WO1998030083A1 - Rg nucleic acids for conferring disease resistance to plants - Google Patents

Abstract

The present invention provides RG nucleic acids and proteins which confer disease resistance to plants. The nucleic acids can be used to produce transgenic plants resistant to pests. Antibodies to proteins of the invention are also provided.

Description

RG NUCLEIC ACIDS FOR CONFERRING DISEASE RESISTANCE TO PLANTS

The present application is a continuation-in-part application ("OP") of U.S. Patent Application Serial No. ("USSN") 08/781,734, filed January 10, 1997. The aforementioned application is explicitly incorporated herein by reference in its entirety and for all purposes.

This invention was made with Government support under Grant Nos. 92- 37300-7547 and 95-37300-1571, awarded by the United States Department of Agriculture. The Government has certain rights in this invention.

FIELD OF THE INVENTION

The present invention relates generally to plant molecular biology. In particular, it relates to nucleic acids and methods for conferring pest resistance in plants. particularly lettuce.

BACKGROUND OF THE INVENTION

Recently, several resistance genes have been cloned by several groups from several plants. Many of these genes are sequence related. The derived amino acid sequences of the most common class, RPS2, RPM1 (bacterial resistances in Arabidopsis (Mindrinos et al. Cell 78:1089-1099 (1994)); Bent et al. Science 265:1856-1860 (1994); Grant et al. , Science 269:843-846 (1995)), L6 (fiingal resistance in flax; Lawrence, et al., The Plant Cell 7: 1195-1206 (1995)), and N, (virus resistance in tobacco; Whitham, et al, Cell 78:1101-1115 (1994); and U.S. Patent No. 5,571,706), all contain leucine-rich repeats (LRR) and nucleotide binding sites (NBS).

The NBS is a common motif in several mammalian gene families encoding signal transduction components (e.g., Ras) and is associated with ATP/GTP-binding sites. The NBS is a common motif in several mammalian gene families encoding signal transduction components (e.g., Ras) and is associated with ATP/GTP-binding sites.

LRR domains can mediate protein-protein interactions and are found in a variety of proteins involved in signal transduction, cell adhesion and various other functions. LRRs are leucine rich regions often comprising 20-30 amino acid repeats where leucine and other aliphatic residues occur periodically. LRRs can function extracellularly or intracellularly.

Since the onset of civilization, plant diseases have had catastrophic effects on crops and the well-being of the human population. Plant diseases continue to effect enormous human and economic costs. An increasing human population and decreasing amounts of arable land make all approaches to preventing and treating plant pathogen destruction critical. The ability to control and enhance a plant's protective responses against pathogens would be of enormous benefit. Tissue-specific and temporal control of mechanisms responsible for plant cell death would also be of great practical and economic value. The present invention fulfills these and other needs.

What is needed in the art are plant disease resistance genes and means to create transgenic disease resistance plants, particularly in lettuce. Further, what is needed in the art is a means to DNA fingerprint cultivars and germplasm with respect to their disease resistance haplotypes for use in plant breeding programs. The present invention provides these and other advantages.

SUMMARY OF THE INVENTION

The present invention provides isolated nucleic acid constructs. These constructs comprise an RG (resistance gene) polynucleotide which encodes an RG polypeptide having at least 60% sequence identity to an RG polypeptide selected from the group consisting of: an RG1 polypeptide, an RG2 polypeptide, an RG3 polypeptide, and an RG4 polypeptide. RG1, RG2, RG3, RG4, and the like, represent individual "RG families." Each "RG family," as defined herein, is a group of polypeptide sequences that have at least 60% amino acid sequence identity. Individual members of an RG family, i.e.. individual species of the genus, typically map to the same genomic locus. The invention provides for constructs comprising nucleotides encoding the RG families of the invention, which can include sequences encoding a leucine rich region (LRR), and/or a nucleotide binding site (NBS), or both.

The invention provides for an isolated nucleic acid construct comprising an RG polynucleotide which encodes an RG polypeptide having at least 60% sequence identity to an RG polypeptide from an RG family selected from the group consisting of: an RG1 polypeptide, an RG2 polypeptide, an RG3 polypeptide, an RG4 polypeptide, an RG5 polypeptide, and an RG7 polypeptide. In alternative embodiments, the nucleic acid construct comprises an RG polynucleotide which encodes an RG polypeptide comprising an leucine rich region (LRR), or, an RG polypeptide comprising a nucleotide binding site (NBS). The nucleic acid construct can comprise a polynucleotide which is a full length gene. In another embodiment, the nucleic acid construct encodes a fusion protein. In one embodiment, the nucleic acid construct comprises a sequence encoding an RG1 polypeptide. The RG1 polypeptide can be encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NO: l (RGIA), SEQ ID NO:2 and SEQ ID NO: 137 (RGIB), SEQ ID NO: 3 (RGIC), SEQ ID NO:4 (RGID), SEQ ID NO:5

(RG1E), SEQ ID NO:6 (RG1F), SEQ ID NO:7 (RG1G), SEQ ID NO:8 (RG1H), SEQ ID NO:9 (RG1I), and SEQ ID NO: 10 (RG1J).

In another embodiment, the nucleic acid construct comprises a sequence encoding an RG2 polypeptide. The RG2 polypeptide can be encoded by a polynucleotide sequence selected from the group consisting of: SEQ ID NO:21 and SEQ ID NO: 27

(RG2A); SEQ ID NO:23 and SEQ ID NO:28 (RG2B); SEQ ID NO:29 (RG2C); SEQ ID NO:30 (RG2D); SEQ ID NO:31 (RG2E); SEQ ID NO:32 (RG2F); SEQ ID NO:33 (RG2G); SEQ ID NO:34 (RG2H); SEQ ID NO:35 (RG2I); SEQ ID NO:36 (RG2J); SEQ ID NO:37 (RG2K); SEQ ID NO:38 (RG2L); SEQ ID NO:39 (RG2M); SEQ ID NO:87 (RG2A); SEQ ID NO:89 (RG2B); SEQ ID NO:91 (RG2C); SEQ ID NO:93 (RG2D) and SEQ ID NO:94 (RG2D); SEQ ID NO:96 (RG2E); SEQ ID NO:98 (RG2F); SEQ ID NO: 100 (RG2G); SEQ ID NO: 102 (RG2H); SEQ ID NO: 104 (RG2I); SEQ ID NO: 106 (RG2J) and SEQ ID NO: 107 (RG2J); SEQ ID NO: 109 (RG2K) and (SEQ ID NO: 110 (RG2K); SEQ ID NO: 112 (RG2L); SEQ ID NO: 114 (RG2M); SEQ ID NO: 116 (RG2N); SEQ ID NO: 118 (RG2O); SEQ ID NO: 120 (RG2P); SEQ ID NO: 122 (RG2Q); SEQ ID

NO: 124 (RG2S); SEQ ID NO: 126 (RG2T); SEQ ID NO: 128 (RG2U); SEQ ID NO: 130 (RG2V); and, SEQ ID NO: 132 (RG2W). In other embodiments, the nucleic acid construct comprises a RG3 sequence - (SEQ ID NO: 68) encoding an RG3 polypeptide (SEQ ID NO: 138) (RG3). In other embodiments, the nucleic acid construct comprises an RG4 sequence (SEQ ID NO: 69) encoding an RG4 polypeptide ( SEQ ID NO: 139) (RG4). In other embodiments, the nucleic acid construct comprises a RG5 sequence

( SEQ ID NO: 134) encoding an RG5 polypeptide ( SEQ ID NO: 135). The RG5 polypeptide can be encoded by a polynucleotide sequence as set forth in SEQ ID NO: 134. The invention also provides for a nucleic acid construct which comprises an RG7 sequence encoding an RG7 polypeptide. The RG7 polypeptide can be encoded by a polynucleotide sequence as set forth in SEQ ID NO: 136.

In further embodiments, the nucleic acid construct can further comprise a promoter operably linked to the RG polynucleotide. In alternative embodiments, the promoter can be a plant promoter; a disease resistance promoter; a lettuce promoter; a constitutive promoter; an inducible promoter; or, a tissue-specific promoter. The nucleic acid construct can comprise a promoter sequence from an RG gene linked to a hetero logous polynucleotide.

The invention also provides for a transgenic plant comprising a recombinant expression cassette comprising a promoter operably linked to an RG polynucleotide. The expression cassette can comprise a plant promoter or a viral promoter; the plant promoter can be a heterologous promoter. In one embodiment, the transgenic plant is lettuce. In alternative embodiments, the transgenic plant comprises an expression cassette which includes an RG polynucleotide selected from the group consisting of SEQ ID NO: l (RGIA); SEQ ID NO:2 and SEQ ID NO: 137 (RGIB); SEQ ID NO: 3 (RGIC); SEQ ID NO:4 (RGID); SEQ ID NO:5 (RG1E); SEQ ID NO:6 (RG1F); SEQ ID NO:7 (RG1G); SEQ ID NO:8 (RG1H); SEQ ID NO:9 (RG1I) and SEQ ID NO: 10 (RG1J); SEQ ID

NO:21 and SEQ ID NO:27 (RG2A); SEQ ID NO:23 and SEQ ID NO:28 (RG2B); SEQ ID NO:29 (RG2C); SEQ ID NO:30 (RG2D); SEQ ID NO:31 (RG2E); SEQ ID NO:32 (RG2F); SEQ ID NO:33 (RG2G); SEQ ID NO:34 (RG2H); SEQ ID NO:35 (RG2I); SEQ ID NO:36 (RG2J); SEQ ID NO:37 (RG2K); SEQ ID NO:38 (RG2L); SEQ ID NO:39 (RG2M); SEQ ID NO:87 (RG2A); SEQ ID NO:89 (RG2B); SEQ ID NO:91 (RG2C); SEQ

ID NO:93 (RG2D) and SEQ ID NO:94 (RG2D); SEQ ID NO:96 ( RG2E); SEQ ID NO:98 (RG2F); SEQ ID NO: 100 (RG2G); SEQ ID NO: 102 (RG2H); SEQ ID NO: 104 (RG2I); SEQ ID NO: 106 (RG2J) and SEQ ID NO: 107 (RG2J); SEQ ID NO: 109 (RG2K) and (SEQ ID NO: 110 (RG2K); SEQ ID NO: 112 (RG2L); SEQ ID NO: 114 (RG2M); SEQ ID NO: 116 (RG2N); SEQ ID NO: 118 (RG2O); SEQ ID NO: 120 (RG2P); SEQ ID NO: 122 (RG2Q); SEQ ID NO: 124 (RG2S); SEQ ID NO: 126 (RG2T); SEQ ID NO: 128 (RG2U); SEQ ID NO: 130 (RG2V); and, SEQ ID NO: 132 (RG2W); SEQ ID NO:68 (RG3); SEQ ID NO:69 (RG4); SEQ ID NO: 134 (RG5); or SEQ ID NO: 136 (RG7). The invention provide for a transgenic plant comprising an expression cassette comprising an RG polynucleotide which can encode an RG1 polypeptide selected from the group consisting of SEQ ID NO: 11 (RGIA), SEQ ID NO: 12 (RGIB), SEQ ID NO: 13 (RGIC), SEQ ID NO: 14 (RGID), SEQ ID NO: 15 (RG1E), SEQ ID NO: 16

(RG1F), SEQ ID NO: 17 (RG1G), SEQ ID NO: 18 (RG1H), SEQ ID NO: 19 (RG1I), or SEQ ID NO:20 (RGIJ); or, an RG2 polypeptide selected from the group consisting of SEQ ID NO:22 and SEQ ID NO:41 (RG2A); SEQ ID NO:24 and SEQ ID NO:42 (RG2B); SEQ ID NO:43 (RG2C); SEQ ID NO:44 (RG2D); SEQ ID NO:45 (RG2E); SEQ ID NO:46 (RG2F); SEQ ID NO:47 (RG2G); SEQ ID NO:48 (RG2H); SEQ ID NO:49 (RG2I); SEQ

ID NO:50 (RG2J); SEQ ID NO:51 (RG2K); SEQ ID NO:52 (RG2L); SEQ ID NO:53 (RG2M); SEQ ID NO:88 (RG2A); SEQ ID NO:90 (RG2B); SEQ ID NO:92 (RG2C); SEQ ID NO:95 (RG2D); SEQ ID NO:97 ( RG2E); SEQ ID NO:99 (RG2F); SEQ ID NO: 101 (RG2G); SEQ ID NO: 103 (RG2H); SEQ ID NO: 105 (RG2I); SEQ ID NO: 108 (RG2J); SEQ ID NO: 111 (RG2K); SEQ ID NO: 113 (RG2L); SEQ ID NO: 115 (RG2M); SEQ ID

NO: 117 (RG2N); SEQ ID NO: 119 (RG2O); SEQ ID NO: 121 (RG2P); SEQ ID NO: 123 (RG2Q); SEQ ID NO: 125 (RG2S); SEQ ID NO: 127 (RG2T); SEQ ID NO: 129 (RG2U); SEQ ID NO: 131 (RG2V); and, SEQ ID NO: 133 (RG2W); an RG4 polypeptide as set forth by SEQ ID NO: 72; an RG5 polypeptide with a sequence as set forth by SEQ ID NO: 135; or, an RG7 polypeptide.

The invention also provides for a method of enhancing disease resistance in a plant, the method comprising introducing into the plant a recombinant expression cassette comprising a promoter functional in the plant and operably linked to an RG polynucleotide sequence. In this method, the plant can be a lettuce plant; and, the RG polynucleotide can encode an RG polypeptide selected from the group consisting of an RG1 polypeptide selected from the group consisting of SEQ ID NO: 11 (RGIA), SEQ ID NO: 12 (RGIB), SEQ ID NO: 13 (RGIC), SEQ ID NO: 14 (RGID), SEQ ID NO: 15 (RG1E), SEQ ID NO: 16 (RG1F), SEQ ID NO: 17 (RG1G), SEQ ID NO: 18 (RG1H), SEQ ID NO: 19 (RG1I), or SEQ ID NO:20 (RGIJ); or, an RG2 polypeptide selected from the group consisting of SEQ ID NO:22 and SEQ ID NO:41 (RG2A); SEQ ID NO:24 and SEQ ID NO:42 (RG2B); SEQ ID NO:43 (RG2C); SEQ ID NO:44 (RG2D); SEQ ID NO:45 (RG2E); SEQ ID NO:46 (RG2F); SEQ ID NO:47 (RG2G); SEQ ID NO:48 (RG2H); SEQ ID NO:49 (RG2I); SEQ ID NO:50 (RG2J); SEQ ID NO:51 (RG2K); SEQ ID NO:52 (RG2L); SEQ ID NO:53 (RG2M); SEQ ID NO:72; SEQ ID NO:74; SEQ ID NO:88 (RG2A); SEQ ID NO:90 (RG2B); SEQ ID NO:92 (RG2C); SEQ ID NO:95 (RG2D); SEQ ID NO:97 ( RG2E); SEQ ID NO:99 (RG2F); SEQ ID NO: 101 (RG2G); SEQ ID NO: 103 (RG2H); SEQ ID NO: 105 (RG2I); SEQ ID NO: 108 (RG2J); SEQ ID NO: 111

(RG2K); SEQ ID NO: 113 (RG2L); SEQ ID NO: 115 (RG2M); SEQ ID NO: 117 (RG2N); SEQ ID NO: 119 (RG2O); SEQ ID NO: 121 (RG2P); SEQ ID NO: 123 (RG2Q); SEQ ID NO: 125 (RG2S); SEQ ID NO:127 (RG2T); SEQ ID NO:129 (RG2U); SEQ ID NO:131 (RG2V); and, SEQ ID NO: 133 (RG2W). In this method, the promoter can be a plant disease resistance promoter, a tissue-specific promoter, a constitutive promoter, or an inducible promoter.

The invention also provides for a method of detecting RG resistance genes in a nucleic acid sample, the method comprising: contacting the nucleic acid sample with an RG polynucleotide to form a hybridization complex; and, wherein the formation of the hybridization complex is used to detect the RG resistance gene in the nucleic acid sample. In this method, the RG polynucleotide can be an RG1 polynucleotide, an RG2 polynucleotide. an RG3 polynucleotide, an RG4 polynucleotide, an RG5 polynucleotide or an RG7 polynucleotide. In this method, the RG resistance gene can be amplified prior to the step of contacting the nucleic acid sample with the RG polynucleotide, and, the RG resistance gene can be amplified by the polymerase chain reaction. In one embodiment, the RG polynucleotide is labeled.

The invention further provides for an RG polypeptide having at least 60% sequence identity to a polypeptide selected from the group consisting of: an RG1 polypeptide, an RG2 polypeptide, an RG3 polypeptide, an RG4 polypeptide, an RG5 polypeptide, and an RG7 polypeptide. A further understanding of the nature and advantages of the present invention may be realized by reference to the remaining portions of the specification, the figures and claims.

All publications, patents and patent applications cited herein are hereby expressly incorporated by reference for all purposes.

DETAILED DESCRIPTION OF THE INVENTION

This invention relates to families of RG genes, particularly from Lactuca sativa. Nucleic acid sequences of the present invention can be used to confer resistance in plants to a variety of pests including viruses, fungi, nematodes, insects, and bacteria.

Sequences from within the RG genes can be used to fingerprint cultivars or germplasm for the presence of desired resistance genes. Promoters of RG genes can be used to drive heterologous gene expression under conditions in which RG genes are expressed. Further, the present invention provides RG proteins and antibodies specifically reactive to RG proteins. Antibodies to RG proteins can be used to detect the type and amount of RG protein expressed in a plant sample.

The present invention has use over a broad range of types of plants, including species from the genera Cucurbita, Rosa, Vitis, Juglans, Fragaria, Lotus, Medicago, Onobrychis, Trifolium, Trigonella, Vigna, Citrus, Linum, Geranium, Manihot, Daucus, Arabidopsis, Brassica, Raphanus, Sinapis, Atropa, Capsicum, Datura, Hyoscyamus, Lycopersicon, Nicotiana, Solanum, Petunia, Digitalis, Majorana, Ciahoήum, Helianthus, Lactuca, Bromus, Asparagus, Antirrhinum, Heterocallis, Nemesis, Pelargonium, Panieum, Pennisetum, Ranunculus, Senecio, Salpiglossis, Cucumis, Brσwaalia, Glycine, Pisum, Phaseolus, Lolium, Oryza, Zea, Avena, Hordeum, Secale, Tήticum, and, Sorghum. In particularly preferred embodiments, species from the family Compositae and in particular the genus Lactuca are employed such as L. sativa and such subspecies as crispa, longifolia, and asparagina.

The nucleic acids of the present invention can be used in marker-aided selection. Marker-aided selection does not require the complete sequence of the gene or precise knowledge of which sequence confers which specificity. Instead, partial sequences can be used as hybridization probes or as the basis for oligonucleotide primers to amplify nucleic acid, e.g., by PCR. Partial sequences can be used in other methods, such as to follow the segregation of chromosome segments containing resistance genes in plants. Because the RG marker is the gene itself, there can be negligible recombination between the marker and the resistance phenotype. Thus, RG polynucleotides of the present invention provide an optimal means to DNA fingerprint cultivars and wild germplasm with respect to their disease resistance haplotypes. This can be used to indicate which germplasm accessions and cultivars carry the same resistance genes. At present, selection of plants (e.g., lettuce) for resistance to some diseases is slow and difficult. But linked markers allow indirect selection for such resistance genes. Moreover, RG markers also allow resistance genes to be identified and combined in a manner that would not otherwise be possible. Numerous accessions have been identified that provide resistance to all isolates of downy mildew (Bremia lactucae). However, without molecular markers it is impossible to combine such resistances from different sources. The nucleic acid sequences of the invention provide for a fast and convenient means to identify and combine resistances from different sources. The RG markers of the invention can also be used to identify recombinants that have new combinations of resistance genes in cis on the same chromosome.

In addition, RG markers may allow the identification of the Mendelian factors determining traits, such as field resistance to downy mildew. Once such markers have been identified, they will greatly increase the ease with which field resistance can be transferred between lines and combined with other resistances.

In another application, primers to RG sequences can be also designed to amplify sequences that are conserved in multiple RG family members. This gives genetic information on multiple RG family members. Alternatively, one or more primers can be made to sequences unique to a single resistance gene genus or a single RG specie. This allows an analysis of individual family groups (an RG genus) or an individual family member (a specie). Primers made to individual RGs at the edge of each cluster can be used to select for recombinants within the cluster. This minimizes the amount of linkage drag during introgression. Classical and molecular genetics has shown that pest resistance genes tend to be clustered in the genome. Pest resistance loci comprise arrays of genes and exhibit a variety of complex haplotypes rather than being simple alternate allelic forms. Pest resistance is conferred by families, or genuses, of related RG sequences, individual members, or species, of which have evolved to have a different specificity. Oligonucleotide primers can be designed that amplify members from multiple haplotypes, - or genuses, or amplify only members of one genus, or only amplify an individual specie. This will provide codominant information and allow heterozygotes to be distinguished from homozygotes. Further, comparison of RG sequences will allow a determination of which sequences are critical for resistance and will ultimately lead to engineering resistance genes with new specificities. Resistance gene sequences were not previously available for lettuce. Marker-aided selection will greatly increase the precision and speed of breeding for disease resistance. Transgenic approaches will allow pyramiding of resistance genes into a single Mendelian unit, transfer between sexually-incompatible species, substitute for conventional backcrossing procedures, and allow expression of other genes in parallel with resistance genes.

The RG polynucleotides also have utility in the construction of disease resistant transgenic plants. This avoids lengthy and sometimes difficult backcrossing programs currently necessary for introgression of resistance. It is also possible to transfer resistance polynucleotides between sexually-incompatible species, thereby greatly increasing the germplasm pool that can be used as a source of resistance genes. Cloning of multiple RG sequences in a single cassette will allow pyramiding of genes for resistance against multiple isolates of a single pathogen such as downy mildew or against multiple pathogens. Once introduced, such a cassette can be manipulated by classical breeding methods as a single Mendelian unit.

Transgenic plants of the present invention can also be constructed using an RG promoter. The promoter sequences from RG sequences of the invention can be used with RG genes or heterologous genes. Thus, RG promoters can be used to express a variety of genes in the same temporal and spatial patterns and at similar levels to resistance genes.

Nucleic acids of the Invention and Their Preparation

RG Polynucleotide Families The present invention provides isolated nucleic acid constructs which comprise an RG polynucleotide. In alternative embodiments, the RG polynucleotide is at least 18 nucleotides in length, typically at least 20, 25, or 30 nucleotides in length, more typically at least 100 nucleotides in length, generally at least 200 nucleotides in length, preferably at least 300 nucleotides in length, more preferably at least 400 nucleotides in length, and most preferably at least 500 nucleotides in length.

In particularly preferred embodiments, the RG polynucleotide encodes a RG protein which confers resistance to plant pests. This RG protein can be longer, equivalent, or shorter than the RG protein encoded by an RG gene. In various embodiments, an RG polynucleotide can hybridize under stringent conditions to members of an RG family (an RG genus); e.g., it can hybridize to a member of the RG1 RG family, such as an RG1 polynucleotide selected from the group consisting of: SEQ ID NO: l (RGIA); SEQ ID NO:2 and SEQ ID NO: 137 (RGIB); SEQ ID NO: 3 (RGIC); SEQ ID NO:4 (RGID); SEQ ID NO:5 (RG1E); SEQ ID NO:6 (RG1F); SEQ ID NO:7 (RG1G); SEQ ID NO:8 (RG1H); SEQ ID NO:9 (RG1I) and SEQ ID NO: 10 (RGIJ).

In other embodiments, the polynucleotide can also hybridize under stringent conditions to a member of the RG2 family; such as an RG2 polynucleotide selected from the group consisting of: SEQ ID NO:21 and SEQ ID NO:27 (RG2A); SEQ ID NO:23 and SEQ ID NO:28 (RG2B); SEQ ID NO:29 (RG2C); SEQ ID NO:30 (RG2D); SEQ ID NO:31 (RG2E); SEQ ID NO:32 (RG2F); SEQ ID NO:33 (RG2G); SEQ ID NO:34 (RG2H); SEQ ID NO:35 (RG2I); SEQ ID NO:36 (RG2J); SEQ ID NO:37 (RG2K); SEQ ID NO:38 (RG2L); SEQ ID NO:39 (RG2M); SEQ ID NO:87 (RG2A); SEQ ID NO:89 (RG2B); SEQ ID NO:91 (RG2C); SEQ ID NO:93 (RG2D) and SEQ ID NO:94 (RG2D);

SEQ ID NO:96 (RG2E); SEQ ID NO:98 (RG2F); SEQ ID NO: 100 (RG2G); SEQ ID NO: 102 (RG2H); SEQ ID NO: 104 (RG2I); SEQ ID NO: 106 (RG2J) and SEQ ID NO: 107 (RG2J); SEQ ID NO: 109 (RG2K) and (SEQ ID NO: 110 (RG2K); SEQ ID NO: 112 (RG2L); SEQ ID NO:114 (RG2M); SEQ ID NO:116 (RG2N); SEQ ID NO:118 (RG2O); SEQ ID NO: 120 (RG2P); SEQ ID NO: 122 (RG2Q); SEQ ID NO: 124 (RG2S); SEQ ID NO: 126 (RG2T); SEQ ID NO: 128 (RG2U); SEQ ID NO: 130 (RG2V); and, SEQ ID NO: 132 (RG2W).

In alternative embodiments, each RG2 gene can also include an AC 15 sequence which hybridizes under stringent conditions to a polynucleotide selected from the group consisting of: SEQ ID NO:56 (AC15-2A); SEQ ID NO:57 (AC15-2B); SEQ ID

NO:58 (AC15-2C); SEQ ID NO:59 (AC15-2D); SEQ ID NO:60 (AC15-2E); SEQ ID NO:61 (AC15-2G); SEQ ID NO:62 (AC15-2H); SEQ ID NO:63 (AC15-2I); SEQ ID NO:64 (AC15-2J); SEQ ID NO:65 (AC15-2L); SEQ ID NO:66 (AC15-2N); SEQ ID NO:67 (AC15-2O).

In other embodiments, an RG polynucleotide can hybridize under stringent conditions to an RG3 (SEQ ID NO:68), an RG4 (SEQ ID NO:69), and RG5 (SEQ ID NO: 135), and an RG7 (SEQ ID NO: 137), RG family member.

The present invention further provides nucleic acid constructs which comprise an RG polynucleotide which encodes RG polypeptides from various RG families; such as an RG polypeptide having at least 60% sequence identity to an RG polypeptide selected from the group consisting of: an RG1 polypeptide, an RG2 polypeptide, an RG3 polypeptide, and RG4 polypeptide, and RG5 polypeptide, and an RG7 polypeptide.

Exemplary RG1 polypeptides have the sequences shown in SEQ ID NO: 2 (RGIA), SEQ ID NO:4 (RGIB), SEQ ID NO:6 (RGIC), SEQ ID NO:8 (RGID), SEQ ID NO: 10 (RG1E), SEQ ID NO: 12 (RG1F), SEQ ID NO: 14 (RG1G), SEQ ID NO: 16 (RGIH), SEQ ID NO:20 (RGIJ). Exemplary RG2 polypeptides have the sequences shown in SEQ ID NO:22 and SEQ ID NO:41 (RG2A); SEQ ID NO:24 and SEQ ID NO:42

(RG2B); SEQ ID NO:43 (RG2C); SEQ ID NO:44 (RG2D); SEQ ID NO:45 (RG2E); SEQ ID NO:46 (RG2F); SEQ ID NO:47 (RG2G); SEQ ID NO:48 (RG2H); SEQ ID NO:49 (RG2I); SEQ ID NO:50 (RG2J); SEQ ID NO:51 (RG2K); SEQ ID NO:52 (RG2L); SEQ ID NO:53 (RG2M); SEQ ID NO:88 (RG2A); SEQ ID NO:90 (RG2B); SEQ ID NO:92 (RG2C); SEQ ID NO:95 (RG2D); SEQ ID NO:97 (RG2E); SEQ ID NO:99 (RG2F); SEQ

ID NO:101 (RG2G); SEQ ID NO:103 (RG2H); SEQ ID NO:105 (RG2I); SEQ ID NO:108 (RG2J); SEQ ID NO:l 11 (RG2K); SEQ ID NO:l 13 (RG2L); SEQ ID NO:l 15 (RG2M); SEQ ID NO:l 17 (RG2N); SEQ ID NO:l 19 (RG2O); SEQ ID NO:121 (RG2P); SEQ ID NO:123 (RG2Q); SEQ ID NO:125 (RG2S); SEQ ID NO:127 (RG2T); SEQ ID NO:129 (RG2U); SEQ ID NO: 131 (RG2V); and, SEQ ID NO: 133 (RG2W).

An exemplary RG3 polypeptide has the sequence shown in SEQ ID NO: 138. An exemplary RG4 polypeptide has the sequence shown in SEQ ID NO: 139. RG polynucleotides will have at least 60% identity, more typically at least 65% identity, generally at least 70% identity, and preferably at least 75% identity, more preferably at least 80% identity, and most preferably at least 85% , 90%, or 95% identity at the deduced amino acid level. The regions where substantial identity is assessed can be inclusive or exclusive of the nucleotide binding site or the leucine rich region. Vectors and Transcriptional Control Elements

The invention, providing methods and reagents for making novel species and genuses of RG nucleic acids described herein, further provides methods and reagents for expressing these nucleic acids using novel expression cassettes, vectors, transgenic plants and animals, using constitutive and inducible transcriptional and translational cis- (e.g.. promoters and enhancers) and .raw-acting control elements.

The expression of natural, recombinant or synthetic plant disease resistance polypeptide-encoding or other (i.e., antisense, ribozyme) nucleic acids can be achieved by operably linking the coding region a promoter (that can be plant-specific or not, constitutive or inducible), incorporating the construct into an expression cassette (such as an expression vector), and introducing the resultant construct into an in vitro reaction system or a suitable host cell or organism. Synthetic procedures may also be used. Typical expression systems contain, in addition to coding or antisense sequence, transcription and translation terminators, polyadenylation sequences, transcription and translation initiation sequences, and promoters useful for transcribing DNA into RNA.

The expression systems optionally at least one independent terminator sequence, sequences permitting replication of the cassette in vivo, e.g. , plants, eukaryotes, or prokaryotes, or a combination thereof, (e.g. , shuttle vectors) and selection markers for the selected expression system, e.g. , plant, prokaryotic or eukaryotic systems. To ensure proper polypeptide expression under varying conditions, a polyadenylation region at the 3 '-end of the coding region can be included (see Li (1997) Plant Phy iolA\5:32\-325, for a review of the polyadenylation of RNA in plants). The polyadenylation region can be derived from the natural gene, from a variety of other plant genes, or from T-DNA (e.g., using Agrobacterium tumefaciens T-DNA replacement vectors, see e.g., Thykjaer (1997) Plant Mol Biol. 35:523-530; using a plasmid containing a gene of interest flanked by

Agrobacterium T-DNA border repeat sequences; Hansen (1997) "T-strand integration in maize protoplasts after codelivery of a T-DNA substrate and virulence genes," Proc. Natl. Acad. Sci. USA 94: 11726-11730.

