser Leu Ile Pro Val Lye Ser Asn Asn Ser Asn Lye S..1715 1720 1725 Pro Lye Phe Gly Ile Ser Gly Asn Thr Giu Ser Met Met Thr Ser Thr 1730 1735 1740 Phe Ser Asn Lye Thr His Ile Lye Ser Ser Ala Vai Ile Thr Arg Phe 1745 1750 1755 1760 Aen Tyr Ser Lye Gin Asp Leu Tyr Aen Leu Phe Pro Ile Val Val Ile 1765 1770 1775 Asp Arg Ile Ile Asp His Ser Gly Asn Thr Ala Lys Ser Asn Gin Leu 1780 1785 1790 327 Tyr Thr Thr Thr Ser His Gin Thr Ser Leu Val Arg Asn Ser Ala Ser 1795 1800 1805 Leu Tyr Cys Met Leu Pro Trp His His Val Asn Arg Phe Asn Phe Val 1810 1815 1820 Phe Ser Ser Thr Gly Cys Lys Ile Ser Ile Glu Tyr Ile Leu Lys Asp 1825 1830 1835 1840 Leu Lys Ile Lys Asp Pro Ser Cys Ile Ala Phe Ile Gly Glu Gly Ala 1845 1850 1855 Gly Asn Leu Leu Leu Arg Thr Val Val Glu Leu His Pro Asp Ile Arg 1860 1865 1870 Tyr Ile Tyr Arg Ser Leu Lys Asp Cys Asn Asp His Ser Leu Pro Ile 1875 1880 1885 Glu Phe Leu Arg Leu Tyr Asn Gly His Ile Asn Ile Asp Tyr Gly Glu 1890 1895 1900 Asn Leu Thr Ile Pro Ala Thr Asp Ala Thr Asn Asn Ile His Trp Ser 1905 1910 1915 1920 Tyr Leu His Ile Lys Phe Ala Glu Pro Ile Ser Ile Phe Val Cys Asp 1925 1930 1935 o Ala Glu Leu Pro Val Thr Ala Asn Trp Ser Lys Ile Ile Ile Glu Trp 1940 1945 1950 Ser Lys His Val Arg Lys Cys Lys Tyr Cys Ser Ser Val Asn Arg Cys 1955 1960 1965 Ile Leu Ile Ala Lys Tyr His Ala Gin Asp Asp Ile Asp Phe Lys Leu 1970 1975 1980 Asp Asn Ile Thr Ile Leu Lys Thr Tyr Val Cys Leu Gly Ser Lys Leu 1985 1990 1995 2000 Lys Gly Ser Glu Val Tyr Leu Val Leu Thr Ile Gly Pro Ala Asn Ile 2005 2010 2015 Leu Pro Val Phe Asn Val Val Gin Asn Ala Lys Leu Ile Leu Ser Arg 2020 2025 2030 Thr Lys Asn Phe Ile Met Pro Lys Lys Thr Asp Lys Glu Ser Ile Asp 2035 2040 2045 Ala Asn Ile Lys Ser Leu Ile Pro Phe Leu Cys Tyr Pro Ile Thr Lys 2050 2055 2060 Lys Gly Ile Lys Thr Ser Leu Ser Lys Leu Lys Ser Val Val Ser Gly 328 2065 2070 2075 2080 Asp Ile Leu Ser Tyr Ser Ile Ala Gly Arg Asn Glu Val Phe Ser Asn 2085 2090 2095 Lys Leu Ile Asn His Lys His Met Asn Ile Leu Lys Trp Leu Asp His 2100 2105 2110 Val Leu Asn Phe Arg Ser Ala Glu Leu Asn Tyr Asn His Leu T'yr Met 2115 2120 2125 Ile Glu Ser Thr Tyr Pro Tyr Leu Ser Glu Leu Leu Asn Ser Leu Thr 2130 2135 2140 Thr Asn Glu Leu Lys Lys Leu Ile Lys Ile 2145 2150 Asn Leu Pro Asn Glu Gin 2165 INFORMATION FOR SEQ ID NO:27: SEQUENCE CHARACTERISTICS: LENGTH: 15219 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: ACGGGAA.A.7AA AATGCGTACT ACAAACTTGC ACATTCGA;A1 TTGATAAGTG CTATTTAAGT CTAACCTTTT CAATCAGAAA

I

ATGATAAAGG TTAGATTACA AAATTTATTT GACAATGACG ACATOTTATA CTGATAAATT AATTCTTCTG ACCAATGCAT

'T

ACAATTAAAT TAAACGGCAT AGTTTTTATA.

CATGTTATAA

GATAACAATA TTGTAGTGAA ATCTAACTTT ACAACAATGC

C

TACATATGGG AATTGATTGA GTTGACACAC TGCTCTCAAT

T

AATTGTGAA.A TCAAATTTTC TAAAAGACTA AGTGACTCAG

TI

CAA.ATATCTG ACTTACTTGG GCTTGATCTC AATTCATGAJA

T

Thr Gly Ser Val Leu Tyr 2155 2160 ~AAATGGGGC

AAATAAGAAC

GGGGTGCAA TTCACTGAGC LAGTAGCATT

GTTAAAAATA

AGCCAALAGC

AGCAATACAT

:AAGCAGTGA AGTGTGCCCT AATACTACA

AAATGGAGGA

AAACGGTTT AATGOATGAT 'AATGACTAA TTATATGAAT TATGTTTAG TCTAATTCAA 120 180 240 300 360 420 480 540 329 TAGACATGTG TTTATTACCA TTTTAGTTAA TATAAAAACT CATCAAAGGG AAATGGGGCA

AATAAACTCA

GATTGATGAT

AAGAAATCAT

TTGATGAAAG

AAGTAGGGAG

CCATGCCTAT

AACACACTCC

CCCAACCAAA

CATTTTAGTA

TGGCTCTTAG

GCAAATACAC

AAAAACACCT

TCACAGGATT

AGATACTTAA

GTCAAGATAT

CAGAAATACA

AGATGGGAGA

TGTGTATAGC

CAGTAATTAG

TACCAAAGGA

ATGTTTTCGT

GAATCTTTGC

GAGTTTTAGC

TGGAGCAAGT

ACCATATATT

CCTAATCAAT

CACAGACATG

CACACACAAA

ACAAGCTACA

TACCAA.ATAC

ATTTATCAAT

TATAATATAC

CCAAACTATT

ATTAAAAATA

CAA.AGTCAAG

TATTCAACGT

AAACAAACTA

AATAGGTATG

AGATGCTGGA

AAATGGAAAG

AGTCAATATT

AGTGGCTCCA

TGCACTTGTG

GAGGGCAAAC

TATAGCTAAC

GCACTTTGGC

AGGATTGTTT

CAAATCTGTA

TGTGGAAGTC

GAACAATCCA

CAAACCATGA

AGACCCCTGT

TTCATATACT

TTTACATTCT

AAAAAATACA

CACGGCGGGT

AAATATGACC

CCTCAAACA.A

AAAGTAAAGC

TTGA.ATGATA

AGTACAGGAG

TGTGGTATGC

TTATATGCTA

TATCATGTTA

GAAATGAAAT

GAGATAGAAT

GAATATAGGC

ATAACCAAAT

AATGTCTTAA

AGTTTTTATG

ATTGCACAAT

ATGAATGCCT

AAAAATATCA

TATGAGTATG

AAAGCATCAT

GCACTACAAA

CAATGGATTC

TGATAILACAA

TAGTCAATTA

CTGAATATAA

TTCTAGAATG

TCAACCCGTG

CAGTGCTCAA

CAATAACATA

CATTAAATAA

ATAATATTGA

TATTAATCAC

TGACAACACT

AATAATAACA

TGA.ATGTATT

TGAGATGAAG

TACAAAATAT

TATTGGCATT

AATTCCAACA

TAGTTAAGAA

AATTGGGGCA

GGATCAGCTG

CACTCCCAAT

TGAAGATGCA

a TGTCCAGGTT AGGA.AGGGAA AAGCTAATGG AGTAGATATA TCGAAGTATT AACATTATCA CTAGAAAGTC CTACAAAAAA

ACTATGCAAA

TCTCTTACCA

GTAAGAAAAC

CTACTGCACA

GGCACTTTCC

AAGCCTACALA

AAAAA.ACCAA

GGAGCTAATC

AATACAAAGA

CTGTCATCCA

TATGATGTGC

AATCATAAAT

GACACTATAA

ACAACATATC

AGCTTGACAT

ATGCTAAAAG

ATGATAATAC

GGTCTTACAG

AAGGGCCTCA

CATCTTATAG

AGAGTTGAAG

CTAAGATGGG

CAGGCAGAAA

GCTGGATTCT

CCCAACTTCT

660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100

ATGATTCTCC

TAGCAGCAGG

AAAACGAAAT

AAGTGTTTGA

CATCCACAAG

ATGGTTCAGG

TGCTAGGACA

CACAGAAGTT

TGCTGTCATT

AGACTGTGGG

AGACAGATCA

AAAACGATAC

AAAACACCCT

AGGGGGTAGT

GCAAGTAATG

TGCTAGTGTC

GGGAGGAGIA

AACTCAATTT

330 CAAGTGTGGT CCTAGGCAAT GCAGCAGGTC TAGGCATAAT GGGAGAGTAT

AGAGGTACAC

2160

CAAGAA.ACCA

GAGTAATAAA

GGATCTTTAT

CTACAGTGTA

AACTCAACCC

CAAAGAAGAT

a. a a a a.

a. a a a a.

a..

a a a

AGTCAACATG

CAAATTCCTA

TAGCATAATA

TGGCACCAAC

CTACCCAAGA

TTCTAAGTTG

CTCATATGAA

TGATGAAAAA

ACCCACTTCA

AGAAAAAATA

TAGGAATGAG

AACTTCCAAA

TGATGATTTT

TCAATCCATT

CCAATCAATC

AAA~4GAACAA

ATACACAGCA

AATATGGGTG

AAGCATCAAT

GATTAACTCA

TGTATCATTA

GAGAAGTTTG

GAATCAATAA

TCTGTTAACT

ATCATCAATC

AAACCCCTAG

TACAAGGAAA

GAGATAAATG

TTAAGTGAAA

GCTCGCGATG

AGAGCGGAAG

GAAAGCGAAA

AAATTGAGTG

TGATCAGCGA

GAATCAACTG

AACCAATTGA

GATGGGGCAA

GCTGTTCAGT

CCTATGTTCC

ATACTAGTGA

AGAAGTGCTG

GATGAAAGAA

GATGCAGCTA

TTAGACTTAA

GATGTAGAGC

CACCTGAATT

AGGGCAAGTT

CAATAGATAT

CAACAAGTGA

TAAGCTTCAA

CAATAGAAAC

ATCAAACAAA

TATTAGGAAT

GAATA.AGAGA

CATTAATGAC

TAATGGCAAA

k~CTTGTTGGA rCAACTCACT

W!AGACCGAA

rCAATCAGCA kTATGGAAAC kCAATGTTCT

WGTCATCTGT

WGCAGATCTC

'GCTGGCTCA

;CAAATTAGC

AAGCATATGC

CAGCAGA.AGA

TTTAAGTTA

TCATGGAGAA

CGCATCATcC

AGAAGTAACT

AGCCGACAGT

AGAAGATCTC

ATTTGATAAC

TGACAACATT

GCTCCATACA

TGCTATGGTT

CAATGATAGG

AGACACCTCA

AGACAACGAT

CAGCAATCA

CAAACAAACG

ACCCGACAAA~

ATACGTGAAC

AGAAAAAGAT

GCCAGCAGAC

rACGCCCAAA kATGCCTAGT kTATGATGTA

AGAGCAACTC

ATTGGAAGCC

CAAAAAATAC

GATGCAAATA

AAAGATCCTA

AAAGAGAGCC

ACCCCAGAAA

ACCCCAAGTG

AATGAAGAAG

ACAGCAAGAC

TTAGTAGTTG

GGTCTAAGAG

TTAGAGGCTA

GATGAAGTGT

AGTGACAATG

CAACATCAAT

TCCATCAGTA

ATTAACAATA

A.AGCTTCACG

GATGATCCTG

rTGCTCATAA

GGACCTTCAC

kATTTCATCA kCTACACCTT

AAAGAAAATG

ATAAAGCATC

GGGGCAAATA

ACAAAGCTAC

AGAAGAAAGA

CGATAACATC

CAAAAGCCA

ACAACCCTTT

AATCTAGCTA

TAGATAGAAT

CAAGTGCAGG

A-AGAGATGAT

TGGCAAGACT

CTCTTAATCC

ATCTATCACT

AAAACAGACA

GAACCACCAA

TAGTALACAAA

AAGGCTCCAC

CATCACT.C

AAGAACTTGC

TACGAGTCAC

rAAGCGCAAA 3TGAAATCAA 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 AGCATGCAGT CTAACATGCT TAAAAGTAUA AAGTATGTTA ACTACAGTCA

AAGATCTTAC

3660 331 CATGAAGAC;z

GACATCAAAP

TCTGAACTCA

AATTATTCCT

CAAATATATC

GAGGATATAT

ACTAGAGGAT

ACACACTATA

CCACTCAAAA

AAATAAACC

CATTTATACC

ACAATAGAAC

CTAATCTTTT

CACAAAGCAT

AGTTCCACCA

CCTCTCACAG

TATTTAAA

AATGCAACCA

GATACTCTTA

ATAGCACAA

GCCATAATAT

ACAATAAA

AGGGTTAGTT

ACATCACCCA

ACCACTTCA

LTTCAACCCCA

AGAGTAATAA

*CTAGAAAATA

*TATGCAGGAT

AAACCACAGA

TATGTGACTA

TAAACTTAAT

TCCAAACATC

TCCAAALATCA

AAAATATGGG

GCCAATTCAA

TCACAAGCAA

TACTAATTAT

TCTGCAACAA

TTATGCTGTG

AGTCACGGTG

TTAACATAT

TGTCCAAACA

ATCATCTAAT

TAGCACTATC

TCATCATCTC

ACCACACTGA

CATCCAAGCA

I

ATACAAAATC

I

CACAGACCAA C

CTCATGAGAT

TACCAACCTA

TAGCAACCAC

TAGTGTTAGT

GTCAATTTAT

CTAATTGGAA

TATCAACACT

ATAAACATCT

CTACCAGCCA

GTAAATAGAC

CACATATACT

ATTTTGGcCCC

A.ATCACTATC

AACTCTTGAA

TCAAACCATA

rCGCAAAACC

GATGAATTGT

CAAGAATCAA

rGTAATATCC kGTTTTGGCA

LGCCAATCAC

;AAAACATC

~CCCACAACC1

LGAAACACAC

~AAGCCAAGC

CATTGCTCTA

TCTAAGATCA

CGALATTCAAA

TATCACAGTT

AGTAGATCTT

GCATACAGCT

GAATGACAGG

ACACTACACA

CTATCCGCTA

ATTAGTTAGA

ATAAATCTTA

TATTTTACAC

ATGATTGCAA~

CTAGGACAGA

ATCCTGTATA

ACGCTA.ACCA

rAGTATGAGA

CGCACTGCCA

rCTTGTTTAT

PLTGATAATCT

kAAGTTACAC k.CCACCTACC kCATCACCAA :ATACAACAG

C

LCAA.AACCAC

G

TGTGAATTTG

ATTAGTGTCA

A.ATGCTATCA

ACTGACAATA

GGTGCCTACC

ACACGTTTTT

TCCACATATA

CTTCATCACA

GACCTAGAGT

GTTCAATCAA

AAATGGGAAA

TAATACATAT

CACTAAATA

TGTACCAAAT

TACAAACAAA

rCATGGTAGC

TCAAAACA

GGACTCTAGA

k.CAGATTAAA

MAACCTCTCT

LAACAACGGT

TACTCAAGT

C

~CCACACAAG

'I

ACAAACCAA

A~

TCCAAAAALA

T

AAAATATTAT

AGAACAAGGA

CCAATGCA

ALAGGAGCATT

TAGAAAALAGA

CAATCAAACC

TCCTCAAACT

CAAACCAATC

GCGAATAGGC

TCTTAACAAC

TACATCCATC

GATCTTAACT

GCTAAGTGAA

CAACACACAG

CAAATCCAAT

PTAGAGTAGT

CATTGGGGCA

kAAGACCTGG rTTAAAATCT

:ATAATTGCA

MACAGTTCAA

~TCACCAGAA

TCAGCTACA

LGGCAGAJACC

'CCACCAAAA

3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 AAAGATGATT ACCATTTTGA AGTGTTCAAC TTCGTTCCCT GCAGTATATG

TGGCAACAAT

5220 332

CAACTTTGCA

ATCAAACCCA

GCCAAAACGA

ACAGAAAGAG

ACAGTCCAAC

ACACCCACAG

TAGTTATTCA

AAACCTGGGG

TCTTGCTATT

ATCGACATGT

TAGTGTCATA

TAAAGTAA.AA

GCTACTTATG

TATGAACTAC

ACGAAGATTT

ATCAAAAGTT

AAACAAAGCT

TCTCAAGAAT

CTCCAACATT

CAGAGAATTT

CAGTGAGTTA

GTCAAGCAAT

AGAAGTCCTT

GAAATTGCAC

AACAAGGACT

AATCCATCTG

CAAACA.AACC

CGAAAAAAGA

ACACCAGCAC

AGCAATCCCT

CATCCGAGCC

AAAACTACAT

CA-AATAACCA

AATGCATTGT

AGTGCAGTTA

ACAATAGAAT

CTTATGAA.AC

CAAAACACAC

ACAATCAATA

CTAGGCTTCT

CTACACCTTG

GTAGTCAGTT

TACATAAATA

GAAACAGTTA

AGTGTCAATG

CTATCATTAA

GTTCAGATAG

GCATATGTTG

ACATCGCCTC

GATAGAGGAT

CAAA.ACAATA

AACCACCAAA

AACTACCACC

CTCACAATCC

CCTCTCAACC

CTCCACACCA

CTTAGCAGAG

TGGAGTTGAT

ACCTCACCTC

GCAGAGGTTA

TAAGTAATAT

AAGAATTAGA

CAGCTGTCAA

CCACTAAAAA

TGTTAGGTGT

AAGGAGAAGT

TATCAAATGG

ACCAATTATT

TAGAATTCCA

CAGGTGTAAC

TCAATGATAT

TAAGGCAACA

TACAGCTGCC

TATGCACTAC

GGTATTGTGA

CCAkAGCAACA

ACCACAAACA

AACCCAACAA

ACTGCACTCG

ACCCCCGAAA

AACTCCACCC

ILACCGTGATC

GATCCACAAG

AAGTCAGAAC

TTTTAGTGCT

AAAAGAAACC

TAAGTATAAG

CAACCGGGCC

CCTA7LATGTA

GGGATCTGCA

GAACAAGATC

GGTCAGTGTT

ACCCATAGTA

GCAGAAGAAC

AACACCTTTA

GCCTATALACA

AAGTTATTCC

TATCTATGGT

CAACATCAAA~

TAATGCAGGA

AACCAAAGAA

AAAGAGACCC

AAAAACTAAC

ACACAACCAC

ACACACCCAA

AAAAAACCCA

TATCAAGCAA

TCAAGTGCAA

ATAACTGAGG

TTAAGAACAG

AAATGCAATG

AATGCAGTAA

AGA.AGAGAAG

TCAATAAGCA

ATAGCAAGTG

AAAAATGCTT

TTAACCAGCA

AATCAACAGA

AGCAGATTGT

AGCACTTACA

A.ATGATCAGA

ATCATGTCTA

GTAATAGATA

GAAGGATCAA

TCAGTATCCT

GAAACCAACC

AAAA.ACACCA

CCTCA.AGACC

ATTAAAACAC

CTCCACACAA

GCCACATGCT

GAACGAAATT

TCTTCCTAAC

AGTTTTACCA

GTTGGTATAC

GAACTGACAC

CAGAATTACA

CACCACAGTA

AGAAGAGGAA

GTATAGCTGT

TGTTGTCTAC

AAGTGTTAGA

GCTGTCGCAT

TGGA.AATCAC

TGTTGACAAA

AAAAATTAAT

TAATAAAGGA

CACCTTGCTG

ATATTTGTTT

TCTTTCCACA

5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 GGCTGACACT TGTWAGTAC AGTCCAATCG AGTATTTTGT CACACTATGA ACAGTTTGAC 333

ATTACCAAGT

AATTATGACA

GTCATGCTAT

ATTTTCTAAT

CACTTTATAC

AATAAATTAC

AGTCAATGAA

TAATGTAAAT

CATTGTAGTA

CACACCAGTT

ATAGACAAAA

CAACTTACAA

TACCCACATA

ATCAACCACT

AGAALATCCTT

AGTCATAATT

AACAAGATAC

GCTGAACTGG

ATAGGATCTA

ATTGAGATCA

AAGATAAGAG

CAAACCATCC

ACATTAGATA

CAAAATGACC

CATATTGATC

GAAGTCAGCC

TCAAAAACAG

GGTAAAACTA

GGTTGTGACT

TATGTAAACA

TATGACCCTC

AAAATCAATC

ACTGGCAAAT

TTGTTATCAT

ACACTA.AGCA

AACCACCTGA

CAAATATTTC

ACTAAGCTAG

A.AATCAACAC

GTAAATTTGA

ACTTTGAATG

TCAAGTCAAT

ATAGAACAGA

TAAACAACAT

ATAGTGATGA

TGTACAATAC

ATCTGCTCAA

TCCACAAAAG

AAACCAAAA

TCAAGTGAAA,

TTTGTAACAC

ACATAAGCAG

AATGCACTGC

ATGTGTCAAA

AGCTGGAAGG

TAGTGTTTCC

AAAGTTTAGC

CTACTACAAA

TAkATAGCTAT

AAGACCAACT

TCATGTTTCA

AACATCACAG

ATCCTTAACT

ATCATTCACA

GATTAGAGGT

GCCTCCTCAT

GGACAAAAGC

AGAATATGCT

AACAA.AACAA

CATTAAAAAG

TGTTATATCA

GAGACTACCA

CATAACCATA

TAATGATATT

GCATGGTTGC

TGACATATTC

CTCAGTAATT

ATCCAACAAA

CAAAGGAGTA

CAAGAACCTT

TTCTGATGAG

TTTTATTCGT

TATTATGATA

TGGTTTACTG

AAGTGGAATC

ACAACAATCT

TACAGGCTGA

TATAGTTACA

AAATTAACAG

CATTGCTTGA

GCATTACTAG

ATAGACACTT

CTTGGTATAG

TCAGCATGTG

CTTAGAGATA

TACATTGAGA

GCAGACGTGC

AGCAATCCAA

ACCGGATAAA

TACATTCAAT

AATTCCAAGT

ACTTCTCTTG

AATCGTGGGA

GATACTGTGT

TATGTAAAAG

TTTGATGCAT

AGATCTGATG

ACTACAATTA

TTGTATTGTA

AATAATATTG

GCTGACCACC

ATCATTTCC'r

TAAAAACCTC

CTGGGGCAAJA

ATGGTAGAAG

TGAGGCAAAA

TGTCTGAAAT

TTGGAGTGCT

TTGCTATGAG

ATGAAGAACC

GCAATAGAAA,

TGAAGAAGAC

A-AGAGTCA.AC

rATCCTTGTA

CATAAAAACA

ATGACTGCAA

GAGCTATAGT

TTATAAAGAC

CAGTGGGCAA

GGGAACCTAT

CAATATCTCA

ALATTACTACA

TTATAGTAAT

AAGCCAAAAA

CATTCAGCAA

AATCCCAAAT

CACATCATGC

AAGTATCACA

TATGTCGCGA

ATGTCACTAC

CTTCATGTTA

AAGTGGAGCT

AGAGAGTTAC

TAAACTTCTT

CAATTCACCT

AALACAACAAG

AATAAAGAAC

TGTGAATGAT

GTATATCATC

TATTACAATT

6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 TAACCATAAC TATTTGGATA ACCACCAGCG TTTATTAAAT CATATATTTG

ATGAAATTCA

334 TTGGACACCT AAAAACTTAT TAGATGCCAC TCAACAATTT CTCCAACATC TTA.ACATCCC

TGAAGATATA

TCATCCAACC

GGAAACTCTG

GAGTGTAATG

AACTTAATTA

ACACAGTCAT

TTCCAGTCAT

AACTTACTTA

ATCTTGA-ATA

GATGAAALACT

AATCAATCAT

ACAACACTCT

TGGTTCAATT

AAAAGTCATG

AATCAATATG

AATCAATTTT

TGGATAAGTA

AATGTTGTGT

GILAGGCTTCT

ACAGAAGAAG

GCAGCTATTA

ACAGTGTCTG

TTGATTAAGC

AGAATCTTTG

TGTAATGAAA

TATACAGTAT

ATAAAACTAT

CTAATGTGTA

CTTTAGGGAG

GTAGACAAAG

TAATATCTAG

TACTTATGAC

AAAAAATAAT

AACTAGGATT

CAGTACTTAC

ATACAAATTC

TGAAAAAATT

TATATACAAA

GGTTTATATT

GTTGTATCGT

TGACATGGA

ATTGTTTAAA

TATCACAATT

ACATAATAA

ATCAATTTIA

AGGCTCAAAA

ATAATATCAT

TTGCAGGTGA

GACATCCAAT

CTAGGTTCTA

ATATATTAGT

TTTGATAAGG

TCTAACTGAT

TTATCTTTTT

CCCACTACTA

ATATCATAAA

ATATAAAAGT

ACGAAGAGCC

AAAGGAAAAG

AACCATAATT

AGACAAAAGT

GATGTGTTCA

ATTAAATAAC

AATAGATAAT

TTATCATAAA

AGACATCAGC

TACATTAAAC

ATTTCTTTAT

AGAAGTAGAG

GAAACGATTT

GGACCTACTA

AAATGGTAAA

TAATAATCTC

GGTCGATGA

CTTATTAAGT

GTCATAATGC

TTATGGGACA

AGTTATTTAA

AACGGCCCTT

GAGCATATGA

GGTGAACTGA

ATGTCCTCGT

ATAGAAATAA

GACAGAGTTA

AAAGATGATA

CACTCAGTAA

ATGCAACATC

ATATTAACAC

CAAACTTTAA

GGACTCAA

CTTAGCAGAT

A.AAAGCTTAG

GGAGATTGTA

GGATTTATTA

TATAATAGCA

TCAAGAGTAT

TGGATAATCC

AATAACTTGA

AGACAAGCAA

AGTCTAAGTA

TTGACCATAA

AAATGGATCC

AAGGTGTTAT

ATCTTAAAAA

ATCTTAAAIA

AATTAGAAGA

CTGAACAAAT

GTGATGTAAA

AGCCCAACAA

TACTTTCGGC

ATCAAAATAT

CTCCATCATG

AATATCGATC

GTGGTTTTCA

AAATCACAAC

TAAATGTTTG

GGCTGAGATG

TACTGAAATT

TGTCTTTAAT

TGCTAAATA

GTCACACTTT

TATTAAGTA

GTGAGCTATA

TGGATTCTGT

CATTAAGAGG

CGACTCTATG

CATTATTAAT

CTCTTTTTCA

TGATTACACC

ACTALACTATA

ACCAACTTAT

TGCTACAACT

GGTGTACGCC

TAATTCAGGT

TGTGGAAAAC

CACTATCAAA

GTTAATACAC

AAATGAGGTA

GTTTATTTTA

TACTACTTAC

CTTAATTACT

TGGATTCAAT

ATTTCATAAT

TCTAAACATA

CATCACAGAT

ATTAGACAAG

ATTTCTTAAA

TTTTCTCTTC

AAGAATTAAC

TGCTTTCATT

8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 335 TATAGAATCA TA.AAAGGGTT TGTAAATACC TACAACAGAT GGCCCACCTT AAGGAATGCT 9960