To identify the promoters, the 5' portions of the clones described here are analyzed for sequences characteristic of promoter sequences. For instance, promoter sequence elements include the TATA box consensus sequence (TATAAT), which is usually 20 to 30 base pairs upstream of the transcription start site. In plants, further upstream from the TATA box, at positions -80 to -100, there is typically a promoter element with a series of adenines surrounding the trinucleotide G (or T) N G (see, e.g., Messing, in Genetic Engineering in Plants, pp. 221-227, Kosage, Meredith and Hollaender, eds. 1983). If proper polypeptide expression is desired, a polyadenylation region at the 3 '-end of the RG coding region should be included. The polyadenylation region can be derived from the natural gene, from a variety of other plant genes, or from viral genes, such as T-DNA.

The nucleic acids of the invention can be expressed in expression cassettes, vectors or viruses which are transiently expressed in cells using, for example, episomal expression systems (e.g., cauliflower mosaic virus (CaMV) viral RNA is generated in the nucleus by transcription of an episomal minichromosome containing supercoiled DNA, Covey (1990) Proc. Natl. Acad. Sci. USA 87:1633-1637). Alternatively, coding sequences can be inserted into the host cell genome becoming an integral part of the host chromosomal DNA. Selection markers can be incorporated into expression cassettes and vectors to confer a selectable phenotype on transformed cells and sequences coding for episomal maintenance and replication such that integration into the host genome is not required. For example, the marker may encode biocide resistance, such as antibiotic resistance, particularly resistance to chloramphenicol, kanamycin, G418, bleomycin, hygromycin, or herbicide resistance, such as resistance to chlorosulfuron or Basta, to permit selection of those cells transformed with the desired DNA sequences, see for example, Blondelet-Rouault (1997) Gene 190:315-317; Aubrecht (1997) J. Pharmacol. Exp. Ther. 281 :992-997 . Because selectable marker genes conferring resistance to substrates like neomycin or hygromycin can only be utilized in tissue culture, chemoresistance genes are also used as selectable markers in vitro and in vivo. See also, Mengiste (1997)

"High-efficiency transformation of Arabidopsis thaliana with a selectable marker gene regulated by the T-DNA 1' promoter," Plant J. 12:945-948, showing that the 1' promoter is an attractive alternative to the cauliflower mosaic virus (CaMV) 35S promoter for the generation of T-DNA insertion lines, the 1 ' promoter may be especially beneficial for the secondary transformation of transgenic strains containing the 35S promoter to exclude homology-mediated gene silencing. The endogenous promoters from the RG genes of the present invention can - be used to direct expression of the genes. These promoters can also be used to direct expression of heterologous structural genes. The promoters can be used, for example, in recombinant expression cassettes to drive expression of genes conferring resistance to any number of pathogens or pests, including fungi, bacteria, and the like. Constitutive Promoters

In construction of recombinant expression cassettes, vectors, transgenics, of the invention, a promoter fragment can be employed to direct expression of the desired gene in all tissues of a plant or animal. Promoters that drive expression continuously under physiological conditions are referred to as "constitutive" promoters and are active under most environmental conditions and states of development or cell differentiation. Examples of constitutive promoters include those from viruses which infect plants, such as the cauliflower mosaic virus (CaMV) 35S transcription initiation region; the 1 '- or 2'- promoter derived from T-DNA of Agrobacterium tumafaciens; the promoter of the tobacco mosaic virus; and, other transcription initiation regions from various plant genes known to those of skill. See also Holtorf (1995) "Comparison of different constitutive and inducible promoters for the overexpression of transgenes in Arabidopsis thaliana," Plant Mol. Biol. 29:637-646.

Inducible Promoters Alternatively, a plant promoter may direct expression of the plant disease resistance nucleic acid of the invention under the influence of changing environmental conditions or developmental conditions. Examples of environmental conditions that may effect transcription by inducible promoters include pathogenic attack, anaerobic conditions, elevated temperature, drought, or the presence of light. Such promoters are referred to herein as "inducible" promoters. For example, the invention incorporates the drought- inducible promoter of maize (Busk (1997) supra); the cold, drought, and high salt inducible promoter from potato (Kirch (1997) Plant Mol. Biol. 33:897-909).

Embodiments of the invention also incorporate use of plant promoters which are inducible upon injury or infection to express the invention's plant disease resistance (RG) polypeptides. Various embodiments include use of, e.g., the promoter for a tobacco (Nicotiana tabacum) sesquiterpene cyclase gene (EAS4 promoter), which is expressed in wounded leafs, roots, and stem tissues, and upon infection with microbial pathogens (Yin (1997) Plant Physiol. 115(2):437-451); the ORF13 promoter from Agrobacterium rhizogenes 8196, which is wound inducible in a limited area adjacent to the wound site (Hansen (1997) Mol. Gen. Genet. 254:337-343); the Shpxόb gene promoter, which is a plant peroxidase gene promoter induced by microbial pathogens (demonstrated using a fungal pathogen, see Curtis (1997) Mol. Plant Microbe Interact. 10:326-338); the wound-inducible gene promoter wunl, derived from potato (Siebertz (1989) Plant Cell 1:961-968); the wound-inducible Agrobacterium pmas gene (mannopine synthesis gene) promoter (Guevara-Garcia (1993) Plant J. 4:495-505).

Alternatively, plant promoters which are inducible upon exposure to plant hormones, such as auxins, are used to express the nucleic acids of the invention. For example, the invention can use the auxin-response elements El promoter fragment (AuxREs) in the soybean (Glycine max L.) (Liu (1997) Plant Physiol. 115:397-407); the auxin-responsive Arabidopsis GST6 promoter (also responsive to salicylic acid and hydrogen peroxide) (Chen (1996) Plant J. 10: 955-966); the auxin-inducible parC promoter from tobacco (Sakai (1996) 37:906-913); a plant biotin response element (Streit (1997) Mol. Plant Microbe Interact. 10:933-937); and, the promoter responsive to the stress hormone abscisic acid (Sheen (1996) Science 274: 1900-1902).

Plant promoters which are inducible upon exposure to chemicals reagents which can be applied to the plant, such as herbicides or antibiotics, are also used to express the nucleic acids of the invention. For example, the maize In2-2 promoter, activated by benzenesulfonamide herbicide safeners, can be used (De Veylder (1997) Plant Cell Physiol. 38:568-577); application of different herbicide safeners induces distinct gene expression patterns, including expression in the root, hydathodes, and the shoot apical meristem. Coding sequence can be under the control of, e.g., a tetracycline-inducible promoter, e.g., as described with transgenic tobacco plants containing the Avena sativa L. (oat) arginine decarboxylase gene (Masgrau (1997) Plant J. 11:465-473); or, a salicylic acid-responsive element (Stange (1997) Plant J. 11: 1315-1324. Using chemically- (e.g., hormone- or pesticide-) induced promoters, harvesting of fruits and plant parts would be greatly facilitated. A chemical which can be applied to the transgenic plant in the field and induce expression of a polypeptide of the invention throughout all or most of the plant would make a environmentally safe defoliant or herbicide. Thus, the invention also provides for transgenic plants containing an inducible gene encoding for the RG WO 98/30083 _ _. PCT/US98/00615 lo polypeptides of the invention whose host range is limited to target plant species, such as weeds or crops before, during or after harvesting.

Abcission promoters are activated upon plant ripening, such as fruit ripening, and are especially useful incorporated in the expression systems (e.g. , expression cassettes, vectors) of the invention. In some embodiments, when a plant disease resistant polypeptide-encoding nucleic acid is under the control of such a promoter, rapid cell death, induced by expression of the invention's polypeptide, can accelerate and/or accentuate abcission, increasing the efficiency of the harvesting of fruits or other plant parts, such as cotton, and the like. Induction of rapid cell death at this time would accelerate separation of the fruit from the plant, greatly augmenting harvesting procedures. See, e.g., Kalaitzis (1997) Plant Physiol. 113: 1303-1308, discussing tomato leaf and flower abscission; Payton (1996) Plant Mol. Biol. 31:1227-1231, discussing ethylene receptor expression regulation during fruit ripening, flower senescence and abscission; Koehler (1996) Plant Mol. Biol. 31:595-606, discussing the gene promoter for a bean abscission cellulase; Kalaitzis (1995) Plant Mol. Biol.2%: 647-656, discussing cloning of a tomato polygalacturonase expressed in abscission; del Campillo (1996) Plant Physiol. 111:813-820, discussing pedicel breakstrength and cellulase gene expression during tomato flower abscission. Tissue-Specific Promoters

Tissue specific promoters are transcriptional control elements that are only active in particular cells or tissues. Plant promoters which are active only in specific tissues or at specific times during plant development are used to express the nucleic acids of the invention. Examples of promoters under developmental control include promoters that initiate transcription only in certain tissues, such as leaves, roots, fruit, seeds, ovules, pollen, pistols, or flowers. Such promoters are referred to as "tissue specific". The operation of a promoter may also vary depending on its location in the genome. Thus, an inducible promoter may become fully or partially constitutive in certain locations.

For example, a seed-specific promoter directs expression in seed tissues. Such promoters may be, for example, ovule-specific, embryo-specific, endosperm-specific, integument-specific, seed coat-specific, or some combination thereof. A leaf-specific promoter has been identified in maize, Busk (1997) Plant J. 11:1285-1295. The ORF13 promoter from Agrobacterium rhizogenes exhibits high activity in roots (Hansen (1997) supra). A maize pollen-specific promoter has been identified in maize (Guerrero (1990) Mol. Gen. Genet. 224: 161-168). A tomato promoter active during fruit ripening, senescence and abscission of leaves and, to a lesser extent, of flowers can be used (Blume (1997) Plant J. 12:731-746). A pistol specific promoter has been identified in the potato (Solanum tuberosum L.) SK2 gene, encoding a pistil-specific basic endochitinase (Ficker (1997) Plant Mol. Biol. 35:425-431). The Blec4 gene from pea (Pisum sativum cv. Alaska) is active in epidermal tissue of vegetative and floral shoot apices of transgenic alfalfa, making it a useful tool to target the expression of foreign genes to the epidermal layer of actively growing shoots. The activity of the Blec4 promoter in the epidermis of the shoot apex makes it particularly suitable for genetically engineering defense against insects and diseases that attack the growing shoot apex (Mandaci (1997) Plant Mol Biol. 34:961-965).

The invention also provides for use of tissue-specific plant promoters include a promoter from the ovule-specific BEL1 gene described in Reiser (1995) Cell 83:735-742, GenBank No. U39944. Suitable seed specific promoters are derived from the following genes: MAC1 from maize, Sheridan (1996) Genetics 142: 1009-1020; CatS from maize, GenBank No. L05934, Abler (1993) Plant Mol. Biol. 22:10131-1038; the gene encoding oleosin 18kD from maize, GenBank No. J05212, Lee (1994) Plant Mol. Biol. 26: 1981-1987; vivparous-1 from Arabidopsis, Genbank No. U93215; the gene encoding oleosin from Arabidopsis, Genbank No. Z17657; Atmycl from Arabidopsis, Urao (1996) Plant Mol. Biol. 32:571-576; the 2s seed storage protein gene family from Arabidopsis, Conceicao (1994) Plant 5:493-505; the gene encoding oleosin 20kD from Brassica napus, GenBank No. M63985; napA from Brassica napus, GenBank No. J02798, Josefsson (1987) JBL 26:12196-1301; the napin gene family from Brassica napus, Sjodahl (1995) Planta 197:264-271; the gene encoding the 2S storage protein from Brassica napus, Dasgupta (1993) Gene 133:301-302; the genes encoding oleosin a, Genbank No. U09118, and. oleosin B, Genbank No. U09119, from soybean; and, the gene encoding low molecular weight sulphur rich protein from soybean, Choi (1995) Mol Gen, Genet. 246:266-268. The tissue specific E8 promoter from tomato is particularly useful for directing gene expression so that a desired gene product is located in fruits. Other suitable promoters include those from genes encoding embryonic storage proteins.

One of skill will recognize that a tissue-specific promoter may drive expression of operably linked sequences in tissues other than the target tissue. Thus, as used herein a tissue-specific promoter is one that drives expression preferentially in the target tissue, but may also lead to some expression in other tissues as well.

The invention also provides for use of tissue-specific promoters derived from viruses which can include, e.g., the tobamovirus subgenomic promoter (Kumagai (1995) Proc. Natl. Acad. Sci. USA 92:1679-1683; the rice tungro bacilliform virus

(RTBV), which replicates only in phloem cells in infected rice plants, with its promoter which drives strong phloem-specific reporter gene expression; the cassava vein mosaic virus (CVMV) promoter, with highest activity in vascular elements, in leaf mesophyll cells, and in root tips (Verdaguer (1996) Plant Mol. Biol. 31:1129-1139). In some embodiments, the nucleic acid construct will comprise a promoter functional in a specific plant cell, such as in a species of Lactuca, operably linked to an RG polynucleotide. Promoters useful in these embodiments include RG promoters. In additional embodiments, the nucleic acid construct will comprise a RG promoter operably linked to a heterologous polynucleotide. The heterologous polynucleotide is chosen to provide a plant with a desired phenotype. For example, the heterologous polynucleotide can be a structural gene which encodes a polypeptide which imparts a desired resistance phenotype. Alternatively, the heterologous polynucleotide may be a regulatory gene which might play a role in transcriptional and/or translational control to suppress, enhance, or otherwise modify the transcription and/or expression of an endogenous gene within the plant. The heterologous polynucleotide of the nucleic acid construct of the present invention can be expressed in either sense or anti-sense orientation as desired. It will be appreciated that control of gene expression in either sense or anti-sense orientation can have a direct impact on the observable plant characteristics. Modifying and Inhibiting RG Gene Expression The invention also provides for RG nucleic acid sequences which are complementary to the RG polypeptide-encoding sequences of the invention; i.e., antisense RG nucleic acids. Antisense technology can be conveniently used to modify gene expression in plants. To accomplish this, a nucleic acid segment from the desired gene is cloned and operably linked to a promoter such that the anti-sense strand of RNA will be transcribed. The construct is then transformed into plants and the antisense strand of RNA is produced. In plant cells, it has been shown that antisense RNA inhibits gene expression by preventing the accumulation of mRNA which encodes the enzyme of interest, see, e.g. , Sheehy (1988) Proc. Nat. Acad. Sci. USA 85:8805-8809; Hiatt et al., U.S. Patent No. 4,801,340.

Antisense sequences are capable of inhibiting the transport, splicing or transcription of RG-encoding genes. The inhibition can be effected through the targeting of genomic DNA or messenger RNA. The transcription or function of targeted nucleic acid can be inhibited, e.g., by hybridization and/or cleavage. One particularly useful set of inhibitors provided by the present invention includes oligonucleotides which are able to either bind RG gene or message, in either case preventing or inhibiting the production or function of RG. The association can be though sequence specific hybridization. Such inhibitory nucleic acid sequences can, for example, be used to completely inhibit a plant disease resistance response. Another useful class of inhibitors includes oligonucleotides which cause inactivation or cleavage of RG message. The oligonucleotide can have enzyme activity which causes such cleavage, such as ribozymes. The oligonucleotide can be chemically modified or conjugated to an enzyme or composition capable of cleaving the complementary nucleic acid. One may screen a pool of many different such oligonucleotides for those with the desired activity. Antisense Oligonucleotides

The invention provides for with antisense oligonucleotides capable of binding RG message which can inhibit RG activity by targeting mRNA. Strategies for designing antisense oligonucleotides are well described in the scientific and patent literature, and the skilled artisan can design such RG oligonucleotides using the novel reagents of the invention. In some situations, naturally occurring nucleic acids used as antisense oligonucleotides may need to be relatively long (18 to 40 nucleotides) and present at high concentrations. A wide variety of synthetic, non-naturally occurring nucleotide and nucleic acid analogues are known which can address this potential problem. For example, peptide nucleic acids (PNAs) containing non-ionic backbones, such as N-(2-aminoethyl) glycine units can be used. Antisense oligonucleotides having phosphorothioate linkages can also be used, as described in WO 97/03211; WO 96/39154; Mata (1997) Toxicol Appl Pharmacol 144:189-197; Antisense Therapeutics, ed. Agrawal (Humana Press, Totowa, N.J.. 1996). Antisense oligonucleotides having synthetic DNA backbone analogues provided by the invention can also include phosphoro-dithioate, methylphosphonate, phosphoramidate, alkyl phosphotriester, sulfamate, 3'-thioacetal, methylene(methylimino), . 3'-N-carbamate, and morpholino carbamate nucleic acids, as described herein.

Combinatorial chemistry methodology can be used to create vast numbers of oligonucleotides that can be rapidly screened for specific oligonucleotides that have appropriate binding affinities and specificities toward any target, such as the sense and antisense RG sequences of the invention (for general background information, see, e.g., Gold (1995) /. of Biol. Chem. 270:13581-13584). Inhibitory Ribozymes The invention provides for with ribozymes capable of binding RG message which can inhibit RG activity by targeting rriRNA. Strategies for designing ribozymes and selecting the RG-specific antisense sequence for targeting are well described in the scientific and patent literature, and the skilled artisan can design such RG ribozymes using the novel reagents of the invention. Ribozymes act by binding to a target RNA through the target RNA binding portion of a ribozyme which is held in close proximity to an enzymatic portion of the RNA that cleaves the target RNA. Thus, the ribozyme recognizes and binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cleave and inactivate the target RNA. Cleavage of a target RNA in such a manner will destroy its ability to direct synthesis of an encoded protein if the cleavage occurs in the coding sequence, or, preventing transport of the message from the nucleus to the cytoplasm. After a ribozyme has bound and cleaved its RNA target, it is typically released from that RNA and so can bind and cleave new targets repeatedly.

Catalytic RNA molecules or ribozymes can also be used to inhibit expression of any plant gene. It is possible to design ribozymes that specifically pair with virtually any target RNA and cleave the phosphodiester backbone at a specific location, thereby functionally inactivating the target RNA. In carrying out this cleavage, the ribozyme is not itself altered, and is thus capable of recycling and cleaving other molecules, making it a true enzyme. The inclusion of ribozyme sequences within antisense RNAs confers RNA-cleaving activity upon them, thereby increasing the activity of the constructs. The design and use of target RNA-specific ribozymes is described, e.g., in Haseioff (1988) Nature 334:585-591.

In some circumstances, the enzymatic nature of a ribozyme can be advantageous over other technologies, such as antisense technology (where a nucleic acid molecule simply binds to a nucleic acid target to block its transcription, translation or association with another molecule) as the effective concentration of ribozyme necessary to effect a therapeutic treatment can be lower than that of an antisense oligonucleotide. This potential advantage reflects the ability of the ribozyme to act enzymatically. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, a ribozyme is typically a highly specific inhibitor, with the specificity of inhibition depending not only on the base pairing mechanism of binding, but also on the mechanism by which the molecule inhibits the expression of the RNA to which it binds. That is, the inhibition is caused by cleavage of the RNA target and so specificity is defined as the ratio of the rate of cleavage of the targeted RNA over the rate of cleavage of non-targeted RNA. This cleavage mechanism is dependent upon factors additional to those involved in base pairing. Thus, the specificity of action of a ribozyme can be greater than that of antisense oligonucleotide binding the same RNA site.

The enzymatic ribozyme RNA molecule can be formed in a hammerhead motif, but may also be formed in the motif of a hairpin, hepatitis delta virus, group I intron or RNaseP-like RNA (in association with an RNA guide sequence). Examples of such hammerhead motifs are described by Rossi (1992) Aids Research and Human Retroviruses 8: 183; hairpin motifs by Hampel (1989) Biochemistry 28:4929, and Hampel (1990) Nuc. Acids Res. 18:299; the hepatitis delta virus motif by Perrotta (1992) Biochemistry 31:16; the RNaseP motif by Guerrier-Takada (1983) Cell 35:849; and the group I intron by Cech U.S. Pat. No. 4,987,071. The recitation of these specific motifs is not intended to be limiting; those skilled in the art will recognize that an enzymatic RNA molecule of this invention has a specific substrate binding site complementary to one or more of the target gene RNA regions, and has nucleotide sequence within or surrounding that substrate binding site which imparts an RNA cleaving activity to the molecule.

Sense Supression

Another method of suppression is sense suppression. Introduction of nucleic acid configured in the sense orientation has been shown to be an effective means by which to block the transcription of target genes. For an example of the use of this method to modulate expression of endogenous genes see, Napoli et al., The Plant Cell 2:279-289 (1990), and U.S. Patent No. 5,034,323. Cloning ofRG Polypeptides Synthesis and/or cloning of RG polynucleotides and isolated nucleic acid constructs of the present invention are provided by methods well known to those of ordinary skill in the art. Generally, the nomenclature and the laboratory procedures in recombinant DNA technology described below are those well known and commonly employed in the art. Standard techniques are used for cloning, DNA and RNA isolation, amplification and purification. Generally enzymatic reactions involving DNA ligase, DNA polymerase, restriction endonucleases and the like are performed according to the manufacturer's specifications. These techniques and various other techniques are generally performed according to Sambrook et al. , Molecular Cloning - A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, (1989).

The isolation of RG genes may be accomplished by a number of techniques. For instance, oligonucleotide probes based on the sequences disclosed here can be used to identify the desired gene in a cDNA or genomic DNA library. To construct genomic libraries, large segments of genomic DNA are generated by random fragmentation, e.g. using restriction endonucleases, and are ligated with vector DNA to form concatemers that can be packaged into the appropriate vector. To prepare a cDNA library, mRNA is isolated from the desired organ, such as roots and a cDNA library which contains the RG gene transcript is prepared from the mRNA. Alternatively, cDNA may be prepared from mRNA extracted from other tissues in which RG genes or homologs are expressed. The cDNA or genomic library can then be screened using a probe based upon the sequence of a cloned RG gene such as the genes disclosed herein. Probes may be used to hybridize with genomic DNA or cDNA sequences to isolate homologous genes in the same or different plant species.

Those of skill in the art will appreciate that various degrees of stringency of hybridization can be employed in the assay; and either the hybridization or the wash medium can be stringent. As the conditions for hybridization become more stringent, there must be a greater degree of complementarity between the probe and the target for duplex formation to occur. The degree of stringency can be controlled by temperature, ionic strength, pH and the presence of a partially denaturing solvent such as formamide. For example, the stringency of hybridization is conveniently varied by changing the polarity of the reactant solution through manipulation of the concentration of formamide within the range of 0% to 50% . Alternatively, the RG nucleic acids of the invention can be amplified from nucleic acid samples using a variety of amplification techniques, such as polymerase chain reaction (PCR) technology, to amplify the sequences of the RG and related genes directly from genomic DNA, from cDNA, from genomic libraries or cDNA libraries. PCR and other in vitro amplification methods may also be useful, for example, to clone nucleic acid sequences that code for proteins to be expressed, to make nucleic acids to use as probes for detecting the presence of the desired mRNA in samples, for nucleic acid sequencing, or for other purposes.

Oligonucleotides can be used to identify and detect additional RG families and RG family species using a variety of hybridization techniques and conditions. Suitable amplification methods include, but are not limited to: polymerase chain reaction, PCR (PCR PROTOCOLS, A GUIDE TO METHODS AND APPLICATIONS, ed. Innis, Academic Press, N.Y. (1990) and PCR STRATEGIES (1995), ed. Innis, Academic Press, Inc., N.Y. (Innis )), ligase chain reaction (LCR) (Wu (1989) Genomics 4:560; Landegren (1988) Science 241 : 1077 ; Barringer ( 1990) Gene 89: 117); transcription amplification (Kwoh ( 1989) Proc. Natl. Acad. Sci. USA 86: 1173); and, self-sustained sequence replication (Guatelli (1990) Proc. Natl. Acad. Sci. USA, 87:1874); Q Beta replicase amplification and other RNA polymerase mediated techniques (e.g. , NASBA, Cangene, Mississauga, Ontario); see Berger (1987) Methods Enzymol. 152:307-316, Sambrook, and Ausubel, as well as Mullis (1987) U.S. Patent Nos. 4,683,195 and 4,683,202; Arnheim (1990) C&EN 36-47; Lomell J. Clin. Chem. , 35:1826 (1989); Van Brunt, Biotechnology, 8:291-294 (1990); Wu (1989) Gene 4:560; Sooknanan (1995) Biotechnology 13:563-564. Methods for cloning in vitro amplified nucleic acids are described in Wallace, U.S. Pat. No. 5,426,039.

The degree of complementarity (sequence identity) required for detectable binding will vary in accordance with the stringency of the hybridization medium and/or wash medium. The degree of complementarity will optimally be 100 percent; however, it should be understood that minor sequence variations in the probes and primers may be compensated for by reducing the stringency of the hybridization and/or wash medium as described earlier. In some preferred embodiments, members of this class of pest resistance genes can be identified by their ability to be amplified by PCR primers based on the sequences disclosed here. Appropriate primers and probes for identifying RG sequences from plant tissues are generated from comparisons of the sequences provided herein. See, . e.g., Table 1. For a general overview of PCR see PCR Protocols: A Guide to Methods and Applications. (Innis, M, Gelfand, D., Sninsky, J. and White, T. , eds.), Academic Press. San Diego (1990), incorporated herein by reference. Briefly, the first step of each cycle of the PCR involves the separation of the nucleic acid duplex formed by the primer extension. Once the strands are separated, the next step in PCR involves hybridizing the separated strands with primers that flank the target sequence. The primers are then extended to form complementary copies of the target strands. For successful PCR amplification, the primers are designed so that the position at which each primer hybridizes along a duplex sequence is such that an extension product synthesized from one primer, when separated from the template (complement), serves as a template for the extension of the other primer. The cycle of denaturation, hybridization, and extension is repeated as many times as necessary to obtain the desired amount of amplified nucleic acid. In the preferred embodiment of the PCR process, strand separation is achieved by heating the reaction to a sufficiently high temperature for an sufficient time to cause the denaturation of the duplex but not to cause an irreversible denaturation of the polymerase (see U.S. Patent No. 4,965,188). Template-dependent extension of primers in PCR is catalyzed by a polymerizing agent in the presence of adequate amounts of four deoxvribonucleotide triphosphates (typically dATP, dGTP, dCTP, and dTTP) in a reaction medium comprised of the appropriate salts, metal cations, and pH buffering system. Suitable polymerizing agents are enzymes known to catalyze template-dependent DNA synthesis.

Polynucleotides may also be synthesized by well-known techniques as described in the technical literature. See, e.g., Carruthers et al. , Cold Spring Harbor Symp. Quant. Biol. 47:411-418 (1982), and Adams et al. , J. Am. Chem. Soc. 105:661 (1983). Double stranded DNA fragments may then be obtained either by synthesizing the complementary strand and annealing the strands together under appropriate conditions, or by adding the complementary strand using DNA polymerase with an appropriate primer sequence.

RG Proteins The present invention further provides isolated RG proteins encoded by the . RG polynucleotides disclosed herein. One of skill will recognize that the nucleic acid encoding a functional RG protein need not have a sequence identical to the exemplified genes disclosed here. For example, because of codon degeneracy a large number of nucleic acid sequences can encode the same polypeptide. In addition, the polypeptides encoded by the RG genes, like other proteins, have different domains which perform different functions. Thus, the RG gene sequences need not be full length, so long as the desired functional domain of the protein is expressed.

The resistance proteins are at least 25 amino acid residues in length. Typically, the RG proteins are at least 50 amino acid residues, generally at least 100, preferably at least 150, more preferably at least 200 amino acids in length. In particularly preferred embodiments, the RG proteins are of sufficient length to provide resistance to pests when expressed in the desired plants. Generally then, the RG proteins will be the length encoded by an RG gene of the present invention. However, those of ordinary skill will appreciate that minor deletions, substitutions, or additions to an RG protein will typically yield a protein with pest resistance characteristics similar or identical to that of the full length sequence. Thus, full-length RG proteins modified by 1, 2, 3, 4, or 5 deletions, substitutions, or additions, generally provide an effective degree of pest resistance relative to the full-length protein. The RG proteins which provide pest resistance will typically comprise at least one of an LRR or an NBS. Preferably, both are present. LRR and/or NBS regions present in the RG proteins of the present invention can be provided by RG genes of the present invention. In some embodiments, the LRR and/or NBS regions are obtained from other pest resistance genes. See, e.g., Yu et al, Proc. Natl Acad. Sci. USA, 93: 11751- 11756 (1996); Bent et al. , Science, 265: 1856-1860 (1994).

Modified protein chains can also be readily designed utilizing various recombinant DNA techniques well known to those skilled in the art. For example, the chains can vary from the naturally occurring sequence at the primary structure level by amino acid substitutions, additions, deletions, and the like. Modification can also include swapping domains from the proteins of the invention with related domains from other pest resistance genes. Pests that can be targeted by RG genes and proteins of the present invention . include such bacterial pests as Erwinia carotovora and Pseudomonas marginalis. Fungal pests which can be targeted by the present invention include Bremia lactucae, Marssonina panattoniana, Rhizoctonia solani, Olpidium brassicae, root aphid, Sclerotinia sclerotiorum and S. minor, and Botrytis cinerea which causes gray mold. RG genes also provide resistance to viral diseases such as lettuce and turnip mosaic viruses. Fusion Proteins

RG polypeptides can also be expressed as recombinant proteins with one or more additional polypeptide domains linked thereto to facilitate protein detection, purification, or other applications. Such detection and purification facilitating domains include, but are not limited to, metal chelating peptides such as polyhistidine tracts and histidine-tryptophan modules that allow purification on immobilized metals, protein a domains that allow purification on immobilized immunoglobulm, and the domain utilized in the FLAGS extension/affinity purification system (Immunex Corp, Seattle WA). The inclusion of a cleavable linker sequences such as Factor Xa or enterokinase (Invitrogen, San Diego CA) between the purification domain and plant disease resistant polypeptide may be useful to facilitate purification. One such expression vector provides for expression of a fusion protein comprising the sequence encoding a plant disease resistant polypeptide of the invention and nucleic acid sequence encoding six histidine residues followed by thioredoxin and an enterokinase cleavage site (e.g., see Williams (1995)

Biochemistry 34:1787-1797). The histidine residues facilitate detection and purification while the enterokinase cleavage site provides a means for purifying the desired protein(s) from the remainder of the fusion protein. Technology pertaining to vectors encoding fusion proteins and application of fusion proteins are well described, see e.g. , Kroll (1993) DNA Cell. Biol, 12:441-53.

Antibodies Reactive to RG Polypeptides and Immunological Assays

The present invention also provides antibodies which specifically react with RG proteins of the present invention under immunologically reactive conditions. An antibody immunologically reactive with a particular antigen can be generated in vivo or by recombinant methods such as selection of libraries of recombinant antibodies in phage or similar vectors. "Immunologically reactive conditions" includes reference to conditions which allow an antibody, generated to a particular epitope of an antigen, to bind to that epitope to a detectably greater degree than the antibody binds to substantially all other epitopes, generally at least two times above background binding, preferably at least five times above background. Immunologically reactive conditions are dependent upon the format of the antibody binding reaction and typically are those utilized in immunoassay protocols.

"Antibody" includes reference to an immunoglobulin molecule obtained by in vitro or in vivo generation of the humoral response, and includes both polyclonal and monoclonal antibodies. The term also includes genetically engineered forms such as chimeric antibodies (e.g., humanized murine antibodies), heteroconjugate antibodies (e.g., bispecific antibodies), and recombinant single chain Fv fragments (scFv). The term

"antibody" also includes antigen binding forms of antibodies (e.g., Fab' , F(ab')_, Fab, Fv, rlgG. and, inverted IgG). See, Pierce Catalog and Handbook, 1994-1995 (Pierce Chemical Co. , Rockford, IL). An antibody immunologically reactive with a particular antigen can be generated in vivo or by recombinant methods such as selection of libraries of recombinant antibodies in phage or similar vectors. See, e.g., Huse et al. (1989)

Science 246:1275-1281; and Ward, et al (1989) Nature 341:544-546; and Vaughan et al (1996) Nature Biotechnology, 14:309-314.

Many methods of making antibodies are known to persons of skill. A number of immunogens are used to produce antibodies specifically reactive to an isolated RG protein of the present invention under immunologically reactive conditions. An isolated recombinant, synthetic, or native RG protein of the present invention is the preferred immunogens (antigen) for the production of monoclonal or polyclonal antibodies.

The RG protein is then injected into an animal capable of producing antibodies. Either monoclonal or polyclonal antibodies can be generated for subsequent use in immunoassays to measure the presence and quantity of the RG protein. Methods of producing monoclonal or polyclonal antibodies are known to those of skill in the art. See, e.g., Coligan (1991) Current Protocols in Immunology Wiley/Greene, NY; and Harlow and Lane (1989) Antibodies: A Laboratory Manual Cold Spring Harbor Press, NY); Goding (1986) Monoclonal Antibodies: Principles and Practice (2d ed.) Academic Press, New York, NY.

Frequently, the RG proteins and antibodies will be labeled by joining, either covalently or non-covalently, a substance which provides for a detectable signal. A wide variety of labels and conjugation techniques are known and are reported extensively in both the scientific and patent literature. Suitable labels include radionucleotides, enzymes, substrates, cofactors, inhibitors, fluorescent moieties, chemiluminescent moieties, magnetic particles, and the like. Patents teaching the use of such labels include U.S. Patent Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241.

The antibodies of the present invention can be used to screen plants for the expression of RG proteins of the present invention. The antibodies of this invention are also used for affinity chromatography in isolating RG protein. The present invention further provides RG polypeptides that specifically bind, under immunologically reactive conditions, to an antibody generated against a defined immunogen, such as an immunogen consisting of the RG polypeptides of the present invention. Immunogens will generally be at least 10 contiguous amino acids from an RG polypeptide of the present invention. Optionally, immunogens can be from regions exclusive of the NBS and/or LRR regions of the RG polypeptides. Nucleic acids which encode such cross-reactive RG polypeptides are also provided by the present invention. The RG polypeptides can be isolated from any number plants as discussed earlier. Preferred are species from the family Compositae and in particular the genus Lactuca such as L. sativa and such subspecies as crispa, longifolia, and asparagina. "Specifically binds" includes reference to the preferential association of a ligand, in whole or part, with a particular target molecule (i.e., "binding partner" or "binding moiety") relative to compositions lacking that target molecule. It is, of course, recognized that a certain degree of non-specific interaction may occur between a ligand and a non-target molecule. Nevertheless, specific binding, may be distinguished as mediated through specific recognition of the target molecule. Typically specific binding results in a much stronger association between the ligand and the target molecule than between the ligand and non-target molecule. Specific binding by an antibody to a protein under such conditions requires an antibody that is selected for its specificity for a particular protein. The affinity constant of the antibody binding site for its cognate monovalent antigen is at least 10⁷, usually at least 10⁸, preferably at least 10⁹, more preferably at least 10¹⁰, and most preferably at least 10¹¹ liters/mole. A variety of immunoassay formats are appropriate for selecting antibodies specifically reactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select monoclonal antibodies specifically reactive with a protein. See Harlow and Lane (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor Publications, New York, for a description of immunoassay formats and conditions that can be used to determine specific reactivity. The antibody may be polyclonal but preferably is monoclonal. Generally, antibodies cross- reactive to such proteins as RPS2, RPM1 (bacterial resistances in Arabidopsis, L6 (fungal resistance in flax, PRF (resistance to Pseudomonas syringae in tomator), and N, (virus resistance in tobacco), are removed by immunoabsorbtion.

Immunoassays in the competitive binding format are typically used for cross-reactivity determinations. For example, an immunogenic RG polypeptide is immobilized to a solid support. Polypeptides added to the assay compete with the binding of the antisera to the immobilized antigen. The ability of the above polypeptides to compete with the binding of the antisera to the immobilized RG polypeptide is compared to the immunogenic RG polypeptide. The percent cross-reactivity for the above proteins is calculated, using standard calculations. Those antisera with less than 10% cross-reactivity with such proteins as RPS2, RPM1, L6, PRF, and N are selected and pooled. The cross- reacting antibodies are then removed from the pooled antisera by immunoabsorbtion with these non-RG resistance proteins.

The immunoabsorbed and pooled antisera are then used in a competitive binding immunoassay to compare a second "target" polypeptide to the immunogenic polypeptide. In order to make this comparison, the two polypeptides are each assayed at a wide range of concentrations and the amount of each polypeptide required to inhibit 50% of the binding of the antisera to the immobilized protein is determined using standard techniques. If the amount of the target polypeptide required is less than twice the amount of the immunogenic polypeptide that is required, then the target polypeptide is said to specifically bind to an antibody generated to the immunogenic protein. As a final determination of specificity, the pooled antisera is fully immunosorbed with the immunogenic polypeptide until no binding to the polypeptide used in the immunosorbtion is detectable. The fully immunosorbed antisera is then tested for reactivity with the test polypeptide. If no reactivity is observed, then the test polypeptide is specifically bound by the antisera elicited by the immunogenic protein. Production of transgenic plants of the invention

Isolated nucleic acid constructs prepared as described herein can be introduced into plants according techniques known in the art. In some embodiments, the introduced nucleic acid is used to provide RG gene expression and therefore pest resistance in desired plants. In some embodiments, RG promoters are used to drive expression of desired heterologous genes in plants. Finally, in some embodiments, the constructs can be used to suppress expression of a target endogenous gene, including RG genes.

To use isolated RG sequences in the above techniques, recombinant DNA vectors suitable for transformation of plant cells are prepared. Techniques for transforming a wide variety of higher plant species are well known and described in the technical and scientific literature. See, for example, Weising et al. Ann. Rev. Genet. 22:421-477 (1988).

A DNA sequence coding for the desired RG polypeptide, for example a cDNA or a genomic sequence encoding a full length protein, will be used to construct a recombinant expression cassette which can be introduced into the desired plant. An expression cassette will typically comprise the RG polynucleotide operably linked to transcriptional and translational initiation regulatory sequences which will direct the transcription of the sequence from the RG gene in the intended tissues of the transformed plant. Such DNA constructs may be introduced into the genome of the desired plant host by a variety of conventional techniques. For example, the DNA construct may be introduced directly into the genomic DNA of the plant cell using techniques such as electroporation. PEG poration, particle bombardment and microinjection of plant cell protoplasts or embryogenic callus, or the DNA constructs can be introduced directly to plant tissue using ballistic methods, such as DNA particle bombardment. Alternatively, the DNA constructs may be combined with suitable T-DNA flanking regions and introduced into a conventional Agrobacterium tumefaciens host vector. The virulence functions of the Agrobacterium tumefaciens host will direct the insertion of the construct and adjacent marker into the plant cell DNA when the cell is infected by the bacteria. Transformation techniques are known in the art and well described in the scientific and patent literature. The introduction of DNA constructs using polyethylene glycol precipitation is described in Paszkowski et al. Embo J. 3:2717-2722 (1984). Electroporation techniques are described in Fromm et al. Proc. Natl. Acad. Sci. USA 82:5824 (1985). Ballistic transformation techniques are described in Klein et al Nature 327:70-73 (1987).

Agrobacterium tumefaciens-meditated transformation techniques are well described in the scientific literature. See, for example Horsch et αl. Science 233:496-498 (1984), and Fraley et αl. Proc. Nαtl. Acαd. Sci. USA 80:4803 (1983). Although Agrobacterium is useful primarily in dicots, certain monocots can be transformed by Agrobacterium. For instance, Agrobacterium transformation of rice is described by Hiei et al, Plant J. 6:271-282 (1994). A particularly preferred means of transforming lettuce is described in Michelmore et al, Plant Cell Reports, 6:439-442 (1987).

Transformed plant cells which are derived by any of the above transformation techniques can be cultured to regenerate a whole plant which possesses the transformed genotype and thus the desired RG-controlled phenotype. Such regeneration techniques rely on manipulation of certain phytohormones in a tissue culture growth medium, typically relying on a biocide and/or herbicide marker which has been introduced together with the RG nucleotide sequences. Plant regeneration from cultured protoplasts is described in Evans et al. , Protoplasts Isolation and Culture, Handbook of Plant Cell Culture, pp. 124-176, Macmillilan Publishing Company, New York, 1983; and Binding, Regeneration of Plants, Plant Protoplasts, pp. 21-73, CRC Press, Boca Raton, 1985. Regeneration can also be obtained from plant callus, explants, organs, or parts thereof. Such regeneration techniques are described generally in Klee et al. Ann. Rev. of Plant Phys. 38:467-486 (1987).

The methods of the present invention are particularly useful for incorporating the RG polynucleotides into transformed plants in ways and under circumstances which are not found naturally. In particular, the RG polypeptides may be expressed at times or in quantities which are not characteristic of natural plants.

One of skill will recognize that after the expression cassette is stably incorporated in transgenic plants and confirmed to be operable, it can be introduced into other plants by sexual crossing. Any of a number of standard breeding techniques can be used, depending upon the species to be crossed.

Detection of RG Resistance Genes The present invention further provides methods for detecting RG resistance ^• genes in a nucleic acid sample suspected of comprising an RG resistance gene. The means by which the RG resistance gene is detected is not a critical aspect of the invention. For example, RG resistance genes can be detected by the presence of amplicons using RG resistance gene specific primers. Additionally, RG resistance genes can be detected by assaying for specific hybridization of an RG polynucleotide to an RG resistance gene. In some embodiments, the RG resistance gene can be amplified prior to the step of contacting the nucleic acid sample with the RG polynucleotide.

In a typical detection method, the nucleic acid sample is contacted with an RG polynucleotide to form a hybridization complex. The hybridization complex may be detected directly (e.g. , in Southern or northern blots), or indirectly (e.g., by subsequent primer extension during PCR amplification). The RG polynucleotide hybridizes under stringent conditions to an RG polynucleotide of the invention. Formation of the hybridization complex is directly or indirectly used to indicate the presence of the RG resistance gene in the nucleic acid sample.

Detection of the hybridization complex can be achieved using any number of well known methods. For example, the nucleic acid sample, or a portion thereof, may be assayed by hybridization formats including but not limited to, solution phase, solid phase, mixed phase, or in situ hybridization assays. Briefly, in solution (or liquid) phase hybridizations, both the target nucleic acid and the probe or primer are free to interact in the reaction mixture. In solid phase hybridization assays, probes or primers are typically linked to a solid support where they are available for hybridization with target nucleic in solution. In mixed phase, nucleic acid intermediates in solution hybridize to target nucleic acids in solution as well as to a nucleic acid linked to a solid support. In in situ hybridization, the target nucleic acid is liberated from its cellular surroundings in such as to be available for hybridization within the cell while preserving the cellular morphology for subsequent interpretation and analysis. The following articles provide an overview of the various hybridization assay formats: Singer et al., Biotechniques 4(5j:230-250 (1986); Haase et al, Methods in Virology, Vol. VII, pp. 189-226 (1984); Wilkinson, "The theory and practice of in situ hybridization" In: In situ Hybridization, Ed. D.G. Wilkinson. IRL Press, Oxford University Press, Oxford; and Nucleic Acid Hybridization: A Practical Approach, Ed. Hames, B.D. and Higgins, S.J., IRL Press (1987). The effect of the modification of RG gene expression can be measured by . detection of increases or decreases in mRNA levels using, for instance, Northern blots. In addition, the phenotypic effects of gene expression can be detected by measuring nematode, fungal, bacterial, viral, or other pest resistance in plants. Suitable assays for determining pest resistance are well known. Michelmore and Crute, Trans. Br. my col. Soc, 79(3): 542-546 (1982).

The means by which hybridization complexes are detected is not a critical aspect of the present invention and can be accomplished by any number of methods currently known or later developed. RG polynucleotides can be labeled by any one of several methods typically used to detect the presence of hybridized nucleic acids. One common method of detection is the use of autoradiography using probes labeled with³H, ¹²⁵I, ⁵⁵S, ¹⁴C, or ³²P, or the like. The choice of radioactive isotope depends on research preferences due to ease of synthesis, stability, and half lives of the selected isotopes. Other labels include ligands which bind to antibodies labeled with fluorophores, chemiluminescent agents, and enzymes. Alternatively, probes can be conjugated directly with labels such as fluorophores, chemiluminescent agents or enzymes. The choice of label depends on sensitivity required, ease of conjugation with the probe, stability requirements, and available instrumentation. Labeling the RG polynucleotide is readily achieved such as by the use of labeled PCR primers. The choice of label dictates the manner in which the label is bound to the probe. Radioactive probes are typically made using commercially available nucleotides containing the desired radioactive isotope. The radioactive nucleotides can be incorporated into probes, for example, by using DNA synthesizers, by nick translation with DNA polymerase I, by tailing radioactive DNA bases to the 3' end of probes with terminal deoxynucleotidyl transferase, by treating single-stranded M13 plasmids having specific inserts with the Klenow fragment of DNA polymerase in the presence of radioactive deoxy nucleotides, dNTP, by transcribing from RNA templates using reverse transcriptase in the presence of radioactive deoxynucleotides, dNTP, or by transcribing RNA from vectors containing specific RNA viral promoters (e.g., SP6 promoter) using the corresponding RNA polymerase (e.g., SP6 RNA polymerase) in the presence of radioactive ribonucleotides rNTP. The probes can be labeled using radioactive nucleotides in which the isotope resides as a part of the nucleotide molecule, or in which the radioactive component is attached to the nucleotide via a terminal hydroxyl group that has been esterified to a radioactive component such as inorganic acids, e.g., 32P phosphate or 14C organic acids, or esterified to provide a linking group to the label. Base analogs having nucleophilic linking groups, such as primary amino groups, can also be linked to a label.

Non-radioactive probes are often labeled by indirect means. For example, a ligand molecule is covalently bound to the probe. The ligand then binds to an anti-ligand molecule which is either inherently detectable or covalently bound to a detectable signal system, such as an enzyme, a fluorophore, or a chemiluminescent compound. Enzymes of interest as labels will primarily be hydrolases, such as phosphatases, esterases and glyco- sidases, or oxidoreductases, particularly peroxidases. Fluorescent compounds include fluorescein and its derivatives, rhodamine and its derivatives, dansyl, umbelliferone, etc. Chemiluminescers include luciferin, and 2,3-dihydrophthalazinediones, e.g. , luminol. Ligands and anti-ligands may be varied widely. Where a ligand has a natural anti-ligand, namely ligands such as biotin, thyroxine, and cortisol, it can be used in conjunction with its labeled, naturally occurring anti-ligands. Alternatively, any haptenic or antigenic compound can be used in combination with an antibody.

Probes can also be labeled by direct conjugation with a label. For example, cloned DNA probes have been coupled directly to horseradish peroxidase or alkaline phosphatase, (Renz. M., and Kurz, K. (1984) A Colorimetric Method for DNA Hybridization. Nucl. Acids Res. 12: 3435-3444) and synthetic oligonucleotides have been coupled directly with alkaline phosphatase (Jablonski, E., et al. (1986) Preparation of Oligodeoxynucleotide-Alkaline Phosphatase Conjugates and Their Use as Hybridization Probes. Nuc. Acids. Res. 14: 6115-6128; and Li P., et al. (1987) Enzyme-linked Synthetic Oligonucleotide probes: Non-Radioactive Detection of Enterotoxigenic Escherichia Coli in Faeca Specimens. Nucl. Acids Res. 15:5275-5287).

Definitions Units, prefixes, and symbols can be denoted in their SI accepted form.

Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, nucleic acids are written left to right in 5' to 3' orientation, respectively. The WO 98/30083 _ _. PCT/US98/00615

35 headings provided herein are not limitations of the various aspects or embodiments of the . invention which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification as a whole. As used herein, the term "plant" includes reference to whole plants, plant organs (e.g., leaves, stems, roots, etc.), seeds and plant cells and progeny of same. The class of plants which can be used in the methods of the invention is generally as broad as the class of higher plants amenable to transformation techniques, including both monocotyledonous and dicotyledonous plants. As used herein, "pest" includes, but is not limited to, viruses, fungi, nematodes, insects, and bacteria.

As used herein, "heterologous" is a nucleic acid that originates from a foreign species, or, if from the same species, is substantially modified from its original form. For example, a promoter operably linked to a heterologous structural gene is from a species different from that from which the structural gene was derived, or, if from the same species, one or both are substantially modified from their original form.

As used herein, "RG gene," alternatively referred to as "RLG gene," is a gene encoding resistance to plant pests, such as viruses, fungi, nematodes, insects, and bacteria, and which hybridizes under stringent conditions and/or has at least 60% sequence identity at the deduced amino acid level to the exemplified sequences provided herein. RG genes encode "RG polypeptides," alternatively referred to as "RLG polypeptides," which can comprise LRR motifs and/or NBS motifs. The RG polypeptides encoded by RG genes have at least 55% or 60% sequence identity, typically at least 65% sequence identity, preferably at least 70% sequence identity, often at least 75% sequence identity, more preferably at least 80% sequence identity, and most preferably at least 90% sequence identity at the deduced amino acid level relative to the exemplary RG sequences provided herein. The term "RG family" or "RG family genus" or "genus" includes reference to a group of RG polypeptide sequence species that have at least 60% amino acid sequence identity, and, the nucleic acids encoding these polypeptides. The individual species of a genus, i.e., the members of a family, typically are genetically mapped to the same locus.

As used herein, "RG polynucleotide" includes reference to a contiguous sequence from an RG gene of at least 18, 20, 25, 30, 40, or 50 nucleotides in length, up to at least about 100 or at least about 200 nucleotides in length. In some embodiments, the - polynucleotide is preferably at least 100 nucleotides in length, more preferably at least 200 nucleotides in length, most preferably at least 500 nucleotides in length. Thus, RG polynucleotide may be a RG gene or a subsequence thereof. As used herein, "isolated," when referring to a molecule or composition, such as, for example, an RG polypeptide or nucleic acid, means that the molecule or composition is separated from at least one other compound, such as a protein, other nucleic acids (e.g., RNAs), or other contaminants with which it is associated in vivo or in its naturally occurring state. Thus, an RG polypeptide or nucleic acid is considered isolated when it has been isolated from any other component with which it is naturally associated, e.g.. cell membrane, as in a cell extract. An isolated composition can, however, also be substantially pure. An isolated composition can be in a homogeneous state and can be in a dry or an aqueous solution. Purity and homogeneity can be determined, for example, using analytical chemistry techniques such as polyacrylamide gel electrophoresis (SDS- PAGE) or high performance liquid chromatography (HPLC).

The term "nucleic acid" or "nucleic acid molecule" or "nucleic acid sequence" refers to a deoxy ribonucleotide or ribonucleotide oligonucleotide in either single- or double-stranded form. The term encompasses nucleic acids, i.e. , oligonucleotides, containing known analogues of natural nucleotides which have similar or improved binding properties, for the purposes desired, as the reference nucleic acid. The term also includes nucleic acids which are metabolized in a manner similar to naturally occurring nucleotides or at rates that are improved thereover for the purposes desired. The term also encompasses nucleic-acid-like structures with synthetic backbones. DNA backbone analogues provided by the invention include phosphodiester, phosphorothioate, phosphorodithioate, methylphosphonate, phosphoramidate, alkyl phosphotriester, sulfamate, 3'-thioacetal, methylene(methylimino), 3'-N-carbamate, morpholino carbamate, and peptide nucleic acids (PNAs); see Oligonucleotides and Analogues, a Practical Approach, edited by F. Eckstein, IRL Press at Oxford University Press (1991); Antisense Strategies, Annals of the New York Academy of Sciences, Volume 600, Eds. Baserga and Denhardt (NYAS 1992); Milligan (1993) J. Med. Chem. 36:1923-1937; Antisense

Research and Applications (1993, CRC Press). PNAs contain non-ionic backbones, such as N-(2-aminoethyl) glycine units. Phosphorothioate linkages are described in WO 97/03211; WO 96/39154; Mata (1997) Toxicol Appl Pharmacol 144:189-197. Other synthetic backbones encompasses by the term include methyl-phosphonate linkages or alternating methylphosphonate and phosphodiester linkages (Strauss-Soukup (1997) Biochemistry 36:8692-8698), and benzylphosphonate linkages (Samstag (1996) Antisense Nucleic Acid Drug Dev 6: 153-156). The term nucleic acid is used interchangeably with gene. cDNA, mRNA, oligonucleotide primer, probe and amplification product. Unless otherwise indicated, a particular nucleic acid sequence includes the complementary sequence thereof.

The term "exogenous nucleic acid" refers to a nucleic acid that has been isolated, synthesized, cloned, ligated, excised in conjunction with another nucleic acid, in a manner that is not found in nature, and/or introduced into and/or expressed in a cell or cellular environment other than or at levels or forms different than the cell or cellular environment in which said nucleic acid or protein is be found in nature. The term encompasses both nucleic acids originally obtained from a different organism or cell type than the cell type in which it is expressed, and also nucleic acids that are obtained from the same cell line as the cell line in which it is expressed, invention.

The term "recombinant," when used with reference to a cell, or to the nucleic acid, protein or vector refers to a material, or a material corresponding to the natural or native form of the material, that has been modified by the introduction of a new moiety or alteration of an existing moiety, or is identical thereto but produced or derived from synthetic materials. For example, recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise expressed at a different level, typically, under-expressed or not expressed at all. The term "recombinant means" encompasses all means of expressing, i.e., transcription or translation of, an isolated and/or cloned nucleic acid in vitro or in vivo. For example, the term "recombinant means" encompasses techniques where a recombinant nucleic acid, such as a cDNA encoding a protein, is inserted into an expression vector, the vector is introduced into a cell and the cell expresses the protein. "Recombinant means" also encompass the ligation of nucleic acids having coding or promoter sequences from different sources into one vector for expression of a fusion protein, constitutive expression of a protein, or inducible expression of a protein, such as the plant disease resistant, or RG. polypeptides of the invention. The term "specifically hybridizes" refers to a nucleic acid that hybridizes, . duplexes or binds to a particular target DNA or RNA sequence. The target sequences can be present in a preparation of total cellular DNA or RNA. Proper annealing conditions depend, for example, upon a nucleic acid's, such as a probe's length, base composition, and the number of mismatches and their position on the probe, and can be readily determined empirically providing the appropriate reagents are available. For discussions of nucleic acid probe design and annealing conditions, see, e.g., Sambrook and Ausubel.

The terms "stringent hybridization," "stringent conditions," or "specific hybridization conditions" refers to conditions under which an oligonucleotide (when used, for example, as a probe or primer) will hybridize to its target subsequence, such as an RG nucleic acid in an expression vector of the invention but not to a non-RG sequence. Stringent conditions are sequence-dependent. Thus, in one set of stringent conditions an oligonucleotide probe will hybridize to only one specie of the genus of RG nucleic acids of the invention. In another set of stringent conditions (less stringent) an oligonucleotide probe will hybridize to all species of the invention's genus but not to non-RG nucleic acids. Longer sequences hybridize specifically at higher temperatures. Stringent conditions are selected to be about 5 C lower than the thermal melting point (T_m) for the specific sequence at a defined ionic strength and pH. The T_m is the temperature (under defined ionic strength, pH, and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium (if the target sequences are present in excess, at T_m, 50% of the probes are occupied at equilibrium). Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, i.e., about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30°C for short probes (e.g., 10 to 50 nucleotides) and at least about 60 C for long probes (e.g., greater than 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. Often, high stringency wash conditions preceded by low stringency wash conditions to remove background probe signal. An example of medium stringency wash conditions for a duplex of, e.g., more than 100 nucleotides, is lx SSC at 45 C for 15 minutes (see Sambrook for a description of SSC buffer). An example low stringency wash for a duplex of, e.g., more than 100 nucleotides, is 4-6x SSC at 40°C for 15 minutes, a signal to noise ratio of 2x (or higher) than that observed for an unrelated probe in the particular hybridization assay indicates detection of a "specific hybridization." Nucleic acids which do not hybridize to each other under stringent conditions can still be substantially identical if the polypeptides which they encode are substantially identical. This can occurs, e.g. , when a nucleic acid is created that encodes for conservative substitutions. Stringent hybridization and stringent hybridization wash conditions are different under different environmental parameters, such as for Southern and Northern hybridizations. An extensive guide to the hybridization of nucleic acids is found in, e.g., Sambrook, Tijssen (1993) supra.

As used herein "operably linked" includes reference to a functional linkage between a promoter and a second sequence, wherein the promoter sequence initiates and mediates transcription of the DNA sequence corresponding to the second sequence. Generally, operably linked means that the nucleic acid sequences being linked are contiguous and, where necessary to join two protein coding regions, contiguous and in the same reading frame. In the expression of transgenes one of skill will recognize that the inserted polynucleotide sequence need not be identical and may be "substantially identical" to a sequence of the gene from which it was derived. As explained herein, these variants are specifically covered by this term.

In the case where the inserted polynucleotide sequence is transcribed and translated to produce a functional RG polypeptide, one of skill will recognize that because of codon degeneracy, a number of polynucleotide sequences will encode the same polypeptide. These variants are specifically covered by the term "RG polynucleotide sequence". In addition, the term specifically includes those full length sequences substantially identical (determined as described herein) with an RG gene sequence which encode proteins that retain the function of the RG protein. Thus, in the case of RG genes disclosed here, the term includes variant polynucleotide sequences which have substantial identity with the sequences disclosed here and which encode proteins capable of conferring resistance to nematodes, bacteria, viruses, fungi, insects or other pests on a transgenic plant comprising the sequence. Two polynucleotides or polypeptides are said to be "identical" if the sequence of nucleotides or amino acid residues, respectively, in the two sequences is the same when aligned for maximum correspondence, as described below. The term "complementary to" is used herein to mean that the complementary sequence is identical to- all or a specified contiguous portion of a reference polynucleotide sequence.

The terms "sequence identity," "sequence similarity" and "homology" refer to when two sequences, such as the nucleic acid and amino acid sequences or the polypeptides of the invention, when optimally aligned, as with, for example, the programs PILEUP, BLAST, GAP, FASTA or BESTFIT (see discussion, supra). "Percentage amino acid/ nucleic acid sequence identity" refers to a comparison of the sequences of two polypeptides/nucleic acids which, when optimally aligned, have approximately the designated percentage of the same amino acids/nucleic acids, respectively. For example, "60% sequence identity" and "60% homology" refer to a comparison of the sequences of two RG nucleic acids or polypeptides which, when optimally aligned, have 60% identity. For example, in one embodiment, nucleic acids encoding RG polypeptides of the invention comprise a sequence with at least 50% nucleic acid sequence identity to SEQ ID NO:l. In other embodiments, the RG polypeptides of the invention are encoded by nucleic acids comprising a sequence with at least 50% sequence identity to SEQ ID NO:l, or, are encoded by nucleic acids comprising SEQ ID NO: l, or, have at least 60% amino acid sequence identity to the polypeptide of SEQ ID NO:2.

"Percentage of sequence identity" is determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity.

The term "substantial identity" of polynucleotide sequences means that a polynucleotide comprises a sequence that has at least 55% or 60% sequence identity, generally at least 65%, preferably at least 70%, often at least 75% , more preferably at least 80% and most preferably at least 90%, compared to a reference sequence using the programs described above (preferably BESTFIT) using standard parameters. One of skill will recognize that these values can be appropriately adjusted to determine corresponding identity of proteins encoded by two nucleotide sequences by taking into account codon degeneracy, amino acid similarity, reading frame positioning and the like. Substantial identity of amino acid sequences for these purposes normally means sequence identity of at least 55% or 60% , preferably at least 70%, more preferably at least 80%, and most preferably at least 95% . Polypeptides having "sequence similarity" share sequences as noted above except that residue positions which are not identical may differ by conservative amino acid changes. Conservative amino acid substitutions refer to the interchangeability of residues having similar side chains. For example, a group of amino acids having aliphatic side chains is glycine, alanine, valine, leucine, and isoleucine; a group of amino acids having aliphatic-hydroxyl side chains is serine and threonine; a group of amino acids having amide-containing side chains is asparagine and glutamine; a group of amino acids having aromatic side chains is phenylalanine, tyrosine, and tryptophan; a group of amino acids having basic side chains is lysine, arginine, and histidine; and a group of amino acids having sulfur-containing side chains is cysteine and methionine. Preferred conservative amino acids substitution groups are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine- valine, and asparagine-glutamine.

Another indication that nucleotide sequences are substantially identical is if two molecules hybridize to each other under appropriate conditions. Appropriate conditions can be high or low stringency and will be different in different circumstances. Generally, stringent conditions are selected to be about 5°C to about 20°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. Typically, stringent wash conditions are those in which the salt concentration is about 0.02 molar at pH 7 and the temperature is at least about 50°C. However, nucleic acids which do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This may occur, e.g., when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code.

Nucleic acids of the invention can be identified from a cDNA or genomic library prepared according to standard procedures and the nucleic acids disclosed here used as a probe. Thus, for example, stringent hybridization conditions will typically include at least one low stringency wash using 0.3 molar salt (e.g., 2X SSC) at 6_?C. The washes are preferably followed by one or more subsequent washes using 0.03 molar salt (e.g., 0.2X SSC) at 50°C, usually 60°C, or mosre usually 65°C. Nucleic acid probes used to identify the nucleic acids are preferably at least 100 nucleotides in length.