ATTGTCCTAC

GAAATCACAG

CTGCCTAAAA

GATCTAATAT

GAACATGAAA

TTGAGAGATA

CTCAACAACT

AGAATGTTTG

ATAGCTGAAA

CTTCAAAAGA

AACTACAACA

GCATTTAGAT

CAATCTCTGT

AGACATGCAC

AGTGGATTAT

ATTGAAGCTA

CTGATAAATG

CAGACCCATG

GAGTATGCAG

CAGTTCATGA

GTCCTGAGAG

TCTATAGGCA

ATATTTAGGA

TGTAACAATA

AATCTTGATA

CTCTAAGATG

AAAATGATTT

AAGTGGATCT

GGACTAGTTT

AGTTGAAGTT

ATAA.ATTCAA

CTA.ATCACGT

CTATGCAACC

ATATTTTACA

TATTAGAATT

ATTATATCAG

ATGAAACATC

TCTCTTGGTT

CTCCTTTCAT

ACAGATATCA

TATCATTATT

GTGATAATCA

CACAAGCAGA

GTATAGGCCA

GCAAAACAAT

TAGGTCCATG

GCTTAACACA

ACATTTGGTT

AGCTATATTT

GCATTGATAT

GTTAAACTAC

GATTATTTTA

TGAAATGATA

TCCTAGAAAT

CTCTGAA.AGC

TGAATGCGAT

GGTATCACTA

AGGTATGTTT

ATTCTTCCCT

AAAAGCAGGA

TAAATGTTCT

ATGTATCTGC

GCATTTAACA

AAAGGATCAT

TATGGGTGGT

AGATCTAATA

GTCAATTGAT

TTATTTGTTA

TAAGCTTAAG

CCAGCACAAT

GATAALACACG

GGAGTTAGAA

ATACAATCAA

AGATATATTG

GGCTTTATCA

TATAA.ACTTA

TCAGGATTGC

ATAAATGACA

TACATGCCAT

GACAGATCGA

CTATACAATT

ACTGGTAAAG

AGGCAAATCC

GAGAGTTTGA

ATAAGCAACA

ATCATTACAG

AGTGATGTAT

ATACCTCTTG

GTTGTTAATC

ATTGAGGGCT

TCTCTCAAAG

ATAAGCAAAC

GCATTAAATA

GGAACAGAGA

GGAGTGTACT

ATACTTGATG

TACAGAGGAG

ATTGCTTTGC

AAAGTATTAA

TTGTATATGA

ATACTTATCC

GGTTCTATCG

AAGCCATTTC

CACATATACA

GA.AGAGTACT

GTGTAGTCAA

AAAGAGAGCT

AAATCTTAGC

CAAGATATGG

AGTCAAATCG

ATCTTAGCAA

TAGATGAACT

TCACAATAAT

TTAATGAGGT

GGTGTCAAAA

GGAAATTCTC

CAGTTAGACT

GCCTTAAATT

CCTATATATC

ATCCAGCCAG

ATTTTAAAGT

AAAGCTTATT

AACTCCGAA-A

AACACTTA;A

ATTTGCCTAT

ATCTCTACTT

TGAGTTTCAT

ACCTCCAAAA

AAATTATATA

AGAGTATTAC

TCAAAGCTAT

CAGTGTAGGT

AGAGAAAATG

TGATCTAGAG

TTATAATGAT

ATTCAATCAG

GCATGGAGTA

ATGTACATAT

TGATGAACAA

ACTGTGGACC

TATCACAGCT

TATAGAGGGT

GTTATATAAA

CCGAGATATG

TATCAAAAAA

TAGTTTAGAA

ATGCAGTTTA

TCATGCATTA

AACTTTTTTT

GCTGTTTGGT

10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 336 GGTGGTGATC CTAATTTGTT ATATCGAAGC TTTTATAGGA GAACTCCAGA

CTTCCTTACA

GAAGCTATAG

AAGCTCCAGG

GATAAAAATC

GAAAGGCAAG

TACATTCAGT

ATCTTCCAGA

CCAATGCCGA

CTAAKATTAC

ATAGCCCCAA

ACAAAATATT

a a a. a a a

CTAAATGACA

GAAAGTTTAC

ATAACTAATA

GATATGATGA

GACAAAAGAG

AGAGAA.AGAT

ACAATGAACA

AATGTTALATA

ACGCAGGAGA

GACCAAATAG

GAATTCATGG

TTGTTTCCAC

TGTGAATTCC

CCTATCAATC

AATTGCATAA

CCTAATAGAA

TTTACAGGAG

CTACCAGATA

AAATCTGGAT

CATAATGCTT

TTATGCAAAA

CTTTTTATAA

TACT TGAAAA

GGAAAA.ATAT

AGTTATTAAG

CTTGGTCATT

TTAAATATAC

GTTTAACTCG

AAAA.AACAAT

ATTTATTAGC

AAGAACTGAG

AATATCTAAG

CTGCATCAAT

ATGTATTA2AC

GTTTTGGTCT

TTATTCTCAT

ATGTTGATAT

AA.ATAAGTTT

CTCACATCA

ATATTTTAAG

GTTTGTGTTG

TGATAGACTG

GTTTGTAACA

TAGTGAGATT

TTCTAAAAGT

TATAGAACCA

AGCAGAAAA-A

AACATCAGCA

AACTTTACTT

TTTAGAAAAT

ATCCAATATA

AACTAGCACT

TGGTGAAAGA

GCCAGTGTAC

AAAATTAGAC

TACTGGAkACA

TGTCAATTAT

ACCAGCTTAT

AGAAAAGTAT

TAGCCTGATG

hCCGAAGCTG

CATCAAGTTG

k.ACCCAATAT

:TCTAATTTA

rACTAATTTA

AGCTATTATA

AACAAATTCT

TTGATGAGCG

AATAGATTAG

GCACAACATT

ACTTACCCTC

ATAGTTAATC

ATAGATACAA

ATAAGGATAC

CTTAGTATAA

GTAGGAGTAA

ATAGCCAGTG

GGACCCACCA

AACAGACAAG

TGGGTATATG

CTTGGACTGT

TTACACCGTT

AGAACAACAA

GGAGATGAG

TCGGTTGTGG

AATGAGATAC

P.AGCAAGTGA

GTAGAATTAT

ATATTAGTAC

GCTGGAATT

CTGGTCACGA

TGACATGTGT

ATCCACAGGC

CAGTAACAGA

ATACTACCAC

ATGGATTAAG

TTATATCAGG

CTGATATTAA

TTCCACTAGA

CTGAATTAAG

CATCGCCAAG

GTATAATAAT

AGCCATGGGT

TTTTAACCAA

CATCCATAGA

CATATGAAAIA

TALACAGTCAG

ATTATCATTT

ATATCGACAT

AACAATTCAC

ATTTGATGAA

TACAAAAGCA

TCTTAAGTAA

ATAAAATGTC

GGATTCTGAT

TTTACAAGAT

CATCACATTT

TTTAGGGTCT

AGTCTTA.AGT

TGAGATTGAT

AGTTGTTTAT

AACAAAATCC

TAGGGCTACT

TTGTAACAAA

CAAGTATGTA

TATTATGTTC

AGAAAAATAT

AGGCTCATCC

AAAGCAAAGA

CAACAAAGAT

AGCCAAAAAG

TAGTAGACCA

TGATACTAGT

TGTGTTTCAA

AAACATATGT

PCCTCCTATA

GACATGTTC

CAAAGCACTT

TGATTATTTT

TATTCAACTT

11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 337

ATGAAAGATT

ATGTTCATTA

AAAGGTTATG

TTGGAGTTAA

GTCATAAAAT

TTTAAGTTGT

GTTAACATAG

AGAATGGGGT

GAATTTTACA

CTAACAAAAC

CACCCAACCC

AACAAACCTA

AGTAAAATGC

TTGTACAATT

GCAAAATCTA

GCATCACTTT

TCCACAGGAT

AGTTGTATAG

CTTCATCCAG

CCTATTGAAT

ACCATTCCTG

GCAGAACCTA

AAAATTATAA

AGATGCATTT

ATTACTATAT

TTAATCCTTA

CAAAAGGTAT

ATTTGAATGT

GTAAAGCAAjA

TAGACAGTAG

ACATAGTCALA

GGTTTTTAAA

ATTATCACCC

TAATAAATGT

CATCAAATCT

AAATA.AGAAT

CAGAAACTTT

AATTTTGTAT

ATATTAAATC

TATTTCCAAT

ACCAACTTTA

ATTGCATGCT

GCAAGATCAG

CATTCATAGG

ACATAAGATA

TTCTAAGGTT

CTACAGATGC

TTAGCATCTT

TTGAATGGAG

TAATTGCAAA

TAAAAACTTA

CAATAGGCCC

TTTTGAAAAA

TTTCTTTAAT

ATTAGAATGT

CTACTGGAAA

TCAAGACACA

ACGCCTTAAT

AACACACATG

AGATAAATTA

CTTTTACATT

TGCTAATTCA

AGAAAATATG

AAGTGGAAAT

TTCCACTGTT

TGTTGTGATA

CACCACCACT

TCCTTGGCAT

TATAGAGTAT

TGAAGGAGCT

CATTTACAGA

ATACAACGGG

AACTAATAAC

TGTCTGCGAT

TAAGCATGTA

ATATCATGCT

CGTGTGCCTA

TGCAA.ATATA

GATTGGGGAG

GCTTATAAGA

GATATGAACA

TCTATGTCTA

AGTTTGCGTA

AATGCTAAAT

AILAGCTATAT

ACCATTAAAA

AGTTATAACT

GAATTAGAAG

TCATTAATTC

ACCGAATCTA

ACCACAAGAT

GACAAGATTA

TCACATCAGA

CATGTCAATA

ATTTTAAAAG

GGTAACTTAT

AGTTTAAA-AG

CATATAAACA

ATTCATTGGT

GCTGAATTAC

AGAAAGTGCA

CAAGATGACA

GGTAGCAAGT

CTTCCTGTTT

AGGGGTACAT

CTTATTTGCT

CTTCAGATCT

AAGTTTTCCT

GAATAAAAGG

TTACCGTATG

TATCTTACAT

ATAAAAACAJA

TTTCAGACAA~

ATAATTATAA

CTGTTAAAAG

TGATGATGTC

TCAATTATAG

TAGATCATTC

CATCTTTAGT

GATTTAACTT

ATCTTAAGAT

TATTACGTAC

ATTGCAATGA

TAGATTATGG

CTTATTTACA

CTGTTACAGC

AGTACTGTTC

rTGATTTCA rAAAAGGATC rTGATGTTGT

AACTGATCAT

ATGTTTTCAT

TCTTTGTGTT

AGAACAAAA

CTGTCACAGT

CCCTTGGGTT

AGATTTAGTT

ATTCAATGAT

CACTCATTTG

CAAACTATAT

TAATAATAGT

AACATTCTCT

CAAACAAGAC

AGGTA.ATACA

AAGGAATAGT

TGTATTTAGT

TAAGGACCCC

GGTAGTAGA.A

TCATAGTTTA

TGAGA.ATTTA

TATAAAATTT

CAATTGGAGT

TTCTGTAAAT

AiTTAGATAAC

TGAAGTTTAC

ACAAAATGCT

13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 338

AAATTGATAC

ATCGATGCAA

ATTAAGACTT

ATAGCTGGAC

CTAAAATGGC

TACATGATAG

GAGCTCAAGA

TAGTTTAAAA

TAGTTATTAA

TTTTAGTCTT

ACACILACGAG

TTTCAAGAAC

ATATTAAAAG

CATTGTCAAA

GTAATGAAGT

TAGATCATGT

AGTCCACATA

AGCTGATTAA

TATCATTAAC

AGAATATACA

AAGGGGTTAA

TAAAAATTTC

CTTAATACCT

ATTGA.AGAGT

ATTCAGCA.AC

TTTAA.ATTTT

TCCTTACTTA

KATAACAGGT

AAGTTTGGTC

AACTTTTCA-A

ATAAAAGTCT

ATTATGCCTA

TTCCTTTGTT

GTAGTTAATG

AAGCTTATAA

AGATCAGCTG

AGTGAATTGT

AGTGTGCTAT

AAATTTAGAT

TAATTTAGCA

AAAACTAACA

AAAAAACTGA

ACCCTATAAC

GAGATATATT

ACCACAAGCA

AACTTAATTA

TAAATAGTTT

ACA.ACCTTCC

GCTAACACAT

TATTGATTCC

ATTATACATG

CAAGGAATCT

AAAAAAAGGA

ATCATATTCT

TATGA.ATATC

CAATCATTTA

AACAACCAAT

CAACGAACAG

CATTATATTA

AAAATTATCA

TGCATTCACA

14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15219 ACATTAGTTT TTGACACTTT TTTTCTCGT INFORMATION FOR SEQ ID NO:28: SEQUENCE CHARACTERISTICS: LENGTH: 2166 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) Met SEQUENCE DESCRIPTION: SEQ ID NO:28: Asp Pro Ile Ile Asn Gly Asn Ser Ala 10 Asn Val Tyr Leu Thr Asp Ser Tyr Leu Lys Giy Val Ile Ser Phe 25 Ser Tyr Leu Phe Asn Gly Pro Tyr Leu Ile Ser Arg Gin Ser Pro Leu Leu Glu 55 Thr Ile Thr Gin Ser Leu Ile Ser Arg 70 Ser Giu Cys Asn Lys Asn Asp His Met Asn Tyr His Lys Ala Leu Gly Thr Asn Leu Lys Lys Leu Giy Giu Leu 339 Leu Glu Met Ser Ile Arg Asn Lys 130 Ser Gly 145 Leu Ser His Ser Leu Met Asn Leu 210 Glu Val 225 Phe Leu LysAs Ser Asn 290 Phe Asn 305 *Leu Lys *see Gly Phe Giu Pro Ser Ser 1.00 Arg Ala 115 Leu Gly Asp Glu Ala Val Val Asn 180 Cys Ser 195 Tyr Thr Lys Ser Gin Phe Lys Lys 260 Ile Ser 275 Cys Leu Asn Val Leu Phe Ile Met 340 Thr Tyr Giu Gin Ile Glu Leu Lys Asn Ser 150 Giu Asn 165 Gin Asn Met Gin Lys Leu His Gly 230 Ile Leu 245 Ile Thr Leu Ser Asn Thr Val Leu 310 His Asn 325 Ser Leu Phe Ile Ile Giu 135 Vai Asn Ile His Asn 215 Phe Asn Thr Arg Leu 295 Ser Glu Ile Gin Ala Ser 120 Lys Leu Gin Thr Pro 200 Asn Ile Gin Thr Leu 280 Asn Gin Giy Leu Ser Thr 105 Asp Asp Thr Ser Ile 185 Pro Ile Leu Tyr Thr 265 Asn Lys Leu Phe Asn 345 Leu 90 Thr Val Arg Thr Tyr 170 Lys S er Leu Ile Gly 250 Tyr Val Ser Phe Tyr 330 Ile Leu As n Lys Val Ile 155 Thr Thr Trp Thr Asp 235 Cys Asn Cys Leu Leu 315 Ile Thr Met Leu Val Lys 140 Ile Asn Thr Leu Gin 220 Asn Ile Gin Leu Gly 300 Tyr Ile Giu Thr Leu Tyr 125 Pro Lys Ser Leu Ile 205 Tyr Gin Val Phe Ile 285 Leu Giy Lys Glu Tyr Lys 110 Aia Asn Asp Asp Leu 190 His Arg Thr Tyr Leu 270 Thr Arg Asp Giu Asp 350 Lys Lys Ile Asn Asp Lys 175 Lys Trp Ser Leu His 255 Thr Trp Cys Cys Val 335 Gin Ser Ile Leu Asn Ile 160 Ser Lys Phe Asn Ser 240 Lys Trp Ile Gly Ile 320 Glu Phe 340 Lys Ile Asp 385 Leu Asn Met Glu Phe 465 Pro Tyr Leu Lys Pro 545 His Asp Aen Asn Val Lye Lye 370 Lys Ser Asn Val Thr 450 Ile Thr Lye Ile Lys 530 Lye Ile Arg Glu Ser 610 Gly Arg 355 Ala Thr Lye Leu Asp 435 Arg Tyr Leu Leu Ile 515 Va1 Asp Gin Ser Cys 595 Asn Arg Phe Gin Val Phe Ser 420 Glu Phe Arg Arg Asn 500 Leu Asp Leu Asn Arg 580 Asp His Met Tyr Lye Ser Leu 405 Glu Arg Tyr Ile Asn 485 Thr Ser Leu Ile Tyr 565 Arg Leu Val Phe Asn Asp Asp 390 Lye Leu Gin Leu Ile 470 Ala Tyr Gly Glu Trp 550 Ile Val Tyr Val Ala Ser Leu 375 Asn Leu Tyr Ala Leu 455 Lys Ile Pro Leu Met 535 Thr Glu Leu Asn Ser 615 Met Met 360 Leu Ile Ile Phe Met 440 Ser Gly Val Ser Arg 520 Ile Ser His Glu Cys 600 Leu Gin Leu Ser Ile Lye Leu 425 Asp Ser Phe Leu Leu 505 Phe Ile Phe Glu Tyr 585 Va1 Thr Pro Asn Arg Asn Leu 410 Phe Ser Leu Val Pro 490 Leu Tyr Asn Pro Lys 570 Tyr Val Gly Gly Asn Val Gly 395 Ala Arg Val Ser Asn 475 Leu Glu Arg Asp Arg 555 Leu Leu Asn Lye Met Ile Cys 380 Lys Gly Ile Arg Thr 460 Thr Arg Ile Glu Lye 540 Asn Lye Arg Gin Glu 620 Phe Thr 365 His Trp Asp Phe Ile 445 Leu Tyr Trp Thr Phe 525 Ala Tyr Phe Asp Ser 605 Arg Arg Asp Thr Ile Asn Gly 430 Asn Arg Asn Leu Glu 510 His Ile Met Ser Asn 590 Tyr Glu Gin Ala Leu Ile Asn 415 His Cys Gly Arg Asn 495 Aen Leu Ser Pro Glu 575 Lye Leu Leu Ile Ala Leu Leu 400 Leu Pro Asn Ala Trp 480 Tyr Asp Pro Pro Ser 560 Ser Phe Asn Ser Gln 0 o t *as* 0 0.

*5 S S

S.

341 625 Ile Glu Leu Asn Asn 705 Asp Ile Ile Leu Trp 785 Lys Ile Asp Ala Asp 865 Pro Leu Ser Lys Asn 690 Gin Glu Pro Lys Tyr 770 Thr Phe Ser Tyr Gly 850 Met Ala Ala Leu Ala 675 Tyr Ala Leu Leu Asp 755 Arg Ile Ser Lys Leu 835 Ile Gin Ser Glu Lys 645 Thr Arg 660 Gly Ile Ile Ser Phe Arg His Gly 725 Val Thr 740 His Val Tyr His Glu Ala Ile Thr 805 Pro Vai 820 Leu Ala Gly His Phe Met Ile Lys 885 630 Met Tyr Ser Lys Tyr 710 Val Ile Val Met Ile 790 Ala Arg Leu Lys Ser 870 Lys Ile Gly Asn Cys 695 Glu Gin Ile Asn Gly 775 Ser Leu Leu Asn Leu 855 Lys Val Ala Asp Lys 680 Ser Thr Ser Cys Leu 760 Gly Leu Ile Ile Ser 840 Lys Thr Leu Glu Leu 665 Ser Ile Ser Leu Thr 745 Asn Ile Leu Asn Glu 825 Leu Gly Ile Arg 635 Asn Ile 650 Glu Leu Asn Arg Ile Thr Cys Ile 715 Phe Ser 730 Tyr Arg Glu Val Glu Gly Asp Leu 795 Gly Asp 810 Gly Gin Lys Leu Thr Glu Gin His 875 Val Gly 890 Leu Gin Tyr Asp 700 Cys Trp His Asp Trp 780 Ile Asn Thr Leu Thr 860 Asn Pro Gin Lys Asn 685 Leu Ser Leu Ala Glu 765 Cys Ser Gin His Tyr 845 Tyr Gly Trp Phe Ile 670 Asp Ser Asp His Pro 750 Gin Gin Leu Ser Ala 830 Lys Ile Val Ile Pho 655 Leu Asn Lys Val Leu 735 Pro Ser Lys Lys Ile 815 Gin Glu Ser Tyr Asn 895 640 Pro Glu Tyr Phe Leu 720 Thr Phe Gly Leu Gly 800 Asp Ala Tyr Arg Tyr 880 Thr e g.

C

CC CC

C

C

COCC

C C CC C

C.

C

C.

CCC...

C

C

C

C

0@

C

C CC

CCC.

cCC.

Ile Lou Asp Asp Phe Lys Val Ser Leu Glu Ser Ile Gly 900 905 Ser Lou Thr 910 342 Gin Giu Leu Giu Tyr Arg Gly Giu Ser Leu Leu Cys Ser Leu Ile Phe 915 920 925 Arg Asn Ile Trp Leu Tyr Asn Gin Ile Ala Leu Gin Leu Arg Asn His 930 935 940 Ala Leu Cys Asn Asn Lys Leu Tyr Leu Asp Ile Leu Lys Val Leu Lys 945 950 955 960 His Leu Lys Thr Phe Phe Asn Leu Asp Ser Ile Asp Met Ala Leu Ser 965 970 975 Leu Tyr Met Asn Leu Pro Met Leu Phe Gly Gly Gly Asp Pro Asn Leu 980 985 990 Leu Tyr Arg Ser Phe Tyr Arg Arg Thr Pro Asp Phe Leu Thr Giu Ala 995 1000 1005 Ile Val His Ser Val Phe Val Leu Ser Tyr Tyr Thr Gly His Asp Leu 1010 1015 1020 Gin Asp Lys Leu Gin Asp Leu Pro Asp Asp Arg Leu Asn Lys Phe Leu 1025 1030 1035 1040 Thr Cys Val Ile Thr Phe Asp Lys Asn Pro Asn Ala Giu Phe Val Thr *1045 1050 1055 Leu Met Arg Asp Pro Gin Ala Leu Gly Ser Glu Arg Gin Ala Lys Ile .1060 1065 1070 Thr Ser Giu Ile Asn Arg Leu Ala Val Thr Giu Val Leu Ser Ile Ala **1075 1080 1085 Pro Asn Lys Ile Phe Ser Lys Ser Ala Gin His Tyr Thr Thr Thr Giu 1090 1095 1100 Ile Asp Leu Asn Asp Ile Met Gin Asn Ile Giu Pro Thr Tyr Pro His *1105 1110 1115 1120 *Gly Leu Arg Val Val Tyr Giu Ser Leu Pro Phe Tyr Lys Ala Giu Lys 1125 1130 1135 Ile Val Asn Leu Ile Ser Gly Thr Lys Ser Ile Thr Asn Ile Leu Giu 1140 1145 1150 Lys Thr Ser Ala Ile Asp Thr Thr Asp Ile Asn Arg Ala Thr Asp Met 1155 1160 1165 Met Arg Lys Asn Ile Thr Leu Leu Ile Arg Ile Leu Pro Leu Asp Cys 1170 1175 1180 343 Asn Lys Asp Lys Arg Giu Leu Leu Ser Leu Giu Asn Leu Ser Ile Thr 1185 1190 1195 1200 Giu Leu Ser Lye Tyr Val Arg Giu Arg Ser Trp, Ser Leu Ser Asn Ile 1205 1210 1215 Val Gly Val Thr Ser Pro Ser Ile Met Phe Thr Met Asn Ile Lys Tyr 1220 1225 1230 Thr Thr Ser Thr Ile Ala Ser Gly Ile Ile Ile Giu Lys Tyr Asn Val 1235 1240 1245 Aen Ser Leu Thr Arg Giy Glu Arg Gly Pro Thr Lye Pro Trp Val Gly 1250 1255 1260 Ser Ser Thr Gin Giu Lys Lys Thr Met Pro Val Tyr Asn Arg Gin Val 1265 1270 1275 1280 Leu Thr Lys Lys Gin Arg Asp Gin Ile Asp Leu Leu Ala Lye Leu Asp 1285 1290 1295 Trp Val Tyr Ala Ser Ile Asp Asn Lys Asp Giu Phe Met Glu Giu Leu 1300 1305 1310 :Ser Thr Gly Thr Leu Gly Leu Ser Tyr Giu Lys Ala Lys Lye Leu Phe 1315 1320 1325 Pro Gin Tyr Leu Ser Val Asn Tyr Leu His Arg Leu Thr Val Ser Ser 1330 1335 1340 Arg Pro Cys Glu Phe Pro Ala Ser Ile Pro Ala Tyr Arg Thr Thr Aen 1345 1350 1355 1360 Tyr His Phe Asp Thr Ser Pro Ile Aen His Val Leu Thr Glu Lye Tyr 1365 1370 1375 Gly Asp Giu Asp Ile Asp Ile Val Phe Gin Aen Cys Ile Ser Phe Gly 1380 1385 1390 Leu Ser Leu Met Ser Val Val Giu Gin Phe Thr Asn Ile Cys Pro Asn *1395 1400 1405 Arg Ile Ile Leu Ile Pro Lys Leu Aen Giu Ile His Leu Met Lye Pro 1410 1415 1420 Pro Ile Phe Thr Gly Asp Val Asp Ile Ile Lye Leu Lye Gin Val Ile 1425 1430 1435 1440 Gin Lye Gin His Met Phe Leu Pro Asp Lye Ile Ser Leu Thr Gin Tyr 1445 1450 1455 Val Glu Leu Phe Leu Ser Asn Lye Ala Leu Lye Ser Gly Ser His Ile 344 1460 1465 1470 Aen Ser Asn Leu Ile Leu Val His Lys Met Ser Asp Tyr Phe His Asn 1475 1480 1485 Ala Tyr Ile Leu Ser Thr Asn Leu Ala Gly His Trp Ile Leu Ile Ile 1490 1495 1500 Gin Leu Met Lye Asp Ser Lys Gly Ile Phe Glu Lys Asp Trp Gly Giu 1505 1510 1515 1520 Gly Tyr Ile Thr Asp His Met Phe le. Asn Leu Asn Val Phe Phe Asn 1525 1530 1535 Ala Tyr Lys Thr Tyr Leu Leu Cys Phe His Lys Gly Tyr Gly Lys Ala 1540 1545 1550 Lye Leu Giu Cys Asp Met Asn Thr Ser Asp Leu Leu Cys Val Leu Giu 1555 1560 1565 Leu Ile Asp Ser Ser Tyr Trp Lye Ser Met Ser Lye Val Phe Leu Giu 1570 1575 1580 Gin Lye Val Ile Lye Tyr Ile Val Asn Gin Asp Thr Ser Leu Arg Arg 1585 1590 1595 1600 I .le Lys Gly Cys Hie Ser Phe Lys Leu Trp Phe Leu Lye Arg Leu Aen 1605 1610 1615 Ala Lye Phe Thr Val Cye Pro Trp Val Val Aen Ile Asp Tyr His 1620 1625 1630 *Pro Thr His Met Lye Ala Ile Leu Ser Tyr Ile Asp Leu Val Arg Met 1635 1640 1645 Gly Leu Ile Aen Val Asp Lye Leu Thr Ile Lye Aen Lye Asn Lye Phe 1650 1655 1660 **Aen Asp Giu Phe Tyr Thr Ser Asn Leu Phe Tyr Ile Ser Tyr Aen Phe 1665 1670 1675 1680 Ser Asp Asn Thr His Leu Leu Thr Lye Gin Ile Arg Ile Ala Aen Ser .**1685 1690 1695 Glu Leu Giu Asp Aen Tyr Asn Lye Leu Tyr His Pro Thr Pro Giu Thr 1700 1705 1710 Leu Giu Asn Met Ser Leu Ile Pro Val Lye Ser Aen Asn Ser Aen Lye 1715 1720 1725 Pro Lye Phe Cys Ile Ser Gly Aen Thr Glu Ser Met Met Met Ser Thr 1730 1735 1740 345 Phe Ser Ser Lys Met His Ile Lys Ser Ser Thr Val Thr Thr Arg Phe 1745 1750 1755 1760 Asn Tyr Ser Lys Gin Asp Leu Tyr Asn Leu Phe Pro Ile Val Val Ile 1765 1770 1775 Asp Lys Ile Ile Asp His Ser Giy Asn Thr Ala Lys Ser Asn Gin Leu 1780 1785 1790 Tyr Thr Thr Thr Ser His Gin Thr Ser Leu Val Arg Asn Ser Ala Ser 1795 1800 1805 Leu Tyr Cys Met Leu Pro Trp His His Val Asn Arg Phe Asn Phe Val 1810 1815 1820 Phe Ser Ser Thr Gly Cys Lys Ile Ser Ile Giu Tyr Ile Leu Lys Asp 1825 1830 1835 1840 Leu Lys Ile Lys Asp Pro Ser Cys Ile Ala Phe Ile Gly Giu Giy Ala 1845 1850 1855 Gly Asn Leu Leu Leu Arg Thr Val Val Glu Leu His Pro Asp Ile Arg 1860 1865 1870 :e*Tyr Ile Tyr Arg Ser Leu Lys Asp Cys Asn Asp His Ser Leu Pro Ile *1875 1880 1885 *Giu Phe Leu Arg Leu Tyr Asn Gly His Ile Asn Ile Asp Tyr Gly Glu .1890 1895 1900 Asn Leu Thr Ile Pro Ala Thr Asp Ala Thr Asn Asn Ile His Trp Ser **1905 1910 1915 1920 Tyr Leu His Ile Lys Phe Ala Giu Pro Ile Ser Ile Phe Val Cys Asp 1925 1930 1935 *Ala Giu Leu Pro Val Thr Ala Asn Trp Ser Lys Ile Ile Ile Glu Trp 1940 1945 1950 *Ser Lys His Val Arg Lys Cys Lys Tyr Cys Ser Ser Val Asn Arg Cys 1955 1960 1965 Ile Leu Ile Ala Lys Tyr His Ala Gin Asp Asp Ile Asp Phe Lys Leu 1970 1975 1980 Asp Asn Ile Thr Ile Leu Lys Thr Tyr Val Cys Leu Gly Ser Lys Leu 1985 1990 1995 2000 Lys Gly Ser Giu Val Tyr Leu Ile Leu Thr Ile Gly Pro Ala Asn Ile 2005 2010 2015 346 Leu Pro Val Phe Asp Val Val Gin Asn Ala Lys Leu Ile Leu Ser Arg 2020 2025 2030 Thr Lys Asn Phe Ile Met Pro Lys Lys Thr Asp Lys Giu Ser Ile Asp 2035 2040 2045 Ala Asn Ile Lys Ser Leu Ile Pro Phe Leu Cys Tyr Pro Ile Thr Lys 2050 2055 2060 Lys Gly Ile Lys Thr Ser Leu Ser Lys Leu Lys Ser Val Val Asn Gly 2065 2070 2075 2080 Asp Ile Leu Ser Tyr Ser Ile Ala Gly Arg Asn Glu Val Phe Ser Asn 2085 2090 2095 Lys Leu Ile Asn His Lys His Met Asn Ile Leu Lys Trp Leu Asp His 2100 2105 2110 Val Leu Asn Phe Arg Ser Ala Giu Leu Asn Tyr Asn His Leu Tyr Met 2115 2120 2125 Ile Glu Ser Thr Tyr Pro Tyr Leu Ser Glu Leu Leu Asn Ser Leu Thr 2130 2135 2140 *Thr Asn Giu Leu Lys Lys Leu Ile Lys Ile Thr Gly Ser Val Leu Tyr *2145 2150 2155 2160 *Aen Leu Pro Asn Giu Gin 2165 INFORMATION FOR SEQ ID NO:29: SEQUENCE CHARACTERISTICS: LENGTH: 15219 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii)MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: ACGGGAAAA.A AATGCGTACT ACAAACTTGC ACATTCGAAA AAAATGGGGC AAATAAGAAC TTGATAAGTG CTATTTAAGT CTAACCTTTT CAATCAGAAA~ TGGGGTGCAA TTCACTGAGC 120 ATGATAAAGG TTAGATTACA AAATTTATTT GACAATGACG ALAGTAGCATT GTTAAAAATA 180 ACATGTTATA CTGATAAATT AATTCTTCTG ACCA.ATGCAT TAGCCAAAGC AGCAATACAT 240 347 C.

C

C

Cs CC..