As used herein, "nucleotide binding site" or "nucleotide binding domain" ("NBS") includes reference to highly conserved nucleotide-, i.e., ATP/GTP-, binding domains, typically included in the "kinase domain" of kinase polypeptides, such as a kinase-la, kinase 2, or a kinase 3a motif, as described herein. For example, the tobacco N and Arabidopsis RPS2 genes, among several recently cloned disease-resistance genes, share highly conserved NBS sequence. Kinase NBS subdomains further consist of three subdomain motifs: the P-loop, kinase-2, and kinase-3a subdomains (Yu (1996) Proc. Acad. Sci. USA 93:11751-11756). As discussed in detail herein, examples include the Arabidopsis RPP5 gene (Parker (1997) supra), the A. thaliana RPS2 gene (Mindrinos (1997) supra), and the flax L6 rust resistance gene (Lawrence (1995) supra) which all encode proteins containing an NBS; and Mindrinos (1994) Cell 78:1089-1099; and Shen (1993) FEBS 335:380-385. Using the teachings disclosed and incorporated herein and standard nucleic acid hybridization and/or amplification techniques, one of skill can identify members having NBS domains, including any of the genus of NBS-containing plant disease resistant polypeptides of the invention.

As used herein, "leucine rich region" ("LRR") includes reference to a region that has a leucine content of at least 20% leucine or isoleucine, or 30% of the aliphatic residues: leucine, isoleucine, methionine, valine, and phenylalanine, and arranged with approximate repeated periodicity. The length of the repeat may vary in length but is generally about 20 to 30 amino acids. An LRR-containing polypeptide typicially will have the canonical 24 amino acid leucine-rich repeat (LRR) sequence , which is present in different proteins that mediates molecular recognition and/or interaction processes; as described in Bent (1994) Science 265:1856-1860; Parker (1997) Plant Cell. 9:879-894; Hong (1997) Plant Physiol. 113:1203-1212; Schmitz (1997) Nucleic Acids Res. 25:756-763; Hipskind (1996) Mol Plant Microbe Interact . 9:819-825; Tornero (1996) Plant J. 10:315-330; Dixon (1996) Cell 84:451-459; Jones (1994) Science 266:789-793; Lawrence (1995) Plant Cell 7: 1195-1206; Song (1995) Science 270: 1804-1806; as discussed in further detail supra. Using the teachings disclosed and incorporated herein and standard nucleic acid hybridization and/or amplification techniques, one of skill can identify polypeptides having LRR domains, including any member of the genus of LRR- containing RG polypeptides of the invention.

The term "promoter" refers to a region or sequence determinants located upstream or downstream from the start of transcription and which are involved in recognition and binding of RNA polymerase and other proteins to imtiate transcription. A "plant promoter" is a promoter capable of initiating and/or regulating transcription in plant cells; see also discussion on plant promoters, supra.

The term "constitutive promoter" refers to a promoter that initiates and helps control transcription in all tissues. Promoters that drive expression continuously under physiological conditions are referred to herein as "constitutive" promoters and are active under most environmental conditions and states of development or cell differentiation; see also detailed discussion, supra.

The term "inducible promoter" refers to a promoter which directs transcription under the influence of changing environmental conditions or developmental conditions. Examples of environmental conditions that may effect transcription by inducible promoters include anaerobic conditions, elevated temperature, drought, or the presence of light. Such promoters are referred to herein as "inducible" promoters; see also detailed discussion, supra.

The term "abscission-induced promoter" or "abcission promoter" refers to a class of promoters which are activated upon plant ripening, such as fruit ripening, and are especially useful incorporated in the expression systems (e.g., expression cassettes, vectors) of the invention. When the plant disease resistant polypeptide-encoding nucleic acid is under the control of an abcission promoter, rapid cell death, induced by expression of the invention's polypeptide, accelerates and/or accentuates abcission of the plant part, increasing the efficiency of the harvesting of fruits or other plant parts, such as cotton, and the like; see also detailed discussion, supra.

The term "tissue-specific promoter" refers to a class of transcriptional control elements that are only active in particular cells or tissues. Examples of plant promoters under developmental control include promoters that initiate transcription only (or primarily only) in certain tissues, such as roots, leaves, fruit, ovules, seeds, pollen, pistols, or flowers; see also detailed discussion, supra. As used herein "recombinant" includes reference to a cell, or nucleic acid, - or vector, that has been modified by the introduction of a heterologous nucleic acid or the alteration of a native nucleic acid to a form not native to that cell, or that the cell is derived from a cell so modified. Thus, for example, recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all.

As used herein, a "recombinant expression cassette" or "expression cassette" is a nucleic acid construct, generated recombinantly or synthetically, with a series of specified nucleic acid elements which permit transcription of a particular nucleic acid in a target cell. The expression vector can be part of a plasmid, virus, or nucleic acid fragment. Typically, the recombinant expression cassette portion of the expression vector includes a nucleic acid to be transcribed, and a promoter.

As used herein, "transgenic plant" includes reference to a plant modified by introduction of a heterologous polynucleotide. Generally, the heterologous polynucleotide is an RG structural or regulatory gene or subsequences thereof.

As used herein, "hybridization complex" includes reference to a duplex nucleic acid sequence formed by selective hybridization of two single-stranded nucleic acids with each other.

As used herein, "amplified" includes reference to an increase in the molarity of a specified sequence. Amplification methods include the polymerase chain reaction (PCR), the ligase chain reaction (LCR), the transcription-based amplification system (TAS), the self-sustained sequence replication system (SSR). A wide variety of cloning methods, host cells, and in vitro amplification methodologies are well-known to persons of skill. As used herein, "nucleic acid sample" includes reference to a specimen suspected of comprising RG resistance genes. Such specimens are generally derived, directly or indirectly, from lettuce tissue.

The term "antibody" refers to a polypeptide substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments or synthetic or recombinant analogues thereof which specifically bind and recognize analytes and antigens, such as a genus or subgenus of polypeptides of the invention, as described supra. It is understood that the examples and embodiments described herein are for - illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims.

EXAMPLES The following examples are offered to illustrate, but not to limit the claimed invention. Example 1 Example 1 describes the use of PCR to amplify RG genes from lettuce.

Multiple primers with low degeneracy, particularly at the 3' end, were designed based on the sequences of two known resistance genes from tobacco and flax. DNA Templates

Lettuce genomic DNA was extracted from cultivar Diana and a mutant line derived from cultivar Diana using a standard CTAB protocol. To generate cDNA templates, RNA was isolated from cultivar Diana and the mutant following standard procedures; first strand cDNA was synthesized using Superscript reverse transcriptase from 1 Φg total RNA as specified by the manufacturer (Life Technologies). BAC (bacterial artificial chromosome) clones from the Dm3 region were isolated from a BAC library of over 53,000 clones using marker AC15 that was known to be closely linked to DmS. Bacterial plasmids containing clones of L6 and RPS2 were used as positive controls.

PCR with degenerate oligonucleotide primers

Oligonucleotide primers were designed based on conserved motifs in the nucloetide binding sites (NBS) of L6, RPS2, and N. Eight primers were made corresponding to the GVGKTT motif in the sense direction; each had 64-fold degeneracy. Six primers were made to the GLPLAL motif in the anti-sense direction; with either 16 or 256-fold degeneracy (Table 1).

Oligonucleotides included 14-mer adaptors of (CUA)₄ at the 5' end of the sense primers and (CAU)₄ at the 5' end of the antisense primers to allow rapid cloning of the PCR products into pAMPl (Life Technologies). PCR amplification was performed in 50 Φl reaction volume with 1 ΦM of . each of a pair of sense and antisense primers. The templates were denatured by heating to 94EC for 2 min. This was followed by 35 cycles of 30 sec at 94EC, 1 min at 50EC, 2 min at 72EC, with a single final extension of 5 min at 72EC. 25 ng of genomic DNA or cDNA was used. BAC clones as templates required less. The final dNTP concentration was 0.2 mM; MgCl₂ was 1.5 mM.

Forty-eight combinations of sense and antisense primers were tested on a panel of nine templates consisting of two genomic DNA samples, two cDNA preparations, three BAC clones and plasmids containing L6 and RPS2 as positive controls. Amplification from L6 and RPS2 resulted in fragments of 516 and 513 repectively. Seven combinations of primers resulted in fragments of approximately this size with multiple templates (Table 2). Primers that gave RLG products were: PLOOPAA, PLOOPAG, PLOOPGA, PLOOPGG, PLOOPAC, GLPL3, GLPL4.

(Intentionally left blank)

DEGENERATE PRIMER SEQUENCES for NBS PCR

Sense primers based on GVGKTT amino acid sequence from L6, N and rps2 PLOOP motif:

PLOOPAG 5' GGN GTN GGNAAAACGAC 3*

PLOOPAA 5' GGN GTN GGNAAAACAAC 3'

PLOOPAT 5' GGN GTN GGN AAAACT AC 3'

PLOOPAC 5' GGN GTN GGN AAAACC AC 3'

PLOOPGG 5' GGNGTNGGNAAGACGAC 3'

PLOOPGA 5' GGN GTN GGN AAGACAAC 3'

PLOOPGT 5' GGN GTN GGN AAGACT AC 3'

PLOOPGC 5' GGN GTN GGNAAGACC AC 3*

Antisense primers based on GLPLAL amino acid sequence:

GLPL1 5' AGN GCN AGN GGN AGG CC 3'

GLPL2 5' AGN GCN AGN GGN AGA CC 3' ^•

GLPL3 5' AGN GCN AGN GGN AGT CC 3'

GLPL4 5^* AGN GCN AGN GGN AGC CC 3'

GLPL5 5" AAN GCC AAN GGC AAA CC 3'

GLPL6 5' AAN GCC AAN GGC AAT CC 3*

TABLE 2. Characteristics of RLGs isolated from lettuce.

^a Number of RLG sequences out of total number of clones seguenced. ^b Size of fragment amplified from the nucleotide bindind domain. ^c Estimated copy number from genomic Southern blot analysis and numbers of clones in the BAC library.

Example 2

Example 2 describes the genetic analysis used to obtain a preliminary indication of the linkage relationships of the amplified products and known clusters of resistance genes.

Bulked segregant analysis was performed to obtain a preliminary indication of the linkage relationships of the amplified products and known clusters of resistance genes. DNA from individuals were pooled for each susceptible and resistant bulk. Amplified products were then mapped by RFLP analysis from our intraspecific mapping population. Resistances from four clusters of resistance genes as well as over six hundred markers have now been mapped on this population. Linkage analysis was done using JIONMAP or MAPMAKER mapping programs. Due to a suppression of recombination in the Dm3 region, sequences were mapped relative to Dm3 using a panel of deletion mutants that provided greater genetic resolution than the mapping population (Anderson et αl 1996). All blots were washed twice at 63EC in 2x SSC/1 % SDS for 20 min, followed by one wash at 63EC in lx SSC/0.1 % SDS for 10 or 30 min. Most of the RLG sequences were analyzed by bulked segregant analysis (BSA) using pools of resistant and susceptible individuals for each of the four clusters of resistance genes. In genomic Southern analyses, all the RLGs revealed numerous fragments of varying intensity. The numbers of bands was highly dependent of the stringency of hybridization. BSA demonstrated that RLG1 was linked to the Dm4, 7 and Dml3 clusters. Segregation analysis confirmed this linkage.

RLG2 was derived from BAC H8 that was known to be from the Dm3 region. BSA with RLG2 demonstrated that the polymorphic bands that distinguished the parents of our mapping population mapped to the Dml,Dm3 cluster. Several bands absolutely cosegregated with Dml or Dm3. To provide finer genetic resolution, RLG2 was also mapped using a panel of Dm3 deletion mutants. A number of fragments were missing in largest deletion mutant demonstrating that several RLG2 family members are physically located very close to Dm3. No fragment was missing in all deletion mutants; however, this is not unexpected as there is extensive duplication within the region.

Example 3

Example 3 describes the screening of a bacterial artificial chromosome library.

Over 53,000 BAC clones containing lettuce genomic DNA were screened with two of the amplified products. High density filters each containing 1536 clones were hybridized to ³²P labelled probes. Filters were washed at 65EC with 40 mM N%PO₄/0.1 % SDS for 5 min followed by 20 min in the same solution.

To isolate additional RLG sequences we screened our genomic BAC library. Clones were identified that hybridized to RLG1 and RLG2. Nearly all the clones that hybridized to RLG2 also hybridized to marker AC 15 that had already been shown by deletion mutant analysis to be clustered around Dm3. This provided further evidence for clustering of RLG2 sequences.

Using primers conserved within each family, part of the NBS was amplified from each unique BAC clone and sequenced. This revealed that members within each family varied from 64% identical at the deduced amino acid level. The most divergent members only weakly cross-hybridized to each other. Currently, RLG sequences are considered to be part of the same family of sequences if they are at least 55 % identical at . the deduced amino acid level and map to the same region of the chromosome.

Example 4: Example 4 describes the cloning, identification, sequencing and characterization of RG polynucleotide sequences; including use of RG sequences from plasmid and PCR products.

Doubled stranded plasmid DNA clones and PCR products were sequenced using an ABI377 automated sequencer and fluorescently labelled di-deoxy terminators. Sequences were assembled using Sequencher (Genecodes), DNAStar (DNAStar) and Genetics Computer Group (GCG, Madison, WI) software. Database searches were performed using BLASTX and FASTA (GCG) algorithms.

Sequences flanking the NBS region for RLG2 and for some of RLGl were obtained by a series of IPCR and the products sequenced directly. IPCR worked less well for RLGl. Therefore RLGl was subcloned from a BAC clone into pBSK (Stratagene) and the double stranded plasmid sequenced by long range sequencing.

Initially, a total of 30 clones were sequenced. Three of these seven primer combinations yielded sequences that comprised continuous open reading frames with sequence identity to the NBS of known resistance genes. Seven out of 10 clones amplified from genomic DNA with the primer pair PLOOPGA/GLP6 were 522 bp long; they were identical to each other and named RLGl. All six clones amplified from genomic DNA or cDNA using the primers PLOOP AA/GLP6 were similar/the same as RLGl . All three clones sequenced from BAC clone H8 were 510 bp long, identical to each other but different from RLGl and were therefore designated RLG2. The 11 clones sequenced from four other primer combinations had no similarity to any NBS motifs and therefore were not studied further. Therefore, sequencing resulted in the identification of clones containing NBS motifs representing four RLG sequences.

Comparison of the deduced amino acid sequences of RLGl and RLG2 to those of known resistance genes revealed that RLGl and RLG2 are as similar to each other as they are to resistance genes from other species and that this is the same level of identity shown between the known resistance genes (Table 3). The percent identity (upper quadrant) and percent identity (lower quadrant) were determined using the MEGALIGN routine of the DNASTAR package. Identity refers to the proportion of identical amino acids: identity refers to the proportion of identical and similar amino acids and takes into account substitutions of amino acids with similar chemical characteristics. RG1 and RG2 are as similar to each other and to cloned resistance genes as cloned resistance genes from a variety of species are to each other. L6, resistance to Melampsora lini in flax (Lawrence et al.. 1995). N, resistance to tobacco mosaic virus in tobacco (Whitham et al , 1994). PRF, required for resistance to Pseudomonas syringae in tomato. RPS2, resistance to Pseudomonas syringae in Arabidopsis thaliana (Bent et al. , 1994; Mindrinos et al , 1994). RPM1, resistance to Pseudomonas syringae pv. maculicola in _4. thaliana (Grant et al , 1995). The initial RG1 and RG2, sequences were amplified from lettuce using degenerate primers.

Table 3

IDENTITIES OF

RESISTANCE GENE HOMOLOGUES

Lettuce

Lettuce

Lettuce

Lettuce

Tobacco

Arabidopsis

The regions homologous to the primers are included in this analysis as the genomic sequences for RLGl and RLG2 were determined by IPCR. Interestingly, the genomic sequences for RLGl exactly matched that of the primers used.

To obtain further evidence that we had amplified resistance genes, we amplified the regions flanking the NBSs of RLG la and RLG2a by IPCR of BAC clones. These products were then directly sequenced without cloning to minimize the introduction of PCR artifacts. Sequence analysis of the 5' regions failed to detect any homology to known resistance genes. However, the sequence of the 3' region contained leucine-rich repeats (LRRs). When this sequence was used to search GENBANK using BLASTX, it detected identity to the Arabidopsis resistance gene, RPS2. This region does not contain as regular LRRs as in some resistance genes; however, the repeat structure seems to be consistent with that of the flax resistance gene, L6. Therefore, the presence of an LRR region is further evidence that the sequences we amplified using degenerate oligonucleotide primers are probably resistance genes.

The sequences of the IPCR products also provided the genomic sequences of the regions complementary to the sequences of the degenerate oligonucleotide primers. The genomic sequences for RLGl were identical to one of the primers in the mixture. The RLG sequences are resistance genes as supported by three criteria: the presence of multiple sequence motifs characteristic of resistance genes, genetic cosegregation with known resistance genes, and their existence as clustered multi-gene families. The presence of LRR regions in a similar position relative to the NBS as in cloned resistance genes provides stronger evidence than relying solely sequence similarity between NBS regions. The clustering of RLG sequences at the same position as the known clusters of resistance genes make them strong candidates for encoding resistance genes. The hybridization patterns and genetic distribution of the RLG sequences are similar to that of cloned resistance genes in other species. Most of these hybridize to small multigene families and preliminary genetic evidence indicates that they are clustered in the genome. Therefore, the degenerate primers that we designed from other resistance genes seemed to have been specific enough to amplify resistance genes rather than P-loop containing proteins in general.

(intentionally left blank)

HLHA [Strand] ι AI 'CΓΓAACCGTΓCGTACGAG AN∞C GTCCCTCCTTCATC TTGTCATATGTCATATTC TCAΏ^JATITΓΓGCCACATTXT ₈i AATTTTGTGGTTAT_ΪTTAAA TTAA'ΠTITATTCCACATGT CATITTATGAGTTTTTCTAT TTTATTGAGTTTCACATAAT ₁₆₁ ATΓTAAATGTAATAACAATA AATGCATATTTAΠ I'I'L Γ TAAATAAACGCATATAATAT ATAGATTAAAATJCATATAAT

₂₄₁ AC_A AGG TAAACTCATATA ATACATA GTTCATCCCCAG T TATTTATATGTCTCATCC TTAATTTATTTATTATTTAT

₃₂₁ TTATTAGAGTAGATGATCTT TGTGATATTAAAAATTTAAT TTGT_\_AAAATTTAAAATTA TAATAATCCCACAATT GA

₄₀₁ ATAAAATTAAAAAAAATGGN CCCACCATTAGTCCATCΛC TT TCAGCTCATCAATATCG TGAGTATnrrCCTTCGTT C

₄₈₁ CACXT AATCAATATTTCCA GCGAATGACAGACΓCCTACG GCGTTTCTGAATTTGCGTTC CGAC_ACTXπTCATTGAAGGA

561 GATAATAAATCAAATGGAGC TCXR_CCAATGTTC_ATTGCTG ATGAAAGGTA ATTGTATGT GAAGANAATGTCAGCGATCN 641 ATCTCCATCCGGAACCCACC ACATTATCAGTGTACCACCA AACCACTCAAAACGGYGGAA GTAGRRAKAOIJRKAAAGTCA 721 TGAAGAATAGATTATTTTTG TCCTCATGGGCTGACTGAGG AGCGGGTTTAGTTCATCATT TT CTTTGANCAAAGAATTA 801 TCGGTCCATCGAATTTTTAC ATCGACAAAGAAGTTTCACT TCGC_AATGTTTTGTTAAACA ATTTTTAATCTTT TATCTT 8B1 TTCG GAAACTCCTCAATT GC^CTIGC_AACTTGCAACT TTTGGGCCCA _AAATTTGTG GTGGGCGTTAATTTAA CCA 961 CATATTCACTG AAACAATA ATTCΛAAT∞ATCTCTGTTC ATO_AATI _ATCAACATCTC TTGATAATTGAAATCATTCA 1041 x rrcAT cATT C TccA CATCTATACTATATTCTCTG CTCΪ ATCATATTAAACGAT GGCTGAAATCGTΓCTTTCTG 1121. c 'ri' ^,:':'GAc_ G^ιι _^,iiJrι GAAAAGCΓGGCATYTGAAGC C TGAAGAAGATIGTTCGCT CC_AAAAGAATTGAATCTGAG

1201 CTTAAG_UUV_TGAAGGAGAC ATIfcGACCAAATCCAAGATC TGCITAA∞ATGCTTCCCAG AAGGAAGTAACTAATGAAGC 1281 CGTTAAAAGATGGCIGAATG ATCTCCAACATTTGGCTTAT GACATAGACGACCTACITGA TGATYTTGCAACTGAAGCTG 1361 TTCM-CGTGAGTTGACCGAG GAGGG GGAGCCTCCTCCAG TATGGTAAGAAAACTAATCC C_AAGTTGTTGCACAAGTTTC 1441 TCACAAAGTAATAGGATGCA TGCCAAGTTAGA GATAT G CCACCAGGTTACAAGAACTG GTAGAGGCAAAAAATAA C 1521 TGGTTTAAGTGTGATAACAT ATGAAAAGCCAAAAATTGAA AJΞGTA GAGGCGTL riUGT AGATGAAAGCGGTACTGTCG 1601 GACGTGAAGATGATAAGAAA AAATTGCTGGAGAAGCTGTT GGGGGATAAAGATGAATCAG GGAGTCAAAAC TCAGCATC 1681 GTGCCCATAG TGGTATGGG TGGAGTTGGTAAAACAACTC TAGCTAGAL ITIGTAGAT GAAAAGAAAGTGAAGGATCA 1761 <_ TCGAACTCAGGGCTTGGG TTTGTGTTTCTGATGAGTTC AGTGTTCCCAATATAAGCAG AGTTATTTATCAATCTGTGA 1841 CTGGGGAAAAGAAGGAGTTT GAAGA^TAAATCTCCTTCA AGAAGC CTTAAAGAGAAAC TTAGGAACCAGCTA'XTIVI'A 1921 ATAGTTTTGGATGA GTG G GTCTGAAAGC ATGG GATT GGGAGAAATTAG GGGCCCA TTCXTITGCGGGGTCTCCTQG 2001 AAGTAGAATAATCATGACAA CTICGGAAGGAGCAATTGCTC AGAAAGCTGGG l l'l'L'l'CA TCAAGACX TCTGGAGGGTC 2081 TATCACAAGATGATGCTTTG TCTTTGTTTGCTCAACACGC ATITGG GTACCAAACTTTG ATTCACATCCAACACTAAQG 2161 CCACATGGAGAACl'Lrrri'L. GAAGAAATGTGATGGCTTAC CTCTAGC_TTAAGAACACTT GGAAGGT ATTAAGGACAAA 2241 AACAGACGAGGAACAATGGA AGGAGCTGTTGGATAGTGAG ATATGGAGGTTAGGAAAGAG CGATGAGATTGTTCCGGCTC 2321 T AGAC AAGCTACAATGAT C I IGCCT.'CTTTGAAGCT RTTRTTTGCATAYTGCTCCT TGTITCCCAAGGACTATGAG 2401 TTTGACAAGGAGGAGTTGAT TCTATTGTGGATGGCAGAAG GGTTTTTGCACCAACCAACT AYAAACAAGTCAAAGCAACG 2481 TTGGGTCTTGAATATTTTR AAGAGTTRTGTCAAGRTCR TTTITTCAACATGCTCCTAA TRRC_AAATCΞTTGTTTGTGA 2561 TGCATGACCTAATGAATGAT TIGGCTAC^TTTGTTGCTGG AGAATTTTTTTCAAGGTTAG ACATAGAGATGAAGAAGGAA 2641 TITAGGATGSAATCTTTGGA RAAGCACCQ'CATATGTCAT TTGTATGTGAGRATTACATA GGTTACAAAARGT CGAGOC 2721 ATTTAGAGGAGCTAAAAATT TGAGAACA' ITΓAGCATTG TCTGTTGGGGTGGTAGAAGA TTGGAAGATGTnTACTTAT 2801 (-AAACAAGGTCTTGAATGAC WTACTTCARGATTTACCATT GTTAAGGG CCTRA T TGA TTRHTCTTAYAATAASYRAG 2881 GTACCARAAK CGTSGGTAG TATGAASCACTTGCGGTATC T AATCTA CKGRAACTT/IA ATCAOICATTTACCGGAAWA 2961 TKTCTGCAATC T ATAATT TACARACC TGATTG KTC GGCTCTIXSAMTATTTAGTΓAA KTTGCCCAARAC l'l'Cl' AA 3041 AS IΓΓAAAAATTTGCASCAT TTTGACATGAGGGRTACTCC AAKTT AARAACA GCCC TARGGATTGGTGARTTGAAA 3121 ARTCTACAAACTCTCTTYKG TAACATTGGCATAGCAATAA CCGAGCTTAAGAACTTGCAM AAYCTCCATGGGAAARTTTG 3201 TATTCXXXX3GCTGGGAAAAA GGAAAA GCMGT GGATGC ACX3TTAAGCGAACTTGTCTC AAAAAAGGTTWAATGARTTA 3281 NAAACrrGGRVJTKGGGGGTGA TRAATTTAATGTTTTCCGAA ATGGGAACACTTGAAAAAGA AGTCCTCAATGAAGTGATGC 3361 CTCATAATGGTACTCTANAA AAAACCCANAATTATGTCTA TAGGGGGTATAGAGTTTCCA AATTGGGTTGGTTNCACTAA 3441 GGGTTTCTGAAACTAGAGAT GTGTTCATGG GTA GAAAA AGAOTGTTTTA∞TAGTTTC ATCAATCACCAAG GGGAAA 3521 TAGATGATATTTTCAGGGCY TACTGATGAGATGTGGAGAG GTATGATAGGGTOTCTTGGG GCGGTAGAAGAAATAAGCAT 3601 CCATT TTGTAATGAAATAA GATATYTGTGGGAATCAGAA GCAGAGGCAAGTAAGGTTCT TATGAATTTAAAGAAGTTQG 3681 ATTTAGGTGAATGTGAAAAT TTGGTGAGTTTAGGGGAGAA AAAGGAGGATAATCATAATA TTAATAGTGGGAGCAGCCTA 3761 ACAT ΓTTTAGGAGGTTGAA TGTATGGAGATGTAACAGCT TGGAGCATTGCAGGTGTCCA GATAGCATGGAGAATTTGTA 3841 TATGCACATGTGTGATTCAA TIIAGATCOSTCTCCTI'CCA ACAGGAGGAGGACAGAAGAT CAAGTCACTTACCATCACTG 3921 ATTGCAAGAAGCTTTCGGAA GAGGAGTTGGGAGGACGAGA GAGGACAAGAGTGCTTATAA ACTCAAAAATGCAGATGCTT 4001 GAATCAGTAGATATACGTAA TTGGCC_^AATCTGAAATCTA TC^GTGAATTGAGTTGCTTC ATTCACCTGAACAGATTATA 4081 TATATCAAACTGTCCGAGTR TGGAGTCA'X l'CCTGACCAT GAGTTGCCAAATCTCACCTC CTTAACAGATCGAAGGAGAG 4161 GACAGCGATITTCGTACGAA CGGTTACGATTCGACTGGCC

[Stzarxl]

1 AACCGTTCGT ACGAGAATCG CTGTCCTCTC CTTCCTGTAA TATAATGATA AGAAAAAATA TGATTAAAQG

71 TTTAAATCCA AAATCCATTA TTCCACCGGT GATATGATGC ACTAGCTGTA GTATGCAAAA ACAGTATTAT

141 AAATGCTAAC CAAAACAGCA GCTAAGAAAC AATATAAATA ATGGTTTGAA TCGTCCTTTC TCCGTACACT

211 CATTTCTTCC AAATCCCTAT CATTCATACA TACAAGTGCT CCCATATTAG GTTTTCACTA TAAGCAATGG

281 CTGAAATCCT TGGTTCTGCG TTCTTTGCGG TGTTCTTTGA AAAGCTTGCT TCTGAAGCCT TGAAGAGGGT

351 TGCTTGCTCC AAAGTAATTG ACAAGGAGCT CGAGAAATTG AATAGCTCAT GAATCAATAT AAAAGCTCTG

421 CTCAATGATG CTTCTCAGAA GGAAATAAGT AAGGAAGCTG TTAAAGAATG GTTGAATGCT CTTCAACATT

491 TGCCTTACGA CATAGATGAT CTACTTGGCG ATTTGGCAAC CAAAGCTATC CATCGTAAGT TCTCTGAGGA

561 ATACGGGGCC ACCATCAACA AGGTACGAAA GTTAATTCCA TCTTGTTTCT CTAGTTTGTC AAGTACTAAG

631 ATGCGCAACA AGATACATAA TATTACCAGC AAGTTACAAG AACTATTAGA AGAGAGAAAT AATCTTGGAT

701 TATGTGAAAT TGGTGAAAGC CGAAAACTTC GAAATAGAAA ATCAGAGACC TCTNTGCTAG ATCCATCTAG

771 TATTG TGGA CGCACAGATG ATAAGGAAGC GTTGCTTCTC AAGCTATATG AACCATGTGA TAGAAACTΪT

841 AGCATCTTGC CNATAGTTGG TATGGGTGGG TTAGATAAGA CCACTTTAGG TAGACTTTTG TATGATNAAA

911 TGCAAGTGAA GGATCACTTC GAACTCAAGG CGTGGGTTTG TGTTTCTGAT GAGTTTGATA TCTTCGGTAT

981. AAGCAAAACC ATTTTCGAAT CGATAGAGGG GGGAAACCAA GAGTTTAAGG ATTTAAATCT GCTTCAGGTG

1051 GCTTTAAAGG AGAAAATCTC AAAGAAACGA TTTCTTGTTG TTCTTGATGA TGTATGGAGC GAGAGCTATA

1121 CTGATTGGGA AATTCTAGAA CGTCCATTTC TAGCAGGAGC ACCAGGAAGT AAAGTAATCA TCACAACCCG

1191 CAAGTIGTCG TTGCTAAACC AATTGGGTCA TGATCAACCA TACCAATTGT CTGATTTGTC ACATGACAAT

1261 GCTCΓATCCT TATΠTGTCA ACACGCATTT GGTGTAAATA GCTTTGATTC ACATCCGATA CTTAAACCAC

1331 ATGGTGAAGG TATTGTTGAA AAATGTGATG GTTTGCCATT GGCTTTGATT GCACTTGGGA GGTTATTGAG 1401 GACAAAAAGA GATGAGGAAG AATGGAAGGA ACTATTGAAT AGTGAGATAT GGAGGTTAGG AAAGAGAGAT 1471 GAGATTATTC CGGYTCTTAG ACTAAGCTAT AATGATCTTT CIGCCTCTTT GAAGCAGTTG TTTGCATATT 1541 GCTCCTTGTT CCCCAAAGAC TATGTGTTCA ACAAGGAGAA GTTGATTTTA TTATGGATGG CAGAAGGGTT 1611 TTTGCACAAT GAAAATACAA ACAAGTCAAT GGAACGCTTA GNTCTTGAAT ATTTTGACGA CTTGTTGTCA 1681 AGGTCATTTT TTCAACATGC ACTCGATGAC AAATCGTTGT TTGTGGTGCA CGACCTCATG AATGACTTOG 1751 CCACATCTGT TGCTGGAGAT TATTTTTTAA GATTAGACAT TGAAATGAAA AAGGAAGCTT TGGAAAAATA 1821 CCGACATATG TCATITGTTT GTGAGAGTTA CATGGTTTAC AAAAGGTTCG AACCATTTAA AGGAGCTAAA 1891 AAATTGAGAA CTTTCTTAGC AATGCCTGTT GGGATGATAA AAAGTTGGAC AACATTTTAC TTATCAAATA 1961 AGGTCCTTGA TGACTTACTT CACGAATTAC CATTGTTGAG AGTTCTAAGT TTGAGTTATC TTAGCATCAA 2031 GGAGGTACCT GAAATAATAG GCAATTTGAA ACACTTGCGG TATCTTAATT TATCACACAC GAGTATCACA 2101 CATTTACCAG AAAATGTCTG CAATCTTTAC AACTTACAAA CATTGATCCT TTGTGGCTGT TGTTTTATAA 2171 CCAAGT_TCC CAACAACTTC TTAAAGCTTA GAAATTTACG GCATTTGGAC ATTAGCGATA CTCCCGGTTT 2241 GAAGAAGATG TCCTCGGGGA TTGGTGAATT GAAGAACCTA CACACYCTCT CCAAGCTCAT TATTGGAGGT 2311 GAAAAT GAC TAAACGAGCT TAAGAACTTA CAAAATCTCC ATG