C

ACAATTAAAT

GATAACAATA

TACATATGGG

AATTGTGAAA

CAAATATCTG

TAGACATGTG

AATAAACTCA

GATTGATGAT

AAGAAATCAT

TTGATGAA.AG

AAGTAGGGAG

CCATGCCTAT

AACACACTCC

CCCAACCAAA

CATTTTAGTA

TGGCTCTTAG

GCAAATACAC

AAAAACACCT

TCACAGGATT

AGATACTTAA

GTCAAGATAT

CAGAAATACA

AGATGGGAGA

TGTGTATAGC

CAGTAA.TTAG

TACCAAAGGA

TAAACGGCAT

TTGTAGTGA.A

AATTGATTGA

TCAAkATTTTC

ACTTACTTGG

TTTATTACCA

CCTAATCAAT

CACAGACATG

CACACACAAA

ACAAGCTACA

TACCAAATAC

ATTTATCAAT

TATAATATAC

CCAAACTATT

ATTAAAAATA

CAAAGTCAAG

TATTCAACGT

AAACAAACTA

AATAGGTATG

AGATGCTGGA

A.AATGGAAAG

AGTCAATATT

AGTGGCTCCA

TGCACTTGTG

GAGGGCAAAc

TATAGCTAAC

AGTTTTTATA

ATCTAkACTTT

GTTGACACAC

TAAA.AGACTA

GCTTGATCTC

TTTTAGTTAA

CAAACCATGA

AGACCCCTGT

TTCATATACT

TTTACATTCT

AAAAAATACA

CACGGCGGGT

AAATATGACC

CCTCAAACAA

AAAGTAAAGC

TTGAATGATA

AGTACAGGAG

TGTGGTATGC

TTATATGCTA

TATCATGTTA

GAAATGAAAT

GAGATAGAAT

GAATATAGGC

ATAACCAAAT

AATGTCTTAA

AGTTTTTATG

CATGTTATAA

ACAkACAATGC

TGCTCTCAAT

AGTGACTCAG

AATTCATGAA

TATAAAAACT

GCACTACAAA

CAATGGATTC

TGATAAACAA

TAGTCAATTA

CTGAATATAA

TTCTAGAATG

TCAACCCGTG

CAGTGCTCAA

CALATAACATA

CATTAAATAA

ATAATATTGA

TATTAATCAC

TGTCCAGGTT

AAGCTAATGG

TCGAAGTATT

CTAGAAAGTC

ATGATTCTCC

TAGCAGCAGG

AAAACGAAAT

AAGTGTTTGA

CAAGCAGTGA

CAATACTACA

TAAACGGTTT

TAATGACTAA

TTATGTTTAG

CATCAAAGGG

TGACAACACT

AATAATAACA

TGAATGTATT

TGAGATGAAG

TACAAAATAT

TATTGGCATT

A.ATTCCAACA

TAGTTAAGAA

AATTGGGGCA

GGATCAGCTG

CACTCCCAAT

TGAAGATGCA

AGGAAGGGAA

AGTAGATATA

AACATTATCA

CTACAAAAA

AGACTGTGGG

AGACAGATCA

AAAACGATAC

AAAACACCCT

AGTGTGCCCT

AAATGGAGGA

AATGGATGAT

TTATATGAAT

TCTAATTCAA

AAATGGGGCA

ACTATGCAA.A

TCTCTTACCA

GTAAGAA.AAC

CTACTGCACA

GGCACTTTCC

AAGCCTACAA

AAA.AAACCAA

GGAGCTAATC

AATACAAAGA

CTGTCATCCA

TATGATGTGC

AATCATAAAT

GACACTATAA

ACAACATATC

AGCTTGACAT

ATGCTAAAAG

ATGATAATAC

GGTCTTACAG

AAGGGCCTCA

CATCTTATAG

300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 348

S

S

S S

ATGTTTTCGT

GAATCTTTGC

GAGTTTTAGC

TGGAGCAAGT

ACCATATATT

CAAGTGTGGT

CAAGAAACCA

GAGTAATAAA

AACTCAACCC

AGTCAACATG

CAAATTCCTA

TAGCATAATA

TGGCACCAAC

CTACCCAAGA

TTCTAAGTTG

CTCATATGAA

TGATGAAAAA

ACCCACTTCA

AGAAAAAATA

TAGGAATGAG

AACTTCCAAA

TGATGATTTT

TCAATCCATT

CCAATCAATC

AAAAGAACAA

GCACTTTGGC

AGGATTGTTT

CAAATCTGTA

TGTGGA.AGTC

GAACA-ATCCA

CCTAGGC.T

GGATCTTTAT

CTACAGTGTA

CAAAGAAGAT

GAGAAGTTTG

GAATCAATA

TCTGTTAACT

ATCATCAATC

AAACCCCTAG

TACAAGGA

GAGATAAATG

TTAAGTGAIA

GCTCGCGATG

AGAGCGGAAG

GAAAGCGAAA

AAATTGAGTG

TGATCAGCGA

GAATCAACTG

AACCAATTGA

GATGGGGCA2A

ATTGCACAAT

ATGA.ATGCCT

AAAAATATCA

TATGAGTATG

AAAGCATCAT

GCAGCAGGTC

GATGCAGCTA

TTAGACTTAA

GATGTAGAGC

CACCTGAATT

AGGGCAAGTT

CAATAGATAT

CAACAAGTGA

TAAGCTTCAA

CAATAGAAAC

ATCAAACAA

TATTAGGAAT

GAATAAGAGA

CATTAATGAC

AAATGGCAAA

ACTTGTTGGA

TCAACTCACT

CCAGACCGAA

TCAATCAGCA

ATATGGAAAC

CATCCACAAG

ATGGTTCAGG

TGCTAGGACA

CACAGAAGTT

TGCTGTCATT

TAGGCATAAT

AAGCATATGC

CAGCAGAAGA

TTTAAGTTAA

TCATGGAGA

CGCATCATCC

AGAAGTAACT

AGCCGACAGT

AGAAGATCTC

ATTTGATAAC

TGACAACATT

GCTCCATACA

TGCTATGGTT

CAATGATAGG

AGACACCTCA

AGACAACGAT

CAGCAATCAA

CAAACAAACG

ACCCGACAA

ATACGTGAAC

AGGGGGTAGI

GCAAGTAATG

TGCTAGTGTC

GGGAGGAGAA

AACTCAATTT

GGGAGAGTAT

AGAGCAACTC

ATTGGAAGCC

CAAAAAATAC

GATGCAIAATA

AAAGATCCTA

AAAGAGAGCC

ACCCCAGAAA~

ACCCCAAGTG

AATGAAGAAG

ACAGCAAGAC

TTAGTAGTTG

GGTCTAAGAG

TTAGAGGCTA

GATGAAGTGT

AGTGACAATG

CAACATCAAT

TCCATCAGTA

ATTAACAATA

AAGCTTCACG

AGAGTTGAAG

CTAAGATGGG

CAGGCAGAAA

GCTGGATTCT

CCCAACTTCT

AGAGGTACAC

AAAGAAAATG

ATAAAGCATC

GGGGCA;ATA

ACAAAGCTAC

AGAAGAAAGA

CGATAACATC

CAAAAGCCAA

ACAACCCTTT

AATCTAGCTA

TAGATAGA.AT

CAAGTGCAGG

AAGAGATGAT

TGGCAAGACT

CTCTTAATCC

ATCTATCACT

AAAACAGACA

GAACCACCAA

TAGTAACAAA

AAGGCTCCAC

1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360

*SSSSS

S

S S *5

S.C.

S 5 ATACACAGCA GCTGTTCAGT ACAATGTTCT AGAAAAAGAT GATGATCCTG CATCACTAAC 349 AATATGGGTG CCTATGTTCC AGTCATCTGT GCCAGCAGAC TTGCTCATAA AAGAACTTGC

S

AAGCATCAAT

GATTA-ACTCA

TGTATCATTA

AGCATGCAGT

CATGAAGACA

GACATCAAAA

TCTGAACTCA

AATTATTCCT

CAAATATATC

GAGCATATAT

ACTAGAGGAT

ACACACTATA

CCACTCAAAA

AAATAAAACC

CATTTATACC

ACAATAGAAT

CTAATCTTTT

CATAAAGCAT

AGTTCTACCA

CTTCTCACAG

TATTTAAAAA

AATGCAACCA

GATACTCTTA

ATAGCACAAA

GCCATAATAT

ATACTAGTGA

AGAAGTGCTG

GATGAAAGAA

CTAACATGCT

TTCAACCCCA

AGAGTAATAA

CTAGAAAATA

TATGCAGGAT

AALACCACAGA

TATGTGACTA

TAAACTTAAT

TCCAILACATC

TCCAAAATCA

AAALATATGGG

GCCAATTCAA

TCACAAGCAA

TACTAATTAT

TCTGTAACAA

TTATGCTGTG

AGTCATGGTG

TTAACATAAT

TGTCCAAACA

ATCATCTAAT

TAGCACTATC

TCATCATCTC

AGCAGATCTC

TGCTGGCTCA

GCAAATTAGC

TAAAAGTAAA

CTCATGAGAT

TACCA.ACCTA

TAGCALACCAC

TAGTGTTAGT

GTCAATTTAT

CTAATTGGAA

TATCAACACT

ATAALACATCT

CTACCAGCCA

GTAAATAGAC

CACATATACT

ATTTTGGCCC

A.ATCACTATT

AACTCTTGAA

TCAAATTATA

TCGCAAAACC

GATGAATTGT

CAAGAATCA

TGTAATATCC

AGTTTTGGCA

TGCCAATCAC

GCATACAGCT

GAATGACAGG

ACACTACACA

CTATCTGCTA

ATTAGTTAGA

ATAALATCTTA

TATTTTACAC

ATGATTGCAA

CTAGGACAGA

ATCCTGTATA

ACGCTAA CTA

TAGTATGAGA

CGCACTGCCA

TCTTGTTTAT

ATGATAATCT

AAAGTTACAC

ACACGTTTTT

TCCACATATA

CTTCATCACA

GACCTAGAGT

GTTCAATCAA

AAATGGGAAA

TAATACATAT

TACTAALATAA

TGTATCAAAT

TATAAACAAA

TCATGGTAGC

TCAAAAACAA

GGACTCTAGA

ACAGATTAAA

CAACCTCTCT

TAACAACGGT

TACGCCCAAA GGACCTTCAC AATGCCTAGT AATTTCATCA ATATGATGTA ACTACACCTT ALAGTATGTTA ACTACAGTCA CATTGCTCTA TGTGAATTTG TCTAAGATCA ATTAGTGTCA CGA.ATTCAAA AATGCTATCA TATCACAGTT ACTGACAATA AGTAGATCTT GGTGCCTACC

TACGAGTCAC

TAAGCGCAAA

GTGA.AATCAA

A.AGATCTTAC

AAAATATTAT

AGAACAAGGA

CCAATGCAAA

AAGGAGCATT

TAGAAAAAGA

CAATCAAACC

TCCTCAAACT

CAAACCAATC

GCGAATAGGT

TCTTAkACAAC

TACATCCATC

GATCTTAACT

GCTAAGTGAA

CAACACATAG

CAAkATCCAAT

ATAGAGTAGT

CATTGGGGCA

AAAGACCTGG

TTTAAAATCT

CATAATTGCA

CACAGTTCAA

3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 41.40 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 350 a.

S.

4

ACAATAAAAA

AGGGTTAGTT

ACATCACCCA

ACCACTTCAA

AAAGATGATT

CAACTTTGCA

ATCAAACCCA

GCCAAAACGA

ACAGAAAGAG

ACAGTCCAAC

ACACCCACAG

TAGTTATTCA

AAACCTGGGG

TCTTGCTATT

ATCGACATGT

TAGTGTCATA

TAAAGTAAAA

GCTACTTATG

TATGAACTAC

ACGAAGATTT

ATCAA.AAGTT

AAACAAAGCT

TCTCAAGAAT

CTCCAACATT

CAGAGAATTT

ACCACACTGA

CATCCAAGCA

ATACAAALATC

CACAGACCAA

ACCATTTTGA

AATCCATCTG

CAAACA.AACC

CGAAAAAAGA

ACACCAGCAC

AGCAATCCCT

CATCCGAGCC

AAIAACTACAT

CAAATAACCA

AATGCATTGT

AGTGCAGTTA

ACAATAGAAT

CTTATGAAAC

CAAAACACAC

ACAATCAATA

CTAGGCTTCT

CTACACCTTG

GTAGTCAGTT

TACATAAATA

GAAACAGTTA

AGTGTCAATG

AAAAAACATC

ACCCACAACC

AGAAACACAC

CAAGCCA.AGC

AGTGTTCAAC

CAAAACAATA

AACCACCAAA

AACTACCACC

CTCACAATCC

CCTCTCAACC

CTCCACACCA

CTTAGCAGAG

TGGAGTTGAT

ACCTCACCTC

GCAGAGGTTA

TAAGTAATAT

AAGAATTAGA

CAGCTGTCAA

CCACTAAAAA

TGTTAGGTGT

AAGGAGAAGT

TATCAAATGG

ACCAATTATT

TAGAATTCCA

CAGGTGTAAC

ACCACCTACC

ACATCACCAA

CATACAACAG

ACAAAACCAC

TTCGTTCCCT

CCAAGCAACA

ACCACAAACA

AACCCAACAA

ACTGCACTCG

ACCCCCGAAA

AACTCCACCC

AACCGTGATC

GATCCACAAG

AAGTCAG.ZAC

TTTTAGTGCT

AAAAGAAACC

TAAGTATAAG

CAACCGGGCC

CCTAAATGTA

GGGATCTGCA

GAACAAGATC

GGTCAGTGTT

ACCCATAGTA

GCAGAAGAAC

AACACCTTTA

CTACTCAAGT

TCCACACAAG

CACAAACCAA

GTCCAAAAAA

GCAGTATATG

AACCA.AAGAA

AAAGAGACCC

A.AJAAACTAAC

ACACAACCAC

ACACACCCAA

AAAAA-ACCCA

TATCAAGCAA

TCAAGTGCAA

ATAACTGAGG

TTAAGAACAG

AAATGCAATG

AATGCAGTAA

AGAAGAGAAG

TCAATAAGCA

ATAGCAAGTG

AA.AAATGCTT

TTAACCAGCA

AATCAACAGA

AGCAGATTGT

AGCACTTACA

CTCACCAGA.A

TTCAGCTACA

AGGCAGAACC

TCCACCAAA

TGGCAACAAT

GAAACCAACC

AAAAACACCA

CCTCAAGACC

ATTAAAACAC

CTCCACACAA

GCCACATGCT

GAACGAAATT

TCTTCCTAAC

AGTTTTACCA

GTTGGTATAC

GAACTGACAC

CAGAATTACA

CACCACAGTA

AGAAGAGGAA

GTATAGCTGT

TGTTGTCTAC

AAGTGTTAGA

GCTGTCGCAT

TGGWATCAC

TGTTGACAAA

4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 CAGTGAGTTA CTATCATTAA TCAATGATAT GCCTATAACA AATGATCAGA AAAAATTAAT 351

S

S..

GTCAAGCAAT

AGAAGTCCTT

GAAATTGCAC

AACAAGGACT

GGCTGACACT

ATTACCAAGT

AATTATGACA

GTCATGCTAT

ATTTTCTAAT

CACTTTATAC

AATAAATTAC

AGTCAATGAA

TAATGTAAAT

CATTGTAGTA

CACACCAGTT

ATAGACAA;A

CAACTTACAA

TACCCACATA

ATCAACCACT

AGAAATCCTT

AGTCATA.ATT

AACAPLGATAC

GCTGIAACTGG

ATAGGATCTA

ATTGAGATCA

GTTCAGATAG

GCATATGTTG

ACATCGCCTC

GATAGAGGAT

TGTAAAGTAC

GAAG3TCAGCC

TCAAAAACAG

GGTAAAACTA

GGTTGTGACT

TATGTAAACA

TATGACCCTC

AAAATCAATC

ACTGGCAAAT

TTGTTATCAT

ACACTAAGCA

AACCACCTGA

CAAATATTTC

ACTAAGCTAG

AAATCAACAC

GTAAATTTGA

ACTTTGAATG

TCAAGTCAAT

ATAGAACAGA

TAAACAACAT

ATAGTGATGA

TAAGGCAzACA

TACAGCTGCC

TATGCACTAC

GGTATTGTGA

AGTCCAATCG

TTTGTAACAC

ACATAAGCAG

AATGCACTGC

ATGTGTCAAA

AGCTGGA.AGG

TAGTGTTTCC

AAAGTTTAGC

CTACTACAAA

TAATAGCTAT

AAGACCAACT

TCATGTTTCA

AACATCACAG

ATCCTTAACT

ATCATTCACA

GATTAGAGGT

GCCTCCTCAT

GGACAAA.AGC

AGAATATGCT

AACAAAACAA

CATTAAAAAG

AAGTTATTCC

TATCTATGGT

CAACATCAA.A

TAATGCAGGA

AGTATTTTGT

TGACATA'XTC

CTCAGTAATT

AT CCAACAAA

CAA.AGGAGTA

CAAGAACCTT

TTCTGATGAG

TTTTATTCGT

TATTATGATA

TGGTTTACTG

AAGTGGAATC

ACAACAATCT

TACAGGCTGA.

TATAGTTACA

AZAATTAACAG

CATTGCTTGA

GCATTACTAG

ATAGACACTT

CTTGGTATAG

TCAGC-ATGTG

ATCATGTCTA

GTAATAGATA

GAAGGATCAA

TCAGTATCCT

GACACTATGA

AATTCCAAGT

ACTTCTCTTG

AATCGTGGGA

GATACTGTGT

TATGTAAAAG

TTTGATGCAT

AGATCTGATG

ACTACAATTA

TTGTATTGTA

AATAATATTG

GCTGACCACC

ATCATTTCCT

TAAAAACCTC

CTGGGGCAAA

ATGGTAGAAG

TGAGGCAAAA

rGTCTGAAAT rTGGAGTGCT

TTGCTATGAG

TAATAAAGGA

CACCTTGCTG

ATATTTGTTT

TCTTTCCACA

ACAGTTTGAC

ATGACTGCAA

GAGCTATAGT

TTATAAAGAC

CAGTGGGCAA

GGGAACCTAT

CAATATCTCA

AATTACTACA

TTATAGTAAT

AAGCCAAAAA

CATTCAGCAA

A.ATCCCAAAT

CACATCATGC

A.AGTATCACA

TATGTCGCGA

ATGTCACTAC

CTTCATGTTA

A~AGTGGAGCT

A~GAGAGTTAC

TAAACTTCTT

CAATTCACCT

6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 CTTAGAGATA ATGAAGAACC AAGATAAGAG TGTACA.ATAC TGTTATATCA TACATTGAGA GCAATAGAAA

AAACAACAAG

352

CAAACCATCC

ACATTAGATA

CAAAATGACC

CATATTGATC

TAACCATAAC

TTGGACACCT

TGAAGATATA

TCATCCAACC

GGAAACTCTG

GAGTGTAATG

AACTTAATTA

ACACAGTCAT

TTCCAGTCAT

AACTTACTTA

ATCTTGAATA

GATGAAAACT

AATCAATCAT

ACAACACTCT

TGGTTCAATT

AAAAGTCATG

AATCAATATG

AATCAATTTT

TGGATAAGTA

AATGTTGTGT

GAAGGCTTCT

ACAGAAGAAG

ATCTGCTCAA

TCCACAAAAG

AAACCAAAAA

TCA.AGTGAAA

TATTTGGATA

AAAAACTTAT

TATACAGTAT

ATAAAACTAT

CTAATGTGTA

CTTTAGGGAG

GTAGACAALAG

TAATATCTAG

TACTTATGAC

AAAAAATAAT

AACTAGGATT

CAGTACTTAC

ATACAAATTC

TGAAAAAATT

TATATACAAA

GGTTTATATT

GTTGTATCGT

TGACATGGAA

ATTGTTTAAA

TATCACAATT

ACATA.ATAAA

ATCALATTTAG

GAGACTACCA

CATAACCATA

TAATGATATT

GCATGGTTGC

ACCACCAGCG

TAGATGCCAC

ATATATTAGT

TTTGATAAGG

TCTAACTGAT

TTATCTTTTT

CCCACTACTA

ATATCATAA.A

ATATAAAAGT

ACGAAGAGCC

AAAGGAAAAG

AACTATAATT

AGACAAALAGT

GATGTGTTCA

ATTAAATAAC

AATAGATAAT

TTATCATAL

AGACATCAGC

TACATTAAAC

ATTTCTTTAT

AGAAGTAGAG

GAAACGATTT

GCAGACGTGC

AGCAATCCAA

ACCGGATAAA

TACATTCA-AT

TTTATTAA-AT

TCAACAATTT

GTCATAATGC

TTATGGGACA

AGTTATTTAA

AACGGCCCTT

GAGCATATGA

GGTGAACTGA

ATGTCCTCGT

ATAGAAATAA

GACAGAGTTA

AAAGATGATA

CACTCAGTAA

ATGCAACATC

ATATTAACAC

CAAACTTTAA

GGACTCAAAA

CTTAGCAGAT

AAAAGCTTAG

GGAGATTGTA

GGATTTATTA

TATAATAGCA

TGAAGAAGAC

AAGAGTCAAC

TATCCTTGTA

CATAAAAACA

CATATATTTG

CTCCA.ACATC

TTGACCATAA

AAATGGATCC

AAGGTGTTAT

ATCTTAAAA

AT CT TAAAAA

AATTAGAAGA

CTGAACAAAT

GTGATGTAAA

AGCCCAACAA

TACTTTCGGC

ATCAAAATAT

CTCCATCATG

AATATCGATC

GTGGTTTTCA

AAATCACAAC

TAAATGTTTG

GGCTGAGATG

TACTGAAATT

TGTCTTTAAT

TGCTAAATAA

AATAAAGAAC

TGTGAATGAT

GTATATCATC

TATTACAATT

ATGAAATTCA

TTAACATCCC

CGACTCTATG

CATTATTAAT

CTCTTTTTCA

TGATTACACC

ACTAACTATA

ACCAACTTAT

TGCTACAACT

GGTGTACGCC

TALATTCAGGT

TGTGGAAAAC

CACTATCAA.A

GTTAATACAC

AAATGAGGTA

GTTTATTTTA

TACTACTTAC

CTTAATTACT

TGGATTCAAT

ATTTCATAAT

TCTAAACATA

CATCACAGAT

8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9420 9480 9540 9600 353 GCAGCTATTA AGGCTCAAAA GGACCTACTA TCAAGAGTAT GTCACACTTT ATTAGACAAG 9660

ACAGTGTCTG

TTGATTAAGC

AGAATCTTTG

TGTAATGAAA

TATAGAATCA

ATTGTCCTAC

GAAATCACAG

CTGCCTAAA-A

GATCTAATAT

GAACATGAAA

TTGAGAGATA

CTCAACAACT

AGAATGTTTG

ATAGCTGA7A

CTTCAAAAGA

AACTACAACA

GCATTTAGAT

CAATCTCTGT

AGACATGCAC

AGTGGATTAT

ATTGALAGCTA

CTGATAAATG

CAGACCCATG

GAGTATGCAG

CAGTTCATGA

ATAATATCAT

TTGCAGGTGA

GACATCCAAT

CTAAGTTCTA

TAAAAGGGTT

CTCTAAGATG

AAAATGATTT

AAGTGGATCT

GGACTAGTTT

AGTTGA.AGTT

ATAA.ATTCAA

CTAATCACGT

CTATGCAACC

ATATTTTACA

TATTAGAATT

ATTATATCAG

ATGAAACATC

TCTCTTGGTT

CTCCTTTCAT

ACAGATATCA

TATCATTATT

GTGATAATCA

CACAAGCAGA

GTATAGGCCA

GCAAALACAAT

AAATGGTAAA

TAATAATCTC

GGTCGATGAA

CTTATTALAGT

TGTAAATACC

GTTAAACTAC

GATTATTTTA

TGAA.ATGATA

TCCTAGAAAT

CTCTGAAAGC

TGAATGCGAT

GGTATCACTA

AGGTATGTTT

ATTCTTCCCT

AAAAGCAGGA

TAAATGTTCT

ATGTATCTGC

GCATTTAACA

AAAGGATCAT

TATGGGTGGT

AGATCTAATA

GTCALATTGAT

TTATTTGTTA

TAAGCTTALAG

CCAGCACAAT

TGGATAATCC

AATAACTTGA

AGACAAGCAA

AGTCTAAGTA

TACAACAGAT

TATAAACTTA

TCAGGATTGC

ATAAATGACA

TACATGCCAT

GACAGATCGA

CTATACAATT

ACTGGTAAAG

AGGCAAATCC

GAGAGTTTGA

ATAAGCAACA

ATCATTACAG

AGTGATGTAT

ATACCTCTTG

GTTGTTAATC

ATTGAGGGCT

TCTCTCAAAG

ATAAGCAAAC

GCATTAAATA

GGAACAGAGA

GGAGTGTACT

TATTAAGTAA

GTGAGCTATA

TGGATTCTGT

CATTAAGAGG

GGCCCACCTT

ATACTTATCC

GGTTCTATCG

AAGCCATTTC

CACATATACA

GAAGAGTACT

GTGTAGTCAA

AAAGAGAGCT

AAATCTTAGC

CAAGATATGG

AGTCAAATCG

ATCTTAGCAA

TAGATGAACT

TCACAATAAT

TTAATGAGGT

GGTGTCAA

GGAA)ATTCTC

CAGTTAGACT

GCCTTAAATT

CCTATATATC

ATCCAGCCAG

ATTTCTTAAA

TTTTCTCTTC

AAGAATTAAC

TGCTTTCATT

AAGGAATGCT

ATCTCTACTT

TGAGTTTCAT

ACCTCCAAAA

AAATTATATA

AGAGTATTAC

TCAILAGCTAT

CAGTGTAGGT

AGAGAAAATG

TGATCTAGAG

TTATAATGAT

ATTCAATCAG

GCATGGAGTA

ATGTACATAT

TGATGAACAA

ACTGTGGACC

TATCACAGCT

TATAGAGGGT

GTTATATAAA

CCGAGATATG

TATCAAAAAA

9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 354

GTCCTGAGAG

TCTATAGGCA

ATATTTAGGA

TGTAACAATA

AATCTTGATA

GGTGGTGATC

GAAGCTATAG

AAGCTCCAGG

GATAA.AAATC

GAAAGGCAAG

ATAGCCCCAA

CTAAATGACA

GAAAGTTTAC

ATAACTAATA

GATATGATGA

GACAAAAGAG

AGAGAAAGAT

ACAATGGACA

AATGTTAATA

ACGCAGGAGA

GACCAAATAG

GAATTCATGG

TTGTTTCCAC

TGTGAATTCC

CCTATCAATC

AATTGCATAA

TAGGTCCATG

GCTTAACACA

ACATTTGGTT

AGCTATATTT

GCATTGATAT

CTAATTTGTT

TACATTCAGT

ATCTTCCAGA

CCAATGCCGA

CTAAAATTAC

ACAAAATATT

TTATGCAAAA

CTTTTTATAA

TACTTGAAA

GGAAAAATAT

AGTTATTAAG

CTTGGTCATT

TTAAATATAC

GTTTAACTCG

AAAAAACAAT

ATTTATTAGC

AAGAACTGAG

AITATCTAAG

CTGCATCAAT

ATGTATTAAC

GTTTTGGTCT

GATAAACACG

GGAGTTAGAA

ATACAATCAA

AGATATATTG

GGCTTTATCA

ATATCGAAGC

GTTTGTGTTG

TGATAGACTG

GTTTGTAACA

TAGTGAGATT

TTCTAAAAGT

TATAGAACCA

AGCAGAAAAA

AACATCAGCA

AACTTTACTT

TTTAGAAAAT

ATCCAATATA

AACTAGCACT

TGGTGAAAGA

GCCAGTGTAC

AAAATTAGAC

TACTGGAACA

TGTCAATTAT

ACCAGCTTAT

AGAAAAGTAT

TAGCCTGATG

ATACTTGATG

TACAGAGGAG

ATTGCTTTGC

AAAGTATTAA

TTGTATATGA

TTTTATAGGA

AGCTATTATA

AACAAATTCT

TTGATGAGGG

AATAGATTAG

GCACAACATT

ACTTACCCTC

ATAGTTAATC

ATAGATACAA

ATAAGGATAC

CTTAGTATAA~

GTAGGAGTAA~

ATAGCCAGTG

GGACCCACCA

AACAGACAAG

TGGGTATATG

CTTGGACTGT

TTACACCGTT

AGAACAACAA~

GGAGATGAAG

TCGGTTGTGG

ATTTTAAAGT

AAAGCTTATT

AACTCCGAAA

AACACTTAAA

ATTTGCCTAT

GAACTCCAGA

CTGGTCACGA

TGACATGTGT

ATCCACAGGC

CAGTAACAGA

ATACTACCAC

ATGGATTAAG

TTATATCAGG

CTGATATTAA

TTCCACTAGA

CTGAATTAAG

CATCGCCAAG

GTATAATAAT

AGCCATGGGT

TTTTAACCAA

CATCCATAGA

CATATGAAAA

TAACAGTCAG

ATTATCATTT

ATATCGACAT

AACAkTTCAC

TAGTTTAGAA

ATGCAGTTTA

TCATGCATTA

AACTTTTTTT

GCTGTTTGGT

CTTCCTTACA

TTTACAAGAT

CATCACATTT

TTTAGGGTCT

AGTCTTAAGT

TGAGATTGAT

AGTTGTTTAT

AACAAAATCC

TAGGGCTACT

TTGTAACA7A

CAAGTATGTA

TATTATGTTC

AGAAAAATAT

AGGCTCATCC

AAAGCAAAGA

CAACAAAGAT

AGCCAAAAAG

TAGTAGACCA

TGATACTAGT

TGTGTTTCAA

AAACATATGT

11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 a '1 a *.aa a 355 CCTAATAGAA TTATTCTCAT ACCGALAGCTG AATGAGATAC ATTTGATGAA

ACCTCCTATA

4 *4 *4 4 4 *44*44 4 444444

TTTACAGGAG

CTACCAGATA

AAATCTGGAT

CATAATGCTT

ATGAAAGATT

ATGTTCATTA

AALAGGTTATG

TTGGAGTTAA

GTCATAAAZAT

TTTAAGTTGT

GTTAACATAG

AGAATGGGGT

GAATTTTACA

CTAACAAAAC

CACCCAACCC

AACAAACCTA

AGTAAALATGC

TTGTACAATT

GCAAALATCTA

GCATCACTTT

TCCACAGGAT

AGTTGTATAG

CTTCATCCAG

CCTATTGAAT

ACCATTCCTG

ATGTTGATAT

AALATAAGTTT

CTCACATCAA

ATATTTTA.AG

CAAA.AGGTAT

ATTTGAATGT

GTAAAGCAAA

TAGACAGTAG

ACATAGTCAA

GGTTTTTA;A

ATTATCACCC

TAATAAATGT

CATCAAATCT

AAATAAGAAT

CAGAAACTTT

AATTTTGTAT

ATATTAAATC

TATTTCCAAT

ACCAACTTTA

ATTGCATGCT

GCAAGATCAG

CATTCATAGG

ACATAAGATA

TTCTAAGGTT

CTACAGATGC

CATCAAGTTG

AACCCAATAT

CTCTAATTTA

TACTAATTTA

TTTTGAAAAA

TTTCTTTAAT

ATTAGAATGT

CTACTGGAAA

TCAAGACACA

ACGCCTTAAT

AACACACATG

AGATAAATTA

CTTTTACATT

TGCTAATTCA

AGAA.AATATG

AAGTGGAAAT

TTCCACTGTT

TGTTGTGATA

CACCACCACT

TCCTTGGCAT

TATAGAGTAT

TGAAGGAGCT

CATTTACAGA

ATACAACGGG

AACTAATAAC

AAGCAAGTGA

GTAGAATTAT

ATATTAGTAC

GCTGGACATT

GATTGGGGAG

GCTTATAAGA

GATATGAACA

TCTATGTCTA

AGTTTGCGTA

AATGCTAAAT

AAAGCTATAT

ACCATTAAAA

AGTTATAACT

GAATTAGAAG

TCATTAATTC

ACCGAATCTA

ACCACAAGAT

GACAAGATTA

TCACATCAGA

CATGTCAATA

ATTTTAAAG

GGTAACTTAT

AGTTTAAAAG

CATATAAACA

ATTCATTGGT

TACAA-AAGCA

TCTTAAGTAA

ATAAAATGTC

GGATTCTGAT

AGGGGTACAT

CTTATTTGCT

CTTCAGATCT

AAGTTTTCCT

GAATAAAAUGG

TTACCGTATG

TATCTTACAT

ATAAAACAA

TTTCAGACAA

ATAATTATAA

CTGTTAAAAG

TGATGATGTC

TCAATTATAG

TAGATCATTC

CATCTTTAGT

GATTTAACTT

ATCTTAAGAT

TATTACGTAC

ATTGCAATGA

TAGATTATGG

CTTATTTACA

GCACATGTTC

CAAAGCACTT

TGATTATTTT

TATTCAACTT

AACTGATCAT

ATGTTTTCAT

TCTTTGTGTT

AGAACAAAAA

CTGTCACAGT

CCCTTGGGTT

AGATTTAGTT

ATTCAATGAT

CACTCATTTG

CAA.ACTATAT

TAATAATAGT

AACATTCTCT

CAAACAAGAC

AGGTAATACA

AAGGAATAGT

TGTATTTAGT

TAAGGACCCC

GGTAGTAGAA

TCATAGTTTA

TGAGAATTTA

TATAAAATTT

12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 356

GCAGAACCTA

AAAATTATAA

AGATGCATTT

ATTACTATAT

TTAATCCTTA

AAATTGATAC

ATCGATGCAG

ATTAAGACTT

ATAGCTGGAC

CTAAAATGGC

TACATGATAG,

GAGCTCAAGA

TAGTTTAAA

TAGTTATTAA

TTTTAGTCTT

TTAGCATCTT

TTGAATGGAG

TAATTGCAAA

TAAAAACTTA

CAATAGGCCC

TTTCAAGA2AC

ATATTAAAAG

CATTGTCAA

GTAATGAAGT

TAGATCATGT

AGTCCACATA

AGCTGATTAA

TATCATTAAC

AAAATATACA

AAGGGGTTAA

TGTCTGCGAT

TAAGCATGTA

ATATCATGCT

CGTGTGCCTA

TGCAAATATA

TAAAATTTC

CTTAATACCT

ATTGAAGAGT

ATTCAGCAAC

TTTAAATTTT

TCCTTACTTA

AATAACAGGT

AAGTTTGGTC

AACTTTTCAA

ATAAAAGTCT

GCTGAATTAC

AGAAAGTGCA

CAAGATGACA

GGTAGCAAGT

CTTCCTGTTT

ATTATGCCTA

TTCCTTTGTT

GTAGTTAATG

AAGCTTATAA

AGATCAGCTG

AGTGAATTGT

AGTGTGCTAT

AAATTTAGAT

TAATTTAGCA

AAAACTAACA

TTTTCTCGT

CTGTTACAGC

AGTACTGTTC

TTGATTTCAA

TAAAAGGATC

TTGATGTTGT

AAAAAACTGA

ACCCTATAAC

GAGATATATT

ACCACAAGCA

AACTTAATTA

TAAATAGTTT

ACAACCTTCC

GCTAACACAT

TATTGATTCC

ATTATACATG

CAATTGGAGT

TTCTGTAA.AT

ATTAGATAAC

TGAAGTTTAC

ACAAAATGCT

CAAGGAATCT

AAAAAAAGGA.

ATCATATTCT

TATGAATATC

CAATCATTTA

AACAACCAAT

CALACGAACAG

CATTATATTA

AAAATTATCA

TGCATTCACA

14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15219 ACACAACGAG ACATTAGTTT

TTGACACTTT

INFORMATION FOR SEQ ID SEQUENCE

CHARACTERISTICS:

LENGTH: 2166 amino acids TYPE: amino acid STRANflEDNESS: TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID Met Asp Pro Ile Ile Asn Gly Asn Ser Ala Asn Val Tyr Leu Thr Asp 1 5 10 Ser Tyr Leu Lys Gly Val Ile Ser Phe Ser Glu Cys Asn Ala Leu Gly 357 25 Ser Tyr Leu Phe Asn Giy Pro Tyr Leu Lys Asn Asp Tyr Thr Asn Leu 40 Ile Ser Arg Gin Ser Pro Leu Leu Giu His Met Asn Leu Lys Lys Leu 55 Thr Ile Thr Gin Ser Leu Ile Ser Arg Tyr His Lys Giy Glu Leu Lys 70 75 Leu Giu Giu Pro Thr Tyr Phe Gin Ser Leu Leu Met Thr Tyr Lys Ser 90 Met Ser Ser Ser Giu Gin Ile Ala Thr Thr Asn Leu Leu Lys Lys Ile 100 i05 Ile Arg Arg Aia Ile Giu Ile Ser Asp Vai Lye Val Tyr Ala Ile Leu 115 120 125 Asn Lye Leu Gly Leu Lys Giu Lye Asp Arg Vai Lye Pro Asn Asn Asn 130 135 140 Ser Gly Asp Giu Asn Ser Val Leu Thr Thr Ile Ile Lys Asp Asp Ile *145 150 155 160 Leu Ser Ala Val Giu Asn Asn Gin Ser Tyr Thr Asn Ser Asp Lys Ser *165 170 175 His Ser Val Aen Gin Asn Ile Thr Ile Lys Thr Thr Leu Leu Lye Lys 180 185 190 *Leu Met Cys Ser Met Gin His Pro Pro Ser Trp, Leu Ile His Trp Phe 195 200 205 Asn Leu Tyr Thr Lys Leu Asn Asn Ile Leu Thr Gin Tyr Arg Ser Aen **210 215 220 Giu Val Lys Ser His Gly Phe Ile Leu Ile Asp Aen Gin Thr Leu Ser 225 230 235 240 *Gly Phe Gin Phe Ile Leu Asn Gin Tyr Gly Cys Ile Val Tyr His Lye 245 250 255 Gly Leu Lye Lye le Thr Thr Thr Thr Tyr Asn Gin Phe Leu Thr Trp, 260 265 270 Lye Asp Ile Ser Leu Ser Arg Leu Asn Val Cys Leu Ile Thr Trp Ile 275 280 285 Ser Asn Cys Leu Asn Thr Leu Asn Lye Ser Leu Giy Leu Arg Cys Gly d. -7 v 295 358 Asn Asn Val Val Leu Ser Gin Leu Phe Leu Tyr Gly Asp Cys Ile 310'AI9-

S

.5

S

.5 S. S S *5 S

S

S.

S

S.

S

S

a.

S 5@

S

Leu Giy Arg Ile Asp 385 Leu Asn Met Giu Phe 465 Pro Tyr Leu Lys Pro 545 Lys Phe Lys Lys 370 Lys Ser Asn Vali Thr 450 Ile Thr Lye Ile Lys 530 Lys Leu Ile Arg 355 Aia Thr Lye Leu Asp 435 Lye Tyr Leu Leu Ile 51i5 Vai Asp Phe Met 340 Phe Gin Vai Phe Ser 420 Giu Phe Arg Arg Asn 500 Leu Asp Leu His 325 Ser Tyr Lye Ser Leu 405 Giu Arg Tyr Ile Asn 485 Thr Ser Leu Ile Asn Leu Asn Asp Asp 390 Lys Leu Gin Leu Ile 470 Aila Tyr Giy Giu Trp 550 Giu Ile Ser Leu 375 Asn Leu Tyr Aia Leu 455 Lys Ile Pro Leu Met 535 Thr Giy Leu Met 360 Leu Ile Ile Phe Met 440 Ser Giy Vai Ser Arg 520 Ile Ser Phe Asn 345 Leu Ser Ile Lye Leu 425 Asp Ser Phe Leu Leu 505 Phe Ile Phe Tyr 330 Ile Asn Arg Aen Leu 410 Phe S er Leu Vai Pro 490 Leu Tyr Asn Pro Ile Thr Asn Vai Gly 395 Ala Arg Vai Ser Asn 475 Leu Glu Arg Asp Arg 555 Ile Giu Ile cys 380 Lye Giy Ile Arg Thr 460 Thr Arg Ile Giu Lys 540 Asn Lye Giu Thr 365 His Trp Asp Phe Ile 445 Leu Tyr Trp Thr Phe 525 Aila Tyr Giu Asp 350 Asp Thr Ile Aen Giy 430 Aen Arg Asn Leu Giu 510 His Ile Met Val2 335 Gin Aia Leu Ile Asn 415 His Cys Giy Arg Asn 495 Asn Leu Ser Pro Giu Phe Ala Leu Leu 400 Leu Pro Aen Aila Trp 480 Tyr Asp Pro Pro Ser 560 His Ile Gin Asn Tyr Ile Giu His Giu Lys 570 Leu Lys Phe Ser Giu Ser 575 359 Asp Arg Ser Arg Arg Val Leu Glu Tyr Tyr Leu Arg Asp Asn Lys Phe 580 585 590 Asn Glu Cys Asp Leu Tyr Asn Cys Val Val Asn Gin Ser Tyr Leu Asn 595 600 605 Asn Ser Asn His Val Val Ser Leu Thr Gly Lys Glu Arg Glu Leu Ser 610 615 620 Val Gly Arg Met Phe Ala Met Gin Pro Gly Met Phe Arg Gin Ile Gin 625 630 635 640 Ile Leu Ala Glu Lys Met Ile Ala Glu Asn Ile Leu Gin Phe Phe Pro 645 650 655 Glu Ser Leu Thr Arg Tyr Gly Asp Leu Glu Leu Gin Lys Ile Leu Glu 660 665 670 Leu Lys Ala Gly Ile Ser Asn Lys Ser Asn Arg Tyr Asn Asp Asn Tyr 675 680 685 Asn Asn Tyr Ile Ser Lys Cys Ser Ile Ile Thr Asp Leu Ser Lys Phe 690 695 700 0* S*Asn Gin Ala Phe Arg Tyr Glu Thr Ser Cys Ile Cys Ser Asp Val Leu 705 710 715 720 *000 Asp Glu Leu His Gly Val Gin Ser Leu Phe Ser Trp Leu His Leu Thr 725 730 735 Ile Pro Leu Val Thr Ile Ile Cys Thr Tyr Arg His Ala Pro Pro Phe 740 745 750 Ile Lys Asp His Val Val Asn Leu Asn Glu Val Asp Glu Gin Ser Gly 755 760 765 S. Leu Tyr Arg Tyr His Met Gly Gly Ile Glu Gly Trp Cys Gin Lys Leu 770 775 780 Trp Thr Ile Glu Ala Ile Ser Leu Leu Asp Leu Ile Ser Leu Lys Gly 785 790 795 800 Lys Phe Ser Ile Thr Ala Leu Ile Asn Gly Asp Asn Gin Ser Ile Asp 805 810 815 Ile Ser Lys Pro Val Arg Leu Ile Glu Gly Gin Thr His Ala Gin Ala 820 825 830 Asp Tyr Leu Leu Ala Leu Asn Ser Leu Lys Leu Leu Tyr Lys Glu Tyr 835 840 845 Ala Gly Ile Gly His Lys Leu Lys Gly Thr Glu Thr Tyr Ile Ser Arg 360 850 855 860 Asp Met Gin Phe Met Ser Lys Thr Ile Gin His Ann Giy Vai Tyr Tyr 865 870 875 880 Pro Ala Ser Ile Lys Lys Val Leu Arg Val Gly Pro Trp Ile Ann Thr 885 890 895 Ile Leu Asp Asp Phe Lys Val Ser Leu Glu Ser Ile Giy Ser Leu Thr 900 905 910 Gin Giu Leu Glu Tyr Arg Gly Giu Ser Leu Leu Cys Ser Leu Ile Phe 915 920 925 Arg Ann Ile Trp Leu Tyr Ann Gin Ile Ala Leu Gin Leu Arg Ann His 930 935 940 Ala Leu Cys Asn Ann Lys Leu Tyr Leu Asp Ile Leu Lys Val Leu Lys 945 950 955 960 His Leu Lye Thr Phe Phe Ann Leu Asp Ser Ile Asp Met Ala Leu Ser *965 970 975 :Leu Tyr Met Ann Leu Pro Met Leu Phe Gly Gly Gly Asp Pro Asn Leu 980 985 990 *Leu Tyr Arg Ser Phe Tyr Arg Arg Thr Pro Asp Phe Leu Thr Giu Ala 995 1000 1005 Ile Val His Ser Val Phe Vai Leu Ser Tyr Tyr Thr Gly His Asp Leu 1010 1015 1020 Gin Asp Lye Leu Gin Asp Leu Pro Asp Asp Arg Leu Asn Lys Phe Leu 1025 1030 1035 1040 Thr Cys Val Ile Thr Phe Asp Lye Ann Pro Ann Ala Giu Phe Val Thr 1045 1050 1055 Leu Met Arg Asp Pro Gin Ala Leu Gly Ser Giu Arg Gin Ala Lye Ile 1060 1065 1070 Thr Ser Giu Ile Ann Arg Leu Ala Val Thr Giu Val Leu Ser Ile Ala 1075 1080 1085 Pro Ann Lye Ile Phe Ser Lye Ser Ala Gin His Tyr Thr Thr Thr Glu 1090 1095 1100 Ile Asp Leu Ann Asp Ile Met Gin Asn Ile Giu Pro Thr Tyr Pro His 1105 1110 1115 1120 Gly Leu Arg Val Val Tyr Giu Ser Leu Pro Phe Tyr Lye Ala Glu Lye 1125 1130 1135 361 Ile Val Asn Leu Ile Ser Gly Thr Lys Ser Ile Thr Asn Ile Leu Giu 1140 1145 1150 Lys Thr Ser Ala Ile Asp Thr Thr Asp Ile Asn Arg Ala Thr Asp Met 1155 1160 1165 Met Arg Lys Asn Ile Thr Leu Leu Ile Arg Ile Leu Pro Leu Asp Cys 1170 1175 1180 Asn Lys Asp Lys Arg Giu Leu Leu Ser Leu Glu Asn Leu Ser Ile Thr 1185 1190 1195 1200 Giu Leu Ser Lys Tyr Val Arg Glu Arg Ser Trp Ser Leu Ser Asn Ile 1205 1210 1215 Val Gly Val Thr Ser Pro Ser Ile Met Phe Thr Met Asp Ile Lys Tyr 1220 1225 1230 Thr Thr Ser Thr Ile Ala Ser Gly Ile le Ile Glu Lys Tyr Aen Val 1235 1240 1245 Asn Ser Leu Thr Arg Gly Giu Arg Gly Pro Thr Lye Pro Trp Val Giy 1250 1255 1260 *Ser Ser Thr Gin Glu Lys Lys Thr Met Pro Val Tyr Asn Arg Gin Val *1265 1270 1275 1280 Thr Lys Lys Gin Arg Asp Gin Ile Asp Leu Leu Ala Lys Leu Asp 1285 1290 1295 **Trp Val Tyr Ala Ser Ile Asp Asn Lys Asp Giu Phe Met Giu Glu Leu 1300 1305 1310 Ser Thr Gly Thr Leu Gly Leu Ser Tyr Glu Lys Ala Lys Lys Leu Phe 1315 1320 1325 *.Pro Gin Tyr Leu Ser Val Asn Tiyr Leu His Arg Leu Thr Val Ser Ser 1330 1335 1340 Arg Pro Cys Glu Phe Pro Aia Ser Ile Pro Ala Tyr Arg Thr Thr Asn *::*1345 1350 1355 1360 Tyr His Phe Asp Thr Ser Pro Ile Asn His Val Leu Thr Giu Lys Tyr 1365 1370 1375 Gly Asp Glu Asp Ile Asp Ile Val Phe Gin Aen Cys Ile Ser Phe Gly 1380 1385 1390 Leo Ser Leu Met Ser Val Val Glu Gin Phe Thr Asn Ile Cys Pro Asn 1395 1400 1405 362 Arg Ile Ile Leu Ile Pro Lys Leu Asn Giu Ile His Leu Met Lys Pro 1410 1415 1420 Pro Ile Phe Thr Gly Asp Val Asp Ile Ile Lys Leu Lys Gin Val Ile 1425 1430 1435 1440 Gin Lys Gin His Met Phe Leu Pro Asp Lys Ile Ser Leu Thr Gin Tyr 1445 1450 1455 Vai Giu Leu Phe Leu Ser Asn Lys Ala Leu Lys Ser Giy Ser His Ile 1460 1465 1470 Asn Ser Asn Leu Ile Leu Vai His Lys Met Ser Asp Tyr Phe His Asn 1475 1480 1485 Ala Tyr Ile Leu Ser Thr Asn Leu Ala Giy His Trp Ile Leu Ile Ile 1490 1495 1500 Gin Leu Met Lys Asp Ser Lys Giy Ile Phe Giu Lys Asp Trp Gly Giu 1505 1510 1515 1520 Gly Tyr Ile Thr Asp His Met Phe Ile Asn Leu Asn Vai Phe Phe Asn 1525 1530 1535 .Ala Tyr Lys Thr Tyr Leu Leu Cys Phe His Lys Gly Tyr Gly Lys Ala *..1540 1545 1550 .*.Lys Leu Glu Cys Asp Met Asn Thr Ser Asp Leu Leu Cys Val Leu Giu *..1555 1560 1565 Leu Ile Asp Ser Ser Tyr Trp Lys Ser Met Ser Lys Val Phe Leu Giu 1570 1575 1580 Gin Lys Val Ile Lys Tyr Ile Val Asn Gin Asp Thr Ser Leu Arg Arg 1585 1590 1595 1600 Ile Lys Gly Cys His Ser Phe Lys Leu Trp Phe Leu Lys Arg Leu Asn 1605 1610 1615 Asn Ala Lys Phe Thr Val Cys Pro Trp Val Val Asn Ile Asp Tyr His *1620 1625 1630 Pro Thr His Met Lys Ala Ile Leu Ser Tyr Ile Asp Leu Val Arg Met 1635 1640 1645 Gly Leu Ile Asn Val Asp Lys Leu Thr Ilie Lys Asn Lys Asn Lys Phe 1650 1655 1660 Asn Asp Giu Phe Tyr Thr Ser Asn Leu Phe Tyr Ile Ser Tyr Asn Phe 1665 1670 1675 1680 Ser Asp Asn Thr His Leu Leu Thr Lys Gin Ile Arg Ile Ala Asn Ser 363 1685 1690 1695 Giu Leu Giu Asp Asn Tyr Asn Lys Leu Tyr His Pro Thr Pro Glu Thr 1700 1705 1710 Leu Giu Asn Met Ser Leu Ile Pro Val Lys Ser Asn Asn Ser Asn Lys 1715 .1720 1725 Pro Lyse Phe Cys Ile Ser Gly Asn Thr Glu Ser Met Met Met Ser Thr 1730 1735 1740 Phe Ser Ser Lys Met His Ile Lys Ser Ser Thr Val Thr Thr Arg Phe 1745 1750 1755 1760 Asn Tyr Ser Lys Gin Asp Leu Tyr Asn Leu Phe Pro Ile Val Val Ile 1765 1770 1775 Asp Lys Ile Ile Asp His Ser Gly Asn Thr Ala Lys Ser Asn Gin Leu 1780 1785 1790 Tyr Thr Thr Thr Ser His Gin Thr Ser Leu Val Arg Asn Ser Ala Ser 1795 1800 1805 *Leu Tyr Cys Met Leu Pro Trp His His Val Asn Arg Phe Asn Phe Vai *1810 1815 1820 Phe Ser Ser Thr Gly Cys Lys Ile Ser Ile Glu Tyr Ile Leu Lys Asp 1825 1830 1835 1840 Leu Lye Ile Lys Asp Pro Ser Cys Ile Ala Phe Ile Gly Giu Gly Ala 1845 1850 1855 .e Giy Asn Leu Leu Leu Arg Thr Val Val Glu Leu His Pro Asp Ile Arg 1860 1865 1870 Tyr Ile Tyr Arg Ser Leu Lys Asp Cys Asn Asp His Ser Leu Pro Ile *1875 1880 1885 Giu Phe Leu Arg Leu Tyr Asn Giy His Ile Asn Ile Asp Tyr Giy Giu 1890 1895 1900 Asn Leu Thr Ile Pro Ala Thr Asp Ala Thr Asn Asn Ile His Trp Ser 1905 1910 1915 1920 Tyr Leu His Ile Lye Phe Ala Giu Pro Ile Ser Ile Phe Val Cys Asp 1925 1930 1935 Ala Giu Leu Pro Val Thr Ala Asn Trp Ser Lys Ile Ile Ile'Glu Trp 1940 1945 1950 Ser Lys His Val Arg Lys Cys Lye Tyr Cys Ser Ser Val Aen Arg Cys 1955 1960 1965 364 Ile Leu Ile Ala Lys Tyr His Ala Gin Asp Asp Ile Asp Phe Lys Leu 1970 1975 1980 Asp Asn Ile Thr Ile Leu Lys Thr Tyr Val Cys Leu Gly Ser Lys Leu 1985 1990 1995 2000 Lys Gly Ser Giu Val Tyr Leu Ile Leu Thr Ile Gly Pro Ala Asn Ile 2005 2010 2015 Leu Pro Val Phe Asp Val Val Gin Asn Ala Lys Leu Ile Leu Ser Arg 2020 2025 2030 Thr Lys Asn Phe Ile Met Pro Lys Lys Thr Asp Lys Giu Ser Ile Asp 2035 2040 2045 Ala Asp Ile Lys Ser Leu Ile Pro Phe Leu Cys Tyr Pro Ile Thr Lys 2050 2055 2060 Lys Gly Ile Lys Thr Ser Leu Ser Lye Leu Lys Ser Val Val Asn Gly 2065 2070 2075 2080 *Asp Ile Leu Ser Tyr Ser Ile Ala Gly Arg Asn Glu Vai Phe Ser Asn *2085 2090 2095 *..Lys Leu Ile Aen His Lys His Met Asn Ile Leu Lys Trp Leu Asp His :::2100 2105 2110 *Val Leu Asn Phe Arg Ser Ala Giu Leu Asn Tyr Asn His Leu Tyr Met 2115 2120 2125 Sle Giu Ser Thr Tyr Pro Tyr Leu Ser Glu Leu Leu Asn Ser Leu Thr 2130 2135 2140 Thr Asn Giu Leu Lye Lye Leu Ile Lye Ile Thr Gly Ser Val Leu Tyr 2145 2150 2155 2160 *Aen Leu Pro Asn Giu Gin 2165 INFORMATION FOR SEQ ID NO:31: SEQUENCE CHARACTERISTICS: LENGTH: 15219 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) 365 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: ACGGGAAAAA AATGCGTACT ACAAACTTGC ACATTCGAAA AAAATGGGGC AAATAAGAAC a.

TTGATAAGTG

ATGATAAAGG

ACATGTTATA

ACAATTAAAT

GATAACAATA

TACATATGGG

AATTGTGAALA

CAAATATCTG

TAGACATGTG

AATAAACTCA

GATTGATGAT

AAGAAATCAT

TTGATGAAAG

AAGTAGGGAG

CCATGCCTAT

AACACACTCC

CCCAACCAAA

CATTTTAGTA

TGGCTCTTAG

GCAAATACAC

AAAAACACCT

TCACAGGATT

AGATACTTAA

GTCAPLGATAT

CTATTTA.AGT

TTAGATTACA

CTGATAAATT

TAAACGGCAT

TTGTAGTGAA

AATTGATTGA

TCAAATTTTC

ACTTACTTGG

TTTATTACCA

CCTAATCAAT

CACAGACATG

CACACACAAA

ACAAGCTACA

TACCAAATAC

ATTTATCAAT

TATAATATAC

CCAAACTATT

ATTAAAAATA

CAAAGTCAAG

TATTCAACGT

AAACAAACTA

AATAGGTATG

AGATGCTGGA

A7LATGGAAAG

CTAACCTTTT

AAATTTATTT

AATTCTTCTG

AGTTTTTATA

ATCTAACTTT

GTTGACACAC

TAAAAGACTA

GCTTGATCTC

TTTTAGTTAA

CAAACCATGA

AGACCCCTGT

TTCATATACT

TTTACATTCT

AAAAALATACA

CACGGCGGGT

AAATATGACC

CCTCAAACAA

AAAGTAAAGC

TTGAATGATA

AGTACAGGAG

TGTGGTATGC

TTATATGCTA

TATCATGTTA

GAAATGAAAT

CAATCAGAAA

GACAATGACG

ACCAATGCAT

CATGTTATA.A

ACAACAATGC

TGCTCTCAAT

AGTGACTCAG

AATT CAT GA.A

TATAAAALACT

GCACTACAAA

CAkATGGATTC

TGATAAACAA

TAGTCAATTA

CTGA.ATATALA

TTCTAGAATG

TCAACCCGTG

CAGTGCTCAA

CAATAACATA

CATTAAATAA

ATAATATTGA

TATTAATCAC

TGTCCAGGTT

AAGCTAATGG

TCGAAGTATT

TGGGGTGCAA

AAGTAGCATT

TAGCCAAAGC

CAAGCAGTGA

CAATACTACA

TAAACGGTTT

TAATGACTAA

TTATGTTTAG

CATCAXAGGG

TGACAACACT

AATA.ATAACA

TGAATGTATT

TGAGATGAAG

TACAA.AATAT

TATTGGCATT

AATTCCAACA

TAGTTAAGA-A

AATTGGGGCA

GGATCAGCTG

CACTCCCAAT

TGAAGATGCA

AGGAAGGGAA

AGTAGATATA

AACATTATCA

TTCACTGAGC

GTTAAAAATA

AGCAATACAT

AGTGTGCCCT

AAATGGAGGA

ALATGGATGAT

TTATATGAAT

TCTAATTCALA

AA.ATGGGGCA

ACTATGCAAA

TCTCTTACCA

GTAAGAAAAC

CTACTGCACA

GGCACTTTCC

AAGCCTACAA

AAAAAACCAA

GGAGCTAATC

AATACAAAGA

CTGTCATCCA

TATGATGTGC

AATCATAAAT

GACACTATAA

ACAACATATC

AGCTTGACAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 a a a a 366

CAGAAATACA

AGATGGGAGA

TGTGTATAGC

CAGTAATTAG

TACCAAAGGA

ATGTTTTCGT

GAATCTTTGC

GAGTTTTAGC

TGGAGCAAGT

ACCATATATT

CA.AGTGTGGT

CAAGAAACCA

GAGTAATAAA

AACTCAACCC

AGTCAACATG

CAAATTCCTA

TAGCATAATA

TGGCACCAAC

CTACCCAAGA

TTCTAAGTTG

CTCATATGAA

TGATGAAAAA

ACCCACTTCA

AGAAAAAATA

TAGGAATGAG

AGTCAATATT

AGTGGCTCCA

TGCACTTGTG

GAGGGCAAAC

TATAGCTAAC

GCACTTTGGC

AGGATTGTTT

CAAATCTGTA

TGTGGAAGTC

GAACAATCCA

CCTAGGCAAT

GGATCTTTAT

CTACAGTGTA

CAAAGAAGAT

GAGAAGTTTG

GAATCAATAA

TCTGTTAACT

ATCATCAATC

AAACCCCTAG

TACAAGGAAA

GAGATAAATG

TTAAGTGAAA

GCTCGCGATG

AGAGCGGAAG

GAAAGCGAAA

GAGATAGAAT

GAkATATAGGC

ATAACCA.AAT

AATGTCTTAA

AGTTTTTATG

ATTGCACAAT

ATGAATGCCT

AAAAATATCA

TATGAGTATG

AAAGCATCAT

GCAGCAGGTC

GATGCAGCTA

TTAGACTTAA

GATGTAGAGC

CACCTGAATT

AGGGCA.AGTT

VAATAGATAT

CAACAAGTGA

TAAGCTTCAA

CAATAGAAAC

ATCAAACAAA

TATTAGGAAT

GAATAAGAGA

CATTAATGAC

AAATGGCAAA

CTAGAAAGTC

ATGATTCTCC

TAGCAGCAGG

AAAACGAAAT

AAGTGTTTGA

CAT CCACAAG

ATGGTTCAGG

TGCTAGGACA

CACAGAAGTT

TGCTGTCATT

TAGGCATAAT

AAGCATATGC

CAGCAGAAGA

TTTAAGTTAA

TCATGGAGAA

CGCATCATCC

AGAAGTAACT

AGCCGACAGT

AGAAGATCTC

ATTTGATAAC

TGACAACATT

GCTCCATACA

TGCTATGGTT

CAATGATAGG

AGACACCTCA

CTACAAAAAA

AGACTGTGGG

AGACAGATCA

A.AAACGATAC

AAAACACCCT

AGGGGGTAGT

GCAAGTAATG

TGCTAGTGTC

GGGAGGAGAA

AACTCAATTT

GGGAGAGTAT

AGAGCAACTC

ATTGGAAGCC

CAAAAAATAC

GATGCAAATA

AAAGATCCTA

AAAGAGAGCC

ACCCCAGAAA

ACCCCAAGTG

AATGAAGAAG

ACAGCAAGAC

TTAGTAGTTG

GGTCTAAGAG

TTAGAGGCTA

GATGAAGTGT

ATGCTAAAAG

ATGATAATAC

GGTCTTACAG

AAGGGC CTCA

CATCTTATAG

AGAGTTGAAG

CTAAGATGGG

CAGGCAGAA.A

GCTGGATTCT

CCCAACTTCT

AGAGGTACAC

AAAGAAAATG

ATAAAGCATC

GGGGCAAATA

ACAAAGCTAC

AGAAGAAAGA

CGATAACATC

CAAAAGCCAA

ACAACCCTTT

AATCTAGCTA

TAGATAGAAT

CAAGTGCAGG

AAGAGATGAT

TGGCAAGACT

CTCTTAATCC

1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 AACTTCCAAA AAATTGAGTG ACTTGTTGGA AGACAAcGAT AGTGACAATG ATCTATCACT 367 .000 0 .0 0 0* 0 **00