RTGlfo - Diana [Strand]

TACTACTACT AGAATTCGGT GTTGGTAAGA CGArtCTAGC TAGACTTTTG TATGAGGAAA TGCAAGGGM GGATCACTTC GAACTTAAGG CGTGGGTATG TGTTTCTGAT GAGTTTGATA TCTTCAATAT AAGCAAAATT ATCTTACAAT CGATAGGTGG TGGAAACCAA GAATTTACGG ACTTAAACCT GCTTCGAGTA GCTTTAAΔAG AGAAGATΛC AAAGAAAAGa TTTCTTCTTG TTCTTGATGA TGTTTGGAGT GAAAGCTATA CCGATTGGGA AATTNTAGAA CGCCCATTTC TTGCAGGGGC ACCTGGAAGT AAGATTATTA TCACCACCCG GAAGCTGTCA TTGTTAAACA AACTCGGTTA CAATCAACCT TACAACCTTT CGGTTTTGTC ACATGAGAAT GCΓΓ GTCTT TATTCTGTCA GCATGCATTG GGTGAAGATA ACTTCAATTC ACATCCAACA CTTAAACCAC ATGGCGnAGG TATTGTTGAA AAATGTGATG GaTTGCCATT GGCATTGTCG ACATGATGAT GATG

J

[Strand] ι TCCCGTGCAA CGTNTATCAT TCAGAAGMGC CCAAAGACCA HAGATT.ΓGTT TAANGNTGNT TNTCAGAAGG

71 AAGTAATTGA TGAAGCTGTTI AAAAGATGGC TGATTGATNT CCAACAATTG GCTTACGACA CTGANGACMA

141 ACTTGATGAT NTCGCAACAG AAGCTATTCA TCGTGAGTTG ATCCGTGAAA CTGGAGCTTC racCAGCATG

211 GTAAGAAAGC TAATCCCAAG TTGTTGCACA AGTTTCTCAC AAAGTAATAG GATGCATGCC AGGTTAGATG

281 ATATTGCCGC TAAGTKACAA GAACTGGTAG AGGCGAAAAA TAATCTTGGT TTAAGTGTGA TAACATACGA

351 AAAACCCAAA ATTGAAAGAG ATGAGGCGTN TTTGGTAGAT GCAAGTGGTA TCATTGGACG TGAAGATGAT

421 AAGAAAAAAT TGCTTCAGAA GCTGTTGGGG GATACTTATG AATCAAGTAG TCAAAACTTC AACATCGTGC

491 CCATAGTTGG TATGGGTGGG GTAGGTAAAA CAACTCTAGC TAGACTTTTG TATGATGAAA AAAAAGTGAA

561 GGATCACTTC GAACTCAGGG TTTGGGTTTG TCTTTCTGAT GAGTTCAGTG TTCCCAATAT AAGCAGAGTT

631 ATCTATCAAT CTGTGACTGG TGAAAACAAA GAATTTGCAG ATTTAAATCT GCTTCAAGAA GCCCTTAAAG

701 AGAAACTTCA GAACAAACTA TTTCTAATAG TTTTAGATGA TGTATGGTCT GAAAGCTATG GTGATTGGGA

771 GAAATTAGTG GGCCCATTTC ATGCTGGGAC TTCTGGAAGT AGAATAATCA TGACTACTCG GAAGGAGCAA

841 TTACTCAAAC AGCTGGGTTT TTCTCATGAA GACCCTCTGC ATAGTATAGA CTCCCTGCAA CGTCTATCAC

911 AAGAAGATGC TTTGTCTTTG TTTTCTCAAC ACGCATTTGG TGTACCTAAC TTTGATTCAC ATCCAACACT

981 AAGGCCATAT GGGGAACAGT TTGTGAAAAA ATGTGGGGGA TTGCCTTTGG CCTTGT

tsiO.-q α-3TACC_?_TC TACGAGATCG CTGTCCCTCC TCGATCTGCT TAACGATGCT TCCCAGAAGG AAGTNACTAA

TGAAGCCGTT AAAAGATGGC TGAATGATCT CCAACATTTG GCTTATGACA TANACGACCT ACTTGATGAT

CTTGCAACAS AAAGCTATTC NTCSTGAGTT GACCGANGAA GGTGGAGCCT CCACCAGTAT GGTAAGAAAA

CTAATCCCAA GTTGTTG AC AAGTTTCTCA CAAAGTTATA GGATGCATGC CAAGTTAGAT GATATTGCCA

CCAGGTTACA AGAACTGGTA GAGGCAAAAA ATAATCTTGG TTTAAGTGTG ATAACATATG AAAAGCCCAA

AATTGAAAGG TATGAGGCAT CTTTGGTAGA CGAAAGTGGT ATTTTTGGAC GTTNAGATGA TNAGAAAAAA

TTGATGGAGA AGCTGTTGGA GGATAAAGAT GAATCCGGAG TCNAAACTTC AGCATCCTGC CCATAATTGG

TATGGGTGGA GTTGGC AAA CAACTCTAGC TAGACTCTTG TTTGATGAAA AGACAGTGAA GGATCACTTC

GAACTCAGGG CTTGGGTTTG TGTITCTGAT GAATTCAGTA TTCTCAACAT AAGCAAAGTT ATCTATCAAT

CTGTGACCGG GGAAAAGAAA GAGTTTGAAG ACTTAAATCT GCTTCAAGAA GCTCTTAGAG GGAAACTACA

AAACAAACTA TTTCTAATAG TTTTGGATGA TGTATGGTCG GAAAGCTATG GTGATTGGGA GAAATTAGTG

GX3CCCATTTC ATGCTGGGAC TTCTGGAAGT AGAATAATCA TGACTACTCG GAAGGAGCAA TTACTCAAAC

AGTTGGGTTT TTCTCATCAA GACCCTCTGC GTTGTATAGA CTCCCTGCAA CGTCTATCAC AAGATGATGC

'I'l'ir^,"!" "I .'Ti'TlGG TTTGCTCAAC ACGCATTTGG TGWCCA

RΓPΠE

[Strand]

TCTAGCTAGA CTTTTGTATG ACGAGATGCA AGAGAAGGAT CACTTCGAAC TCAAGGCGTG GGTTTGTGTT TCTGATGAGT TTGATATATT CAATATAAGC AAAATTATTT TCCAATCGAT AGGAGGTGGA AACCAAGAAT TTAAGGACTT AAATCTCCTT CAAGTAGCTG TAAAAGAGAA GATTTCAAAG AAACGATTTC TACTTGTTςT TGATGATGTT TGGAGTGAAA GCTATGCGGA TTGGGAAATT CTGGAACGCC CA I L JΛJC AGGGGCAGCC GGAAGTAAAA TTATCATGAC GACCCGGAAG CAGTCATTGC TAACCAAACT CGGTTACAAG CAACCTTACA ACCTTTCCGT TTTGTCACAT GACAGTGCTC TCTCTTTATT CTGTCAGCAT GCATTGGGTG AAGATAACTT CGATTCACAT C ACACTTA AACCACATGG CGAAGGCATT GTTGAAAAAT GTGCT

RDΞLF [Strand]

1 ATTTTCNGCT CNAAACAAAN AAAAGCAATG GCTGAAATCT TTCTTTCNGC ATTCTAGACC AGTATTCTTT

71 GAAAAGNTGG CrTTCTGAAGC CTTGAAGAAG ATCGCTCGCT TCCATCGGAT TGATTCTGAG CTCAAGAAAC 141 TGAAGAGGTC ATTAATCCAG ATCAGATCTG TGCTTAATGA TGCTTCTGAG AAGGAAATAA GTGATGAACJC 211 TGTTAAAGAA TGGCTGAATG GTCTCCAACA TTTGTCTTAC GACATAGACG ACCTACTTGA TGATTTGGCA 281 ACCGAAACTA TGCATCGTGA GTTGACCCAC GGATCTGGAG CCTCCACCAG CTTGTAAGAA AGATAATCCC 351 AACT GTTGC ACAGATTTCT CACTAAGTAG TAAGATGCGT AACAAGTTAG ATAATATTAC CATCAAGTTA 421 CAAGAACTGG TAGAGGAAAA AGATAATCTT GGCTTAAGTG TGAAAGGTGA AAGCCCAAAA CATACCAACA 491 GAAGATTACA GAC.CTCTTTG GTAGATGCAT CTAGCATTAT TGGTCGTGAA GGTGATAAGG ATGCATTGCT 561 CCATAAGCTG CTGGAGGATG AACCAAGTGA TAGAAACTTT AGCATCGTGC CAATAGTTGG TATGGGTGGT 631 GTGGGTAAGA CGACTCTAGC TAGACTTTTG TATGACGAGA TGCAAGAGAA GGATCACTTC GAACTCAAGG 701 CGTGGGTTTG TGTTTCTGAT GAGTTTGATA TCTTCAATAT AAGCAAAGTT ATCTTCCAAT CGATAGGTQG 771 TGGARACCAA GAATTTAAGG ACTTAAATCT CCTTCAAGTA GCTGTAAAAG AGAAGATTTC AAAGAAACGA 841 TTTCTVTYTTG TTCTGGATGA TGTTTGGAGT GAAAGCTATA CAGAATGGGA AATTCTAGCA CGTCCATTTC 911 TGCAGGGGC ACCAGGAAGT AAGATTATCA TGACGACCCG GAAGTTGTCG TTGCTAACCA AACTCGGTTA 981- CAATCAACCT TACAACCTTT CΞGTTTTGTC ACATGATAAT GCTYTGTCTT TATTCTGTCA GCAYGCATTG 1051 GGTGAAGATA ACTTCGATTC ACATCCAACA CTTAAACCAC ASGGTGAAAG TATTGTTGAA AAATGTGACG 1121 GTTTACCATT GGCTTTRATT GCACTTGGGA GRTTGTTGAR GACAAAAACA GATGAGGAAG AATGGAARGA 1191 AGTGTTGAAT AGTGAAATAT GGGGGTCAGG AAAGGGAGAT GAGATTGTTC CGGCTCTTAA ACTAAGCTAC 1261 AATGATCTCT CTGCCTCTTT GAAGAAGTTG TTTGCATACT GCTCCTTGTT CCCAAAAGAC TATGTGTTCG 1331 ATAAGGAGGA GTTGATTTTG TTGTGGATGG CAGAAGGGTT TTTGCACCAA TCAACCACAA GCAAGTCBAT 1401 GGAACGCTTG GGHCATGAAG GTTTTGATGA ATTGTTGTCA AGATCATTTT TTCAACATGC CCCTGATGCC 1471 AAATCGATGT TTGTGATGCA TGACCTGATG AATGACTTGG CHACATCTGT TGCTGGAGAT TTTTTTTCAA 1541 GGATGGACAT TGAGATGAAG AARGAATTTA GGAAGGAAGC TTTGSAAAAG YAYCGCCATA TGTCA'ΛTTGT 1611 TTGTGAKGAT TACATGGTK ACAAAAGGTT CRAGCCATTS ACAAGGAGCT AG

RΠHG

[Strand]

GTGAAGGATC ACTTCGAACT CAGGGCTTGG GTTTGTGTTT CTGATGAATT TAATATCCTC AATATAAGCA AAGTAATTTA TCAATCTGTA ACCGGGGAAA AAAAGGAGTT TGAAGACTTA AATCTGCTTC AAGAAGCTCT

TAAAGAAAAA CTTTGGAATC AGTTATTTCT AATAGTTCTG GATGATGTGT GGTCTGAAAG CTATCGTGAT TGGGAGAAAT TAGTGGGCCC ATTTTTTTCG GGGTCTCCTG GAAGTATGAT TATCATGACA ACTCGGAAGG AGCAATTGCC AAGAAAGCTG GGTTTTCCTC ATCAAGACCC TTTGCAAGGT CTATCACATG ACGATGCTTT GTCΓTGTTT GCTCAACACG CATTTGGTGT ACCA

EΠSH

[Strand] ι TCTAGCTAGA CTTTTGTATG AGGAAATGCA AGGGAAGGAT CACTTCGAAC TCAAGGCGTG GGTATGTGTT

71 TCTGATGAGT TTGATATCTT CAATATAAGC AAAATTATCT TACAATCGAT AGGTGGTGGA AACCAAGAAT

141 TTACGGACTT AAACCTGCTT CAAGTAGCTT TAAAAGAGAA GATCTCAAAG AAAAGATTTC TTCTTGTTςT

211 TGATGATGTT TGGAGTGAAA GCTATACCGA TTGGGAAATT CTAGAACGCC CATTTCTTGC AGGGGCACCT

281 GGAAGTAAGA TTATTATCAC CACCCGGAAG CTGTCATTGT TAAACAAACT CGGTTACAAT CAACCTTACA

351 ACCTTTCGGT TTTGTCACAT GAGAATGCTT TGTCTTTATT CTGTCAGCAT GCATTGGGTG AAGATAACTT

421 CAATTCACAT CCAACACTTA AACCACATGG CGAAGGTATT GTTGAAAAAT GTGAT

KLGU [Strand]

TCTAGCTAGA CTTGTGTATG ATGAGATGCA AGAGAAGGAT CACTTTGAAC TCAAGGCGTG GGTATGTGTT TCTGATGAGT TTGATATATT CAATATAAGC AAAATTATTT TCCAATCGAT AGGAGGTGGA AACCAAGAAT TTAAGGACTT AAACCTCCTT CAAGTAGCTG TAAAAGAGAA GATTTTAAAG AAACGATTTC TTCTTGTTCT TGACGACGTT TGGAGTGAAA GCTATGCCGA TTGGGAAATT OTGGAACGCC CA'IT C ΓGC AGGGGCAGCC GGAAGTAAAA TTATCATGAC AACCCGAAAG CAGTCATTGC TAACCAAACT CGGTTACAAG CAACCTTACA ACCTTTCCGT TTTGTCACAT GACAGTGCTC TGTCTTTATT CTGTCAGCAT GCATTGGGTG AAGGTAACTT CGATTCACAT C AACACTTA AACCACATGG CGAAGGCATT GTTGAAAAAT GTGCTGGATT GCCATTGGCA TTGTCGACA

R ΞU [Strand] ι TACTACTACT AGAATTCGGT GTTGGTAAGA CGAcTCTAGC TAGACTTTTG TATGAGGAAA TGCAAGGGAA

71 GGATCACTTC GAACTTAAGG CGTGGGTATG TGTTTCTGAT GAGTTTGATA TCTTCAATAT AAGCAAAATT

141 ATCTTACAAT CGATAGGTGG TGGAAACCAA GAATTTACGG ACTTAAACCT GCTTCGAGTA GCTTTAAAAG

211 AGAAGATcTC AAAGAAAAGa TTTCTTCTTG TTCTTGATGA TGTTTGGAGT GAAAGCTATA CCGATTGGGA

281 AATT TAGAA CGCCCATTTC TTGCAGGGGC ACCTGGAAGT AAGATTATTA TCACCACCCG GAAGCTGTCA

351 TTGTTAAACA AACTCGGTTA CAATCAACCT TACAACCTTT CGGTTTTGTC ACATGAGAAT GCTTTGTCTT

421 TATTCTGTCA GCATGCATTG GGTGAAGATA ACTTCAATTC ACATCCAACA CTTAAACCAC ATGGCGnAGG

491 TATTGTTGAA AAATGTGATG GaTTGCCATT GGCATTGTCG ACATGATGAT GATG

R I fir c^-c^ .

I\ RTR?LSLLHLLSYV!FS?I?PH?ILWLF.INFYSTCHFMSFSILLSFT.YLNVITINAYLFFFK.THIIYR

LKSYNTNKLI.YICSSPVYLYVSSLIYLLFIY.SR.SLY.KFNLFKI.NY..SHNLNKIKKNGPT!SPSLFQUNIV

SIUJ^MPNQYFQRMTDSYGVSEFAFRHCSL ELINQ ELL^^

YHQTTQNGGSR?T?KS.RIDYFCPHGLTEERV.F!!FL?K YRSIEFLHR^QRSFTSQCFVKQFLIFLSFR.NS

SIATCNLGLLGPQICGGR.FNPHIHCKQ.FKSISVHPIHQHLLIIEILHASSISSTSILYSLLLSY.T AEIV S

AFLTWFE<1_A?EAU IVRSKR1ESE1_KKI_KEΞTIOQIQDLJJ^

DLLDD?ATEAV?RELTEEGGASSSMVRKLIPSCCTSFSQSNRMHAKLDDIATRLQELVEAKNNLGLSVI

TYEKPKIERYEASLVDΞSGWGREDDKKKLI_E.OLGDKDESGSQ VKDHFΈ RAVWCVSDEFSVPNISRVIYQSN^

GDWEKLVGPF1_AGSFGSRIIMTTRKEQUJ^KLGFSHQDPLΞGLSQDDA1_S1_FAQH^

PHGEU=VKKCDGLPL_ UTΓLGRI±RTKTD__EQWKEU^

YCSL_F^KDYETOKEEUL WMAEGF1ΗQPT?N^^

LΛTFVAGE_FFSR IB/1KKEFRM?SLEKHRHMSFVCE?YIGYK?FEPFRGAK LRTFI_ALSVGWEDWK

MFYLSNKVLND?LQDLPLLRVL?L1?L?I??VP??VGS ?HLRYLNLS?T?ITHLPE??CNLYNLQTL!V

SGC?YLV?LPKTFS?LKNL?HFDMR?TP?LKNMPL?1GELK?LQTLF?NIGIAITELKNL?NLHGK?C!GG

LGKMENAVGCTLSELVSKKV?.??NW??G..I.CFPKWEHLKKKSS K.CLIMVL?KKP?IMSIGGIEFPN

\WGS VSE_7ΗDVR..WEK?CF . ^QSPSGK. IFSG?TDEMWRGM!G?LGAVEEISIHSCNEIRYLWE

SEAEASKV /1N!_KKI_DLGECENLVSL

MHMCDSTTSVSFPTGGG^QKIKSLTITDCKKLSEEELGGRERTRVUNSKM^QMLΞSVDIRNWPNLXSISEL

SCFIHLNRLYISNCPS7ESFPDHELPNLTSLTDRRRGQRFSYERLRFDWPSF

R toug c .c*~- .

NRSYENRCPLLPVI...EK].LKV.IQNPLFHR.YDA1_AWCKNSIINANQNSS.EΞTI.IMV.IVLSPYTHFFQIPII

HTYKCSH!RFS1^MAEILGSAFFAVFFEKI_ASEΞALKRVACSKVIDKELEK1_WSS.INIKALL DASQKE1S

KEAVKEVL ALQHU^YDIDDI GDI^TKAIHRKFSEEYGATINKVRKLIPSCFSSLSSTKMRNKIHNITS

KLQELL_EΞRNNLGLCEIGESRKlJ NRKSE_TS? PSSiVGRTDDKEΞAI_LLi

DKTTLGRLLYD?MQVKDHFEL AWVCVSDEFD!FGISi iFΕS!EGGNQEFKDL_NL QVALKEK!SKKRF^

W D\/WSESYTDWElLERPFι_AGAPGSKVI!TmKl_^

VNSFOSHPILJ<PHGEGIVEKCDGI ³!_ALIALGRLJ__^^

LSASU<QLFAYCS1_FPKDWFNKEKLIUNVMAE^

LJ=WHDL_ ND .TSVAGDYR.R IEMKKEALEKYRHMSRCESYMWKRFEPFK^

GMIKSWTΓFYLSNKVI_DDI_I_HELPLLRVLSLSYLSIKEΞVPEIIGNI_KHLRYIJNILS

LQTL!LCGCCFITKFPNNΠ_KLRNIJ HI_DLSDTPG!_KK SSG!GEU<NUH^

H

[\L(X ( ^ C.C.

SRAT?!1QK?PKT?D?F????QKEVIDEAVKRWLID?QQLAYDT?D?LDD?ATE_AIHREL1RETGAS?S VRKLIPSCCTSFSQSNRMHARLDDIAAK?QELVEAKNNLGLSVITYEKPKIERDEA?LVDASGI!GRED

DKKKL QKLLGDTYESSSQNFNIVPIVGMGGVGKTTLA^

RVIYQS\/TGENKEFAD._JN.I_LQEALKEKLQNKU^^

KEQU QI SFSHEDP S!DSLQRl^QEDAI_SI SQHAFGVPNFDSHPTl_ PYGEQFVKKCGGLPLAL

?T?LRDRCPSS!CLTMLPRRK?L KPLKDG. iSNiW T?πYLM!LQ?KAI??ELT?EGGASTSMVRK

LiPSCCTSFSQSYRMHAKLDD!ATRLQELVEAK NLGLSVITYEKPKIERYEASLVDESGIFGR?DD?KK EKU-EDKDESGVKLQHLPIIGMGGVG?TIlARLU=DEKTVKDHFEU^vWCVSD vTGEKKEFEDI_Nl_LQEAU GKLQNKlJ=UVI_DDVWSESYGDWEKLVGPFl^

QLGFSHQDPLRCIDSLQRLSQDDALSLFAQHAFG?

[?L.b « £

l_ARL±YDE QEKDHFEU<AWVCVSDEFDi iSKIIFQS!GGGNQEFKDI_ LLQVAVKEKISKKRFLLVLD

D\ΛΛ SESYADWE!LΕRPFI_AGAAGSKIIMTTRKQS!_LTKLGYKQPYNLSVLSHDSALSLFCQ_IHALGEDNF DSHPTLKPHGEGIVEKCA

FSA?NK?K^QWLKSFF?HSRPVFFEK?ASEALKKIARFHRIDSELKKLKRSUQIRSVLNDASEKEISDEA VKEW1_WGLQHLSYDIDDU_DDLΛTE_TMHRELTTDI_EPPPACK1<DNPTCCTDFS1_SSK^

^QELVEEKDNLGI^VKGESPKHT RRL^QTSLVDASSIIGREGDKDA1_LHKLLEDEPSDRNFSIVPIVGMGG VG.CITLARL±YDEMQEKDHFEI_KAVWCV^^

F ?VLDD\ΛVSESYTEWEII_ARPFL_AGAPGSKIIMTTRKLSLITKLGYNQPYNL_SVLSHDNALSLFCQHA LGEDNFOSHPTU<P?GES1VEKCDGLP!_AUALGR1_L?TKTDEEEWK^

YNDL_3ASU<KlJ^rAYCSIJ^!<D FDKE i_LvvT^EGF Q AKSMR MHD NDU\TSVAGDFTSRMDIEMKKEFRKEAL?K?RHMS?VC?DYMV?KRF?P?TRS.

RLfe,! $

VKDHFEL_^WVCVSDEFNIUWSKVIYQSVTC DWEKLVGPFFSGSPGSMii^iπRKEQLPRKLGFPHQDPLQGLSHDDALSLFAQHAFGVP

RLC-, I

i_ΛRL YE_3v1QGKDHFEU<AWVCVSDEFDIFNISKIILQSlGGGNQEFTO L±QVAU<EKISKKRF Vl_D

DVWSESYTDWEiLERPFlΛGAPGSKII.TTRKLS!_l slKL^^

SHPTLXPHGEGIVEKCD

R L6) (

l_ARLWDE2v.QEKDHFEU AWVCVSDEFDiFNISKIIFQSIGGGNQEFKD i_LQVAVKEKILKKRFLLVLD

D VSESYADWEi?ERPFl ^GMGSKIIMTTOKQSLLTKLGYKQPYNLSVLSHDSALSLPCQHALGEGN

DSHPTLKPHGEGIVEKCAGLPI_ALST

EFGVGKTTl_ARLlYEEMQGKDHFEU<AWVCVSDEFDIF^!SKI!LQSiGGGNQEFTOUSlLJ_RVA

KRFU_VU DVWSESYTDWEI?ERPFl_AGAPGSKlirr KLSl_IΗKLGYNQPYNLSVLSHENALSU^^

ALGEDNR^SHPTI_KPHG?GIVEKCDG1_PL_ALS

TTNACACCAT AAATTCTCNA CCTGNGGGGA CAAAAACCTA AAAATGGTCC ATAATGCNCA AATCAGNAAG 1 GTTGANAAAG CTCTAAGTTT TTNACCTCCA NCTGATGCNC NNTCCTCNTA AAGTTCAMAT CCAAGCTTGC 41 CCTCCAACTC TANCNCCTTC AATGGCACCT CCTTCTCTTC AAAAGCACAC AAGAACACTT TCAAGCTC^A 11 CCACACTCAC ACAAGCTCTA GAAC AGGGT TAGGGCACAT TTAGGGTTTT GCTCTCTGGA AATGGTGTCT 81 AAAAGTGAGG CCATAATGTT CCTTATATAA GGCTCACTCC CACAATTAGG CTTTCAATCT GAACGTAHTA 51 CGCCCAGTGT ACACTATGGT ACGCCCAACG TACTCGGTAG TCTCCGCGTC AANAATACAC TCATGAGTAC 21 GCGCAACGTA CTTTCCCTTA CGCCCAGCGT ACTCAAAAGC CAAACATTCT TTTCAAGGAC TAATTTTGAC 491 AACTTGAGGA AAGAAAAGGA TCAAAGANAT ATACTTGAAT TCCGGGATGT TACAATGAAG TTGANACCTT 561 GGCTAAAAAA TTAAATTGGT TGTGGAAGCC GTTGGCTGAG CAAGCAACAA GGGTAAAATT CGTAATCTAC 631 AAATGGTGTT ATTTTCTATT TCTTCTTATT ATTTTACTTG ATTTACGGGT AGTTTTTTTT TCTTACAAAA 701 AATATTAAAG TTGATAAAGT ATAGCCACTA AAATTGACTT TTTCCAAAAC ATAATGTCAA ATGGTGCGTA 771 TATGTATCAT GTTGTATTAN ATAATGAATA TGATGATTJCT GTTCTATTTA ANCCGAAAAA ATTATCTAAT 841 GATTTTATAT TGGAAAACAA AGTTGTGATT TTTNGCATAA TATAATCAAA TCCNCTTTTG TNTGGGAGGT 911 GGATAAATGT GGTAAATTTA NAACAAGTGT TTTNACNITG AAGGGTOTGG AAAGGTTGAA AAAAGTTAAA 981 ATGATAAAAT GTTTACACAA ATGTTGTATC CGACTGAATA TNATGTTTAA GGATNATTGT ATTAAATTGT 1051 TGATATATAG TAAGCATAAA TATTTAGAAT TGTGACTTAA ATTTATAAGT TATNCNAACT GGATTGAAAC 1121 ATTTTTGATA TANATTAGGA ATGAAAATGA GCAACCCTAA CATACTTATC TTTGGTAGTT TGGTTATTAT 1191 ATTTTTATTA NAATATAGAA NCATCCCTTT ATTTTAAACC CATATTGTGG ACGGACTTGA ATAAATGGGA 1261 AAAATGTACC TTGCTATTTA GCACAAAAAA ATTATAAAAA TGTACATTGC TATTTAGCAC AAACAAAAAA 1331 AAAAAACTTA TCCTTTTTGC ATTAGGTCAC AAAGAAATAT AAAATGGGAA ATGTGTTGCT ATTTAATGCA 1401 CTAAAAGAAA CTATTTTGCC TTTATTAAAC CGGGTAAACC AATAGAAAAA TGGAAGTACA TTGTCATTTA 1471 GCATGAAAAA AAATAACTTT CCATTTTTTG CATCCGGTCA CAATAATAGA AAAATGAAAG TACGTTGCTA 1541 TTTAGCGAAA CTAACTTCCT TTTTTCTTTT TGGCATCGTA TCATAAAATA TAGACTAAAA TACGTTAGTT 1611 TTACATTTTT AATACATTGA AATGTCTAAT CCACATGTTA TTCTATAAAA AGGGAAATGT AATTTACTTA 1681 TTCTTTGATT CTTTGGCTTC TTTTTAGTAC CCAAAACATC CCTCTATCCA TCTATTCCAA CTAAAATAAT 1751 GAAAAC ATA TTCCTTCCAT TGTAGGGATG TTATAAATTT TGTAATTGTT TTTATGCAAA AAAGTGTTTT 1821 TTGTTAACTA GATTAACGAG ATTCATTTTT CAGCATTTTA GGAGAAGTTC ATCCATCTTT TGGATATGAA 1891 GTGCAAGCCA AGTTCTTTAA CATGGAATAT GAGGTCCCTA TATGCTCAAA AAATAGCAAA TGAGAAATTT 1961 TTTAAATTGG ATCCCCATAA AAGAAAATTT GTTAATGGTT GTTTTAATAT TGGTCAATGT GTCCACCGGA 2031 TGAGCATAAT ACTAGTTTAT AAGGGGTAAA GGTGGGTTTG GTGGGCCCAT TTATCTTTAT TATTTCTAAA 2101 AGTCAGAATT AAGTAAAAAA AATTATAAGA TAAATACCAT AAGGATAAAA AATCATTTTA TTTGGACCAA 2171 AGACCAAAGT TGTTAAGGGG CTGTTTGTTT TTTTTGTGAA GAGCTGTGCA ACCACTTTTG TCTGCGCCGC 2241 ACAGACAACG TGCAGACATA TGCCCTCGCA GAGTGTTTGT TTTTTGAAAG TGCGCAGACC AAAAAAACGT 2311 CTGCGCGAGG TCATCCTGGC GCATATATGT GTCACTGTCT TCAAAGGTCT TCAGACCTCA TTTTAACCAA 2381 AAAAAAAAAA GACCACCGGT TTITTTTTTT TTTTTNTTCT TTCTCTTGTA GCTGAAAATG CATTTTTAAT 2451 CTTTATGACA TGAAATTAAG TTTGAAAAAT TAATTTATTT CAACAGCTGT AGACGTTAAA AACAAACAGT 2521 CTTCTTGTTG CAGACTGTGG ACATTTGGTC CACCTCTTCT ACCGCAGAGA CTTGCAGATG TGGTCCGCAG 2591 ACTGCAGACA TTTTGGCTTC AAATAAACAA ACATCACCTA ATTTGACTAC ACCACACGGA CCTCCAATGT 2661 AACAAAAAAA AGGTTGAAAC AAAGTTGCCT ATTTCTCCAT ATCCAGGGGC CATTTATGTA AGAGTTATCT 2731 AAATTTTAGT TCGGTAGATC AGTTCTCACA TTTTAACCGG GTAAAGTGTA TGTGTGTACG CGCGCACCTG 2801 AAAGGTTTGA ANGTAACTTC CAAACTGAAN CAANAATCGA TATGAAGTAT CAAGTTAGAG GTTCAATTGG 2871 TGAAGGAATC AGCTGGAGGT TGGGGAATCG AGCTTCCACT ATTAAGGTAA AATCCATAAC CCTAAATGTT 2941 GGTACGCTCA TATATCAAAT TGCGTGTTTT GTTGAATGAA AAAAGCATGC TCAAAAAACC AGTGTAAGGC 3011 ACGGTATATG ACATATTTAT AGTTACTGAT AACAAATTAT GATAATTTTG GGTTTACGTA AGTTAGGATT 3081 CGTACTTCAA CCAAATGTAA TAGTTTTTGT GAGTCTATCT ATGTATTTGG GGAATCACAT TAGCAACGGG 3151 ATTGTACTAG TAATTCGAAA AAGTCTTTTA AATAATTTTT CTGTTTATAA TTTATGAATA GTTTTAGCGA 3221 CATCTAATAT TAAATAGAAT GTATCTGATA TTGAATTAAT GTCCTTAATG TGAACATAGA CCTTTTCCAT 3291 TTACTAATGC CTAATTATTA GTTTCTAATC AATAAATTTT AATTTCTGTT TTATGCTTCT AAGACAATAA 3361 AAATCCATGA TTTACCTTTA AATATTAACA AAAATGACCA TAAATAAATA AAAAATTAGG ATACCAAACC 3431 CCCCCGCCAT GCCCAATGTC TAAATATTCT TGATGCTTTT GCTTTTCCCT CTTTTCCTTG TTAGTCTATT 3501 ATTCTGGAGA GTTTGAGAGA GTTTCATACA AGAAAATTTC AAGAAGAAAG CAAAGGTCCA GGTATTCTCT 3571 TTTCTTAATT ATGTATTAAC TTACAAGCAT TTTTTACACG ATCCATGGTT TTTTGTGTAT GTTTTTCAAA 3641 TTGAAACTAG ATTGGGACTT TTGCCCTTGA TGATTCATAA GATATTGCAT GGAGTTGAGA TTGTGTAAGA 3711 AAAGTGGTGA ATAGAAAGAG CAAGTGAATC CAGATATAGT ATTGGTAATA TATGATGATG AGATAGAGAT 3781 ATGTTAAAAC TGGCTAGAAA ATTGTTTTAA TTTGAAATTT AGGTTGTTGA ATTTGAAAGA TACCAAGCTA 3851 ATAACTAATT AGTTATGCTA AATAGTTATA AAGAACAACA AACTCGTAGT TTTTTTTTCA TGATTTTCAA 3921 CCTCTTCGTA CCAAACTAAA TTATAACAAA ATTGAATATC ATTCTCTGCA ATCAATTTTA ACTTTTGTTA 3991 TTATCATCAT GTCTAAAATT GCCACAAGTT TATTTTCATA GTCATATTGG ATTATGAAAG GACTATTTTT 4061 ACCAAT ACA TCTTTACTTT ATGGCCAAAG CTAATACAAT CCGACTAAAC TAAAGGATTC TAGGATGCAT