TGATGATTTT

TCAATCCATT

CCAATCAATC

A.AAAGAACAA

ATACACAGCA

AATATGGGTG

AAGCATCAAT

GATTA.ACTCA

TGTATCATTA

AGCATGCAGT

CATGAAGACA

GACATCAAAA

TCTGAACTCA

AATTATTCCT

CAAATATATC

GAGCATATAT

ACTAGAGGAT

ACACACTATA

CCACTCAAAA

AAATAAAACC

CATTTATACC

ACAATAGAAC

CTAATCTTTT

CACAAAGCAT

AGTTCCACCA

CCTCTCACAG

TGATCAGCGA

GAATCAACTG

AACCAATTGA

GATGGGGCAA

GCTGTTCAGT

CCTATGTTCC

ATACTAGTGA

AGAAGTGCTG

GATGAAAGAA

CTAACATGCT

TTCAACCCCA

AGAGTAATAA

CTAGAAIAATA

TATGCAGGAT

AALACCACAGA

TATGTGACTA

TAAACTTAAT

TCCAAACATC

TCCAAAATCA

AAAATATGGG

GCCAATTCAA

TCACAAGCAA

TACTAATTAT

TCTGCAACAA

TTATGCTGTG

AGTCACGGTG

TCAACTCACT

CCAGACCGAA

TCAATCAGCA

ATATGGAAAC

ACAATGTTCT

AGTCATCTGT

AGCAGATCTC

TGCTGGCTCA

GCAAATTAGC

TAAAAGTAIA

CTCATGAGAT

TACCAACCTA

TAGCAACCAC

TAGTGTTAGT

GTCAATTTAT

CTA.ATTGGAA

TATCAACACT

ATAILACATCT

CTACCAGCCA

GTAAATAGAC

CACATATACT

ATTTTGGCCC

AATCACTATC

AACTCTTGAA

TCAAACCATA

TCGCAAAACC

CAGCAATCAA

CAAACAAACG

ACCCGACAAA

ATACGTGAAC

AGAAAAAGAT

GCCAGCAGAC

TACGCCCAAA

AATGCCTAGT

ATATGATGTA

AAGTATGTTA

CATTGCTCTA

TCTAAGATCA

CGAATTCA.AA

TATCACAGTT

AGTAGATCTT

GCATACAGCT

GAATGACAGG

ACACTACACA

CTATCCGCTA

ATTAGTTAGA

ATAAATCTTA

TATTTTACAC

ATGATTGCAA

CTAGGACAGA

ATCCTGTATA

ACGCTAACCA

CAACATCAAT

TCCATCAGTA

ATTAACAATA

AAGCTTCACG

GATGATCCTG

TTGCTCATAA

GGACCTTCAC

AATTTCATCA

ACTACACCTT

ACTACAGTCA

TGTGAATTTG

ATTAGTGTCA

AATGCTATCA

ACTGACAATA

GGTGCCTACC

ACACGTTTTT

TCCACATATA

CTTCATCACA

GACCTAGAGT

GTTCAATCAA

AAATGGGAAA

TAATACATAT

CACTAAATAA

TGTACCAAAT

TACAAACAAA

TCATGGTAGC

AAALACAGACA

GAACCACCAA

TAGTAACAA.A

AAGGCTCCAC

CATCACTAAC

AAGAACTTGC

TACGAGTCAC

TAAGCGCAA-A

GTGAAATCAA

AAGATCTTAC

AAAATATTAT

AGAACAAGGA

CCAATGCAAA

AAGGAGCATT

TAGAAAAAGA

CAATCAAACC

TCCTCAAACT

CAAACCAATC

GCGAATAGGC

TCTTAACAAC

TACATCCATC

GATCTTAACT

GCTAAGTGAA

CAACACACAG

CAAATCCAAT

ATAGAGTAGT

3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 368 TATTTAAAAA TTAACATAAT GATGAATTGT TAGTATGAGA TCAAAAACAJA

CATTGGGGCA

AATGCAACCA

TGTCCAAACA

GATACTCTTA

ATCATCTAAT

U

a a a a.

a

ATAGCACAA

GCCATAATAI

ACAATAAAA.A

AGGGTTAGTT

ACATCACCCA

ACCACTTCAA

AAAGATGATT

CAACTTTGCA

ATCAAACCCA

GCCAAAACGA

ACAGAAAGAG

ACAGTCCAAC

ACACCCACAG

TAGTTATTCA

AAACCTGGGG

TCTTGCTATT

ATCGACATGT

TAGTGTCATA

TAAAGTAAA

GCTACTTATG

TATGAACTAC

ACGAAGATTT

ATCAAAAGTT

TAGCACTATC

*TCATCATCTC

*ACCACACTGA

CATCCAAGCA

ATACAAAATC

CACAGACCAA

ACCATTTTGA

AATCCATCTG

CAAACAAACC

CGAAAAAAGA

ACACCAGCAC

AGCAATCCCT

CATCCGAGCC

AAAA.CTACAT

CAAATAACCA

AATGCATTGT

AGTGCAGTTA

ACAATAGAAT

CTTATGAAAC

CA.AAACACAC

ACAATCAATA

CTAGGCTTCT

CTACACCTTG

*CAAGAATCAA

TGTA.ATATCC

AGTTTTGGCA

TGCCAATCAC

AAAAAACATC

ACCCACAAcC

AGAAACACAC

CAAGCCA.AGC

AGTGTTCAAC

CAAAACAATA

AACCACCAAA

AACTACCACC

CTCACAkATCC

CCTCTCAACC

CTCCACACCA

CTTAGCAGAG

TGGAGTTGAT

ACCTCACCTC

GCAGAGGTTA

TAAGTAATAT

AAGAATTAGA

CAGCTGTCAA

CCACTAAAAA

TGTTAGGTGT

AAGGAGAAGT

*CGCACTGCCP,

TCTTGTTTA7

ATGATAATCT

AAAGTTACAC

ACCACCTACC

ACATCACCAA

CATACAACAG

ACAAAACCAC

TTCGTTCCCT

CCAAGCAACA

ACCACAAACA

AACCCAACAA

ACTGCACTCG

ACCCCCGAAA

AACTCCACCC

AACCGTGATC

GATCCACAAG

AAGTCAGAAC

TTTTAGTGCT

AAAAGAAACC

TAAGTATAAG

CAACCGGGCC

CCTAALATGTA

GGGATCTGCA

GAACAAGATC

GGACTCTAGA AAAGACCTGG

ACAGATTAAJP

CAACCTCTCI

TAACAACGGT

CTACTCAAGT

TCCACACAAG

CACAAACCA

GTCCAAAjAJA

GCAGTATATG

AACCAAAGAA

AAAGAGACCC

AAAAACTAAC

ACACAACCAC

ACACACCCAA

AAAAAACCCA

TATCAAGCAA

TCAAGTGA

ATAACTGAGG

TTAAGAACAG

AAATGCAATG

AATGCAGTAA

AGAAGAGAAG

TCAATAAGCA

ATAGCAAGTG

AAAAATGCTT

TTTAAAATCT

CATA.ATTGCA

CACAGTTCAA

CTCACCAGAA

TTCAGCTACA

AGGCAGAACC

TCCACCAAAA

TGGCAACAAT

GAAACCAACC

AAAAACACCA

CCTCAAGACC

ATTAAAACAC

CTCCACACAA

GCCACATGCT

GAACGAAATT

TCTTCCTAAC

AGTTTTACCA

GTTGGTATAC

GAACTGACAC

CAGAATTACA

CACCACAGTA

AGAAGAGGAA

GTATAGCTGT

TGTTGTCTAC

4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 a a a.

a 369 C SC

C

C. Ce C C

C

CC eb C C e

*CCC

C.

C

Ce a. C

AAACAAAGCT

TCTCAAGAAT

CTCCA.ACATT

CAGAGAATTT

CAGTGAGTTA

GTCAAGCAAT

AGAAGTCCTT

GAAATTGCAC

AACAAGGACT

GGCTGACACT

ATTACCAAGT

AATTATGACA

GTCATGCTAT

ATTTTCTAAT

CACTTTATAC

AATAAATTAC

AGTCAATGAA

TAATGTAAAT

CATTGTAGTA

CACACCAGTT

ATAGACAA.AA

CAACTTACAA

TACCCACATA

ATCAACCACT

AGAAATCCTT

AGTCATAATT

GTAGTCAGTT

TACATAAATA

GAAACAGTTA

AGTGTCAATG

CTATCATTAA

GTTCAGATAG

GCATATGTTG

ACATCGCCTC

GATAGAGGAT

TGTAAAGTAC

GAAGTCAGCC

TCAAAAACAG

GGTAAAACTA

GGTTGTGACT

TATGTAAACA

TATGACCCTC

AAAATCAATC

ACTGGCAAAT

TTGTTATCAT

ACACTAAGCA

AACCACCTGA

CAAATATTTC

ACTAAGCTAG

AAATCAACAC

GTAAATTTGA

ACTTTGAATG

TATCAAATGG

ACCAATTATT

TAGAATTCCA

CAGGTGTAAC

TCAATGATAT

TAAGGCAACA

TACAGCTGCC

TATGCACTAC

GGTATTGTGA

AGTCCAATCG

TTTGTALACAC

ACATAAGCAG

AATGCACTGC

ATGTGTCAAA

AGCTGGAAGG

TAGTGTTTCC

AALAGTTTAGC

CTACTACAAA

TAATAGCTAT

AAGACCAACT

TCATGTTTCA

AACATCACAG

ATCCTTA.ACT

ATCATTCACA

GATTAGAGGT

GCCTCCTCAT

GGTCAGTGTT

ACCCATAGTA

GCAGA.AGAAC

AACACCTTTA

GCCTATAACA

AAGTTATTCC

TATCTATGGT

CAACATCAAA

TAATGCAGGA

AGTATTTTGT

TGACATATTC

CTCAGTAATT

ATCCALACAAA

CAAAGGAGTA

CAAGAACCTT

TTCTGATGAG

TTTTATTCGT

TATTATGATA

TGGTTTACTG

A.AGTGGAATC

ACAACAATCT

TACAGGCTGA

TATAGTTACA

AAATTAACAG

CATTGCTTGA

GCATTACT'AG

TTAACCAGCA

AATCAACAGA

AGCAGATTGT

AGCACTTACA

AATGATCAGA

ATCATGTCTA

GTAATAGATA

GAAGGATCAA

TCAGTATCCT

GACACTATGA

AATTCCAAGT

ACTTCTCTTG

AATCGTGGGA

GATACTGTGT

TATGTAAAAG

TTTGATGCAT

AGATCTGATG

ACTACAATTA

TTGTATTGTA

AATAATATTG

GCTGACCACC

ATCATTTCCT

TAAAAACCTC

CTGGGGCA;A

ATGGTAGAAG

TGAGGCAAAA

AAGTGTTAGA

GCTGTCGCAT

TGGAAATCAC

TGTTGACAAA

AAAAATTAAT

TAATAAAGGA

CACCTTGCTG

ATATTTGTTT

TCTTTCCACA

ACAGTTTGAC

ATGACTGCAA

GAGCTATAGT

TTATA2LAGAC

CAGTGGGCAA

GGGAACCTAT

CAATATCTCA

AATTACTACA

TTATAGTAAT

AAGCCAAAAA

CATTCAGCAA

AATCCCAAAT

CACATCATGC

AAGTATCACA

TATGTCGCGA

ATGTCACTAC

CTTCATGTTA

6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740

C

C

C CC C

*CSC

370

AACA.AGATAC

GCTGAACTGG

ATAGGATCTA

ATTGAGATCA

AAGATAAGAG

CAAACCATCC

ACATTAGATA

CAAAATGACC

CATATTGATC

TAACCATAAC

TTGGACACCT

TGAAGATATA

TCATCCAACC

GGAAACTCTG

GAGTGTAATG

AACTTAATTA

ACACAGTCAT

TTCCAGTCAT

AACTTACTTA

ATCTTGAATA

GATGAAAACT

AATCAATCAT

ACAACACTCT

TGGTTCAATT

AAAAGTCATG

AATCAATATG

TCA.AGTCAAT

ATAGAACAGA

TA.AACAACAT

ATAGTGATGA

TGTACAATAC

ATCTGCTCAA

TCCACAAAAG

AAACCAAAAA

TCAAGTGAAA

TATTTGGATA

AA.AAACTTAT

TATACAGTAT

ATAAAACTA'r

CTAATGTGTA

CTTTAGGGAG

GTAGACAAAG

TAATATCTAG

TACTTATGAC

AAAAAATAAT

AACTAGGATT

CAGTACTTAC

ATACAAATTC

TGAAAAAATT

TATATACAAA

GGTTTATATT

GTTGTATCGT

GGACAAAAGC

AGAATATGCT

AACAAAACAA

CATTAAAAAG

TGTTATATCA

GAGACTACCA

CATAACCATA

TAATGATATT

GCATGGTTGC

ACCACCAGCG

TAGATGCCAC

ATATATTAGT

TTTGATAAGG

TCTAACTGAT

TTATCTTTTT

CCCACTACTA

ATATCATAAA

ATATAAAAGT

ACGAAGAGCC

AAAGGAAAAG

AACCATAATT

AGACAAAAGT

GATGTGTTCA

ATTAAATAAC

AATAGATAAT

TTATCATAIA

ATAGACACTT

CTTGGTATAG

TCAGCATGTG

CTTAGAGATA

TACATTGAGA

GCAGACGTGC

AGCAATCCAA

ACCGGATAAA

TACATTCAAT

TTTATTAAAT

TCAACAATTT

GTCATAATGC

TTATGGGACA

AGTTATTTAA

AACGGCCCTT

GAGCATATGA

GGTGAACTGA

ATGTCCTCGT

ATAGAAATAA

GACAGAGTTA

AAAGATGATA

CACTCAGTAA

ATGCAACATC

ATATTAACAC

CAAACTTTAA

GGACTCAAAA

TGTCTGAAAT

TTGGAGTGCT

TTGCTATGAG

ATGAAGA-ACC

GCAATAGAAA

TGAAGAAGAC

AAGAGTCAAC

TATCCTTGTA

CATAAAAACA

CATATATTTG

CTCCAACATC

TTGACCATAA

AAATGGATCC

AAGGTGTTAT

ATCTTAAAAA

ATCTTAAAAA

AATTAGAAGA

CTGAACAAAT

GTGATGTAAA

AGCCCAACAA

TACTTTCGGC

ATCAAAATAT

CTCCATCATG

AATATCGATC

GTGGTTTTCA

AAATCACAAC

AAGTGGAGCT

AGAGAGTTAC

TAAACTTCTT

CAATTCACCT

AAACAACAAG

AATAAAGAAC

TGTGA.ATGAT

GTATATCATC

TATTACAATT

ATGAAATTCA

TTAACATCCC

CGACTCTATG

CATTATTAAT

CTCTTTTTCA

TGATTACACC

ACTAACTATA

ACCAACTTAT

TGCTACAACT

GGTGTACGCC

TAATTCAGGT

TGTGGAAALAC

CACTATCAAA

GTTAATACAC

AAATGiGGTA

GTTTATTTTA

TACTACTTAC

7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 371

AATCAATTTT

TGGATAAGTA

AATGTTGTGT

GAAGGCTTCT

ACAGAAGAAG

GCAGCTATTA

ACAGTGTCTG

TTGATTAAGC

AGAATCTTTG

TGTAATGAAA

TATAGAATCA

ATTGTCCTAC

GAILATCACAG

CTGCCTAAAA

GATCTAATAT

GAACATGAAA

TTGAGAGATA

CTCAACAACT

AGAATGTTTG

ATAGCTGAAA

CTTCAAAAGA

AACTACAACA

GCATTTAGAT

CAATCTCTGT

AGACATGCAC

TGACATGGALA

ATTGTTTAAA

TATCACAATT

ACATAATAAA

ATCAATTTAA

AGGCTCAAAA

ATAATATCAT

TTGCAGGTGA

GACATCCAAT

CTAAGTTCTA

TAAALAGGGTT

CTCTAAGATG

AAAATGATTT

AAGTGGATCT

GGACTAGTTT

AGTTGAAGTT

ATAAATTCAA

CTAATCACGT

CTATGCAACC

ATATTTTACA

TATTAGAATT

ATTATATCAG

ATGAAACATC

TCTCTTGGTT

CTCCT TCAT

AGACATCAGC

TACATTAAAC

ATTTCTTTAT

AGAAGTAGAG

GAAACGATTT

GGACCTACTA

AAATGGTAAA

TA.ATAATCTC

GGTCGATGAA

CTTATTAAGT

TGTAAATACC

GTTAAACTAC

GATTATTTTA

TGAAATGATA

TCCTAGAAAT

CTCTGAAAGC

TGAATGCGAT

GGTATCACTA

AGGTATGTTT

ATTCTTCCCT

AAAAGCAGGA

TAAATGTTCT

ATGTATCTGC

GCATTTAACA

AAAGGATCAT

CTTAGCAGAT

AA.AAGCTTAG

GGAGATTGTA

GGATTTATTA

TATAATAGCA

TCALAGAGTAT

TGGATAATCC

AATAACTTGA

AGACAAGCAA

AGTCTAAGTA

TACAACAGAT

TATAAACTTA

TCAGGATTGC

ATAILATGACA

TACATGCCAT

GACAGATCGA

CTATACAATT

ACTGGTAAAG

AGGCAAATCC

GAGAGTTTGA

ATAAGCAACA

ATCATTACAG

AGTGATGTAT

ATACCTCTTG

GTTGTTAATC

TAAATGTTTG

GGCTGAGATG

TACTGAAATT

TGTCTTTAAT

TGCTAAATAA

GTCACACTTT

TATTAAGTAA

GTGAGCTATA

TGGATTCTGT

CATTAAGACG

GGCCCACCT'r

ATACTTATCC

GGTTCTATCG

AAGCCATTTC

CACATATACA

GAAGAGTACT

GTGTAGTCAA

AAAGAGAGCT

AAATCTTAGC

CAAGATATGG

AGTCAAATCG

ATCTTAGCALA

TAGATGAACT

TCACAATAAT

TTAATGAGGT

CTTAATTACT

TGGATTCA.AT

ATTTCATAAT

TCTAAkACATA

CATCACAGAT

ATTAGACAAG

ATTTCTTAAA

TTTTCTCTTC

AAGAkATTAAC

TGCTTTCATT

A.AGGAATGCT

ATCTCTACTT

TGAGTTTCAT

ACCTCCAAAA

AAATTATATA

AGAGTATTAC

TCAAAGCTAT

CAGTGTAGGT

AGAGAAAATG

TGATCTAGAG

TTATAATGAT

ATTCA.ATCAG

GCATGGAGTA

ATGTACATAT

TGATGAACAA

9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 10620 10680 10740 10800 10860 AGTGGATTAT ACAGATATCA TATGGGTGGT ATTGAGGGCT GGTGTCAAA ACTGTGGACC 372

ATTGAAGCTA

CTGATAAATG

CAGACCCATG

GAGTATGCAG

CAGTTCATGA

GTCCTGAGAG

TCTATAGGCA

ATATTTAGGA

TGTAACAATA

AATCTTGATA

GGTGGTGATC

GAAGCTATAG

AAGCTCCAGG

GATAAAKATC

GAAAGGCAAG

ATAGCCCCAA

CTAAATGACA

GAAAGTTTAC

ATAACTAATA

GATATGATGA

GACAAAAGAG

AGAGAAAGAT

ACAATGAACA

AATGTTAATA

ACGCAGGAGA

GACCAAATAG

TATCATTATT

GTGATAATCA

CACALAGCAGA

GTATAGGCCA

GCAAALACAAT

TAGGTCCATG

GCTTAACACA

ACATTTGGTT

AGCTATATTT

GCATTGATAT

CTAATTTGTT

TACATTCAGT

ATCTTCCAGA

CCAATGCCGA

CTAAAATTAC

ACAAAATATT

TTATGCAA;A

CTTTTTAT;A

TACTTGAA;A

GGAAAAATAT

AGTTATTAAG

CTTGGTCATT

TTAAATATAC

GTTTAACTCG

AAAAAACAAT

ATTTATTAGC

AGATCTA.ATA

GTCAATTGAT

TTATTTGTTA

TAAGCTTAAG

CCAGCACAAT

GATAA.ACACG

GGAGTTAGAA

ATACAATCAA

AGATATATTG

GGCTTTATCA

ATATCGAAGC

GTTTGTGTTG

TGATAGACTG

GTTTGTAACA

TAGTGAGATT

TTCTAAAAGT

TATAGAACCA

AGCAGAAAAA

AACATCAGCA

AACTTTACTT

TTTAGAAAAT

ATCCAATATA

AACTAGCACT

TGGTGAAAGA

GCCAGTGTAC

AA.AATTAGAC

TCTCTCAAAG

ATAAGCAAAC

GCATTAATA

GGAACAGAGA

GGAGTGTACT

ATACTTGATG

TACAGAGGAG

ATTGCTTTGC

AAAGTATTALA

TTGTATATGA

TTTTATAGGA

AGCTATTATA

AACAAATTCT

TTGATGAGGG

ALATAGATTAG

GCACAACATT

ACTTACCCTC

ATAGTTAATC

ATAGATACAA

ATAAGGATAC

CTTAGTATAA~

GTAGGAGTA

ATAGCCAGTG

GGACCCACCA.

AACAGACA-G

TGGGTATATG

GGAAATTCTC

CAGTTAGACT

GCCTTAAATT

CCTATATATC

ATCCAGCCAG

ATTTTAILAGT

AAAGCTTATT

AACTCCGAAA

AACACTTAAA

ATTTGCCTAT

GAACTCCAGA

CTGGTCACGA

TGACATGTGT

ATCCACAGGC

CAGTAACAGA

ATACTACCAC

ATGGATTAAG

TTATATCAGG

CTGATATTAA

TTCCACTAGA

CTGAATTAAG

CATCGCCAAG

GTATAATAAT

AGCCATGGGT

TTTTAACCAA

CATCCATAGA

TATCACAGCT

TATAGAGGGT

GTTATATAAA

CCGAGATATG

TATCAAAAAA

TAGTTTAGAA

ATGCAGTTTA

TCATGCATTA

AACTTTTTTT

GCTGTTTGGT

CTTCCTTACA

TTTACAAGAT

CATCACATTT

TTTAGGGTCT

AGTCTTA.AGT

TGAGATTGAT

AGTTGTTTAT

AACAAAATCC

TAGGGCTACT

TTGTAACAIA

CAAGTATGTA

TATTATGTTC

AGAAAAATAT

AGGCTCATCC

AAAGCAAAGA

CAACAAAGAT

10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 12180 12240 12300 12360 12420 373 0.0

GAATTCATGG

TTGTTTCCAC

TGTGAATTCC

CCTATCAATC

AATTGCATAA

CCTAATAGAA

TTTACAGGAG

CTACCAGATA

AAATCTGGAT

CATAATGCTT

ATGAAAGATT

ATGTTCATTA

AAAGGTTATG

TTGGAGTTAA

GTCATAAAAT

TTTAAGTTGT

GTTAACATAG

AGAATGGGGT

GAATTTTACA

CTAACAAAAC

CACCCAACCC

AACAAACCTA

AGTAAAATGC

TTGTACAATT

GCAAAATCTA

GCATCACTTT

A.AGAACTGAG

AATATCTAAG

CTGCATCAAT

ATGTATTAAC

GTTTTGGTCT

TTATTCTCAT

ATGTTGATAT

AAATAAGTTT

CTCACATCAA

ATATTTTAAG

CA.AAAGGTAT

ATTTGAATGT

GTAAAGCAAA

TAGACAGTAG

ACATAGTCAA

GGTTTTTAA-A

ATTATCACCC

TAATAAATGT

CATCAAATCT

AAATAAGAAT

CAGAAACTTT

AATTTTGTAT

ATATTAA.ATC

TATTTCCAAT

ACCAACTTTA

ATTGCATGCT

TACTGGAACA

TGTCAkATTAT

ACCAGCTTAT

AGAAAAGTAT

TAGCCTGATG

ACCGAAGCTG

CATCAAGTTG

AACCCAATAT

CTCTAATTTA

TACTAATTTA

TTTTGAAAA.A

TTTCTTTAAT

ATTAGAATGT

CTACTGGAAA

TCAAGACACA

ACGCCTTAAT

ILACACACATG

AGATAILATTA

CTTTTACATT

TGCTILATTCA

AGAAAATATG

AAGTGGAALAT

TTCCACTGTT

TGTTGTGATA

CACCACCACT

TCCTTGGCAT

CTTGGACTGT

TTACACCGTT

AGAACAACAA

GGAGATGAAG

TCGGTTGTGG

AATGAGATAC

ALAGCAAGTGA

GTAGAAT TAT

ATATTAGTAC

GCTGGACATT

GATTGGGGAG

GCTTATAAGA

GATATGAACA

TCTATGTCTA

AGTTTGCGTA

AATGCTAAAT

AAAGCTATAT

ACCATTAAAA

AGTTATAACT

GAATTAGAAG

TCATTILATTC

ACCGAATCTA

ACCACAAGAT

GACAAGATTA

TCACATCAGA

CATGTCAATA

CATATGAAAA

TAACAGTCAG

ATTATCATTT

ATATCGACAT

AACAATTCAC

ATTTGATGAA

TACAAAAGCA

TCTTAAGTAA

ATAAAATGTC

GGATTCTGAT

AGGGGTACAT

CTTATTTGCT

CTTCAGATCT

AAGTTTTCCT

GAATAAAAGG

TTACCGTATG

TATCTTACAT

ATAAAAACAA

TTTCAGACAA

ATAATTATAA

CTGTTAAAAG

TGATGATGTC

TCAATTATAG

TAGATCATTC

CATCTTTAGT

GATTTAACTT

AGCCAAAA.AG

TAGTAGACCA

TGATACTAGT

TGTGTTTCAA

AAACATATGT

ACCTCCTATA

GCACATGTTC

CAAAGCACTT

TGATTATTTT

TATTCAACTT

AACTGATCAT

ATGTTTTCAT

TCTTTGTGTT

AGAACAAAAA

CTGTCACAGT

CCCTTGGGTT

AGATTTAGTT

ATTCAATGAT

CACTCATTTG

CAAACTATAT

TAATAATAGT

AACATTCTCT

CAAACAAGAC

AGGTAATACA

ILAGGALATAGT

TGTATTTAGT

12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 13740 13800 13860 13920 13980 374

TCCACAGGAT

AGTTGTATAG

CTTCATCCAG

CCTATTGAAT

ACCATTCCTG

GCAGAACCTA

AAAATTATA.A

AGATGCATTT

ATTACTATAT

TTAATCCTTA

AAATTGATAC

ATCGATGCAA

ATTAAGACTT

ATAGCTGGAC

CTAAAATGGC

TACATGATAG

GAGCTCAAGA

TAGTTTAAAA

TAGTTATTAA

TTTTAGTCTT

GCAAGATCAG

CATTCATAGG

ACATAAGATA

TTCTAAGGTT

CTACAGATGC

TTAGCATCTT

TTGAATGGAG

TAATTGCAAA

TAAAAACTTA

CAATAGGCCC

TTTCAAGAAC

ATATTAAAAG

CATTGTCAAA

GTAATGAAGT

TAGATCATGT

AGTCCACATA

AGCTGATTAA

TATCATTAAC

AGAATATACA

AAGGGGTTAA

TATAGAGTAT

TGAAGGAGCT

CATTTACAGA

ATACAACGGG

AACTAATAAC

TGTCTGCGAT

TAAGCATGTA

ATATCATGCT

CGTGTGCCTA

TGCAAATATA

TAAAAATTTC

CTTAATACCT

ATTGAAGAGT

ATTCAGCAAC

TTTAAATTTT

TCCTTACTTA

AATAACAGGT

AAGTTTGGTC

AACTTTTCA.A

ATAAAAGTCT

ATTTTAAAAG

GGTA.ACTTAT

AGTTTAAAAG

CATATAAACA

ATTCATTGGT

GCTGAATTAC

AGAAAGTGCA

CAAGATGACA

GGTAGCAAGT

CTTCCTGTTT

ATTATGCCTA

TTCCTTTGTT

GTAGTTAATG

AAGCTTATAA

AGATCAGCTG

AGTGAATTGT

AGTGTGCTAT

AAATTTAGAT

TAATTTAGCA

AAAACTAACA

TTTTCTCGT

ATCTTAAGAT

TATTACGTAC

ATTGCAATGA

TAGATTATGG

CTTATTTACA

CTGTTACAGC

AGTACTGTTC

TTGATTTCAA

TAAAAGGATC

TTGATGTTGT

AAAAAACTGA

ACCCTATAAC

GAGATATATT

ACCACAAGCA

AACTTAATTA

TAAATAGTTT

ACAACCTTCC

GCTAACACAT

TATTGATTCC

ATTATACATG

TAAGGACCCC

GGTAGTAGAA

TCATAGTTTA

TGAGAATTTA

TATAAAATTT

CAATTGGAGT

TTCTGTAAAT

ATTAGATAAC

TGAAGTTTAC

ACAAA.ATGCT

CALAGGAATCT

AAAAAXAGGA

ATCATATTCT

TATGAATATC

CAATCATTTA

AACAACCAAT

CAACGAACAG

CATTATATTA

AAAATTATCA

TGCATTCACA

14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15219 ACACAACGAG ACATTAGTTT TTGACACTTT INFORMATION FOR SEQ ID NO:32: SEQUENCE CHARACTERISTICS: LENGTH: 2166 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein 375 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: Met Asp Pro Ile Ile Aen Gly Asn Ser Ala Asn Val Tyr Leu Thr Asp