4131 ATAGTTTGCT CCCCGATTAT AGATTTCTAT CTAATTTGTC TATTGTACTA ATTTAGGTGC CACCACAAGT 4201 AAATTCCTGA AATGGATGTC GTTAATGCCA TTCTTAAACC AGTTGTCGAG ACTCTCATGG TACCCGTTAA 4271 GAAACACATA GGGTACCTCA TTTCCTGCAG GCAATATATG AGGGAAATGG GTATCAAAAT GAGGGGATTG 4341 AATGCTACAA GACTTGGTGT CGAAGAGCAC GTGAACCGGA ACATAAGCAA CCAGCTTGAG GTTCCAGCCC 4411 AAGTCAGGGG TTGGTTTGAA GAAGTAGGAA AGATCAATGC AAAAGTGGAA AATTTCCCTA GCGATGTTGG 4481 CAG. 1 1TTC AATCTTAAGG TTAGACACGG GGTCGGAAAG AGAGCCTCCA AGATAATTGA GGACATCGAC 4551 AGTGTCATGA GAGAACACTC TATCATCATT TGGAATGATC ATTCCATTCC TTTAGGAAGA ATTGATTCCA 4621 CGAAAGCATC CACCTCAATA CCATCAACCG ATCATCATGA TGAGTTCCAG TCAAGAGAGC AAACTTTCAC 4691 AGAAGCACTA AACGCACTCG ATCCTAACCA CAAATCCCAC ATGATAGCCT TATGGGGAAT GGGCGGAGTG 4761 GGGAAGACGA CAATGATGCA TCGGCTCAAA AAGGTTGTGA AAGAAAAGAA AATGTTTAAT TTTATAATTG 4831 AGGCGGTTGT AGGGGAAAAA ACAGACCCCA TTGCTATTCA ATCAGCTGTA GCAGATTACC TAGGTATAGA 4901 GCTCAATGAA AAAACTAAAC CAGCAAGAAC TGAGAAGCTT CGGAAATGGT TTGTGGACAA TTCTGGTGGT 4971 AAGAAGATCC TAGTCATACT CGACGATGTA TGGCAGTTTG TGGATCTGAA TGATATTGGT TTAAGTCCTT 5041 TACCAAATCA AGGTGTCGAC TTCAAGGTGT TGTTGACATC ACGAGACAAA GATGTTTGCA CTGAGATGGG 5111 AGCTGAAGTT AATTCAACTT TTAATGTGAA AATGTTAATA GAAACAGAAG CACAAAGTTT ATTCCACCAA 5181 TTTATAGAAA TTTCGGATGA TGΓTGATCCT GAGCTCCATA ATATAGGAGT GAATATTGTA AGGAAGTGTG 5251 GGGGTCTACC CATTGCCATA AAAACCATGG CGTGTACTCT TAGAGGAAAA AGCAAGGATG CATGGAAGAA 5321 TGCACTTCTT CGTTTAGAGC ACTATGACAT TGAAAATATT GTTAATGGAG TTTTTAAAAT GAGTTACGAC 5391 AATCT CAAG ATGAGGAGAC TAAATCCACC TTTTTGCTTT GTGGAATGTA TCCCGAARAC TTTGATATTC 5461 TTACCGAGGA GTTGGTGAGG TATGGATGGG GGTTGAAATT ATTTAAAAAA NTGTATACTA TAGGAGAAGC 5531 AAGAACCAGG CTCAACACAT GCATTGAGCG GCTCATTCAT ACAAATTTGT TGATGGAAGT TGATGATGTT 5601 AGGTGCATCA AGATGCATGA TCTTGITCGT GCTTTTGTTT TGGATATGTA TTCTAAAGTC GAGCATGCTT 5671 CCATTGTCAA CCATAGTAAT ACACTAGAGT GGCATGCAGA TAATATGCAC GACTCTTGTA AAAGACTTTC 5741 ATTAACATGC AAGGGTATGT CTAAGTTTCC TACAGACCTG AAGTTTCCAA ACCTCTCCAT TTTGAAACTT 5811 ATGCATGAAG ATATATCATT GAGGTTTCCC AAAAACTTTT ATGAAGAAAT GGAGAAGCTT GAGGTTATAT 5881 CCTATGATAA AATGAAATAT CCATTGCTTC CCTCATCACC TCAATGTTCC GTCAACCTTC GCGTGTTTCA 5951 TCTACATAAA TGCTCGTTAG TGATGTTTGA CTGCTCTTGT ATTGGAAATC TGTCGAATCT AGAAGTGCTT 6021 AGCTTTGCTG ATTCTGCCAT TGACCGGTTG CCTTCCACAA TCGGAAAGTT GAAGAAGCTA AGGCTACTG3 6091 ATTTGACGAA TTGTTATGGT GTTCGTATAG ATAATGGTGT CTTAAAAAAA TTGGTCAAAC TGGAGGAGCT 6161 CTATATGACA GTGGTTGATC GAGGTCGAAA GGCGATTAGC CTCACAGATG ATAACTGCAA GGAGATGGCA 6231 GAGCGTTCAA AAGATATTTA TGCATTAGAA CTTGAGTTCT TTGAAAACGA TGCTCAACCA AAGAATATGT 6301 CATTTGAGAA GCTACAACGA TTCCAGATCT CAGTGGGGCG CTATTTATAT GGAGATTCCA TAAAGAGTAG 6371 GCACTCGTAT GAAAACACAT TGAAGTTGGT TCTTGAAAAA GGTGAATTAT TGGAAGCTCG AATGAACGAG 6441 TTGT AAGA AAACAGAGGT GTTATGTTTA AGTGTGGGAG ATATGAATGA TCTTGAAGAT ATTGAGGTTA 6511 AGTCATCCTC ACAACTTCTT CAATC1TC1T CGTTCAACAA TTTAAGAGTC CTTGTCGTTT CAAAGTGTGC 6581 AGAGTTGAAA CALTTCTTCA CACCTGGTGT TGCAAACACT TTAAAAAAGC TTGAGCATCT TGAAGTTTAC 6651 AAATGTGATA ATATGGAAGA ACTCATACGT AGCAGGGGTA GTGAAGAAGA GACGATTACA TTCCCCAAGC 6721 TGAAGTTTTT ATCTTTGTGT GGGCTACCAA AGCTATCGGG TTTGTGCGAT AATGTCAAAA TAATTGAGCT 6791 ACCACAACTC ATGGAGTTGG AACTTGACGA CATTCCAGGT TTCACAAGCA TATATCCCAT GAAAAAGTTT 6861 GAAACATTTA GTTTGTTGAA GGAAGAGGTA AATATAAATT TTTAATGCTA ATACATTACA AAGGATCTTT 6931 TCAGTTAAAT CTTTCAAAAT ATATTGTAAT TTGATTGTAT GGGGTATTAT TGTTGGATGG GACTATTAAT 7001 AAATGATTAT CTTGCAGGTT CTGATTCCTA AGTTAGAGAA ACTGCATGTT AGTAGTATGT GGAATCTGAA 7071 GGAGATATGG CCTTGCGAAT TTAATATGAG TGAGGAAGTT AAGTTCAGAG AGATTAAAGT GAGTAACTGT 7141 GATAAGCTTG TGAATTTGTT TCCGCACAAG CCCATATCTC TGCTGCATCA TCTTGAAGAG CTTAAAGTCA 7211 AGAATTGTGG TTCCATTGAA TCGTTATTCA ACATCCATTT GGATTGTGTT GGTGCAACTG GAGATGAATA 7281 CAACAACAGT GGTGTAAGAA TTATTAAAGT GATCAGTTGT GATAAGCTTG TGAATCTCTT TCCACACAAT 7351 CCCAT3TCTA TACTGCATCA TCTTGAAGAG CTTGAAGTCG AGAATTGTGG TTCCATTGAA TCGTTATTCA 7421 ACATTGACTT GGATTGTGCT GGTGCAATTG GGCAAGAAGA CAACAGCATC AGCTTAAGAA ACATCAAAGT 7491 GGAGAATTTA GGGAAGCTAA GANAGGTGTG GAGGATAAAA GGTGGAGATA ACTCTCGTCC CCTTGTTCAT 7561 GGCTTTCAAT CTGTTGAAAG CATAAGGGTT ACNAAATGTN AGAAGTTTAG AAATGTATTC ACACCTACCA 7631 CCACAAATTT TAATCTGGGG GCACTTTTGG AGATTTCAAT AGATGACTGC GGAGAAAACA GGGGAAATGA 7701 CGAATCGGAA GAGAGTAGCC ATGAGCAAGA GCAGGTAAGG ATTTCAATTT CACTGTCTTA ATTAATGATT 7771 AAGCTCCTGC TTTTTGAATA AAAAAGGGAC AAACCATTTC ATGACTTAAT GTAGCAATAC AAGTCATGTA 7841 TAAGAGTGAC CAACTCT TT TTATTTATAA AATGACTACA AAATATTTTT TTTCATTAGA GATCATGTAT 7911 AAATGTGACT AATTTTTCAT CACCTAACTT TAGTTGATAA ATCTTTATAA ATGTCACTAG TTACTTTTCA 7981 GTAAAATAAC AAATTTAATA AATTATCAAC AAAAAGCATC AACTAAAAAA ATCCCACAAC CCGTAATAAT 8051 TTAAAATAAA AGGATTTAAC ATCTAATACG AACAATTTTT TTTCTAAACA TGATTTGGAC CAAATATCAC 8121 CAGCAACTCA AσTTTGGAAT CGATTCAGCT TAAAACTTGA CCAGCATAAT TAGATAGATG AGAGTTGAAG B191 CTAAAGTGCC TATATAAGTT CGTTTCATCT TTTTTCTTGA TCTTGATAGC AAGTTGAATG ATTTTCTTCT ^ ^ l A -^Λ

8261 TCAAAATTGA TAAAAATCTA CATTATAAAG AGACTAGCTT GAAAAAAAAT GGTCTAGGTG GGTCTTGGGT 8331 TCTGGTAGAT GAAGATGGAA GGGGAGAGTA TGATTTCAAA GACACAACAC ATCCTTCATT TTATTTATTT 8401 ATTATTATTA TTATTTTTTG ATATCTTGCT CATATTTGTT ACAGATATGT GAGGTCTATT AATCTTTTTΓA 8471 AATATATAAA AAAATAAATA ACATAAATGA GAAAATTAAA TAAAGAATAA ATTAATAAGG GCACAATAGT B541 CTTTTTAGGT AAGACAAGGA CCAAACACGC AACAAAAATA AACAGTAGGG ACCATCCGAT TTAAAAAAAA 8611 TAATTAGGGA CCAAAAACAT AAATTCCCCC AAACCATAGG GACCATTCAT GTAATTTACT CTTACTTTTC B681 GTTTTGTTCA TATTTGGGTA ACTATTTTTT TTGTACACAT CTAGGTAACG AACTTGTTGA AGTGTTCCCA 8751 TTTAGGATGT GACCTACTAC AACCGATCAT AATAGTCATA TGTGAACACT TCCAACAACT TTATTACTTA 8821 GGTGTGTACA AAAAAACAAT AGTTACCATG ATGTGAACAT ACTGAAAAAT TAATTACCTT AGCAAGTTAT 8891 TTTCCCATTT AGGTTGTATG GAAACAGTTC CGTGAGACCG TGACTTGGAT GGTAGATAAA TTTAGTAAAC 8961 TTAACCCTTC AATTAACCTA CCTTTTTCTT ATTAACTCAA TTTCAACCTA AATTCTGATT CTTGTTTGAA 9031 AGTAAGTTGC ATCTTTATTT TTGTATTATC TTGTTGCATA GGATCCTTAG CATCTTTTAA TAATTTATTT 9101 GAAGGTGAAA GATCCAACTA TTTTTAATCT GTTGGCATTT TCCATCATTT GCAACTGTTT CTTGAAAAAA 9171 AAATACCTAA AATCAAAATA ACCATTTTCA AATCCAAAAT TATAAGAGAG AATTGTAAAT GGACATGGAA 9241 TCATAAATCA TTAACACAGT TCAGTAAACA AGTTGCTAAT TACATTTCTT GCTGTGCAGA TTGAAATTCT 9311 ATCAGAGAAA GAGACATTAC AAGAAGCCAC TGACAGTATT TCTAATGTTG TATTCCCATC CTGTCTCATG 9381 C_ACΓCT TTC ATAACCTCCA GAAACTTATA TGAACAGAG TTAAAGGAGT GGAGGTGGTG TTTGAGATAG 9451 AGAGTGAGAG TCCAACAAGT AGAGAATTGG TAACAACTCA CCATAACCAA CAACAACCTA TTATACTTCC 9521 CAACCT CAG GAATTGATTC TATGGAATAT GGACAACATG AGTCATGTGT GGAAGTGCAG CAACTGGAAT 9591 AAATTCTTCA CTCTTCCAAA ACAACAATCA GAATCCCCAT TCCACAACCT CACAACCATA AAAATTATGT 9661 ATTGCAAAAG CATTAAGTAC TTGTTTTCGC CTCTCATGGC AGAACTTCTT TCCAACCTAA AGCATATCAA 9731 GATAAGAGAG TGTGATGGTA TTGGAGAAGT TGTTTCAAAC AGAGATGATG AGGATGAAGA AATGACTACA 9801 TTTACA CTA CCCACACAAC CACCACTTTG TTCCCTAGTC TTGATTCTCT CACTCTAAGT TTCCTGGAGA 9871 ATCTGAAGTG TATTGGTGGA GGTGGTGCCA AGGATGAAGG GAGCAATGAA ATATCTTTCA ATAATACCAC 9941 TGCAACTACT GCTGTTCTTG ATCAATTTGA GGTATGCTTT GTACATATTC AATTATTTAT TTAATTTCCT 10011 TTTTTATTTG CAATATTCTA TAAATAATAC ATTTTATACC CACTATACTA AGATAATAAT TACCTAGAGG 10081 GATGGATGCT ATGACACAGC TGCTACACTT CAGAAACTCT AGTAAGGGCA GTTATGGAAG TTCAATAAAA 10151 TGATAATGGC ATCTTTTGAT GGGTAATATA GGCAATTTAA GTITTATTTC TGTTAAAGCA GTATTTAGCA 10221 AGTAC 3GCC AGTAGGAGAG GAGAATATCA CCTTTTGTGA AAATCTGGTC ATTGTACCCA GAATTTAGTT 10291 AAATGTAACA TTTTAGATAT CAGGGGTCAT CAGGTGACAG ATATTGTAGA ATAGAACAAT ATATAATATC 10361 ACCCAAAACT ATTTTTTCTA AGGTTATTCT GTTAAATATG TGCTTTCTTG TTTTCATT-GA ATTNGCATTC 10431 GTATA TTTA GGTGTTAAAG TGA'l'lTl'NTC TTCAATAAAT CCCGAAATTA ATTAAAAAAA AAAAAACAAA 10501 AGTACA TTT TGATGTGGAG AGCACTGGTA TCACTTAGTA TATAAAAAGC TTGATTTTGA ATTAACTTTC 10571 TTATACAAAA GTTGTGTATA TAGTTTAATT AGTTTTACAT CATTTTTCCA TGTGGTGTTG CAGTTGTCTG 106 1 AAGCASGTGG TCTΓTTCTTGG AGCTTATGCC AATACGCTAG AGAGATGAGA TAGAATTCT GCAATGCATT 10711 GTCAAGTGTA ATTCCATGTT ATGCAGCAGG ACAAATGCAA AAGCTGAAGG AGAGGACAGC GATTCTCGTA 107B1 CGAACGGTTA CGATTCGACT GGCCGTCGTT TTACA

MDWNAlU PVVE_T VPVKKHIGYLlSCRQYMRE GIK RGL ATRLGVEEHVNRNISNQLEVPAQV

RGWFEΞVGKINAKVENFPSDVGSCF LXVRHGVGKRASKIIEDIDSVMREHSIIIWNDHSIPLGRIDSTK

ASTS!PSTDHHDEFQSREQTFTEAl_NA PNHKSHMIALWGMGGVGKTT HRLKKWKEKK^

ILTEELVRYGWG1_KL ^:KK?YT!G__ARTRI_^C1ERL!HTN1_LME_VDDVRCI1<M ASIVNHSNΓΓ__EWHADNMHDSCKRLSLTCKGMSKFPTDI_KFPNI_SII_KIJ IHEΏ VISYDKML<YPLJJ³SSPQCSVNLRVFH KCSLVMFDCSCIGNLSNLEVLSFADSAIDRLPSTIGKL_KKLJ^:. UJ:LTNCYGVR!DNGVI_KKLVK1_EELY^ TWDRGRKAISLTDDNCKEMAERSKDIYALELEFFENDAQPK

NMSFΕKLQRFQlSVGRYLYGDSlKSRHSYE.mKLVI_EKGEl___^

VKSSSQLJLQSSSFNN VLWSKCAEU HFFΠ^{^}GVA^MJ<KL^HL __WKCDNMEEURSRGSEEET^

KI-KFLSLCGLPKLSGLCDNVKHELPQUVIEI-E DIPGFTSLYPM

W JLKEIWPCEFN SEEVKFREI!WSNCDKLVNI_FPHKP!SL_L_HHLΕEL_KVK^

GDEEYNNSGVRIIKVISCDKLVNLFPHNPMSI HL_EEL≡VENCGSLESLFNIDLDCAGAIG^QEDNSLSLJ.NI

KVENLGKLR?\ΛΛ/RIKGGDNSRPLVHGF^QSVESIRVTKC?KFRNVFTPTTTΗFNLGAU_EISIDDCGENR

GNDESEESSHE^QE^QIEILSEKETL^QEATDSISNWFPSCUVLHSFHNL^QKLIL RVKGVEΞWFEIESESPTS

REL\/TΓHHNQQQPIILPNLQELILWNMDN SHVWKCSNWNKFFTI_PKQQSESPFΉNLTΌ

LFSPUVLAEL SNU<HIKIRECDGIGEWSNRDDEDEEMTRFTST^^

GAKDEGSNELSFNIMTTATTAVLDQFEVCFVHIQLFL.

Q C =-1 ^■ B

TTTTTTT TTTCCCAAT SA TCCATTTATa O

1 AGT A TGCGA£T -TTAT& N TTCTGAAATA ATTTTAT .C^*AA2 AACGC3AGGAA 1 ACAATGTAGA ATAATACTGG TATAATTAAT TATATAAAGT TATTAGGCTG AAATCTTGAG GCTACTATAA

141 TTTAATTATC ATAATTTGAA AATCATCAAA TTGTATTCCA TGTATATTTA TGTTATCAGA TAATTAAT^A 11 TATGTGAGCC ACACAAATCC ACATCATCAG ACACCCCACC TTATTGTCGG CTACCTCACC ACTTGCATGA 81 TCCCGACATC TTCCCAACCC CACCGACGAC TTGGGGTCTC CTTAATATAT CAATTATTTT CTGTAAGTAT 51 TTATTTGTGT AAATGTGTAA TGTCATTTTA CCTTTTTTCT AATATATACA GAAACATAAA TTTTAAATGA 421 AATTCAACTG CXΪTTTCATTC TTGCATTAAA AAAAAAGACT GTACTGTTGT CAATATTTTA CTTATAACCT 491 GATTAAΪTAA TTAAAGCGTA ATTGCATAAT TTGCATTAGG TTGTAATTTT GTGTTTTATA GGGAGGGTGA 561 GGGTCACCGG GAATCAAAGC ACTTATGTAA AAGCAGGGGA AATACAAAAA ATTTACTCGA AACAAATTTT 631 ATTCAATTTA AGTGAGATAA TAATGTTCTG ATTAGATTAT GAGAACTAGG AGATTTAAGT GATATATCCC 701 ATTTAAAAGA AATTGCATTA TTAATTTTGG ATCTCTTGAT GATGACAAAA TTAACTCGTG ACAGGTTATA 771 TATCATATAC AAAATGAGTG GCTATGCTTT CGCTTTCCAA AAAGCAATTA TAGTTATACT ACACCTACAA 841 ATTTTAAAAG GGGTTAAACA TATCAAAATA CTTGATAAGT AATTATATAA ATATGCATTT AACCCTCTAA 911 AGAAAATGCT ACTAAGCTTG GACCATCTCA GAATTACAAT CATACCCTTC CCCTCAAAAA AGATTCGTAT 981 ATATCATGTC ATTTGGCATT CATTTTTTT TCACAATTCA TAGTTCTATT CTCAAAAAAT TCGAGTTCTC 1051 GTATTT3TAA GGAAGATCAG AAGAGACTGT TCACACAGGT ACTCTCTTTT ATTTATTGAT TCACATTCAT 1121 ATATGT ATT GTTTTCTTGC TTAATGGTTT CGTCAGTCTA ACTGCGCTTG CTGATTTAAA TTTCTTCACT 1191 TTCTTCCACG GATTTTTTAA ATATTAGTTT TGTGAATGAA CAATTGGTGA AGGAAAGAAA CATGGGAGTC 1261 TTTTCTAAAG TAAACCTAGA TACTTAGGTT ATAAGGGTAT ATGCTAAAAT GAACTATGCC CATTCACCTT 1331 TGCCTTTTCT TTTACTTTTT AGTTTTTAGA ATCCAAGTTT TCATATGTAT CTCGATGTGT GAGAAGAATA 1401 GGCATTAGAA AGGTAAAGGA CGTACATAAA ATTGATTAAT TAGTGAATGT TCTTTGATAT CATTATTTTT 1471 ACTCTCATAA AAAGCATATA GATCAAACAC AAATTGCTAC TTGTTAGTGT AACAACTTCG ACTTAATAAT 1541 GTTAATAATC AAGATTCTCT TGATTTCAAC TATTTTCTAA CCGAACAAGC TCACTAAAAA CTCATATTGC 1611 TTTGAGTCTG AGTGGTTTAT ATTTGGGGTT TTACATTTAA TTTTTTGTGC ATGAATGTGA AAATAGACTG 1681 CTTATTGATT CTTTGTGTTT CATTGAGTTG ATTTTCATTA TTACTACCTT ACAAATTGCT CAGTGATAGA 1751 TTTCCATTAA TTTGCTAATT CGGTTGCTTC TAAATATGTA GGAGCTACTA AAAGCAAAAA TATCGAGCAA 1821 TGTCGGACCC AACGGGGATT GCTGGTGCCA TTATTAACCC AATTGCTCAG ACGGCCTTGG TTCCCGTTAC 1891 GGACCATGTA GGCTACATGA TTTCCTGCAG AAAATATGTG AGGGTCATGC AGATGAAAAT GACAGAGTTG

1961 AATACCTCAA GAATCAGTGT AGAGGAACAC ATTAGCCGGA ACACAAGAAA TCATCTTCAG TTCCATCTCA 2031 AACTAAGGAA TGGTTGGACC AAGTAGAAGG GATCAGAGCA AATGTGGAAA ACTTTCCGAT TGATGTCATC 2101 ACTTGTTGTA GTCTCAGGAT CAGGCACAAG CTTGGACAGA AAGCNTTCAA GATAACTGAG CAGATTGAAA 2171 GTCTAACGAG ACAACTCTCC CTGATCAGTT GGACTGATGA TCCAGTTCYT CTAGGAAGAG TTGGTTCCAT 2241 GAATGCATCC ACCTCTGCAT CATTAAGTGA TGATTTCCCA TCAAGAGAGA AAACTTTTAC ACAAGCACTA 2311 ATAGCACTCG AACCCAACCA AAAATTCCAC ATGGTAGCCT TGTGTGGGAT GGGTGGAGTG GGGAAGACTA 2381 GAATGATGCA AAGGCTGAAG AAGGCTGMTG AAGAAAAGAA ATTGTTTAAT TATATTGTTG GGGCAGTTAT 2451 AKGGGAAAAG ACGGACCCCT TTGCCATTCA AGAAGCTATA GCAGATTACC TCGGTATACA ACTCAATGAA 2521 AAAACTAAGC CAGCAAGAGC TGATAAGCTT CGTGAATGGT TCAAAAAGAA TTCAGATGGA GGTAAGACTA 2591 AGTTCCTCAT AGTACTTGAC GATGTTTGGC AATTAGTTGA TCTTGAAGAT ATTGGGTTAA GTCCTTTTCC 2661 AAATCAAGGT GTCGACTTCA AGGTCTTGTT GACATCACGA GACTCACAAG TTTGCACTAT GATGGGGGTT 2731 GAAGC AATT CAATTATTAA CGTGGGCCTT CTAACTGAAG CAGAAGCTCA AAGTCTGTTC CAACAATTTG 2801 TAGAAACTTC TGAGCCCGAG CTCCAGAAGA TAGGAGAGGA TATCGTAAGG AAGTGTTGCG GTCTACCTAT 2871 TGCCA AAAA ACCATGGCAT GTWCTC_TAG AAATAAAAGA AAGGATGCAT GGAAGGATGC A TTTCGCGC 2941 ATAGAGCACT ATGACATTCA CAATGTTGCG CCCAAAGTCT TTGAAACGAG CTACCACAAT CTCCAAGAAG 3011 AGGAGACTAA ATCCACTTTT TTAATGTGTG GTTTGTTTCC CGAAGACTTC GATATTCCTA CTGAGGAGTT 3081 GATGAGGTAT GGATGGGGCT TGAAGCTATT TGATAGAGTT TATACGATTA GAGAAGCAAG AACCAGGCTC 3151 AACACCTGCA TTGAGCGACT GGTGCAGACA AATTTGTTAA TTGAAAGTGA TGATGTTGGG TGTGTCAAGA 3221 TGCATGATCT GGTCCGTGCT TTTGTTTTGG GTATGTTTTC TGAAGTCGAG CATGCTTCTA TTGTCAACCA 3291 TGGTAATATG CCTGGGTGGC CTGATGAAAA TGATATGATC GTGCACTCTT GCAAAAGAAT TTCATTAACA 3361 TGCAAGGGTA TGATTGAGAT TCCAGTAGAC CTCAAGTTTC CTAAACTAAC GATTTTGAAA CTTATGCATG 3431 GAGATAAGTC GCTAAGGTTT CCTCAAGACT TTTATGAAGG AATGGAAAAG CTCCATGTTA TATCATACGA 3501 TAAAATGAAG TACCCATTGC TTCCTTTGGC ACCTCGATGC TCCACCAACA TTCGGGTGCT TCATCTCACT 3571 GAATGTTCAT TAAAGATGTT TGATTGCTCT TCTATCGGAA ATCTATCGAA TCTGGAAGTG CTGAGCTTTG 3641 CAAAT TCA CATTGAATGG TTACCTTCCA CAGTCAGAAA TTTAAAGAAG CTAAGGTTAC TTGATCTGAG 3711 ATTTTGTGAT GGTCTCCGTA TAGAACAGGG TGTCTTGAAA AGTTTTGTCA AACTTGAAGA ATTTTATATT 3781 GGAGAToCAT CTGGGTTTAT AGATGATAAC TGCAATGAGA TGGCAGAGCG TTCTTACAAC CITTCTGCAT 3851 TAGAATTCGC GTTCTTTAAT AACAAGGCTG AAGTGAAAAA TATGTCATTT GAGAATCTTG AACGATTCAA 3921 GATCT AGTG GGATGCTCTT TTGATGAAAA TATCAATATG AGTAGCCACT CATACGAAAA CATGTTGCAA 3991 TTGGTGACCA ACAAAGGTGA TGTATTAGAC TCTAAACTTA ATGGGTTATT TTTGAAAACA GAGGTGCTTT 4061 TTTTAAGTGT GCATGGCATG AATGATCTTG AAGATGTTGA GGTGAAGTCG ACACATCCTA CTCAGTCCTC WO 98/30083 _,_g PCT/US98/00615

^ Z ^ ( O^ '

4131 TTCATTCTGC AATTTAAAAG TTCTTATTAT TTCAAAGTGT GTAGAGTTGA GATACCTTTT CAAACTCAAT 4201 CTTGCAAACA CTTTGTCAAG ACTTGAGCAT CTAGAAGTTT GTGAATGTGA GAATATGGAA GAACTCATAC 4271 ATACTGGAAT TGGGGGTTGT GGAGAAGAGA CAATTACTTT CCCTAAGCTG AAGTTTTTAT CTTTGAGTCA 4341 ACTACCGAAG TTATCAAGTT TGTGCCATAA TGTCAACATA ATTGGGCTAC CACATCTCGT AGACTTGATA 4411 CTTAAGGGCA TTCCAGGTTT CACAGTCATT TATCCGCAGA ACAAGTTGCG AACATCTAGT TTGTTGAAGG 4481 AAGGGGTAGA TATATGTTCT TTATGTTAAT ACAATTTAAA TAATATTTTC AACCAAATTT TCATAATATA 4551 TCTGTAATTT GATTGTATGA TGTGTTATTG TTTATATGTG GCTATTAAGG GATGATTATT TTGCAGGTTG 4621 TGATTCCTAA GTTGGAGACA CTTCAAATTG ATGACATGGA GAACTTAGAA GAAATATGGC CTTGTGAACT 4691 TAGTGGAGGT GAGAAAGTTA AGTTGAGAGC GATTAAAGTG AGTAGCTGTG ATAAGCTTGT GAATCTATTT 4761 CCGCGCAATC CCATCTCTCT GTTGCATCAT CTTGAAGAGC TTACAGTCGA GAATTGCGGT TCCATTGAGT 4831 CGTTATTCAA CATTGACTTG GATTGTGTCG GTGCAATTGG AGAAGAAGAC AACAAGAGCC TCTTAAGAAG 4901 CATCAACGTG GAGAATTTAG GGAAGCTAAG AGAGGTGTGG AGGATAAAAG GTGCAGATAA CTCTGATCTC 4971 ATCAACGGTT TTCAAGCTGT TGAAAGCATA AAGATTGAAA AATGTAAGAG GTTTAGAAAT ATATTCACAC 5041 CTATCACCGC (_AATTTTTAT CTGGAGGCAC TTTTGGAGAT TCAGATAGAA GGTTGCGGAG GAAATCACGA 5111 ATCAGAAGAG CAGGTAACGC TTTCAATTTC ACTTTCTTAA TTAATTAAGG ACTAAGCTCC TGTTTTTTGA 5181 ATAATAAAGA GGTGGGATGA CTAAACTTGG GCATCACAAT TGCAACAAAA TGTTACAAAC CATGAAACGT 5251 TCAAACCATT TCTTGAATTA AGGTTTCAAT ACAAGTCATT TAAAAATATG GCTTAAATTT TTTTTATATT 5321 TATGTATCAA CATGATTTTT CATTAGAGAT CATTATTATA ATAGTAAGTT TAAAGCAATT TAAATCAGAA 5391 CTAATTCTAA CTTTAGCTAA TAAATCGTTA TAAATGTAAA TAATTACTTT TTAGTGAAAT AAGCAACGGA 5461 TTTAATAAGT TAACAACTTA AATGTCATTT CCTAACAAAA AAAACTTTGG TTCAGAAAAA CCGCAATTCA 5531 AGATAACTAA AATAAAAATA TTTGACATTC ACTAAGAGCA TTTTTTTTTC TAAATATGAT TGCAAATGAA 5601 TAAAACTTAA ATTTATACAG AAAATTCTTT TATATATGTT ATACAAAATT TACAAATTGA AATTGGATAT 5671 GTTAATTAAC GGTTTATAAT TCTGGTATCA CAAAGGGATA TATAATAAAA TATTATTTTC TGTAGTCATT 5741 TGTAATTGTA CTAGTTTATA ACCCGTGGGA ACCATGAGTT CTAAAATTAG TTAAACTTTC ATAATAAAAA 5811 TTTATAATTA TTATTTATTT TAAATAAATT ATTAATTAAG AGATATATCA AAAATTTAAA GTTATTATAA 5881 CTTCAAATTT AACATATAAT TAGAAAATAT ATGATCATAA CTTCTGCACT CTCTTTGTAT AAATGCAGAG 5951 AAGCTATTAG TATATTTCTA ATCAAGTCCA AACCTAATGA AGCCTATATA ATTTTGTGAA AACTCAATTA 6021 GCATTAGGTT TTAAGAGTCA CCAAATTCAA AGAATAATCC AATGCTTTCA TTACCACTAT GGAGAAAATA 6091 TTTTCTTAGT TTAAATGAAA TGAAAACAAA CATTCAAACT AATTGTTGCT TATTAAACCA AAGACCCATT 6161 ACTTAGCCAA GAGTTTAACA AAAAAAAATT ACATTCATGT ATCATTATTC ATGACTAGAT ATATATGAAC 6231 ATGAAGGGAG TTTTTATAGA AAATATAATC ATAGATATTC AACATAACTT CAGGGAATTC CTCAAAATAA 6301 CCAAGTTATT CAAGAAATTA CATCCAAGTC AACCAAAGAG AAGTTTAGCC TAGCATGGCT AAACTCAAGA 6371 AACTAAAATA AGGATTAGAA GTACCAAACA TGTAGTAAGA ATCACAGTAA AAGATGATGT TGTTCTTGAT 6441 GTTC TCTAA GTTCTTCAAG TCTCCAGTTG CTCCTAATAA TGCAAAGGAG AGCCATTAAA TTCGTATGTA 6511 TTGATCCCTT CAAAAGCTGC ACCAACCTCC CTTAAATAAC ACTCAAAGCA AAAATGACAA AATGCCCTGA 6581 AGGACCCTAT GTGGGTGCCT TGCGCGGGTG GAGCTGCATA CGAAAGGTCT TTGGTCTTTG TGAGGGTGAT 6651 GTTGTGCGGG ATAGCTTGTC GCATGCTTCC GCGCGGTTCA CGCACATGTG CACAGGTGAT GCATGGTGTG 6721 TGCGTTCTTG AGTTTTGAGC CTCCGATGCT TAGTCCACTT GGCCCAATTC GAGTCCAATC AGCTTATAAC 6791 CCAT TTTCT TCAAGTTATC TTCAAGTTAA GCCCAATTTG GCTTCTCCAA ATCATCCATA ACTTCACAGA 6861 ATCGCCCGTT CATCTTAATC CCGGATGCAC AATTATTCTC CCGTCTTCAT TTTAAGCAAG ATACCACCTT 6931 CTTCATGCTT CATCCATCAA TAGTACACTT CATGTATCAT CTCTACTAGT TATTTAGTCC ACAAATCCTT 7001 GTTGTCCTCC AAATTTAATT ATCTCATTTA GTTCCCCGTT CCGCTACTTT CCTTAAAATT TGGAATTAAG 7071 CTCAGAGAAA TATTAAGTAC CCGAAATGGT CATAAAATTA ACAAAAAGGA AAATGCATGA AGATTAACTA 7141 AATGATGAAC GAAATATGCT AAAATAGACT ATAAAATGAA GTAAATAAAA TGAAATTATC GCACTCCGAC 7211 CACCCTTATG GCTTGTAGTC CACCCACCCT TCATTCCTTG TACCAATATG GGATGGAAAC ATCATTAATT 7281 AAGCCAAAAA GCTAACATAT AAGGGTTTAG TGACAAAGGT AAGTACTAAA GATGAAAATA ATCCATTTTT 7351 CΓTGTTTTTA CACAACACAC ACATAGGGGC AGACGTAGGA TTTCAAAGTA CAGATTGTTG GTGGCACATA 7421 AGTGTTGCTG GTGACATTTT TTTTTTCTTT TTACGTGGTG GCACAACAGT AGGAAAAACG AAAAATTCGA 7491 AATT TTTAC AATTTGTCTT AAAAAAAACA GGGGTTGTTG GTGCCACTAT GGACAACAAA GTTGAACTGC 7561 CCTACGCGCG CACACACACA CACACACATA GAGAGAGAGA GAGAGAGAGA GAGAGAGAGA AAGAAAGAAA 7631 GAGAGAGAGA GTTTGGGATG TGATACTTCT TTTAGGAAAA TGGAGTTATA TCTTTGATAT TGTATTTTTT 7701 TAATGTAATT TATNTATTTA ATCATTTTAG TTTATAAGTT NTATTTATTN GGNTATGAAA AAAAAAGTCT 7771 TTTATACATT GGATTTAACA TAAAAATCCA ACAATATTAA TCAAAAAGAC CAAACATGTG GACAATTATG 7841 TATATAATTA ATTCACAATA GTCTTTAGGA ATAGTATTAT ATATATAATT AATTCTCAAT GGTCTTAGGA 7911 ATAGTAAGTT CTTATATTTC AAACTTTTGC CACAATTCTT TGCTTACTTT GACACTTTTC CTTCCTAACT 7981 TTACATATAT ATATATATTA AAGCGCAAAG GTCATAGGAA TATAATATTT TCTATTATTC TACGTTTTGC 8051 CACAAAAGTT TGAACACTTT GCCACTTTTT GTCCCTCCTT AACCTTTTCA ATGTTTTGCG ACAAAAGTTC 8121 CAAAACTTTG CCACTTTGAT CATTCCTCAA CTTTTCACCG CATTAGTTTG TGGAGTTGGC AGTTTTGGTC 8191 CCTC AACTT CGATATTCTC TACTGCTAGC CAAAAAGGGT TCCAGAGTTT CACACTTTTG GTCCCTGACA

8261 GTAACCAAAT GTGAGATGTC AAATTTTTGC CACATTAGTT TGTGGAGTTG TCCCTTTTGG TCCCCCCACA 8331 TTCGATATTC TACTATACGA TCTTATTTTT CTCAAATAAC AACACGTATA TTTCATC : CT AATTGGAAAA 8401 AGAGTTTTAA AA:AAATAAC GACTAGG : : : G : GC : GAGTT TTTTTT:ACA AGTTTGTATC AAATCATATC 8471 AAAATTTAAG GTGGAACGGT GACCACATTA ACCAGAAATG TAATTTATTC TTTGATTTTG ATAATTTTTA 8541 ATATTTTGTT GTGATCTATG TATTTAAAAG TAAACAACAA AGAACATAAT CCAAAACCCT AAATTGCAAG 8611 TCTCGCCCAA TTTCTCTATC ACTAGTCCTC ACTTACGATG GCGTTACGTC GCTCTCTCAC TGCTTACAAC 8681 CCTTTGTTGC TACTCATTAC AATAACGAAA AGTTGAATAT CCATATATTT ATTTGGATGT GGAATTGAAC 8751 GAATCTCGTC AAAATTTTGA TTTTGTTGAT GGATTTGAGT AGAAGTTTGG GCAGAACGGG AATGATGGTC 8821 TGCAAGTGGT TATAAACTTG ATTCTGAGTT ATTACTATAT ATGTAGCCTC TTTACAACGA CCAAGGTTTC 8891 TTCCAGGTAC CATTTGATCT TTTTAGAACT TAGTTTTCTG AAACACCCTG ATTTGGATCA AATATCACCA 8961 ACAACTCTTA AAAACTTGAT TAATCAATTG TTTTCTTCAT CTTGATAACA AGTGGAATGA TTTTCTACTT 9031 AGATTAACTT GAAAAAAAAG GTCCATGTGC GTCTGGTGGA TCTGGTAAAT GAAGATGGAA GGGAGAGCTG 9101 ACTTTAAAGA CACAAACACG TCACCATATC TCTTATTTTA TTTTAAATTT GCTTTTGGTG TATTTTCTTT 9171 TTTCCTATTT CTTTC TTCT TGATCTCCAG ATGGTATGTG GTGTGGATAA TTTACACCTA GAGATTGGGA 9241 ACGATGGGAA GGGGTCTGTG ATTTATGGCT GGCCGAGTTT TACTTATTAA CTCAATTTCA ACCTAAATTC 9311 TGATTCTTGT TTGAAAATAA GTTGCATCTT TATTTTTGTA TTATCTTGTT GCATAGGATC CTTAGCATCT 9381 TTTAATAATT TATTTGAAGG TGAAAGATCC AACTATTTTT TAGCTGTTGG CATTTTCCAT CATTTGCAAC 9451 TGTTTC_TGA AAAAAAAATA CCTAAAATAA AAATAACCAT TTTCAAATCC AAAATTATAA GAGAGAATTG 9521 TAAATGGACA TGGAATCATA AATCATTAAC ACAGTTCAGT AAACAAGTTG CTAATTACAT TTCTTGCTGT 9591 GCAGAT GAA ATTCTATCAG AGAAAGAGAC ATTACAAGAA GCCACTGGCA GTATTTCAAA TCTTGTATTC 9661 CCATCCTGTC TCATGCACTC TTTTCATAAC CTCCGTGTGC TTACATTGGA TAATTATGAA GGAGTGGAGG 9731 TGGTATTTGA GATAGAGAGT GAGAGTCCAA CATGTAGAGA ATTGGTAACA ACTCGCAATA ACCAACAACA 9801 GCCTAT ATA CTTCCCTACC TCCAGGATTT GTATCTAAGG AATATGGACA ACACGAGTCA TGTGTGGAAG 9871 TGCAGCAACT GGAATAAATT CTTCACTCTT CCAAAACAAC AATCAGAATC CCCATTCCAC AACCTCACAA 9941 CCATAAATAT TCTTAAATGC AAAAGCATTA AGTACTTGTT TTCGCCTCTC ATGGCAGAAC TTCTTTCCAA 10011 CCTAAAGGAT ATCCGGATAA GTGAGTGTGA TGGTATTAAA GAAGTTGTTT CAAACAGAGA TGATGAGGAT 10081 GAAGAAATGA CTACATTTAC ATCTACCCAC ACAACCACCA CTTTGTTCCC TAGTCTTGAT TCTCTCACTC 10151 TAAGTTTCCT GGAGAATCTG AAGTGTATTG GTGGAAGTGG TGCCAAGGAT GAGGGGAGCA ATGAAATATC 10221 TTTCAATAAT ACCACTGCAA CTACTGCTGT TCTTGATCAA TTTGAAGTAT GCTTTGTACA TATTCCATTA 10291 TTTATTTAAT TTCCITTTTT ATTTGCAATA TTCTATAAAT AATACATTTT ATACCCACTA TACTAAGATA 10361 ATAATTACCT AGAGGGATGG ATGCTATGAC ACAGCTGCTA CACTTCAGAA ACTCTARTAA GGGCAGTTAT 10431 GGAAGTTCAA TAAAATGATA ATGGCATCTT TTGATGGGTA ATATAGGCAA TTTAAGTTTT ATTTCTGTTA 10501 AAGCAGTATT TAGCAAGTAC TGGCCAGTAG GAGAGGAGAA TATCACCTTT TGTGAAAATC TGGTCATTGT 10571 ACCCAGAATT TAGTTAAATG TAACATTTTA GATATTAGGG GTTATCAGGT GACAGATATT GTAGAATAGA 10641 ACAATATGTA ATATTACCCA AAACTATTTT TTCTAAGGTT GCTCTGTTAA ATATGTGCTT TCTTGATTTC 10711 ATTGAATTTG CATTCCTATA TTTTAGGTGG TAAAGTGATT GTCTCTTCAA TAAATCCCGA AATTTTTTAA 10781 TTAAAAAAAA AAAAAACAAA AGTAAATTTT TGATATGGAG AGCACTGGTA TCATTTAGTA TATAAAAAAC 10851 AGATT GAA TTAAGTTTCT TATATAAAAG CTGTGTATAT AGTTTAATTA GTTTTACATC ATTTTTCCAT 10921 GTGGTGTTGC AGTTGTCTGA AGCAGGTGGT GTTTCTTGGA GCTTATGCCA ATACGCTAGA GAGATAAAAA 10991 TAGGCAACTG CCATGCATTG TCAAGTGTGA TTCCATGTTA TGCAGCAGTA CAAATGCAGA AAGCTT

ol

R L-(= 2 S Λ-

MSDPTGIAGAIINPIA^QTALVP\TTDHVGYMISCRK RV ^QMKMTE1_NTSRISVEEH1SR TRNHLQIP SQTKEWL_D^QVEGLRANVENFP!DVITCCSLRIRHKLG^QKAFKITE^Q!ESLTR^QLSUSVVTDDPV?LGRVG SMNASTSASI_SDDFTSREKTFTQALIAI_EPNQKFΉMVALC^

GAVI?EKTOPFAIQEAIADYLG!Q EKTKPAP^DKLJlEW ^

SPFPNQGVDFKVl±TSRDSQVCTMMGVEΞA SIINVGLLTEAEAQSLFQQFVEΞTSEPELQKIGEDIVRKC

CGLP!Al. r AC? NKRKDAWKDALSRIEHYD!HNVAPIWFETSYH

PTEEI_MRYGWGl_KLJ^RVYΗRE_ARTRLjNra

ASIVNHGN PGWPDENDMIVHSCKRISLTCKGMIEIPVDLKF^KLTILX HGDKSL FPQDFYEGMEKL

HVISYDKMI<YP_J_PLΛPRCST IRV LTECSU<MroCSS!GNLSNLEVLSFA SH!EWl_PSTVRN^

RI_LD FCDGU3!EQGVl_KSF^K!-EE.ΥIGDASGRDDNCNEN ERSYN^

NLJ≡RFKISVGCSroENINMSSHSYENMLQLVTNKGDVLjDS.^

THPTQSSSFCNLJ<VUlSKCVELRYl_FKlJ.!_A.\ITLSRLΕ^

LSLSQLPKLSSLCHNVNIIGLPHLVDLILKGIPGFTVIYPQNKLRTSSLLXEGWIPKLETLQIDDMENl-EE IWPCEL-SGGEKVKLJ^IKVSSCDKLVNL^

KSI_1J^SINVENLGK1_REVWRIKGADNSDLINGFC^VES!KIEKCKRFRNIFTPITANFYLEA1_LE1Q!EGCG GNHESEEQVTLSISLS

SfaroNO'.

RIJG2G GGAAGAC-ACGATGATGAAGAACTC-AAGGAGGTCGTGGGACAAAAGAAATCATTCAA 95- 73

R G2M GCTGAAGAAG-C GC.X2AAGAAAAGAAAT G1TTAAITATATTOT GGGGCAGT ATAGGGGAAAAGACGGACCC 74 - 3<} m iii' a iii mr<A m ■ in ,$ ^• ism ,. , m, a ;,* DOES ,-, mm .",. a ,ι . s » _s e E_>

C_VTTGCTATTCAGCAAGC CTAGCAGAlTACC1XrK7rATAGAGCTGAAA^AAACACrA^^

110 120 130 140 150 160 170 180 190 200

RLG2A CATTGCTAI CAATCAGCIG AGCAGATTACCTAGGΓATAGAGCTCAATGAAAAAACTAAACCAGCAAGA^ 199 R G2B CTTTGCCAT __AGAAGCTATAGCAGATTACCTΑJ3TATACAACRCAATGA 200 RIX32C CATTGCTATTCAGCAAGTTGTAGCACΛTTACCTA GCATAGMCTGAM 192 R G2D CA TTXXHT AGCAAGTRGTAGC^GATTACCTATGCATAGAGCTGAMGAM 170 RIX32E ACT GCTATTCAACAAGC GTAC^XIATTACCTITGTATAGAGTTAAM 195 RIC2F CGT GCCAT CAGGATGCTATAGCAGATΓACCTAGGTGrAGACXrrcAATGAAAAAxrrAAGCAAGCAAGAGC GATAAGCTCCGTCAAGGATI AAGGAC 200 RIG2G TATΓGCAATTCAGCAAGC G ΓAGCAGA . ACCTCTCΓATAGΛGCTGAAAGAAAACACTAAAGAAGCAAGAGCTG A ΓA GCTTCGi AAACGGTΓ GAAGCC 195 RIG2H TAT GC AT CAGCAAGCTGTAGCAGATΓACCTCTCΓATAGAGC GAAAGAAAACACΓAAAGAAGCAAGAGC.X_ A ΓAAGCTΓCGTAAATGGTTCGAGGCC 173 RIG2I T TOxrrATrcAGCAACxrrGTAGCAGAτrccCTCTcrATAGAGC ΓAAGCTTCG AAATGGTΓCGAGGCT 187 RIG2J TATTTX rA CCAGCAAGCTGTAO^GATrACCTCIT TAGAGC^^ 171 RIG2K CATTRCCATCC__GGATGCTGTAGCAGALTATC GGATATGAAGCTAACΛGAAAGCAATGAATCAG.^ I AAACTTCG GAAGGGTTTCAGGCC 199 RIG21, CATΓGCTATTCΛ ACAAGCTGTANCCGA TΓACCTNCG ΓATACAGTTCA AAGAAAGCΛCTAAACCAGCAAGAGC-TGA ΓAAGCITCG ΓGAATGG ΓΓCAAGGCC 1 5 IUX32M CTΠT3CCATΓCAAGAAGCT ATAGCAGA I ACCT GGTATACAACTCAATGAAAAAACTA AGCCAGCAAGAGC GATAAGCTΓCG ΓGAATGGTTCAAAAAG 174

_____βil_H_::«|ia.«:..*.rø AAATCAaTGGAJ-GT GAATAAtπTCCT^AAT CTI^∞AT3-^^

210 220 230 240 250 260 270 280 290 300

RLG2A .AATTCTGGTG GTAAGA AGATCCTAG'IX_ATACTCGAαiATGTA_GGCAGTπx__T3GATC^ 293 RLG2B ^'AATrCAGATGGAGGTAAGACTAAπTCCT ^TAGTACT GAXlAlτπ TGσC^ 300 RXG2C AAATCAGA GGAOnAAC_ACTAAGTrCCrCATAATATTGG^ 292 RIG2D AAA CATm T_GAGGTA ACACTAAGTTCC CATAATAT GGATXIATXTΓC GGCAGTC 270 RIG2E AACTCTGGAGAAGGTA AGAATAAGTRCCR GTAATAT GATTI-TGTRR^^ 295 RIG2F AAATCAGATGGAGGCAAAAATAAGΓΓC ΓKJ ΓAATAC Π»CGATCTTΓGGCAG C GT^ 3 OO RIG2G GATtJOAGGA AAGAATAAGT CCTrσrAATACTTtlAαiATGTATCGCAGTTrσrC^ 289 RIG2H GATGGAGGA AAGAATAAGTTCCTrGTAATACTTGACX__TGTAra_C^^ 267 RIG2I GA TCGAGGAAANAATAAGTTCCTCGTtWTACrrcACGA GTAT^ 281 RIG2J GA GGAGGAAAGMTAAGTTCCTTGTNATACTIGAαiATGTITGGC^^ 265 R1G2K AAA CAGATGGA∞TAAGAATAGGT CC CATAATAC GGATGATGTATtXSCAA CTGTTA^ 299 RIG2L, røCTC G__\GArø3GTAAGAATAAGTrCCTOGTAATATTTG^ 245 RLG2M AAT^ AGA 3GAGG AAGAC AAGT CC^t^TAπ^,ACTTtlAC^ GT^^CGCAA 27

.:iii..>.:Biif:....:.:::.::^^^ GTXn GACTTC AGGTCTTCTTCACTrCA^GACTC-^^

310 320 330 340 350 360 370 380 390 400

R1G2A G GTCGAClTCAAGGTGTlXnT_ACATCAα_ΛGACAAAGATCTT^ 393 RXG2B (ntπ GACTTCAAGGTCrrTστ GACATX_ACGΛGACTCACMGTTrGC^ 400 RLG2C GTGTCGACTTCAAGGTCTTtπTTiACTTCACGAGACGAACATGT^^ 392 RIG2D GlGTX^ACTTCAAGGTCTrσTTCACTTCACGAGACX__ACATtϊITrGC_^ 370 RIG2E GTGTCGACTICAAGGTCTTGTTGACITCACGAGACTAACA GTKTCXJMCAGTAA 395 RIG2F GCGTCGACTTCA AGGTCT GTTGACATCACGAGACΛGACA GTTT-CACAGTXlATGGGGGTrGAAGCCA 400 RXG2G G GTCAACTK__AGGTCTTCTTGACGTCAAGAGATπ_AC_Λ GTTrcCΛ 389 RIG2H GTG TX_AACT CAAGGTCTTGTTGAαπK^AGAGATrcACAlTπTr^ 367 RIG2I GTGTCANCTTCAAGG- TTGTTGAeGTCAAGAGATIX-ACAT^^ 381 RIG2J GTGTOmCTrCAAGGTCTTTTπTΪACGTOaGArø _^^ 365

■will IISIWI: iiβ ut «i:i__a ■ ji>_ra:ιiιi:iιa mt UIIΓBBB UBBBB B;,!I!I HBU IIBB m.taa HI a m m^x

AGCAGAAGCaCAAAGTTπ7T CCA(X_VAT1'TGTAGAAAC^,I'TC TGAGCCCGAGCTCCA TAAGATAGGAGAAGATATTG AAGGAAG

410 420 4~i0 440 4^0 460 4 0 400 490 500

R1G2A f ΛCAl.ΛΛ CACΛ AΛ(_ ITI A TICCA LCAAITI Λ 1 A( J\ΛA . l'lCGGATGATG T1X..A _CCU,Λ(^y_-lCCA I A A I A I AGGAG U JU.1 A TIG 1 AA GAΛG 487 RLG2B AGCAGAAGCTCAAAGTCTGTrCCΛACAAllTGTAGAAACrrC GAGCCCCL^GCTCCΛ-GAAGATAGGAGAGGATA CXiTAAGGAAG 485 RIG2C AGCAG GCACAAAGATTCTTCCAGCAAITΓGTAGAAACTΓC TGAGCCCΛSAGCTC ^-CΛAGATAGGAGAAGATATTGTTAGGAGα 477 RIG2D ANCANAA ^CNAAGATΓG ΓTCCAGCAA ΓΓIG ΓANAAACI-ΓC TGAGCCCGAGCΓCCA CAAGATANGAGAAJMATATΓGTΓAGGAGG 455 HIG2E AGCAGAAGCACAA AGTITG ITCCAGCA A ITIG TAGAAACI _T TGAGCCCGAGCTCCA - 1 AAGA IAGGAGAAGATA ICG TAAGGAAG 80 RIG2F AGCTGAAGCACA AAGTTTCTTCC_.CCAATRIGTTGTCACTR TGAGCCCGAGCTCCA - TAAGATAGGAGAAGATATTGTA AAGAAG 485 RIG2G TGTAGAAGGACA AAG RRTGTTCCGCCAGTΠTXTAAA A ATGCGGGTGATGATGACCTC-GATCCTGCTITCAATCGGATAGCAGATAGTA'RTGCAAGTAGA 89 RIG2H TGTAGAAGGACA AAGTTTG rTCCGCCAGTTrGC ΓAAAAATGCGCXTTGATTΪMGACCTGGATCCTGCTΓTCA^^ 467 RIG2I TGTAGAAGGAAAAAGTTTGTTCO-CC&CΠ'ΓTGCTAAAAATGCGGGTO 4βι RIG2J TGTICAAGGAAAMGTTltπ'-CCGCCAm'rrGCTAAAAATGCGGGTGATimTGACC^^ 464 RIG2K AOAAGAAGCACAAAGTTTGTlTTATCAAT rGTAAAAGTTTCTGATA CCCACCTTGA - TAAGATTGGAAAAGCTATTGTAAGAAAC 84 RIG2L, AGTAGAAGCACIffiAGTCrGTTCCANCAATI GTAGAAACTTN TGAGCC(-GAGC C G-TAAGATA^KlA^IAAG'rTATCGTAAGAAAG 430 RIG2H AGCACΛAGCTCAAAGTCTGTTCCAACAATTrGTAGAAACTTC TGAGCCCGAGCTCCA - GA AGATAGGAGAGGATATCGTAAGGAAG 459 sa β Y B B . r ι,ι s B I, B :SB, B BIIB SKU B ι,s m i' , l i t ,, ,' , ■ v„» m , .■ m

TGTTG CX?GTCTACXX_ATTGCCATC7VAAA X-\TGGCCICTACTCTrAGAA^ AGAGCACCAT

510 520 530 540 550 560 570 580 590 600

R1G2A TGTGG-GGGI TACCCATTGCCATAAAAACCATGGCGTGI ACTCTTAGAGGAAAAAG(_AAGGATGCATGGAAGAATXX VCTTCTTCGTTTAGAGCACTAT 586 RLG2B TGTTG-∞GTCTACCΓATIGCCΛTAAAAACCATGGCATGTWCTCTΓAGAAATAAAAGA^ 584 RIG2C TGTΠJ-CGGTCTACC(_ATTGCCATCAAAACCATGGCGTGTACIXΠ^,AAGAAATAAAAGAAA 576 RIG2D TGTTG-CGGTCTACCCATTGCCATCAAAACCATGGCGTGTACTCTAAGAAATAAAAGAA^ 554 RIG2E TGTTG - TGGTrTACCTATrGCCATTAA A ACCATGGCATGTACTCTAAGAAATAAAAGAAAGGATGCATGGA AGGA IGCACr ITTGCA I TAGAGTACCAT 579 RIG2F TGTIT CXX_ rCTGCCAATIGC ^.X_AAAACCATGC<_._T7rACTCTACGACAT^ 584 RIG2G TG_CAAGG-TTrGCCCATTGCCATCAAAAC<_ATπ_CCTTAAG^,ra^ 588 RLG2H TGTCAAGG-TTTGCCCATTGCCATCMAACCATTGCCTT-JU_TC^ 566 RIG2I TGTC_\AGG-TTTGCCCATΓGCCATCAAAACCΛTTGCCTΓAAGTCTTAAAGGTAGAAC<^A^ 580 RIG2J TGTCNAGGGTITGNCCATTGCCNrCAA A ACαTIGNCrTNAGTCTTAA AGGTAGAAGCA AGTCTGCATGGGACG ΓCGCACTΠCΓCGTCTGGAGAATCAT 56 RIG2K TGTGG- GGTCTACXX^TTGCC_vrc_UlAACC_\TAGCα^^ 583 RIG2L TGTTG -CGGTCTACCTATTGCCATCAAA AC(_ATGGCGTGTTCrCTTAGAAATAAAAGAAAGGATGCΛTGGAAGGATGCΛCrTIxr CGTATAGAGCACTAT 529 R1G2M TG ITG - CGGTCTACCTATTGCCAl AAA A ACCATGGCATGTACrcTTAGAAATAAAAGAAAGGATGCA rGGAAGGATGCACTrrcGCGCATAGAGCACTAT 558