I

Ser Ser Ile Thr Leu Met Ile Asn Ser 145 Leu His Leu Asn Giu Tyr Tyr Ser Ile Giu Ser Arg Lys 130 Gly Ser Ser Met Leu 210 Val Leu Leu Arg Thr Glu S er Arg 115 Leu Asp Al a Val Cys 195 Tyr Lys Lys Phe Gin Gin Pro Ser 100 Aila Gly Glu Val Asn 180 Ser Thr Ser 5 Gly Asn Se r Ser Thr Giu Ile Leu Asn Glu 165 Gin Met Lys His Val Gly Pro Leu 70 Tyr Gin Giu Lys Ser 150 Asn Asn Gin Leu Gly Ile Pro Leu 55 Ile Phe Ile Ile Giu 135 Val Asn Ile His Asn 215 Phe Ser Tyr 40 Leu Ser Gin Ala Ser 120 Lys Leu Gin Thr Pro 200 Asn Ile *Phe 25 Leu Giu Arg Ser Thr 105 Asp Asp Thr Ser Ile 185 Pro Ile Leu 10 Ser Lys His Tyr Leu 90 Thr Val Arg Thr Tyr 170 Lys Ser Leu Ile Giu Asn Met His 75 Leu Asn Lys Val Ile 155 Thr Thr Trp Thr Asp 235 Cys Asp Asn Lys Met Leu Val Lys 140 Ile Asn Thr Leu Gin 220 Asn Asn Tyr Leu Gly Thr Leu Tyr 125 Pro Lys Ser Leu Ile 205 Tyr Gin Al a Thr Lys Giu Tyr Lys 110 Ala Asn Asp Asp Leu 190 His Arg rhr Leu Asn Lys Leu Lye Lye Ile Asn Asp Lye 175 Lys Trp S er Leu *Gly Leu Leu Lys Ser Ile Leu Asn Ile 160 Ser Lys Phe Asn Ser 240 225 230 Gly Phe Gin Phe Ile Leu Asn Gin Tyr Gly Cys Ile Val Tyr His Lys 376 245 250 255 Gly Leu Lys Lys Ile Thr Thr Thr Thr Tyr Asn Gin Phe Leu Thr Trp 260 265 270 Lys Asp Ile Ser Leu Ser Arg Leu Asn Val Cys Leu Ile Thr Trp Ile 275 280 285 Ser Asn Cys Leu Asn Thr Leu Asn Lys Ser Leu Gly Leu Arg Cys Gly 290 295 300 Phe Asn Asn Vai Val Leu Ser Gin Leu Phe Leu Tyr Gly Asp Cys Ile 305 310 315 320 Leu Lys Leu Phe His Asn Giu Giy Phe Tyr Ile Ile Lys Giu Vai Giu 325 330 335 Gly Phe Ile Met Ser Leu Ile Leu Asn Ile Thr Glu Giu Asp Gin Phe 340 345 350 Lys Lys Arg Phe Tyr Asn Ser Met Leu Asn Asn Ile Thr Asp Ala Ala 355 360 365 Ile Lys Ala Gin Lys Asp Leu Leu Ser Arg Vai Cys His Thr Leu Leu 370 375 380 .Asp Lys Thr Vai Ser Asp Asn Ile Ile Asn Gly Lys Trp Ile Ile Leu *385 390 395 400 Leu Ser Lys Phe Leu Lys Leu Ile Lys Leu Ala Gly Asp Asn Asn Leu 405 410 415 Asn Asn Leu Ser Giu Leu Tyr Phe Leu Phe Arg Ile Phe Gly His Pro 420 425 430 *.Met Val Asp Giu Arg Gin Ala Met Asp Ser Vai Arg Ile Aen Cys Asn a...435 440 445 Giu Thr Lys Phe Tyr Leu Leu Ser Ser Leu Ser Thr Leu Arg Gly Ala *450 455 460 Phe Ile Tyr Arg Ile Ile Lys Gly Phe Vai Asn Thr Tyr Asn Arg Trp 465 470 475 480 Pro Thr Leu Arg Asn Aia Ile Val Leu Pro Leu Arg Trp Leu Aen Tyr 485 490 495 Tyr Lys Leu Asn Thr Tyr Pro Ser Leu Leu Glu Ile Thr Giu Aen Asp 500 505 510 Leu Ile Ile Leu Ser Giy Leu Arg Phe Tyr Arg Glu Phe His Leu Pro 515 520 525 377 a a Lys Lys 530 Pro Lys 545 His Ile Asp Arg Asn Giu Asn Ser 610 Vai Giy 625 Ile Leu Giu Ser Leu Lys Asn Asn 690 Asn Gin 705 Asp Giu Ile Pro Ile Lys Leu Tyr 770 Asp Gin S er Cys 595 Asn Arg Al a Leu Ala 675 Tyr Aila Leu Leu Asp 755 Arg Leu Asn Arg 580 Asp His Met Giu Thr 660 Giy Ile Phe His Vai 740 His Tyr Ile Trp 550 Tyr Ile 565 Arg Vai Leu Tyr Vai Vai Phe Aia 630 Lys Met 645 Arg Tyr Ile Ser Ser Lys Arg Tyr 710 Giy Vai 725 Thr Ile Vai Vai His Met Thr Giu Leu Asn Ser 615 Met Ile Giy As n cys 695 Giu Gin Ile Asn Giy 775 S er His Giu Cys 600 Leu Gin Ala Asp Lys 680 S er Thr Ser Cys Leu 760 Giy Phe Glu Tyr 585 Vai Thr Pro Giu Leu 665 Ser Ile Ser Leu Thr 745 Asn Ile Pro Lys 570 Tyr Vai Gly Giy Asn 650 Giu Asn Ile Cys Phe 730 Tyr Giu Giu Arg 555 Leu Leu Asn Lys Met 635 Ile Leu Arg Thr Ile 715 Ser Arg Val.

Giy Asn Lys Arg Gin Giu 620 Phe Leu Gin Tyr Asp 700 Cys Trp His Asp Trp 780 Tyr Phe Asp Ser 605 Arg Arg Gin Lys Asn 685 Leu Ser Leu Aia Giu 765 Cys Met S er Asn 590 Tyr Giu Gin Phe Ile 670 Asp Ser Asp His Pro 750 Gin Gin Pro Giu 575 Lys Leu Leu Ile Phe 655 Leu Asn Lys Vai Leu 735 Pro Ser Lys Ser 560 Ser Phe Asn Ser Gin 640 Pro Giu Tyr Phe Leu 720 Thr Phe Gly Leu Vai Asp Leu Giu Met Ile Ile Asn Asp Lys Aia Ile Ser Pro 535 540 Trp 785 Thr Ile Giu Aia Ile Ser Leu Leu Asp Leu Ile Ser Leu Lys Gly 790 795 800 378 9 9* 9 9 Lys Phe Ser Ile Ser Lys Asp Tyr Leu 835 Ala Gly Ile 850 Asp Met Gin 865 Pro Ala Ser Ile Leu Asp Gin Giu Leu 915 Arg Asn Ile 930 Ala Leu Cys 945 His Leu Lys Leu Tyr Met Leu Tyr Arg 995 Ile Val His 1010 Gin Asp Lys 1025 Thr Cys Val Leu Met Arg Ile Pro 820 Leu Gly Phe Ile Asp 900 Giu Trp Asn Thr Asn 980 Ser Ser Leu Ile Asp Thr Ala Leu Ile Asn 805 Val Arg Leu Ile Giu 825 Ala Leu Asn Ser Leu 840 His Lys Leu Lys Gly 855 Met Ser Lys Thr Ile 870 Lys Lys Val Leu Arg 885 Phe Lys Val Ser Leu 905 Tyr Arg Gly Giu Ser 920 Leu Tyr Asn Gin Ile 935 Asn Lys Leu Tyr Leu 950 Phe Phe ASn Leu Asp 965 Leu Pro Met Leu Phe 985 Phe Tyr Arg Arg Thr 1000 Val Phe Val Leu Ser 10i5 Gin Asp Leu Pro Asp 1030 Thr Phe Asp Lys Asn 1045 Pro Gin Ala Leu Gly Gly Asp Asn Gin Ser Ile Asp 810 815 Gly Gin Thr His Ala Gin Ala 830 Lys Leu Leu Tyr Lys Giu Tyr 845 Thr Giu Thr Tyr Ile Ser Arg 860 Gin His Asn Gly Val Tyr Tyr 875 880 Val Gly Pro Trp Ile Asn Thr 890 895 Giu Ser Ile Gly Ser Leu Thr 910 Leu Leu Cys Ser Leu Ile Phe 925 Ala Leu Gin Leu Arg Asn His 940 Asp Ile Leu Lys Val Leu Lys 955 960 Ser Ile Asp Met Ala Leu Ser 970 975 Gly Gly Gly Asp Pro Asn Leu 990 Pro Asp Phe Leu Thr Giu Ala 1005 Tyr Tyr Thr Gly His Asp Leu 1020 Asp Arg Leu Asn Lys Phe Leu 1035 1040 Pro Asn Ala Giu Phe Val Thr 1050 1055 Ser Giu Arg Gin Ala Lys Ile 1070 Thr Giu Val Leu Ser Ile Ala 1060 Thr Ser Giu Ile Asn Arg 106~ Leu Ala Val 379 1075 1080 1085 Pro Asn Lys Ile Phe Ser Lys Ser Ala Gin His Tyr Thr Thr Thr Giu 1090 1095 1100 Ile Asp Leu Asn Asp Ile Met Gin Asn Ile Glu Pro Thr Tyr Pro His 1105 1110 1115 1120 Gly Leu Arg Val Val Tyr Glu Ser Leu Pro Phe Tyr Lye Ala Giu Lys 1125 1130 1135 Ile Val Asn Leu Ile Ser Gly Thr Ly. Ser Ile Thr Asn Ile Leu Glu 1140 1145 1150 Lys Thr Ser Ala Ile Asp Thr Thr Asp Ile Asn Arg Ala Thr Asp Met 1155 1160 1165 Met Arg Lys An Ile Thr Leu Leu Ile Arg Ile Leu Pro Leu Asp Cys 1170 1175 1180 Asn Lys Asp Lys Arg Giu Leu Leu Ser Leu Glu Aen Leu Ser Ile Thr ***1185 1190 1195 1200 *Giu Leu Ser Lye Tyr Val Arg Giu Arg Ser Trp Ser Leu Ser Asn Ile :1205 1210 1215 .**Val Gly Val Thr Ser Pro Ser Ile Met Phe Thr Met Asn Ile Lye Tyr .*.1220 1225 1230 Thr Thr Ser Thr Ile Ala Ser Gly Ile Ile Ile Giu Lye Tyr Aen Val 1235 1240 1245 Asn Ser Leu Thr Arg Gly Glu Arg Gly Pro Thr Lys Pro Trp Val Gly 1250 1255 1260 *Ser Ser Thr Gin Giu Lye Lye Thr Met Pro Val Tyr Aen Arg Gin Val 1265 1270 1275 1280 Leu Thr Lye Lye Gin Arg Asp Gin Ile Asp Leu Leu Ala Lye Leu Asp *1285 1290 1295 Trp Val Tyr Ala Ser Ile Asp Asn Lye Asp Giu Phe Met Giu Giu Leu 1300 1305 1310 Ser Thr Gly Thr Leu Gly Leu Ser Tyr Giu Lye Ala Lye Lye Leu Phe 1315 1320 1325 Pro Gin Tyr Leu Ser Val Asn Tyr Leu His Arg Leu Thr Val Ser Ser 1330 1335 1340 Arg Pro Cys Giu Phe Pro Ala Ser Ile Pro Ala Tyr Arg Thr Thr Aen 1345 1350 1355 1360 380 Tyr His Phe Asp Thr Ser Pro Ile Asn His Val Leu Thr Giu Lys Tyr 1365 1370 1375* Gly Asp Giu Asp Ile Asp Ile Val Phe Gin Asn Cys Ile Ser Phe Gly 1380 1385 1390 Leu Ser Leu Met Ser Val Val Giu Gin Phe Thr Aen Ile Cys Pro Asn 1395 1400 1405 Arg Ile Ile Leu Ile Pro Lys Leu Asn Giu Ile His Leu Met Lys Pro 1410 1415 1420 Pro Ile Phe Thr Gly Asp Vai Asp Ile Ilie Lys Leu Lys Gin Val Ile 1425 1430 1435 1440 Gin Lys Gin His Met Phe Leu Pro Asp Lys Ile Ser Leu Thr Gin Tyr 1445 1450 1455 Val Giu Leu Phe Leu Ser Aen Lys Ala Leu Lys Ser Giy Ser His Ile 1460 1465 1470 Asn Ser Asn Leu Ile Leu Val His Lye Met Ser Asp Tyr Phe His Aen *1475 1480 1485 *Ala Tyr Ile Leu Ser Thr Asn Leu Ala Gly His Trp Ile Leu Ile Ile *1490 1495 1500 Gin Leu Met Lye Asp Ser Lye Gly Ile Phe Glu Lye Asp Trp, Gly Giu 1505 1510 1515 1520 Gly Tyr Ile Thr Asp His Met Phe Ile Asn Leu Asn Val Phe Phe Asn 1525 1530 1535 C:.:Ala Tyr Lye Thr Tyr Leu Leu Cys Phe His Lys Gly Tyr Gly Lys Ala 1540 1545 1550 Lye Leu Glu Cys Asp Met Asn Thr Ser Asp Leu Leu Cys Val Leu Giu ***1555 1560 1565 Leu Ile Asp Ser Ser Tyr Trp Lye Ser Met Ser Lye Val Phe Leu Giu 1570 1575 1580 Gin Lys Val Ile Lye Tyr Ile Val Aen Gin Asp Thr Ser Leu Arg Arg 1585 1590 1595 1600 Ile Lye Gly Cys His Ser Phe Lye Leu Trp Phe Leu Lye Arg Leu Asn 1605 161.0 1615 Asn Ala Lys Phe Thr Val Cys Pro Trp Val Val Asn Ile Asp Tyr His 1620 1625 1630 381 Pro Thr His Met Lys Ala Ile Leu Ser Tyr Ile Asp Leu Val Arg Met 1635 1640 1645 Gly Leu Ile Asn Val Asp Lys Leu Thr Ile Lys Asn Lys Asn Lys Phe 1650 1655 1660 Asn Asp Giu Phe Tyr Thr Ser Asn Leu Phe Tyr Ile Ser Tyr Asn Phe 1665 1670 1675 1680 Ser Asp Asn Thr His Leu Leu Thr Lys Gin Ile Arg Ile Ala Asn Ser 1685 1690 1695 Giu Leu Glu Asp Asn Tyr Asn Lys Leu Tyr His Pro Thr Pro Giu Thr 1700 1705 1710 Leu Glu Asn Met Ser LeuIle Pro Val Lys Ser Aen Asn Ser Asn Lys 1715 1720 1725 Pro Lys Phe Cys Ile Ser Gly Asn Thr Giu Ser Met Met Met Ser Thr 1730 1735 1740 Phe Ser Ser Lys Met His Ile Lys Ser Ser Thr Val Thr Thr Arg Phe 1745 1750 1755 1760 *Aen Tyr Ser Lys Gin Asp Leu Tyr Asn Leu Phe Pro Ile Val Val Ile *1765 1770 1775 *.*Asp Lye Ile Ile Asp His Ser Gly Asn Thr Ala Lys Ser Asn Gin Leu 1780 1785 1790 Tyr Thr Thr Thr Ser His Gin Thr Ser Leu Val Arg Asn Ser Ala Ser 1795 1800 1805 Leu Tyr Cys Met Leu Pro Trp His His Val Aen Arg Phe Aen Phe Val 1810 1815 1820 Phe Ser Ser Thr Gly Cys Lye Ile Ser Ile Glu Tyr Ile Leu Lys Asp 1825 1830 1835 1840 *Leu Lye Ile Lye Asp Pro Ser Cys Ile Ala Phe Ile Gly Giu Gly Ala 1845 1850 1855 Gly Asn Leu Leu Leu Arg Thr Val Val Glu Leu His Pro Asp Ile Arg 1860 1865 1870 Tyr Ile Tyr Arg Ser Leu Lys Asp Cys Asn Asp His Ser Leu Pro Ile 1875 1880 1885 Glu Phe Leu Arg Leu Tyr Asn Gly His Ile Asi Ile Asp Tyr Gly Glu 1890 1895 1900 Asn Leu Thr Ile Pro Ala Thr Asp Ala Thr Asn Asn Ile His Trp Ser 382 1905 1910 1915 1920 Tyr Leu His Ile Lys Phe Ala Giu Pro Ile Ser Ile Phe Val Cys Asp 1925 1930 1935 Ala Glu Leu Pro Val Thr Ala Asn Trp Ser Lye Ile Ile Ile Giu Trp 1940 1945 1950 Ser Lys His Val Arg Lye Cys Lys Tyr Cys Ser Ser Val Asn Arg Cys 1955 1960 1965 Ile Leu Ile Ala Lys Tyr His Ala Gin Asp Asp Ile Asp Phe Lys Leu 1970 1975 1980 Asp Asn Ile Thr Ile Leu Lye Thr Tyr Val Cys Leu Gly Ser Lye Leu 1985 1990 1995 2000 Lye Gly Ser Giu Val Tyr Leu Ile Leu Thr Ile Gly Pro Ala Asn Ile 2005 2010 2015 Leu Pro Val Phe Asp Val Val Gin Asn Ala Lys Leu Ile Leu Ser Arg .2020 2025 2030 *Thr Lys Asn Phe Ile Met Pro Lys Lys Thr Asp Lye Giu Ser Ile Asp *2035 2040 2045 *Ala Asn Ile Lye Ser Leu Ile Pro Phe Leu Cys Tyr Pro Ile Thr Lye *2050 2055 2060 Lye Gly Ile Lye Thr Ser Leu Ser Lye Leu Lye Ser Val Val Aen Gly 2065 2070 2075 2080 Asp Ile Leu Ser Tyr Ser Ile Ala Gly Arg Aen Giu Val Phe Ser Aen 2085 2090 2095 Lye Leu Ile Asn His Lye His Met Aen Ile Leu Lye Trp Leu Asp His 2100 2105 2110 Val Leu Aen Phe Arg Ser Ala Giu Leu Aen Tyr Aen His Leu Tyr Met *2115 2120 2125 Ile Giu Ser Thr Tyr Pro Tyr Leu Ser Giu Leu Leu Aen Ser Leu Thr 2130 2135 2140 Thr Aen Giu Leu Lye Lye Leu Ile Lye Ile Thr Giy Ser Vai Leu Tyr 2145 2150 2155 2160 Asn Leu Pro Asn Giu Gin 2165 INFORMATION FOR SEQ ID NO:33: 383 SEQUENCE CHARACTERISTICS: LENGTH: 15219 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: ACGGGAAAAA AATGCGTACT ACAAACTTGC ACATTCGAA AAAATGGGGC

AAATAAGAAC

0 .0 0 0.

0 *0 0 .0.90

TTGATAAGTG

ATGATAAAGG

ACATGTTATA

ACAATTAAAT

GATAACAATA

TACATATGGG

AATTGTGAAA

CAAATATCTG

TAGACATGTG

AATAAACTCA

GATTGATGAT

AAGAAATCAT

TTGATGAAAG

AAGTAGGGAG

CCATGCCTAT

AACACACTCC

CCCAACCAAA

CATTTTAGTA

CTATTTAAGT

TTAGATTACA

CTGATAAATT

TAAACGGCAT

TTGTAGTGAA

AATTGATTGA

TCAAATTTTC

ACTTACTTGG

TTTATTACCA

CCTAATCAAT

CACAGACATG

CACACACAAA

ACAAGCTACA

TACCAAATAC

ATTTATCAAT

TATAATATAC

CCAAACTATT

ATTAAAAATA

CTALACCTTTT

AAATTTATTT

AATTCTTCTG

AGTTTTTATA

ATCTAACTTT

GTTGACACAC

TAAAAGACTA

GCTTGATCTC

TTTTAGTTA.A

CAAACCATGA

AGACCCCTGT

TTCATATACT

TTTACATTCT

AAAAAATACA

CACGGCGGGT

AAATATGACC

CCTCAAACAA

AAAGTAAAGC

CAATCAGAAA

GACAATGACG

ACCAATGCAT

CATGTTATAA

ACAACAATGC

TGCTCTCA.AT

AGTGACTCAG

AATTCATGAA

TATAAAAACT

GCACTACAAA

CAATGGATTC

TGATAA.ACA

TAGTCAATTA

CTGAATATA

TTCTAGAATG

TCAACCCGTG

CAGTGCTCAJA

TGGGGTGC~AA

AAGTAGCATT

TAGCCAAAGC

CAAGCAGTGA

CA.ATACTACA

TA.AACGGTTT

TAATGACTAA

TTATGTTTAG

CATCAAAGGG

TGACAACACT

A.ATA.ATAACA

TGAATGTATT

TGAGATGAAG

TACAAAATAT

TATTGGCATT

AATTCCAACA

TAGTTAAGAA

TTCACTGAGC

GTTAAAAATA

AGCAATACAT

AGTGTGCCCT

AALATGGAGGA

AATGGATGAT

TTATATGAAT

TCTAATTCAA

AA.ATGGGGCA

ACTATGCAAA

TCTCTTACCA

GTAAGAAAAC

CTACTGCACA

GGCACTTTCC

AAGCCTACAA

AAAAAACCAA

GGAGCTAATC

AATACAAAGA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 CAATAACATA A.ATTGGGGCA TGGCTCTTAG CAAAGTCAAG TTGAATGATA CATTAAATAA GGATCAGCTG

CTGTCATCCA

384

GCAAATACAC

AAAAACACCT

TCACAGGATT

AGATACTTAA

GTCAAGATAT

CAGAAATACA

TATTCAACGT

AAACAAACTA

AATAGGTATG

AGATGCTGGA

AAATGGA.AAG

AGTCAATATT

AGATGGGAGA

AGTGGCTCCA

*9

TGTGTATAGC

CAGTAATTAG

TACCAAAGGA

ATGTTTTCGT

GAATCTTTGC

GAGTTTTAGC

TGGAGCAAGT

ACCATATATT

CAAGTGTGGT

CAAGAAACCA

GAGTAATAAA~

AACTCAACCC

AGTCAAC-ATG

CAAATTCCTA

TAGCATAATA

TGGCACCc

CTACCCAAGA

TTCTAAGTTG

TGCACTTGTG

GAGGGCAAAC

TATAGCTAA~C

GCACTTTGGC

AGGATTGTTT

CAALATCTGTA

TGTGGAAGTC

GAACAATCCA

CCTAGGCAAT

GGATCTTTAT

CTACAGTGTA

CAAAGAAGAT

GAGAAGTTTG

GAATCAATA

TCTGTTAACT

ATCATCAATC

AAACCCCTAG

TACAAGGAAA

AGTACAGGAG

TGTGGTATGC

TTATATGCTA

TATCATGTTA

GAAATGA.AAT

GAGATAGA.AT

GAATATAGGC

ATAACCAAAT

AATGTCTTA.A

AGTTTTTATG

ATTGCACAAT

ATGAATGCCT

AAAAATATCA

TATGAGTATG

AAAGCATCAT

GCAGCAGGTC

GATGCAGCTA

TTAGACTTAA

SATGTAGAGC

CACCTGAATT

RGGGCAAGTT

2AATAGATAT NAACAAGTGA2 rAAGCTTCAA I MATAGAAAC I

ATAATATTGA

TATTAATCAC

TGTCCAGGTT

AAGCTAATGG

TCGAAGTATT

CTAGAAAGTC

ATGATTCTCC

TAGCAGCACG

AAAACGAAAT

AAGTGTTTGA

CATCCACAAG

ATGGTTCAGG

TGCTAGGACA

CACAGAAGTT

TGCTGTCATT

TAGGCATAAT

AAGCATATGC

CAGCAGAAGA

rTTAAGTTAA rCATGGAGAA

CGCATCATCC

kGAAGTAACT kGCCGACAGT

~GAAGATCTC

~TTTGATAAC

CACTCCCAAT

TGAAGATGCA

AGGAAGGGAA

AGTAGATATA

AACATTATCA

CTACAAAAA.A

AGACTGTGGG

AGACAGATCA

AAAACGATAC

AAAACACCCT

AGGGGGTAGT

GCAAGTAATG

TGCTAGTGTC

GGGAGGAGAA~

AACTCAATTT

GGGAGAGTAT

AGAGCAACTC

ATTGGAAGCC

CAAAAAATAC

GATGCAAATA

AAAGATCCTA

AAAGAGAGCC

A~CCCCAGAAA

ACCCCAAGTG

I

k~ATGAAGAAG

TATGATGTGC

AATCATAAAT

GACACTATAA

ACAACATATC

AGCTTGACAT

ATGCTAAAAG

ATGATAATAC

GGTCTTACAG

AAGGGCCTCA

CATCTTATAG

AGAGTTGAAG

CTAAGATGGG

CAGGCAGAA.A

GCTGGATTCT

CCCAACTTCT

AGAGGTACAC

A.AAGAAAATG

1TAAAGCATC

GGGGCAAATA

A~CAAAGCTAC

k.GAAGAAAGA

CGATACATC

2AAAAGCCAA ~CAACdCTTT

LATCTAGCTA

1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 CTCATATGA GAGATAAATG ATCAAACAAA TGACAACATT ACAGCAAGAC

TAGATAGAT

2760 385 TGATGAAAAA TTAAGTGAAA TATTAGGAAT GCTCCATACA TTAGTAGTTG CAJAGTGCAGG 0000 000G 0* .0 0 0 0* 00 9 0 0000 09 *0 0 00 0 0 000000 0 0 0000 00000.

0 *00..0 0 0* 00 0 00 **00 0 0000

ACCCACTTCA

AGAAAAAATA

TAGGA.ATGAG

AACTTCCAAA

TGATGATTTT

TCAATCCATT

CCAATCAATC

AAAAGA.ACAA

ATACACAGCA

AATATGGGTG

AAGCATCAAT

GATTAACTCA

TGTATCATTA

AGCATGCAGT

CATGAAGACA

GACATCAAAA

TCTGAACTCA

AATTATTCCT

CAAATATATC

GAGCATATAT

ACTAGAGGAT

ACACACTATA

CCACTCAAAA

AAATAAAACC

CATTTATACC

GCTCGCGATG

AGAGCGGAAG

GAAAGCGAAA

AAATTGAGTG

TGATCAGCGA

GAATCAACTG

AACCAATTGA

GATGGGGCIA

GCTGTTCAGT

CCTATGTTCC

ATACTAGTGA

AGAAGTGCTG

GATGAAAGIA

CTAACATGCT

TTCAkACCCCA

AGAGTAATAA

CTAGAWAATA

TATGCAGGAT

AAACCACAGA

TATGTGACTA

TAAACTTAAT

TCCAAACATC

TCCAAAATCA

AAAATATGGG

GCCAkATTCA

GAATALAGAGA

CATTAATGAC

AAATGGCA.AA

ACTTGTTGGA

TCAACTCACT

CCAGACCGAA

TCAATCAGCA

ATATGGAAAC

ACAATGTTCT

AGTCATCTGT

AGCAGATCTC

TGCTGGCTCA

GCAAATTAGC

TAAAAGTAAA

CTCATGAGAT

TACCAACCTA

TAGCAACCAC

TAGTGTTAGT

GTCAATTTAT

CTAATTGGA.A

TATCAACACT

ATAALACATCT

CTACCAGCCA

GTAAATAGAC

CACATATACT

TGCTATGGTT

CAATGATAGG

AGACACCTCA

AGACAACGAT

CAGCAATCAA

CAAACAAACG

ACCCGACAAA

ATACGTGAAC

AGAAAAAGAT

GCCAGCAGAC

TACGCCCAAA

ALATGCCTAGT

ATATGATGTA

AAGTATGTTA

CATTGCTCTA

TCTAAGATCA

CGAATTCAAA

TATCACAGTT

AGTAGATCTT

GCATACAGCT

GAATGACAGG

ACACTACACA

CTATCTGCTA

ATTAGTTAGA

ATAAATCTTA

GGTCTAAGAG

TTAGAGGCTA

GATGAAGTGT

AGTGACAA.TG

CAACATCAAT

TCCATCAGTA

ATTAACAATA

AAGCTTCACG

GATGATCCTG

TTGCTCATAA

GGACCTTCAC

AATTTCATCA

ACTACACCTT

ACTACAGTCA

TGTGAATTTG

ATTAGTGTCA

AATGCTATCA

ACTGACAATA

GGTGCCTACC

ACACGTTTTT

TCCACATATA

CTTCATCACA

GACCTAGAGT

GTTCAATCAA

AAATGGGAAA

AAGAGATGAT

TGGCA.AGACT

CTCTTAATCC

ATCTATCACT

AAAkACAGACA

GAACCACCAA

TAGTAACAAA

AAGGCTCCAC

CATCACTAAC

AAGAACTTGC

TACGAGTCAC

TAAGCGCAAA

GTGAAATCAA

AAGATCTTAC

AAAATATTAT

AGAACAAGGA

CCAATGCAAA

AAGGAGCATT

TAGAAAAAGA

CAATCAAACC

TCCTCAAACT

CAAACCAATC

GCGAATAGGT

TCTTAACAAC

TACATCCATC

2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 386 ACAATAGAAT TCACAAGCAA ATTTTGGCCC TATTTTACAC TAATACATAT GATCTTAACT gee* 0@Se 6* a of 00 6 0 056 000S

CTAATCTTTT

CATAAAGCAT

AGTTCTACCA

CTTCTCACAG

TATTTAAAAA

AATGCAACCA

GATACTCTTA

ATAGCACAAA

GCCATAATAT

ACAATAAAAA

AGGGTTAGTT

ACATCACCCA

ACCACTTCA

AAAGATGATT

CAACTTTGCA

ATCAAACCCA

GCCAAAACGA

ACAGAAAGAG

ACAGTCCAAC

ACACCCACAG

TAGTTATTCA

AAACCTGGGG

TCTTGCTATT

ATCGACATGT

TAGTGTCATA

TACTA.ATTAT

TCTGTAACAA

TTATGCTGTG

AGTCATGGTG

TTAACATAAT

TGTCCAAACA

ATCATCTAAT

TAGCACTATC

TCATCATCTC

ACCACACTGA

CATCCAAGCA

ATACAAAATC

CACAGACCAA

ACCATTTTGA

AATCCATCTG

CAAACAAACC

CGA.AAAAAGA

ACACCAGCAC

AGCAATCCCT

CATCCGAGCC

AAAACTACAT

CAAATAACCA

AATGCATTGT

AGTGCAGTTA

ACAATAGAAT

AATCACTATT

AACTCTTGAA

TCAA.ATTATA

TCGCAAAACC

GATGAATTGT

CAAGA.ATCAA

TGTAATATCC

AGTTTTGGCA

TGCCAATCAC

AAAA.AACATC

ACCCACAACC

AGAAACACAC

CAAGCCAAGC

AGTGTTCAAC

CAAAACAATA

AACCACCAAA

AACTACCACC

CTCACALATCC

CCTCTCAACC

CTCCACACCA

CTTAGCAGAG

TGGAGTTGAT

ACCTCACCTC

GCAGAGGTTA

TAAGTAATAT

ATGATTGCAA

CTAGGACAGA

ATCCTGTATA

ACGCTAACTA

TAGTATGAGA

CGCACTGCCA

TCTTGTTTAT

ATGATAATCT

AA.AGTTACAC

ACCACCTACC

ACATCACCAA

CATACAACAG

ACAAAACCAC

TTCGTTCCCT

CCAAGCAACA

ACCACAAACA

AACCCAACAA

ACTGCACTCG

ACCCCCGAAA

AACTCCACC

AACCGTGATC

GATCCACAAG

AAGTCAGAAC

TTTTAGTGCT

AAAAGAAACC

TACTAAATAA

TGTATCAAAT

TATAAACAAA

TCATGGTAGC

TCAAAAACAA

GGACTCTAGA

ACAGATTAAA

CAACCTCTCT

TAACAACGGT

CTACTCAAGT

TCCACACAAG

CACAAACCAA

GTCCAAAAAA

GCAGTATATG

AACCAAAGAA

AAAGAGACCC

AAAAACTAAC

ACACAACCAC

ACACACCCAA

AAAAAACCCA

TATCAAGCA

TCAAGTGCA.A

ATAACTGAGG

TTAAGAACAG

A.AATGCAATG

GCTAAGTGAA

CAACACATAG

CAAATCCAAT

ATAGAGTAGT

CATTGGGGCA

AAAGACCTGG

TTTAAAATCT

CATAATTGCA

CACAGTTCAA

CTCACCAGAA

TTCAGCTACA

AGGCAGAACC

TCCACCAAAA

TGGCAACAAT

GAAACCAACC

AAAAACACCA

CCTCAAGACC

ATTAAAACAC

CTCCACACAA

GCCACATGCT

GAACGAAATT

TCTTCCTAAC

AGTTTTACCA

GTTGGTATAC

GAACTGACAC

4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 387 TAAAGTAAAA CTTATGAAAC AAGAATTAGA TAAGTATAAG AATGCAGTAA

CAGAATTACA

5940

GCTACTTATC

TATGAACTAC

ACGAAGATTT

ATCAAAAGTT

AAACAAAGCT

TCTCAAGAAT

CTCCAACATT

CAGAGAATTT

CAGTGAGTTA

GTCAAGCAAT

AGAAGTCCTT

GAAATTGCAC

AACAAGGACT

GGCTGACACT

ATTACCAAGT

AATTATGACA

GTCATGCTAT

ATTTTCTAAT

CACTTTATAC

AATAAATTAC

AGTCAATGA

TAATGTAAAT

CATTGTAGTA

CACACCAGTT

CAAAACACAC

ACAATCAATA

CTAGGCTTCT

CTACACCTTG

GTAGTCAGTT

TACATAA.ATA

GAAACAGTTA

AGTGTCAATG

CTATCATTAA

GTTCAGATAG

GCATATGTTG

ACATCGCCTC

GATAGAGGAT

TGTAAAGTAC

GAAGTCAGCC

TCAAAAACAG

GGTAAAACTA

GGTTGTGACT

TATGTAAACA

TATGACCCTC

AAAATCAATC

ACTGGCAAAT

TTGTTATCAT

ACACTAAGCA

CAGCTGTCAA

CCACTAAAAA

TGTTAGGTGT

ALAGGAGA.AGT

TATCAAATGG

ACCAATTATT

TAGAATTCCA

CAGGTGTAAC

TCAATGATAT

TAAGGCAACA

TACAGCTGCC

TATGCACTAC

GGTATTGTGA

AGTCCAATCG

TTTGTAACAC

ACATAAGCAG

AATGCACTGC

ATGTGTCAAA

AGCTGGAAGG

TAGTGTTTCC

AAAGTTTAGC

CTACTACAAA

TAATAGCTAT

AAGACCAACT

*CAACCGGGCC

CCTAAATGTA

GGGATCTGCA

GAACAAGATC

GGTCAGTGTT

ACCCATAGTA

GCAGAAGAAC

AACACCTTTA

GCCTATAACA

AAGTTATTCC

TATCTATGGT

CAACATCAAA

TAATGCAGGA

AGTATTTTGT

TGACATATTC

CTCAGTAATT

ATCCAAcAAA

CA.AAGGAGTA

CAAGAACCTT

TTCTGATGAG

TTTTATTCGT

TATTATGATA

TGGTTTACTG

AAGTGGAATC

TCAATAAGCA

ATAGCAAGTG

AAAAATGCTT

TTAACCAGCA

AATCAACAGA

AGCAGATTGT

AGCACTTACA

AATGATCAGA

ATCATGTCTA

GTAATAGATA

GAAGGATCAA

TCAGTATCCT

GACACTATGA

AATTCCAAGT

ACTTCTCTTG

AATCGTGGGA

GATACTGTGT

TATGTAAAAG

TTTGATGCAT

AGATCTGATG

ACTACAATTA

TTGTATTGTA

AATAATATTG

AGAAGAGGAA

GTATAGCTGT

TGTTGTCTAC

AAGTGTTAGA

GCTGTCGCAT

TGGAAATCAC

TGTTGACAAA

AAAAATTAAT

TAATAAAGGA

CACCTTGCTG

ATATTTGTTT

TCTTTCCACA

ACAGTTTGAC

ATGACTGCAA

GAGCTATAGT

TTATAAAGAC

CAGTGGGCAA

GGGAACCTAT

CAATATCTCA

AATTACTACA

TTATAGTAAT

AAGCCAAAAA

CATTCAGCAA

AGAAGAGAA.G CACCACAGTA 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 ATAGAC3AAA AACCACCTGA TCATGTTTCA ACAACAATCT GCTGACCACC

AATCCCAAAT

388 CAACTTACKA CAAATATTTC AACATCACAG TACAGGCTGA ATCATTTCCT CACATCATGC 0.0.

*.0 o.

0 0.

TACCCACATA

ATCAACCACT

AGAAATCCTT

AGTCATAATT

AACAAGATAC

GCTGAACTGG

ATAGGATCTA

ATTGAGATCA

AAGATAAGAG

CA.AACCATCC

ACATTAGATA

CAAAATGACC

CATATTGATC

TAACCATAAC

TTGGACACCT

TGAAGATATA

TCATCCALACC

GGAAACTCTG

GAGTGTAATG

AACTTAATTA

ACACAGTCAT

TTCCAGTCAT

AACTTACTTA

ATCTTGAATA

ACTAAGCTAG

AAATCAACAC

GTAAATTTGA

ACTTTGAATG

TCAAGTCA.AT

ATAGAACAGA

TAAACAACAT

ATAGTGATGA

TGTACAATAC

ATCTGCTCAA

TCCACAAA-AG

AAACCAAAAA

TCAAGTGAAA

TATTTGGATA

AAAAACTTAT

TATACAGTAT

ATAAILACTAT

CTAATGTGTA

CTTTAGGGAG

GTAGACAJAAG

TALATATCTAG

TACTTATGAC

AAAAAATAAT

AACTAGGATT

ATCCTTAACT

ATCATTCACA

GATTAGAGGT

GCCTCCTCAT

GGACAAAAGC

AGAATATGCT

AACAAAACAA

CATTAAA1AAG

TGTTATATCA

GAGACTACCA

CATAACCATA

TAATGATATT

GCATGGTTGC

ACCACCAGCG

TAGATGCCAC

ATATATTAGT

TTTGATAAGG

TCTAACTGAT

TTATCTTTTT

CCCACTACTA

ATATCATAAA

ATATAAAAGT

ACGAAGAGCC

AAAGGAAAAG

TATAGTTACA

AA.ATTAACAG

CATTGCTTGA

GCATTACTAG

ATAGACACTT

CTTGGTATAG

TCAGCATGTG

CTTAGAGATA

TACATTGAGA

GCAGACGTGC

AGCAATCCAA

ACCGGATAAA

TACATTCAAT

TTTATTAAAT

TCAACAATTT

GTCATAATGC

TTATGGGACA

AGTTATTTAA

AACGGCCCTT

GAGCATATGA

GGTGAALCTGA

ATGTCCTCGT

ATAGAAATAA

GACAGAGTTA

TAAAA.ACCTC

CTGGGGCA

ATGGTAGAAG

TGAGGCAA

TGTCTGAAAT

TTGGAGTGCT

TTGCTATGAG

ATGAAGAACC

GCAATAGA

TGAAGAAGAC

AAGAGTCAAC

TATCCTTGTA

CATAAAAACA

CATATATTTG

CTCCA-ACATC

TTGACCATAA

AAATGGATCC

AAGGTGTTAT

ATCTTAAAAA

ATCTTAAAAA

AATTAGAAGA

CTGAACAAAT

GTGATGTAAA

AGCCCAACAA

AAGTATCACA

TATGTCGCGA

ATGTCACTAC

CTTCATGTTA

AAGTGGAGCT

AGAGAGTTAC

TAAkACTTCTT

CAATTCACCT

AAACAACAAG

AATAAAGAAC

TGTGAATGAT

GTATATCATC

TATTACKATT

ATGAAATTCA

TTAACATCCC

CGACTCTATG

CATTATTAAT

CTCTTTTTCA

TGATTACACC

ACTAACTATA

ACCAACTTAT

TGCTACAACT

GGTGTACGCC

TAATTCAGGT

7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 GATGAAAACT CAGTACTTAC AACTATAATT AAAGATGATA TACTTTCGGC TGTGGAAAC 389 AATCAATCAT ATACAAATTC AGACAAAAGT CACTCAGTAA ATCAAAATAT CACTATCAA 9060

S

ACAACACTCT

TGGTTCAATT

AAAAGTCATG

AATCAATATG

AATCAATTTT

TGGATAAGTA

AATGTTGTGT

GAAGGCTTCT

ACAGAAGAAG

GCAGCTATTA

ACAGTGTCTG

TTGATTAAGC

AGAATCTTTG

TGTAATGAAA~

TATAGAATCA

ATTGTCCTAC

GAAATCACAG

CTGCCTAAAA

GATCTAATAT

GAACATGAAA

TTGAGAGATA

CTCAACAACT

AGAATGTTTG

ATAGCTGAAA

TGAAAAAATT

TATATACAkA

GGTTTATATT

GTTGTATCGT

TGACATGGAA

ATTGTTTAAA

TATCACAATT

ACATAATAAA

ATCAATTTAG

AGGCTCAAAA

ATAATATCAT

TTGCAGGTGA

GACATCCAAT

CTAAGTTCTA

TAAAAGGGTT

CTCTAAGATG

AAAATGATTT

AAGTGGATCT

GGACTAGTTT

AGTTGAAGTT

ATAAATTCAA

CTAATCACGT

CTATGCAACC

ATATTTTACA

GATGTGTTCA

ATTAAATAAC

AATAGATAAT

TTATCATAAA

AGACATCAGC

TACATTAAAC

ATTTCTTTAT

AGAAGTAGAG

GAAACGATTT

GGACCTACTA

AAATGGTAAA

TAATAATCTC

GGTCGATGAA

CTTATTAAGT

TGTAAATACC

GTTAAACTAC

GATTATTTTA

TGAAATGATA

TCCTAGAAAT

CTCTGAAAGC

TGAATGCGAT

GGTATCACTA

AGGTATGTTT

ATTCTTCCCT

ATGCAACATC

ATATTAACAC

CAAACTTTAA

GGACTCAAAA

CTTAGCAGAT

AAAAGCTTAG

GGAGATTGTA

GGATTTATTA

TATAATAGCA

TCAAGAGTAT

TGGATAATCC

AATAACTTGA

AGACAAGCAA

AGTCTAAGTA

TACAACAGAT

TATAALACTTA

TCAGGATTGC

ATAAATGACA

TACATGCCAT

GACAGATCGA

CTATACAATT

ACTGGTAAAG

AGGCAA-ATCC

GAGAGTTTGA

CTCCATCATG

AATATCGATC

GTGGTTTTCA

AAATCACAAC

TAAATGTTTG

GGCTGAGATG

TACTGATT

TGTCTTTAAT

TGCTAAATAA

GTCACACTTT

TATTAAGTAA

GTGAGCTATA

TGGATTCTGT

CATTAAGAGG

GGCCCACCTT

ATACTTATCC

GGTTCTATCG

AAGCCATTTC

CACATATACA

GAAGAGTACT

GTGTAGTCAA

AAAGAGAGCT

AAATCTTAGC

CAAGATATGG

GTTA.ATACAC

AAATGAGGTA

GTTTATTTTA

TACTACTTAC

CTTAATTACT

TGGATTCAAT

ATTTCATAAT

TCTAAACATA

CATCACAGAT

ATTAGACA.AG

ATTTCTTAAA

TTTTCTCTTC

AAGAATTAAC

TGCTTTCATT

AAGGAATGCT

ATCTCTACTT

TGAGTTTCAT

ACCTCCAAA.A

AAATTATATA

AGAGTATTAC

TCAAAGCTAT

CAGTGTAGGT

AGAGAAAATG

TGATCTAGAG

9120 9180 9240 9300 9360 9420 9480 9540 9600 9660 9720 9780 9840 9900 9960 10020 10080 10140 10200 10260 10320 10380 10440 10500 10560 CTTCAAAAGA TATTAGAATT AAAAGCAGGA ATAAGC"CA AGTCAAATCG TTATKATGAT 390 AACTACAACA ATTATATCAG TAAATGTTCT ATCATTACAG ATCTTAGCAA ATTCAATCAG

GCATTTAGAT

CAATCTCTGT

AGACATGCAC

AGTGGATTAT

ATTGAAGCTA

CTGATAAATG

CAGACCCATG

GAGTATGCAG

CAGTTCATGA

GTCCTGAGAG

TCTATAGGCA

ATATTTAGGA

TGTAACAATA

AATCTTGATA

GGTGGTGATC

GAAGCTATAG

AAGCTCCAGG

GATAAAAATC

GAAAGGCAAG

ATAGCCCCAA

CTAAATGACA

GAAAGTTTAC

ATAACTAATA

GATATGATGA

GACAAAAGAG

ATGAA.ACATC

TCTCTTGGTT

CTCCTTTCAT

ACAGATATCA

TATCATTATT

GTGATA.ATCA

CACAAGCAGA

GTATAGGCCA

GCAAAACAT

TAGGTCCATG

GCTTAACACA

ACATTTGGTT

AGCTATATTT

GCATTGATAT

CTAATTTGTT

TACATTCAGT

ATCTTCCAGA

CCAATGCCGA

CTAAAATTAC

ACAAAATATT

TTATGCAAAA

CTTTTTATAA

TACTTGAAAA

GGAAAALATAT

AGTTATTAAG

ATGTATCTGC

GCATTTAA

AAAGGATCAT

TATGGGTGGT

AGATCTAATA

GTCAATTGAT

TTATTTGTTA

TAAGCTTAAG

CCAGCACAAT

GATAAACACG

GGAGTTAGAA

ATACA.ATCAA

AGATATATTG

GGCTTTATCA

ATATCGAAGC

GTTTGTGTTG

TGATAGACTG

GTTTGTAACA

TAGTGAGATT

TTCTAAAAGT

TATAGAAcCA

AGCAGAAAAA

AACATCAGCA

AACTTTACTT

TTTAGAAAAT

AGTGATGTAT

ATACCTCTTG

GTTGTTAATC

ATTGAGGGCT

TCTCTCAAAG

ATAAGCAAAC

GCATTAAATA

GGAACAGAGA

GGAGTGTACT

ATACTTGATG

TACAGAGGAG

ATTGCTTTGC

AAAGTATTALA

TTGTATATGA

TTTTATAGGA

AGCTATTATA

AACAAATTCT

TTGATGAGGG

AATAGATTAG

GCACAACATT

ACTTACCCTC

ATAGTTAATC

ATAGATACAA

ATAAGGATAC

CTTAGTATA6A

TAGATGAACT

TCACAATAAT

TTAATGAGGT

GGTGTCAAAA

GGAAATTCTC

CAGTTAGACT

GCCTTAALATT

CCTATATATC

ATCCAGCCAG

ATTTTAAAGT

AAAGCTTATT

AACTCCGAAA

AACACTTAAA

ATTTGCCTAT

GAACTCCAGA

CTGGTCACGA

TGACATGTGT

ATCCACAGGC

CAGTAACAGA

ATACTACCAC

ATGGATTAAG

TTATATCAGG

CTGATATTAA

TTCCACTAGA

CTGAATTAAG

GCATGGAGTA

ATGTACATAT

TGATGAACAA

ACTGTGGACC

TATCACAGCT

TATAGAGGGT

GTTATATAAA

CCGAGATATG

TATCAAAAA6A

TAGTTTAGALA

ATGCAGTTTA

TCATGCATTA

ALACTTTTTTT

GCTGTTTGGT

CTTCCTTACA

TTTACAAGAT

CATCACATTT

TTTAGGGTCT

AGTCTTAAGT

TGAGATTGAT

AGTTGTTTAT

AACAAAATCC

TAGGGCTACT

TTGTAACAA

CAAGTATGTA

10620 10680 10740 10800 10860 10920 10980 11040 11100 11160 11220 11280 11340 11400 11460 11520 11580 11640 11700 11760 11820 11880 11940 12000 12060 12120 391

AGAGAAAGAT

ACAATGGACA

AATGTTAATA

ACGCAGGAGA

GACCAAATAG

GAATTCATGG

TTGTTTCCAC

TGTGAATTCC

CCTATCAATC

AATTGCATAA

CCTAATAGAA

TTTACAGGAG

CTACCAGATA

AAATCTGGAT

CATAATGCTT

ATGAA.AGATT

ATGTTCATTA

AALAGGTTATG

TTGGAGTTAA

GTCATAAAAT

TTTILAGTTGT

GTTAACATAG

AGAATGGGGT

GAATTTTACA

CTAACAAAAC

CTTGGTCATI

TTAAATATAC

GTTTAACTCG

AAAAAACAAT

ATTTATTAGC

AAGAACTGAG

AATATCTA.AG

CTGCATCAAT

ATGTATTAAC

GTTTTGGTCT

TTATTCTCAT

ATGTTGATAT

AAATAAGTTT

CTCACATC-

ATATTTTAAG

CAAAAGGTAT

ATTTGAATGT

GTAAAGCAAA

TAGACAGTAG

ACATAGTCAA

GGTTTTTAAA

ATTATCACCC

TAATA.AATGT

CATCAAATCT

AAATAAGAAT

ATCCAATATA

AACTAGCACT

TGGTGAAAGA

GCCAGTGTAC

AAAATTAGAC

TACTGGAACA

TGTCAATTAT

ACCAGCTTAT

AGAAAAGTAT

TAGCCTGATG

ACCGAAGCTG

CATCAAGTTG

A.ACCCAATAT

CTCTAATTTA

TACTAATTTA

TTTTGAAAAA

TTTCTTTAAT

ATTAGAATGT

CTACTGGAAA

TCAAGACACA

ACGCCTTGAT

AACACACATG

AGATAAATTA

CTTTTACATT

TGCTAATTCA

GTAGGAGTAA

ATAGCCAGTG

GGACCCACCA

AACAGACAAG

TGGGTATATG

CTTGGACTGT

TTACACCGTT

AGAACAACAA

GGAGATGAAG

TCGGTTGTGG

AATGAGATAC

AAGCAAGTGA

GTAGAATTAT

ATATTAGTAC

GCTGGACATT

GATTGGGGAG

GCTTATAAGA

GATATGAACA

TCTATGTCTA

AGTTTGCGTA

AATGCTAAAT

AAAGCTATAT

ACCATTAA

AGTTATAACT

GAATTAGAAG

CATCGCCAAG

GTATAATAkAT

AGCCATGGGT

TTTTAACCAA

CATCCATAGA

CATATGAAAA

TAACAGTCAG

ATTATCATTT

ATATCGACAT

AACAATTCAC

ATTTGATGAA

TACAAAAGCA

TCTTAAGTAA

ATAAAATGTC

GGATTCTGAT

AGGGGTACAT

CTTATTTGCT

CTTCAGATCT

AAGTTTTCCT

GAATAAAAGG

TTACCGTATG

TATCTTACAT

ATAAA AACAA

TTTCAGACAA

ATAATTATAA

TATTATGTTC

AGAAAAATAT

AGGCTCATCC

AAAGCAAAGA

CAACAAAGAT

AGCCAAAAAG

TAGTAGACCA

TGATACTAGT

TGTGTTTCAA

AAACATATGT

ACCTCCTATA

GCACATGTTC

CAALAGCACTT

TGATTATTTT

TATTCAACTT

AACTGATCAT

ATGTTTTCAT

TCTTTGTGTT

AGAACAAAAA

CTGTCACAGT

CCCTTGGGTT

AGATTTAGTT

PTTCAATGAT

CACTCA:TTTG

CAAACTATAT

12180 12240 12300 12360 12420 12480 12540 12600 12660 12720 12780 12840 12900 12960 13020 13080 13140 13200 13260 13320 13380 13440 13500 13560 13620 13680 CACCCAACCC CAGA.AACTTT AGAAAATATG TCATTAATTC CTGTTAAAAG

TAATAATAGT

392

AACAAACCTA

AGTAAAATGC

TTGTACAATT

GCAAAATCTA

GCATCACTTT

TCCACAGGAT

AGTTGTATAG

CTTCATCCAG

CCTATTGAAT

ACCATTCCTG

GCAGAACCTA

AAAATTATAA

AGATGCATTT

ATTACTATAT

TTAATCCTTA

AAATTGATAC

ATCGATGCAG

ATTAAGACTT

ATAGCTGGAC

CTAAAATGGC

TACATGATAG

GAGCTCAAGA

TAGTTTAA;A

TAGTTATTAA

TTTTAGTCTT

ACACIAACGAG

AATTTTGTAT

ATATTAAATC

TATTTCCAAT

ACCAACTTTA

ATTGCATGCT

GCAAGATCAG

CATTCATAGG

ACATILAGATA

TTCTAAGGTT

CTACAGATGC

TTAGCATCTT

TTGAATGGAG

TAATTGCAAA

TAAAAACTTA

CAATAGGCCC

TTTCAAGAAC

TTATTAAAAG

CATTGTCAA.A

GTAATGAAGT

TAGATCATGT

AGTCCACATA

AGCTGATTAA

TATCATTAAC

AAAATATACA

AAGGGGTTAA

ACATTAGTTT

AAGTGGAAAT

TTCCACTGTT

TGTTGTGATA

CACCACCACT

TCCTTGGCAT

TATAGAGTAT

TGAAGGAGCT

CATTTACAGA

ATACAACGGG

AACTAATAAC

TGTCTGCGAT

TAAGCATGTA

ATATCATGCT

CGTGTGCCTA

TGCAAATATA

TAAAAATTTC

CTTALATACCT

ATTGAAGAGT

ATTCAGCAAC

TTTAAATTTT

TCCTTACTTA

AATAACAGGT

AAGTTTGGTC

AACTTTTCAA

ATAAAAGTCT

TTGACACTTT

ACCGAATCTA

ACCACAAGAT

GACAAGATTA

TCACATCAGA

CATGTCAATA

ATTTTAAAAG

GGTAACTTAT

AGTTTAAJ.AG

CATATAAACA

ATTCATTGGT

GCTGAATTAC

AGAAAGTGCA

CAAGATGACA

GGTAGCAAGT

CTTCCTGTTT

ATTATGCCTA

TTCCTTTGTT

GTAGTTAATG

AAGCTTATAA

AGATCAGCTG

AGTGAATTGT

AGTGTGCTAT

AAATTTAGAT

TAATTTAGCA

AA.AACTAACA

TTTTCTCGT

TGATGATGTC

TCAATTATAG

TAGATCATTC

CATCTTTAGT

GATTTAACTT

ATCTTAAGAT

TATTACGTAC

ATTGCAATGA

TAGATTATGG

CTTATTTACA

CTGTTACAGC

AGTACTGTTC

TTGATTTCAA

TAAAAGGATC

TTGATGTTGT

AAAAAACTGA

ACCCTATAAC

GAGATATATT

ACCACAAGCA

AACTTAATTA

TAALATAGTTT

ACAACCTTCC

GCTAACACAT

TATTGATTCC

ATTATACATG

AACATTCTCT

CAAACAAGAC

AGGTA.ATACA

AAGGAATAGT

TGTATTTAGT

TAAGGACCCC

GGTAGTAGAA

TCATAGTTTA

TGAGAATTTA

TATAA.AATTT

CAATTGGAGT

TTCTGTAAAT

ATTAGATAAC

TGAAGTTTAC

ACAAAATGCT

CAAGGAATCT

AAAAAAAGGA

ATCATATTCT

TATGAATATC

CAATCATTTA

AACAACCAAT

CAACGAACAG

CATTATATTA

kAAATTATCA rGCATTCACA 13740 13800 13860 13920 13980 14040 14100 14160 14220 14280 14340 14400 14460 14520 14580 14640 14700 14760 14820 14880 14940 15000 15060 15120 15180 15219 393 INFORMATION FOR SEQ ID NO:34: SEQUENCE CHARACTERISTICS: LENGTH: 2166 amino acids TYPE: amino acid

STRANDEDNESS:

TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: Met Asp Pro Ile Ile Asn Gly Asn Ser Ala Asn Val Tyr Leu Thr Asp 1 5 10 Ser Tyr Leu Lys Gly Val Ile Ser Phe Ser Giu Cys Asn Ala Leu Gly 25 Ser Tyr Leu Phe Asn Gly Pro Tyr Leu Lys Asn Asp Tyr Thr Asn Leu 40 Ile Ser Arg Gin Ser Pro Leu Leu Giu His Met Asn Leu Lys Lys Leu .50 55 *Thr Ile Thr Gin Ser Leu Ile Ser Arg Tyr His Lys Gly Giu Leu Lys 70 75 Leu Giu Giu Pro Thr Tyr Phe Gin Ser Leu Leu Met Thr Tyr Lye Ser 90 Met Ser Ser Ser Giu Gin Ile Ala Thr Thr Asn Leu Leu Lys Lys Ile *100 105 110 Ile Arg Arg Ala Ile Giu Ile Ser Asp Val Lys Val Tyr Aia Ile Leu 115 120 125 **Asn Lys Leu Gly Leu Lye Giu Lys Asp Arg Val Lye Pro Aen Asn Asn 130 135 140 Ser Giy Asp Glu Asn Ser Val Leu Thr Thr Ile Ile Lys Asp Asp Ile 145 150 155 160 Leu Ser Ala Vai Giu Asn Asn Gin Ser Tyr Thr Aen Ser Asp Lye Ser 165 170 175 His Ser Val Asn Gin Asn Ile Thr Ile Lys Thr Thr Leu Leu Lye Lye 180 185 190 394 Leu Met Cys Ser Met Gin His Pro Pro Ser Trp Leu Ile His Trp Phe 195 200 205 Asn Leu Tyr Thr Lys Leu Asn Asn Ile Leu Thr Gin Tyr Arg Ser Asn 210 215 220 Giu Val Lys Ser His Giy Phe Ile Leu Ilie Asp Asn Gin Thr Leu Ser 225 230 235 240 Giy Phe Gin Phe Ile Leu Asn Gin Tyr Gly Cys Ile Vai Tyr His Lys 245 250 255 Gly Leu Lys Lys Ile Thr Thr Thr Thr Tyr Asn Gin Phe Leu Thr Trp 260 265 270 Lys Asp Ile Ser Leu Ser Arg Leu Asn Val Cys Leu Ile Thr Trp Ile 275 280 285 Ser Asn Cys Leu Asn Thr Lau Asn Lys Ser Leu Giy Leu Arg Cys Gly 290 295 300 Phe Asn Asn Vai Vai Leu Ser Gin Leu Phe Leu Tyr Gly Asp Cys Ile 305 310 315 320 .Leu Lys Leu Phe His Asn Giu Giy Phe Tyr Ile Ile Lys Giu Vai Giu 325 330 335 .Giy Phe Ile Met Ser Leu Ile Leu Aen Ile Thr Giu Giu Asp Gin Phe *340 345 350 Arg Lys Arg Phe Tyr Asn Ser Met Leu Asn Asn Ile Thr Asp Ala Ala 355 360 365 Ile Lys Ala Gin Lye Asp Leu Leu Ser Arg Val Cys His Thr Leu Leu 370 375 380 **Asp Lys Thr Val Ser Asp An Ile Ile Aen Gly Lys Trp Ile Ile Leu 385 390 395 400 Leu Ser Lye Phe Leu Lye Leu Ile Lys Leu Ala Gly Asp Asn Asn Leu 405 410 415 Aen Aen Leu Ser Giu Leu Tyr Phe Leu Phe Arg Ile Phe Giy His Pro 420 425 430 Met Val Asp Giu Arg Gin Ala Met Asp Ser Val Arg Ile Aen Cys Asn 435 440 445 Giu Thr Lys Phe Tyr Lau Leu Ser Ser Leu Ser Thr Leu Arg Giy Ala 450 455 460 Phe Ile Tyr Arg Ile Ile Lye Gly Phe Val Asn Thr Tyr Asn Arg Trp, 395 465 Pro Thr Tyr Lys Leu Ile Lys Lys 530 Pro Lys 545 His Ile Asp Arg Asn Giu Asn Ser 610 Val Gly 625 Ile Leu Giu Ser Leu Lys Asn Asn 690 Asn Gin 705 Asp Giu Leu Leu Ile 515 Vai Asp Gin Ser Cys 595 Asn Arg Aila Leu Ala 675 Tyr Ala Leu Arg Asn 500 Leu Asp Leu Asn Arg 580 Asp His Met Giu Thr 660 Gly Ile Phe His Asn 485 Thr Ser Leu Ile Tyr 565 Arg Leu Val Phe Lys 645 Arg Ile S er Arg Gly 725 470 Ala Tyr Giy Giu Trp 550 Ile Val Tyr Val Ala 630 Met Tyr Ser Lys Tyr 710 Val Ile Pro Leu Met 535 Thr Giu Leu Asn S er 615 Met Ile Gly Asn Cys 695 Giu Gin Val S er Arg 520 Ile Ser His Giu Cys 600 Leu Gin Aia Asp Lys 680 Ser Thr Ser Leu Leu 505 Phe Ile Phe Glu Tyr 585 Val Thr Pro Giu Leu 665 Ser Ile Ser Leu Pro 490 Leu Tyr Asn Pro Lys 570 Tyr Val Gly Gly Asn 650 Glu Asn Ile Cys Phe 730 475 Leu Giu Arg Asp Arg 555 Leu Leu Asn Lys Met 635 Ile Leu Arg Thr Ile 715 Ser Arg Ile Giu Lys 540 Asn Lys Arg Gin Giu 620 Phe Leu Gin Tyr Asp 700 Cys Trp Trp Thr Phe 525 Aila Tyr Phe Asp Ser 605 Arg Arg Gin Lys Asn 685 Leu Ser Leu Leu Giu His Ile Met Ser Asn 590 Tyr Giu Gin Phe Ile 670 Asp Ser Asp Asn 495 Asn Leu Ser Pro Giu 575 Lys Leu Leu Ile Phe 655 Leu Asn Lys Vai 480 Tyr Asp Pro Pro S er 560 Ser Phe Asn Ser Gin 640 Pro Giu Tyr Phe Leu 720 Ile Pro Leu Vai Thr Ile Ile Cys Thr Tyr Arg His Ala 740 745 735 Pro Pro Phe 750 396 Ile Lys Asp His Vai Vai Asn Leu Asn Giu Val Asp Giu Gin Ser Giy 755 760 765 a. a a. *a a a a a.

a a a a.

a Leu Tyr 770 Trp Thr 785 Lys Phe Ile Ser Asp Tyr Ala Gly 850 Asp Met 865 Pro Ala Ile Leu Gin Glu Arg Asn 930 Ala Leu 945 His Leu Leu Tyr Leu Tyr Arg Tyr Ile Giu Ser Ile Lys Pro 820 Leu Leu 835 Ile Giy Gin Phe Ser Ile Asp Asp 900 Leu Giu 915 Ile Trp Cys Asn Lye Thr Met Asn 980 Arg Ser 995 His Met Ala Ile 790 Thr Ala 805 Val Arg Ala Leu His Lye Met Ser 870 Lys Lys 885 Phe Lye Tyr Arg Leu Tyr Asn Lye 950 Phe Phe 965 Leu Pro Phe Tyr Gly Gly Ile 775 Ser Leu Leu Leu Ile Asn Leu Ile Giu 825 Asn Ser Leu 840 Leu Lye Gly 855 Lye Thr Ile Vai Leu Arg Val Ser Leu 905 Gly Glu Ser 920 Aen Gin Ile 935 Leu Tyr Leu Aen Leu Asp Met Leu Phe 985 Arg Arg Thr 1000 Giu Asp Gi y 810 Gly Lye Thr Gin Val1 890 Glu Leu Al a Asp Ser 970 Gly Pro Gly Leu 795 Asp Gin Leu Giu His 875 Gly Ser Leu Leu Ile 955 Ile Giy Asp Trp 780 Ile Asn Thr Leu Thr 860 Asn Pro Ile eye Gin 940 Leu Asp Gly Phe Cye Gin Ser Leu Gin Ser His Ala 830 Tyr Lye 845 Tyr Ile Gly Val Trp Ile Gly Ser 910 Ser Leu 925 Leu Arg Lye Val Met Aia Asp Pro 990 Leu Thr 1005 Lye Lys Ile 815 Gin Giu Ser Tyr Aen 895 Leu Ile Asn Leu Leu 975 Asn Giu Leu Gly 800 Asp Ala Tyr Arg Tyr 880 Thr Thr Phe His Lye 960 Ser Leu Ala Ile Val His Ser Val Phe Val Leu Ser Tyr Tyr Thr Gly His Asp Leu

.LV.LV

1015 1020 397 Gin Asp Lys Leu Gin Asp Leu Pro Asp Asp Arg Leu Asn Lys Phe Leu 1025 1030 1035 1040 Thr Cys Val Ile Thr Phe Asp Lys Asn Pro Asn Ala Giu Phe Val Thr 1045 1050 1055 Leu Met Arg Asp Pro Gin Ala Leu Gly Ser Giu Arg Gin Ala Lys Ile 1060 1065 1070 Thr Ser Giu Ile Asn Arg Leu Ala Val Thr Giu Val Leu Ser Ile Ala 1075 1080 1085 Pro Asn Lys Ile Phe Ser Lys Ser Ala Gin His Tyr Thr Thr Thr Giu 1090 1095 1100 Ile Asp Leu Asn Asp Ile Met Gin Asn Ile Giu Pro Thr Tyr Pro His 1105 1110 1115 1120 Gly Leu Arg Val Val Tyr Giu Ser Leu Pro Phe Tyr Lys Ala Giu Lys 1125 1130 1135 Ile Val Asn Leu Ile Ser Gly Thr Lys Ser Ile Thr Asn Ile Leu Giu C..1140 1145 1150 .Lys Thr Ser Ala Ile Asp Thr Thr Asp Ile Asn Arg Aia Thr Asp Met :1155 1160 1165 Met Arg Lys An Ile Thr Leu Leu Ile Arg Ile Leu Pro Leu Asp CyB *1170 1175 1180 Aen Lys Asp Lys Arg Glu Leu Leu Ser Leu Glu Asn Leu Ser Ile Thr 1185 1190 1195 1200 Gluf Leu Ser Lys Tyr Val Arg Giu Arg Ser Trp Ser Leu Ser Aen Ile 1205 1210 1215 *CVal Gly Val Thr Ser Pro Ser Ile Met Phe Thr Met Asp Ile Lys Tyr 1220 1225 1230 Thr Thr Ser Thr Ile Ala Ser Gly Ile Ile Ile Glu Lys Tyr Asn Val *1235 1240 1245 see* Asn Ser Leu Thr Arg Gly Glu Arg Gly Pro Thr Lye Pro Trp Val Gly 1250 1255 1260 Ser Ser Thr Gin Giu Lys Lye Thr Met Pro Vai Tyr Asn Arg Gin Val 1265 1270 1275 1280 Leu Thr Lys Lye Gin Arg Asp Gin Ile Asp Leu Leu Ala Lye Leu Asp 1285 1290 1295 Trp Val Tyr Ala Ser Ile Asp Asn Lys Asp Giu Phe Met Giu Giu Leu 398 1300 1305 1310 Ser Thr Giy Thr Leu Giy Leu Ser Tyr Glu Lys Ala Lys Lys Leu Phe 1315 1320 1325 Pro Gin Tyr Leu Ser Val Asn Tyr Leu His Arg Leu Thr Val Ser Ser 1330 1335 1340 Arg Pro Cys Giu Phe Pro Ala Ser Ile Pro Ala Tyr Arg Thr Thr Asn 1345 1350 1355 1360 Tyr His Phe Asp Thr Ser Pro Ile Asn His Val Leu Thr Giu Lys Tyr 1365 1370 1375 Giy Asp Giu Asp Ile Asp Ile Val Phe Gin Asn Cys Ile Ser Phe Gly 1380 1385 1390 Leu Ser Leu Met Ser Val Val Glu Gin Phe Thr Asn Ile Cys Pro Asn 1395 1400 1405 Arg Ile Ile Leu Ile Pro Lys Leu Asn Giu Ile His Leu Met Lys Pro 1410 1415 1420 *Pro Ile Phe Thr Gly Asp Vai Asp Ile Ile Lys Leu Lye Gin Val Ile 1425 1430 1435 1440 *Gin Lye Gin His Met Phe Leu Pro Asp Lys Ile Ser Leu Thr Gin Tyr **1445 1450 1455 **Val Giu Leu Phe Leu Ser Asn Lye Ala Leu Lye Ser Gly Ser His Ile 1460 1465 1470 Aen Ser Asn Leu Ile Leu Val His Lye Met Ser Asp Tyr Phe Hie Aen 1475 1480 1485 Ala Tyr Ile Leu Ser Thr Aen Leu Ala Gly His Trp Ile Leu Ile Ile 1490 1495 1500 *.Gin Leu Met Lye Asp Ser Lye Gly Ile Phe Giu Lye Asp Trp Giy Giu 1505 1510 1515 1520 .Gly Tyr Ile Thr Asp His Met Phe Ilie Asn Leu Asn Val Phe Phe Asn 1525 1530 1535 Ala Tyr Lye Thr Tyr Leu Leu Cys Phe His Lye Giy Tyr Gly Lye Ala 1540 1545 1550 Lys Leu Glu Cys Asp Met Aen Thr Ser Asp Leu Leu Cys Val Leu Glu 1555 1560 1565 Leu Ile Asp Ser Ser Tyr Trp Lye Ser Met Ser Lys Val Phe Leu Giu 1570 1575 1580 399 Gin Lys Val Ile Lys Tyr Ile Val Asn Gin Asp Thr Ser Leu Arg Arg 1585 1590 1595 1600 Ile Lys Giy Cys His Ser Phe Lys Leu Trp Phe Leu Lys Arg Leu Asp 1605 1610 1615 Asn Ala Lys Phe Thr Vai Cys Pro Trp Val Val Asn Ile Asp Tyr His 1620 1625 1630 Pro Thr His Met Lys Ala Ile Leu Ser Tyr Ile Asp Leu Val Arg Met 1635 1640 1645 Gly Leu Ile Asn Val Asp Lys Leu Thr Ile Lys Asn Lys Asn Lys Phe 1650 1655 1660 Asn Asp Giu Phe Tyr Thr Ser Aen Leu Phe Tyr Ile Ser Tyr Aen Phe 1665 1670 1675 1680 Ser Asp Asn Thr His Leu Leu Thr Lys Gin Ile Arg Ile Ala Asn Ser 1685 1690 1695 Glu Leu Giu Asp Asn Tyr Asn Lys Leu Tyr His Pro Thr Pro Giu Thr *1700 1705 1710 *Leu Glu Asn Met Ser Leu Ile Pro Val Lye .Ser Asn As Ser An Lye .1715 1720 1725 *Pro Lye Phe Cys Ile Ser Gly Asn Thr Giu Ser Met Met Met Ser Thr .1730 1735 1740 Phe Ser Ser Lye Met His Ile Lye Ser Ser Thr Val Thr Thr Arg Phe 1745 1750 1755 1760 Aen Tyr Ser Lye Gin Asp Leu Tyr Asn Leu Phe Pro Ile Val Val Ile 1765 1770 1775 **Asp Lye Ile Ile Asp His Ser Gly Asn Thr Ala Lye Ser Asn Gin Leu 1780 1785 1790 **Tyr Thr Thr Thr Ser His Gin Thr Ser Leu Val Arg Asn Ser Ala Ser *1795 1800 1805 Leu Tyr Cys Met Leu Pro Trp His His Val Aen Arg Phe Aen Phe Val 1810 1815 1820 Phe Ser Ser Thr Gly Cys Lye Ile Ser Ile Giu Tyr Ile Leu Lye Asp 1825 1830 1835 1840 Leu Lye Ile Lye Asp Pro Ser Cys Ile Ala Phe Ile Gly Giu Gly Ala 1845 1850 1855 400 Gly Asn Leu Leu Leu Arg Thr Val Val Glu Leu His Pro Asp Ile Arg 1860 1865 1870 Tyr Ile Tyr Arg Ser Leu Lys Asp Cys Asn Asp His Ser Leu Pro Ile 1875 1880 1885 Glu Phe Leu Arg Leu Tyr Asn Gly His Ile Asn Ile Asp Tyr Gly Glu 1890 1895 1900 Asn Leu Thr Ile Pro Ala Thr Asp Ala Thr Asn Asn Ile His Trp Ser 1905 1910 1915 1920 Tyr Leu His Ile Lys Phe Ala Glu Pro Ile Ser Ile Phe Val Cys Asp 1925 1930 1935 Ala Glu Leu Pro Val Thr Ala Asn Trp Ser Lys Ile Ile Ile Glu Trp 1940 1945 1950 Ser Lys His Val Arg Lys Cys Lys Tyr Cys Ser Ser Val Asn Arg Cys 1955 1960 1965 Ile Leu Ile Ala Lys Tyr His Ala Gin Asp Asp Ile Asp Phe Lys Leu 1970 1975 1980 Asp Asn Ile Thr Ile Leu Lys Thr Tyr Val Cys Leu Gly Ser Lys Leu S1985 1990 1995 2000 Lys Gly Ser Glu Val Tyr Leu Ile Leu Thr Ile Gly Pro Ala Asn Ile 2005 2010 2015 Leu Pro Val Phe Asp Val Val Gin Asn Ala Lys Leu Ile Leu Ser Arg 2020 2025 2030 Thr Lys Asn Phe Ile Met Pro Lys Lys Thr Asp Lys Glu Ser Ile Asp 2035 2040 2045 Ala Val Ile Lys Ser Leu Ile Pro Phe Leu Cys Tyr Pro Ile Thr Lys 2050 2055 2060 Lys Gly Ile Lys Thr Ser Leu Ser Lys Leu Lys Ser Val Val Asn Gly 2065 2070 2075 2080 Asp Ile Leu Ser Tyr Ser Ile Ala Gly Arg Asn Glu Val Phe Ser Asn 2085 2090 2095 Lys Leu Ile Asn His Lys His Met Asn Ile Leu Lys Trp Leu Asp His 2100 2105 2110 Val Leu Asn Phe Arg Ser Ala Glu Leu Asn Tyr Asn His Leu Tyr Met 2115 2120 2125 Ile Glu Ser Thr Tyr Pro Tyr Leu Ser Glu Leu Leu Asn Ser Leu Thr 401 2130 2135 2140 Thr Asn Glu Leu Lys Lys Leu Ile Lys Ile Thr Gly Ser Val Leu Tyr 2145 2150 2155 2160 Asn Leu Pro Asn Glu Gin 2165 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID CATATCACTC ACTCTGGGAT GGAG 24 INFORMATION FOR SEQ ID NO:36: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: TCAGAACATC AAGCACCGCC S(2) INFORMATION FOR SEQ ID NO:37: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) 402 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: ACAGTCAAGA CTGAGATGAG INFORMATION FOR SEQ ID NO:38: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: AAGAGTCAGA TACATGTGGA INFORMATION FOR SEQ ID NO:39: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear e MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: ACATGAATCA GCCTAAAGTC INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) 403 (xi) SEQUENCE DESCRIPTION: SEQ ID CCGAAAGAGT TCCTGCGTTA CGACC INFORMATION FOR SEQ ID NO:41: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: CAGTCCACAC AAGTACCAGG INFORMATION FOR SEQ ID NO:42: S(i) SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: S GTCAGAAGCT GTGGACCATC INFORMATION FOR SEQ ID NO:43: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) 404 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: AATATTGCTA CAACAATGGC INFORMATION FOR SEQ ID NO:44: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: ACTCTTCATT CCTAGACTGG INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID GTCCAATTAT GACTATGAAC INFORMATION FOR SEQ ID NO:46: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) 405 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: AGAACAGACA TGAAGCTTGC INFORMATION FOR SEQ ID NO:47: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: CCAACAAGGA ATGCTTCTAG INFORMATION FOR SEQ ID NO:48: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: ACAGCACTAT CTATGATTGA CCTGG INFORMATION FOR SEQ ID NO:49: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: 406 GCAACATGGT TTACACATGC INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID AGATTGAGAG TTGATCCAGG INFORMATION FOR SEQ ID NO:51: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear "0 (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: AGGAGATACT TAAACTAAGC INFORMATION FOR SEQ ID NO:52: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: 407 TAAGCTTATG CCTTTCAGCG INFORMATION FOR SEQ ID NO:53: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: TTAACGGACC TAAGCTGTGC INFORMATION FOR SEQ ID NO:54: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: GAAACAGATT ATTATGACGG INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID CGGGCTATCT AGGTGAACTT CAGG 94 408 INFORMATION FOR SEQ ID NO:56: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56: ATTTGGATAT GGAATATGAG INFORMATION FOR SEQ ID NO:57: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear V (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:57: ACTCAACTGA ACTACCAGTG INFORMATION FOR SEQ ID NO:58: SEQUENCE CHARACTERISTICS: S" LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58: AAGAACATCA TGTATTTCAG 409 INFORMATION FOR SEQ ID NO:59: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:59: TTATCAACGC ACTGCTCATG INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:61: GCCTCTGTGC AAACAAGCTG INFORMATION FOR SEQ ID NO:62: INFORMATION FOR SEQ ID N0:62: 410 SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62: TCTCTAGTTA CTCTAGCAGC INFORMATION FOR SEQ ID NO:63: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63: AGGTCGTTGT TTGTGAGGAG INFORMATION FOR SEQ ID NO:64: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid S* STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64: TCGTCCTCTT CTTTACTGTC INFORMATION FOR SEQ ID 411 SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID CCGTCCTCGA GCTAGCCTCG INFORMATION FOR SEQ ID NO:66: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:66: CTCCTCCAGG CTCACATTGG INFORMATION FOR SEQ ID NO:67: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs i TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67: GGGTTGGTAC ATAGCTCTGC INFORMATION FOR SEQ ID NO:68: SEQUENCE CHARACTERISTICS: 412 LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68: CACCCATCTG ATATTTCCCT GATGG INFORMATION FOR SEQ ID NO:69: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) 0 0 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69: TGGTTGACAG TACAAATCTG INFORMATION FOR SEQ ID 00. SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) 9 (xi) SEQUENCE DESCRIPTION: SEQ ID CTGAAATGGG AAGATTGTGC INFORMATION FOR SEQ ID NO:71: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs 413 TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71: AGCAATCTAC ACTGCCTACC INFORMATION FOR SEQ ID NO:72: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72: TCACAGATGA TTCAATTATC INFORMATION FOR SEQ ID NO:73: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear o (ii) MOLECULE TYPE: RNA (genomic) o (xi)-SEQUENCE DESCRIPTION: SEQ ID NO:73: GATCCTAGAT ATAAGTTCTC INFORMATION FOR SEQ ID NO:74: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid 414 STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74: ACCAAACAAA GTTGGGTAAG G 21 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 32 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID SGGGGGATCCA TCCCTAATCC TGCTCTTGTC CC 32 INFORMATION FOR SEQ ID NO:76: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76: GATTCCTCTG ATGGCTCCAC INFORMATION FOR SEQ ID NO:77: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: single 415 TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77: TAACAGTCAA GGAGACCAAA G 21 INFORMATION FOR SEQ ID NO:78: SEQUENCE CHARACTERISTICS: LENGTH: 32 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78: GGGAAGCTTA ACCCTAATCC TGCCCTAGGT GG 32 INFORMATION FOR SEQ ID NO:79: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: single TOPOLOGY: linear MOLECULE TYPE: RNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79: ACCAGACAAA GCTGGGAATA GA 22

Claims (24)

1. An isolated, recombinantly-generated, attenuated, nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales having at least one attenuating mutation in the 3' genomic promoter region and having at least one attenuating mutation in the RNA polymerase gene.

2. The virus of Claim 1 wherein the virus is from the Family Paramyxoviridae.

3. The virus of Claim 2 wherein the virus is from the Subfamily Paramyxovirinae.

4. The virus of Claim 3 wherein the virus is from the Genus Morbillivirus.

5. The virus of Claim 4 wherein the virus -XX- is measles virus.

6. The measles virus of Claim 5 wherein: the at least one attenuating mutation in the 3'.genomic promoter region is selected from the group consisting of Z2 nucleotide 26 (A nucleotide 42 (A T or A C) and nucleotide 96 (G where these nucleotides are presented in positive strand, antigenomic, message sense; and z2 the at least one attenuating mutation in the RNA polymerase gene is selected from the group consisting of nucleotide changes which produce changes in an amino acid selected from the group consisting of residues 331 (isoleucine ->threonine), 1409 (alanine threonine), 1624 (threonine ->alanine), 1649 (arginine -+methionine), 1717 417 (axpartic acid alanine) 1936 (histidine -*tyrosine) 2074 (glutamine -4arginine) and 22.14 (arginine lysine).

7. The virus of. Claim 3 wherein the virus is from the Genus Paramyxovlrus.

8. The virus of Claim 7 wherein the virus is human Parainfluenzaa virus type 3 (PIV-3).

9. The PIV-3 of Claim 8 wherein: the at least one attenuating mutation in the 3' genomic promoter region is selected from the group consisting of nucleotide 23 (T C) nucl.eotide 24 (C nuclectide 28 (G and nucleotide 45 (T where these nucleotiden are presented in positive .*strand, antigenomic, message sense; and the at least one attenuating mutation in the RNA polymerase gene in selected from the group consisting of nucleotide changes which produce changes in an amino acid selected from the group consisting of residues 942 (tyrosine histidine), 992 (leucine phenylalanine) and 1558 (threonine isoleucine). The virus of Claim 3 wherein the virus is from the'.Genus Rubulavirus. *11. The virus of Claim 2 wherein the virus in from the Subfamily Pneumovirinae.

12. The virus of Claim 12 wherein the virus is from the Genus Pneu~ov~Irus. 418

13. The virus of Claim 12 wherein the virus is human respiratory syncytial virus (RSV) subgroup B.

14. The virus of Claim 13 wherein: the at least one attenuating mutation in the 3' genomic promoter region is selected from the group consisting of nucleotide 4 (C and the insertion of an additional A in the stretch of A's at nucleotides 6-11, where these nucleotides are presented in positive strand, antigenomic, message sense; and the at least one attenuating mutation in the RNA polymerase gene is selected from the group consisting of nucleotide changes which produce changes in an amino acid selected from the group consisting of residues 353 (arginine lysine), 451 (lysine arginine), 1229 (aspartic acid asparagine), 2029 (threonine isoleucine) and 2050 (asparagine aspartic acid). The virus of Claim 1 wherein the virus is from the Family Rhabdoviridae.

16. The virus of Claim 1 wherein the virus is from the Family Filoviridae.

17. A vaccine comprising an isolated, recombinantly-generated, attenuated, nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales according to Claim 1 and a physiologically acceptable carrier.

18. The vaccine of Claim 17 comprising a measles virus according to Claim 5 and a physiologically acceptable carrier.

19. The vaccine of claim 18 comprising a measles virus according to claim 6 and a physiologically acceptable carrier. The vaccine of claim 17 comprising a PIV-3 according to claim 8 and a physiologically acceptable carrier.

21. The vaccine of claim 20 comprising a PIV-3 according to claim 9 and a physiologically acceptable carrier.

22. The vaccine of claim 17 comprising an RSV subgroup B according to claim 13 and a physiologically acceptable carrier.

23. The vaccine of claim 22 comprising an RSV subgroup B according to claim 14 and a physiologically acceptable carrier.

24. A method for immunising an individual to induce protection against a nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales which comprises administering to the individual the vaccine of any one of claims 17 to 23. A vaccine of any one of claims 17 to 23 when used for immunising an individual to induce protection against a nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales.

26. Use of a vaccine of any one of claims 17 to 23 in the manufacture of a medicament for immunising an individual to induce protection against a nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales. 20 27. An isolated nucleic acid molecule comprising a measles virus sequence in positive strand, antigenomic message sense selected from the group consisting of 1977 wild-type strain (SEQ ID NO:3), 1983 wild-type strain (SEQ ID NO:5) where the nucleotide 2499 is G or C, Montefiore wild- type strain (SEQ ID NO:7), Rubeovax T M vaccine strain (SEQ ID NO:9), where the nucleotide 2143 is T or C, Moraten vaccine strain (SEQ ID NO:11), Schwarz vaccine strain (SEQ ID NO:11), where the 25 nucleotide 4917 is C and the nucleotide 4924 is C, and Zagreb vaccine strain (SEQ ID NO:13), and -the complementary genomic sequences thereof.

28. An isolated nucleic acid molecule comprising a PIV-3 sequence in positive strand, antigenomic message sense selected from the group consisting of cp45 vaccine strain grown in foetal rhesus lung cells (SEQ ID NO:19) and cp45 vaccine strain grown in Vero cells (SEQ ID NO:21), and the complementary genomic sequences thereof.

29. A composition which comprises a transcription vector comprising an isolated nucleic acid molecule encoding a genome or antigenome of a nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales having at least one attenuating mutation in the 3 genomic promoter region and having at least one attenuating mutation in the RNA polymerase gene, together with at least one expression vector which comprises at least one isolated nucleic acid molecule encoding the trans-acting proteins necessary for encapsidation, transcription and replication, whereby upon expression an infectious attenuated virus is produced. The composition of claim 29 wherein the transcription vector comprises an isolated nucleic acid molecule which encodes a measles virus according to claim 5 and the at least one

04407.doc expression vector comprises at least one isolated nucleic acid molecule encoding the trans-acting proteins N, P and L. 31. The composition of claim 30 wherein the transcription vector comprises an isolated nucleic acid molecule which encodes a measles virus according to claim 6. 32. The composition of claim 29 wherein the transcription vector comprises an isolated nucleic acid molecule which encodes a PIV-3 according to claim 8 and the at least one expression vector comprises at least one isolated nucleic acid molecule encoding the trans-acting proteins NP, P and L. 33. The composition of claim 32 wherein the transcription vector comprises an isolated nucleic acid molecule which encodes a PIV-3 according to claim 9. 34. The composition of claim 29 wherein the transcription vector comprises an isolated nucleic acid molecule which encodes an RSV subgroup B according to claim 13 and the at least one expression vector comprises at least one isolated nucleic acid molecule encoding the trans-acting proteins N, P, L and M2. 35. The composition of claim 34 wherein the transcription vector comprises an isolated nucleic acid molecule which encodes an RSV subgroup B according to claim 14. 36. A method for producing infectious attenuated nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales which comprises transforming or transfecting host cells with the at least two vectors of claim 29 and culturing the host cells under conditions which 20 permit the co-expression of these vectors so as to produce the infectious attenuated virus. 37. The method of claim 36 wherein the virus is the measles virus of claim 38. The method of claim 37 wherein the virus is the measles virus of claim 6. oo*,39. The method of claim 36 wherein the virus is the PIV-3 of claim 8. The method of claim 39 wherein the virus is the PIV-3 of claim 9. 41. The method of claim 36 wherein the virus is the RSV subgroup B of claim 13. 42. The method of claim 41 wherein the virus is the RSV subgroup B of claim 14. 43. An isolated, recombinantly generated, attenuated, nonsegmented, negative sense, single !stranded RNA virus of the Order Mononegavirales, substantially as hereinbefore described with reference to any one of the examples. 44. A vaccine comprising an isolated, recombinantly generated, attenuated, nonsegmented, **negative sense, single stranded RNA virus of the Order Mononegavirales, substantially as hereinbefore described with reference to any one of the examples. An isolated nucleic acid molecule comprising a measles virus sequence in positive strand, antigenomic message sense substantially as hereinbefore described with reference to any one of the examples. 46. An isolated nucleic acid molecule comprising a PIV-3 sequence in positive strand, antigenomic message sense, substantially as hereinbefore described with reference to any one of the examples. 47. A composition which comprises a transcription vector comprising an isolated nucleic acid molecule encoding a genome or antigenome of a nonsegmented, negative-sense, single stranded 04407.doc 421 RNA virus of the Order Mononegavirales substantially as hereinbefore described with reference to any one of the examples. 48. A method for producing infectious attenuated nonsegmented, negative-sense, single stranded RNA virus of the Order Mononegavirales substantially as hereinbefore described with reference to any one of the examples. Dated 6 November 2001 AMERICAN CYANAMID COMPANY THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPARTMENT OF HEALTH AND HUMAN SERVICES Patent Attorneys for the Applicant/Nominated Person SPRUSON&FERGUSON *oo 04407.doc