* ■ BSSI B,:,!. nma-mM m am tar iiuuitβ* ■ ^{• •} I,III.BB ananmu ML (BB_B rø o avii v

GACATrGGTAGiTG ^l GCGCCl<_AAGTrTTTAAAAC(I>VGCraCGAC^

610 620 630 64*0 650 660 670 680 690 700

R G2A .GACATTGAAAATA TIXTITAATGG- GTTTTTAAAATGAGTrACGACAATCTCC_ΛAGATGAGGAGACTAAAT^ 680 RLG2B ^"GACATTCACAATG TI∞XX CAAAG CTTTGAMCGACCTACCΛC__ATC CC^ 678 RLG2C GACATTGGTAATG TTGCTACriXX_AGTTTTT.__AACCΛCCTATGAGM^ 670 RIG2D GACATTGGTAATG TTGC ACTGC^GTrTTTANAACOUJCTATGAGAATCTCCCGGACAAGGAGAC^ 648 RIG2E GACATTAGCAGTG TTGCGCCCA AAGTCTTTGAAACGAGCTACCATAATCTCCACAACAAGGAGACTA A ATCTCTGTTTTIGATGTGTGGTTTTT 673 RIG2F GACATTCAAAGTG TlXnTX:CTAAAGTATTTGAMCGAGCTACAACAATCTC_\AAGACAAGGAGACT 6 8 RIG2G AAGATTGGTAGTGAAGAAGTTGTGCGTGAAGTTTTTAA AATTA£X_TACGAC__ATCTC _^ 688 RIG2H AACΛTTGGTAGTGAAGAAGTrcTGCGTGAAGTTTTTAA AATTAGCTATGACAATCTCCAAGATGAGATTAC1 AA ATCTATTΓTΓTTACTITGTGCTTTAT 666 RIG2I AAGAritX-rAGTGAAGAAGlTGTGCGTGAACT'rTrTAAAATrAGCTAlGAC_.ATCTCCAAI_ATω 680 RIG2J AAGATrcGTAGTGAAGAAGTreTGCGNGAAGTrT rAA TNACKrrATGACAAlCTCC^ 66 RIG2K G ACATTGAGACAA TTGC_.CATX.rixmTTTCAAATGAGCrACGAaUVT^ 677 RLG2L GACATTOJTNGTG TTGCGCCCAAAGTCTrTGAAACAAAAAACCATAATCTCCACAACAAGGAGACTM^ 623 RIG2M GACATTCACAATG TTGCGCCCAAAGTCTTTG7_\ACGAGCTACCACAATCTCCAAGAAGAGG 652 i i B B ffi_ l.i .V.I BS B fl i . M. S3 BSSSS-I ESS* B V B, B β

TTCCΓGAAGACTΓIGATATTCCTACTXIAGGAGTTGATGAGGTAT^^ 1 1 1 1 i 1 I 1 1 r

710 720 730 740 750 760 770 780 790 800

RIG2A ATcccGA AGACTΓTGATATTCTTACCGAGGAGTTGGTGAGGTATGGATGGGGGTTGAAATTATTTAA AAAAGTGTATACT ATAGGAGAAGCAAGAACCAG 780 RIG2B TTCCCGAAGACTTCGATATTCCTACTGAGGAGTTGATGAGGTATG^ 778 P G2C TTCCCGAAGACTICAATATTT TAAXIAGGAGTRGATGAGGTATGGATGGG^ 770 RIG2D TTCCCXIAAGACTTCAATATTCCTACCGAGGAGTTGATGA KN'ATGGATGGGGCRTAAAGTT 7 8 RIG2E TTCCIXMGACTTC^TATTCCAATCGAGGAGITGATGAGGTAT^^ ATACTATTAGACAAGCAAGAATCAG 773 RIG2F TTCCTGA AGACΓTGGATATACCTATCGAGGAGTTGATGAGGTATGGATGGGGCTTAAGATΓATTTGATAG AGTTA ATACTATΓ ACACA AGCAAGAAACAG 778 RIG2G TTCCITϊAAGATrrTGATATTCCTACTGAGGAGTIXXSTGAGGTAT^ 788 RIG2H TTCCTGAAGΛTTTTGATATTCCTACTGAGGAGTTGATGAGGTATG^ 766 RIG2I TIC(_T lAAGATTπτ_ATATTCCTA πtl_GGAGTTGG rGAGGTATGGGTGGGGCTTGAAATTATrTATAGAAGCAA AAACTATAAGAGAAGCAAGAAACAG 780 RIG2J r ΓCCTGA AGATTTTGATATΓCCTATΓGAGGAG ITGG- ΓGAGG ΓA ΓGGG GGGGCTTGAA ATI ATΓTAI AGA AGCAA A AACTATAAGAGAAGCA AGAAACAG 764 RIG2K

77 RIG2L TTCCTGAAGACTTCAATATTCCTACCGAGGAGTΓGA ΓGAGGTATGGATGGGGCTΓAA AGCTATTΓGACAGAG ITΓATACA ATTAGAGA AGCAAGAACCAG 723 RIG2M TΓCCCGAAGACT CGA . AITCCTACTGAGGAGT GA UGAGGI ATGGATGGGGCT TCAAGCTATΓ GATAGAG ΠTATACGATTAGAGAAGCAAGAACCAG 752

. Ht.ll. ... liliW fill.:-: B,lt:_::_: lit i|IB .. «_■,«. BlltUII.::: .:...: mmMm*MmmMXm--ϋm m£< :^•:.. ^•:. .^•..:^•: *.:^•: . ■^•■Ml. :>» :_::_:::::: ■>:;: :_: III" :> CCTt_AACA nτX_Vrτt-AG∞ACTOGTGCAGACAAAT^^

810 820 830 βlo 850 860 870 880 890 900 FXG2 A JSClCAACACA'IGCATIGAGCGGCrCA ITCAl ACAA AmGTIGATGGAAGTrGATGA TGT.AGG lGCATCAAGA IGCATGATCrTGTICGTGCTTITGlT 880

HIG2B GCT ΛACACCΓGCATTGAGCGACTGGTGCAGA(_AAATTTGTΓAATTGA 878

RIG2C G(_TOU\CACCTGCATTGACCGACItXπt>CAGACΛAATTrACTAATTr^^ 870

RIG2D GCTCΛACACCIT_CATTGAGCGACTGGTGCAGGCAAATTTACTAATO^ 848

RIG2E GCTCΛACACCTGCATItlACXX!ACTGGTGCAGA⁽_AAATTrcτT^ 873

RIG2F GCT _ ACACCTGCATTGAGCGACTGGTGCACACAAATTTGTTAAT^^ 878

RIG2G GCTCAACACCTGC-XCTGAGCGGCTTAGGGAGACAAATTTGTTATTT^^ 888

RIG2H GCTCAACACCTGCACrTGAG∞GCTTAGGGAGACAAATTTGTTATT^ 866

RIG2I GCTCMC__CCTGCACTGAGCC^XrrTAGGGAGAC__AATTTGTTATTTGGA^^ 880

RIG2J GCTCAACΛACTGCACIGAGCGGCTTAGGGAGACAAATTTGTTAT^^ 864

R G2K GTTGAA∞CCTAOVTCGAGCπGCrrCAAGGATTCT'AATTTATrGATrGAAAG.^ 877

RIG2 GCTCAACACCTGCATTGAGCGACTTGTGCAGACAAATTIXπTAATlt3AAAGTGAT^ 823

R G2M GCTCAACACCTGCATTGAGCGACTGGTGCAGACAAATTIGTTAATTGAAAGT^ 852 a 'ι ::a &α,v,a , ,ι, i', I',B , ι u , :» «. ->A . r,ι m ι>, ,_a_s a, . E , 1 , a ~m;a ,a___a ,^«, ^•• a

RLG2A TTGGATATGTATTCT-AAGTCC^GCATGCTTCC-VITGTCA ACCATAGTAATA-CACTAGAGTGGC- - - A - - GCAGATAATATG - - CACG - ACTCTTGTA 971 RLG2B TTGGGTATGTTTTCTX-AAGTCGAGCΛTGCαTCTAT^^ 975 RLG2C TTXX>3TATGTATTCTGAAGTCGAGC-_.GCTrCAATTGTC__ACX_ΛTGCT -TGAAAATGATA TtlATCGTGCACTCTrGCA 967 R G2D TTGGGTATGTATTXTΓGAAGTCGAGCAAGCTTC-ΛTTGTC^ 945 RIG2E TTGGTTATGTI rCTGAAGTlGAACΛTXXrrTCAATTATCAACCATC^ AAAATTATATGACCA ACTCTTGCA 964 RIG2F TTGGOAATGTTTΓCTGAAGTGGAG ^TGCTΓCAA'ITGTCA ACCATGGTAATA -TGCCCGAGTGGACTG A A AATGATATGACTG - - - ACTCTTGCA 96 RIG2G TTC<^TATATrCTCAGAAGTCCAAC__CGCTrCAATTGTCAAC 982 RIG2H TTGCATATATTCTCAGAAGTC -.GCACGCTlX_AATrGTC-U CC_.TGGTAAC-GTGT^ 960 RIG2I TIGCATATATTCTCAGAAGTCCAGCACGCTTCAATTGTCAACCATGGTM^ - - AGCATCTACTCTrGTA 974 RIG2J TIGCATATGTTT-CAGAAGTCAAGCATGCTIX-AATΓGTCAACCATGCT ACCAGCAACTCTTGTA 958 R1G2K TTGGATACGTTTAATAGATTCΛAGCΛTTCTITGARIGΤTAACCΛTGGTAATGGTGGTATGT^ 977 RIG2 .TCGGTATGTATTCTGAAGTOIAGCA TGCTR __ATRCTCA ACCATGGTAATA -TGCATGGGTGGACTA A A AATGATATGAACG ACTCTTGCA 914 RIG2M I-ΓGGGTATGTTTTCTGAAGTCGAGCAIX_CΠCTATΓGTCAACCATGGTAATA - TGCCTGGGTGGCCTGA - - TG AAAATGATATGA TCGTGCACTCT GCA 9 9

ii a mi III. lit _'Hi ar itfϋt. B_U* IIIB _oa iiwt.t ■ _ιt J_ a BEBWI _t ω .ι:_ MUX.

AAAGAATTrOVTTAACATGCAAGGGTATG'I K-AGTT

1010 1020 1030 1040 1050 1060 1070 1080 1090 1100

RIG2A JVAAGACTΓΓCATΓAACATGCAAGGGTATG rcrAAGτrrccrAC_AGACcπ_AAGTTTCCΛAACcτcrcCT^ 1071 RG2B AAA _\ATTrCATTAACΛTGCAAC«Xn^,ATGATTGAGATTXXAGTA£_l^^ 1075 RIG2C AAAGAATTTCATTAACATGCAAGGGTATGATrGACnTrCCAGTACACCTCAAGTTIC^ 1067 RIG2D AAAGAATTrcATTAACATGCAAGGGTATGATrGAGATTCCAGTAGACCTC-ΛGTTTCCTAAACTAACra 1045

RIG2F AACAAATΓΓCATTAACATGCAAGAGTATGI GGAGTΓ ΓCCTGGAGACCTC__AGTTTCCA AACCTAAAGATΓΓTGAAACTTATGCATGGAGGI AAGTCAC l o 69 RIG2G AAAGAA _TTCATTAACATGC-VAC _GTATGTCTCAGTTira_^ 1082 R1G2K AAAC_*ATTTCATTAAttTGC-U\GGGTATGTCTGAGTTTCCC^ 1060 RIG2I AAAGAATTTCATTAACATGCfiAGGGTATGTCrGAGTTTCCCAAAGACCTt__AATTrC(_Λ 1074 RIG2J AAAGAATTTCATTA AC_ATGCAAGGGTATGTCTAAI_TTTCCTAAAGAC_ATCAACTATCCAA ACCTI T-^ 1058 RIG2K AAAGA ATlTCATT_ATATGC_ AGGGCATGTCCGATrrrCCTAGAGA^ 1077 RLG2L AAAC-VGTTTCTTTAACATGCGAGAGTGTGTCTGAGTTTCCAGGAGACCrcAA^^ 1014 RLG2M AAAGAATTTCATTAACATG<_AAGGGTATGATTGAGATTCCAGTAGACC^^ 1049

B BB B III 11 B! B 1,1 I B. BSS , 1 III B S&Bil B Hi Bli B li B BE t ii B , , B! B-Blll,ll B B 'ι ,ι

. _σGTITαrrCAAGACnTrTATGAAGGAATGGAAAAGCTrCAGGCT^

1110 1120 1130 1140 1150 1160 1170 1180 1190 1200

R1G2A GAGGTTTCCCAAAAACTTTTATGA AGAAATGGAGA AGCTIX^GGTTATATCCTATGATAAAATGAAATATCCATTGCTTCCXR^ 1171 RIG2B AAGGTTTCCΓC__AC»CTΓTΓATGAAGGAATGGAAAAGCTC-ATGTTATAT^ 1175 PXG2C AAAGTrrcCrCAAGAATTTTATGAAGGAATGGAAAAGCπX-CGGGTrATATCATACC_.TA 1167 R1G2D A GTTTCCTCAAGAATITΓATGAAGGAATGGAA AAGCTC -AGGTTATATCATACGATAAAATGAAGTACX ^ 1145 RIG2E AAGATATCCTT-AAGACTTTTATGAAGGAATGGAAAAGCTCrGGGTTATAT^ 116 RIG2F AAGGTATCCTCAAGACTI TATCΛAGGAATGGAAAAGCrGGAGGTTATATCATACX-ATGAAATGAACT^ 116 RIG2G GAGCT-TCCTGAAAACTT TATGGAAAG ATGGAAAAGGTTCAGGTAATATCATATGATAAATT^ 1182 RIG2H GAGCTITCCTGAAAACTTTTAT-GAAAGATGGAAAAGGTTCΛGGTAATATC^^ 1160 BIG2I GAGCTrTCCr_AAAACTrTTATGGAAAGATGGAAAAGGTTCAGGTAATATCATATGATAA^ 117 RIG2J GTGC TTCCTGA AAACTTTTATGGAAAGATGGAAAAGGTTCAGGTAATATC^TATGATAAATTGATGTATCCA rTGCTTCCCTCATCACTrGAATGCTCC 1158 RIG2K GAAGTTrcC_K_AAGACrTTTAT∞AGAMTGAAGAAGCrTC^^ 1177 RIG2 AAGGTTTTCTX_AAGACTTTTATGAAGGAA .GGAAAAGCTCCΛGGTAA TATCCA rrGCTTCCCTCGTCACCTCAATGCTCC 1114 RIG2M AAGGTTfrCCNCNAGACTTn ATGAAGGA ATGGAAAAGCrCC TGTTATATCA ΓACGATAAAATGAAG INCCCA ri CT ΓCCTΓTGGCACCTCGATGCTCC 11 9

ll'UIIIMI! B ^•• ... : B :^•:.: ylt: .. : :. lilt-:- .aBBIIIBI.B : : ».: . Jll! Wilββ.. ϊ.-fflfc .... : HI... ...ylfc: BB : :.» :.J_: : '.• Illl βBBr. :' BJ . II. ^•:^•:^• :. > .:^• .:lιl B lit; ^•:.. iityLUIII

ACCAACCTKX_AGTGC-TX^TCTCC_m_AATGTIT^^

1210 1220 1230 1240 1250 1260 1270 1280 1290 1300

RLG2A GTc_.ACcrrcGCG G rτcA'rcτA(-ATAAA'α^rcGrrA^ 1271 RLG2B ^'ACCAACATTCGGGTCCTTCATCTCACTGAATGTTC*^ 1275 RIG2C ACCAACΛTT∞GGITXrrTCATCT ΛCGGAATGTTCATTMAGATG ^ 1267 RIG2D AC(-AACATTθχχπGCTTX-ATCrCACTGAATGTTCATTAAAGATGT^^ 1245 RIG2E ATCAAC CTTCGAGTGCTTCACCTCCATCGAT-CΓCΛTΓAAT^ ΓΓGAATCTGGAAGTGCTTAGCTTΓGTTA 1264 RIG2F ACCATCCTrCGAGTGCTTCAϊCTC _ TGAATGTTCATTAAGGATG^ 1269 RLG2G ACCAACGTTCGAGTGCTrCATCTICATrACTGTTCATOA 1282 RIG2H ACTAACσiταiAGTtXπT »TCTCC_ATTATTGTT vTTAAGGATGTTTGA 1260 RLG2I ACCAACCTICGAGTGCTrCATCTCt-ATGAATGTTCATTAAGGA 1274 RIG2J ACTAACGTTCCL>\GTGCriCATCTCXA_TATTGTTC^^ 1258 RIG2K AC(-AACCr CGTGTGCTTCATCTTαvT-AATGCTCATT----GATGTT^ 1274 RLG2L ACC__ACCTTCGAGTGCTTC_VTCTrcATCGGTGTrCATTACGGATG^ 1214 RIG2M ACCAACATTCGGGTGCTTCATCTX-ACTGAATGTTCATrAAAGATGTTTGAT^^ 1249

,ι Ha,, . a,,,ι „',:,B 'a aa,,a B» ,ι * >ι,,ι „ι ,,,, a,,iι B a ^• s ., a a, ,» a ,, « _ , ,

R1G2A ATTCIGCCATRCACCGGTTCCCTTCCA⁽_AATCGGAAAGTRGAAG 1371 RLG2B ATTCICACATTGAATGGTΓACCΠCCACAGTCAGAAATTTAAAG 1375 RIG2C ATTCTTGCATTGAGTGGTTACCTTC Λα^ICAGAAATTrAAA ΓGTTATGGTCTCCGTATAGAACAGGGTG Γ 1367 RIG2D ATTCTGGCATTGAATGGTTACCΓTCCACAGTCAGA AATΓTA AAGAAGCTAAGGTTACrTGATCIGAGATITIX_TGATGGTCTC03TATAGAACAGGGlGT 13 5 RIG2E AATCTG<XlATTGAATGGTrACCTTCCAC__ATAGGAAAl TAAAGAAGCTAAGGTTAC_riGATC^^ 136 RIG2F ATTCrAGCATTGAAlTGTrACCTrcCGTAAT GGAAATTTGAAGMGTTGaX-C GCTAGA TTTGACAAACTG ITATGGTGTTCGTATAGAAAAGGATGT 1369 RIG2G ATTCT U - GAATGGTTACC*TCTACAAl GGAAA1TIGAAGA^ 1382 RLG2H ATTCTAACATTGAATGGTTACCATCTACAAT-GGAAATTTGAAGAAGCT^ 1360 PJ.G2I ATTCTCGCATTGAATGGTTACCATCTACAATrGGAAArrrGAAGMGCT^ 137 RIG2J ATTCTAACATTGAATGGTTACCΛTCTACi^TTGGAAATTTGAAGAAGCTAAGGCTACTAGA^ 1358 RIG2K ATTCIX-GTATTC-AGTGGTTGCCrTCCAt-ftATC∞AAA 1374 RIG2L ATTCTGGCATTGAACGGATACCTTC_\GCAATCGGAAATrTGAAGAAGCTTAGGCAACT^ 1314 RIG2M ATTCTCNO TIAATGGT GCCTrcCCCn G TC^ 1349

1410 1420 1430 1440 1450 1460 1470 1480 1490 1500

RIG2A CrrAAAAAAATrcGTCAAACT-GAGGAGCrCTATAT-GACAGTG GTT GAT CGAGGTCGAAAGG CGA 1437 R1G2B ^'crπX-AAAAGTTrTGTCAAACTTt_AAG-«TTrTATATTtXL.GATGC^ 1475 P1G2C CrrTGAAAAGTTTGGT_υΛCnTGAAGyUVl ITATA_TGGAAATGCATATG 1417 RIG2D CITGAAAAGTπGGTCAAACTIGAAGAATrτrATATTGGAAATGΛTATσGGTrTATAGATσ TAA 1411 IIIG2E CTIGΛ A AΛΛTΓΓGG ΓGA AAATI ΠAAGAACΓΠ ATATΓGGTAGAGCΛGATAT-TTTΛTAGAT AGA- AGI A - A 1 32 1111,21 ⁽THUlΛΛλlWTIT. iΛΛΛ(Tlx Λ(lΛ(_-πiΛIΛriΛ(!GΛΛiυ- GICΓΛC CAGT--"— TTACAGAGGAT AA 1437 RIG2G cr ΓAA AAA ATTIGGTC-UWICTTGAAGAGCTITATATGGGTGTΓA - ATC- - -GTCCGTATGGACAGGCCGT- -TAGCTΓGACAGATGAAAA 1466 R1G2H CTrAAAAAATrTGGTCWWiCITt__AGAGCTTrATATGGGTGTrA-ATC---ATCC^ 1420 RIG2I CTTAAAAAATΓIWΠCAAACTΓGAAGAGCTITATA TGGG GCTA- ATC- - -UTL-H_ ΓΠQGAAAG- -TGC- -CA— TT 1442 RIG2J C ^AAAAAAΤTRTJ3T_AACT^T_AAGAGC R A A^GGGT_T^A-ATC---GTCCGTAT^ 1449 RIG2K CCTAAAGAAATΓGGTGAAACTTGAAGAGCTTTATAT GA GAGTTGGTGG 1423 RIG2I, CTIGnAΛΛΛTITC/nrGΛΛCT-IWΛAGAΛCrrrATΛTTGGAAATGCATCTGXmTAGΛGA 1398 R1G2M CTIGAAAACI'ITΓG ΓCCA- CM IGAANAATΓT- ATπ GGAGACCC-TCTGGGTTTATNNA_GAAAACIGC_ΛTGANATGGCAGA CCTTTCAACC- - 1441 xxxxxx__κxxxxxxrax__q«xxxx

1510 1520 „^_Λ - _, --,

H G2A TΓA- *^ Cθ i : 2.7 1439

RIG2B TrrGCATTAGAATTCGCGTTCTrTA - Sβ2 fP W-^'i? 1500

RIG2C - iεa Vi Nd'T- 1 1417

RIG2D TG -sea to lO' SO 1412

RIG2E - SP« t< ό ' * i 1432

R1G2F TA - Sc?a ZD 0 ? Z- 1438

RIG2G -se& tOHD SS 1466

RIG2H - « <* W«» «J- 1420

RIG2I- < ∞ ^3! _M -, 1442

RIG2J TCGAAATGGCAGANCXΠTΠTCACA - ScQ r_5 W 5-fa 1474

RIG2K TCGATATCAAAAGGC - S &Q &P ttø • 3 1437 1398

RUSH ^A-Λ?WJΓ-9Λ0 '*1 1441

tiBii .. aiifl.li 'jit: BIIK* BBiiβa yi* '•• . K- B__S_> iii'Miinai .>ι _::_:: :_: jiiBiiiniiin: B. A . :..^•«^• ■ a i

, GETTT ___ WEE3αa-r-r_IV-_VVIGE3C-PPIAIOQAVAIJ_IX-I_ K_-πT^ ^→tyO 1 1 1 "— i 1 1 1 1 1 ~T '

10 20 30 40 50 60 70 80 90 100

RIG.A protein GK ^r^Mll^UIV^ΛE_K^IF^π^{^}II_ΛVVGE_πT)^IAIQ_AVADYI IE-_I_^^ 9-"^V' nι«2iι protein κ_τ<-_ιuιu.κκA:_π»κwNϊi.αΛvιxEK--OT^^ loo - Z

RIG2C protein N --AKA___VAK>n<E_3OYII-Λ _GEISDP α^ A^ 98- V3

RIG2D protein EVAK—XK RK--FGYIIE-YV-XEISα.P_AIrørt^Yt£I_ΪJES_θαTT-*-_^ 90^* Vf

RIG2E protein G IOJI-AKV-__W C--mMFrrtι EA IGE3CIT)PωiQQAVAr^^ 99 ~VS~

PJG2F protein LED_T_-QP__KKVVHE_a<MFNFrVEAVIGEKTDPVA^ 100 - YC

RIG2G protein Gron.D-E__L-C_aA/GQKKS_TUIIQVVIGE_nNPIAIQQAVA_W_-. 97- V JL

RIG2I! protein KEΛΛ/OTKKMFSIIVQVVIGra'INPIΛIQQAVAIWI,Siπ-CπriT<EΛ^ 89 - V?

R1G2I protein CKKS K£^VEQKK7T IIVQVVIGEK-NPIAIQQAVADS SI-_-<__.IKEARADKU?KWF--EADGGXI)KFt,VII^ 94 - f

RIG2J protein ERGR GXKKTI^irVQVVIGEKlt.PIAIQQAVADYl-3IEIJEtmCEARADKIJ.KRF--EAι^ 89*Λ>

R1G2K protein t£_rrahKRIJNIIKEraiTTir__V VVIKENMDLISIQDATOD_T_-^ 100-5"/

RIG21. protein F_ M/HA-lGE3m>PIAIQQA.TmYt_UQ_TCESTKPARA]m^ 82 - f_

RLG2M protein AEE AA___K-<__F^^_I GAVIGEKTDPFAIQE-^IAD _GIQL^n_KTKPAR^ 92 ~_-_\

. ».:. ^■:■::. •^":^": . -JR-B.. *B^':^:' B V.,!,ii!.ιlB,i-_SB «K',BB,i ι'S, i EBSS-J B .____», E8H, _6B3 H ^■,' !^■, l.t-l-B B,>l B8: Mill VDFKVI_^TS^SHVCTVM3yEAHSIlMVG^I_A_-\QSLJQQFVETS--E PE_-KIGE-3IVRKC ;LPIAIl mACrπ_ παtKPA tα3A_^^

110 120 130 140 150 160 170 180 190 200

RLG2A protein VDFKVU,TSBI)KOTCTEMGAEVNSTFIWK^I_nΕAQS 196

RLG2B protein VDFKVLLTSRDSQVCTMhJGVEAHSIINVG_i.TEA__\QS FQQFVETS--E PELQKIGEDIVRKCCGLPIAIKi iTlCXIJWKRiαiAWKDALSRlEHYD 195

R1G2C protein VDFKV iTSRDEIWCSWKVEANSIINVGL IEAEAQR F QQFVETS--E PE «IG_I3IVRRCCG PIAIKT»aCTIJ»JKRKnAWKnAI>SRI^lBffl 193

RIG2D protein VXFKV TSRDE_r^SVM3VE_^SIIϊr(Λ_IiI__XX_RI_.MFVXTS--E PE_JWIXEXrviWC∞LPlAIKTh_\CT RtIKRKnAWKnAI£RLQ^[ππ^} 185

RIG2E protein VDFTVIiTSR-DIWCXVMSV-A SILNVGLLVEAEAQSIJ. QQFVETF--E PE_JI_<IG_DlVRKCCGLPIMKTiffiCT «WIUΦAWKI_i XJπ__Y^ 193

R1G2F protein VDFK IiTSRDmπrtrrWiG EAKLIIJ^TCL-jlEA-ΛQSUΗ PEllKIGEDIVKKCFGLPIAIKTTffiCTTJSHKRKDAWKIlΛI^RLEHim 195

RIG2G protein VNFKVIiTSRDSllVtrrLM-AEANSlI-πKVXKIArtJGQSLJT^QFAKNAGDDD 197

RIG2H protein OTKVU. SF-.S.W M-AEANSII-.IK^TAVK^SU^Q 189

RIG2I protein VXFlTΛ TSRDE_.WCΗ«GA__«JSIl-nKVI-ΦVEGKSIJ- RQFAKrmGDDD__3PAFIGIADSIASRCCGI,PIAIKTIALSUGι^KSAW-WALSR___NIIK 194 RIG2J protein TOTmiTS._<SIιVCmi*_A__WSIlrøKVI_<IWQGKSL^ 189

R1G2K protein VDFKVliTS_NKD\Λ-Mαi3VEANLIFDVKFLTEE_ΛQSlfΥQFV/K^ H_ )KIGKA^VRNCGGLPIAlKTIA^π^J<^Knα^\Λ^KI_>_I_JSRlE10_^ 195

R1G2 protein TOFKVIATSRD_røCT 3VXANSXIXVGtiT_Λ>Ε-VX^ PE_CKIXXVIVIUCCGLPIAIKTWACSU«JKIUα_-WKI_U-SRIEH_D 177

RIG2H protein VDFKVIiTSRDSQVCTWM3V_ΛNSI_NVGI__X__\_ΛQSlfQQFVETS--E P_lβKIG_EIVRKC<_G P_AIKTϊftC_T_RrøσUα»WKI_AI^IUE_mJ 187

miiiitt ^■ -Raannm * β amiii ma urn am.- ^" -inn naar Bin S .,;»IIIII n aaiiιiιiιis_«:ι a *

, IGS- - V7U'KV ,-ΕrrSYPN_ =OxD,_ETKSIF_MCG FPEDFDI P .T____MRYGWG__gJTJWAYTI ,KEARNRIJn ,I __tt,VQ xTTJ_ ,.IESD_lVGCVK ,MHDLVRAFV_ _r.

210 220 230 240 250 260 270 280 290 300

RIG2A protein rN--ι MΛTκMΩYmι, r>rr:π<ϊi i πr«^ 294

HIG2B protβin'llW--VAPKVFE-rSΪIWICE_i-.rKSinMCGlJPEDFDIPT___U«ΪGWGll{-f^ 293

PXG2C protein IGN--VATAVFRT_πr__nPD.--TK-π/FI_*53lJ. PEDFNIPT^^ 291

RIG2D protein IGN-- -T*TAV X £m_m. DK_rrcSvnMθπf mFmPTEE 283

RIG2E protein ISS--VAPKVFETSYH iO«-πTSVπ-*CGFFPEDFNlPI_-_(iΦYGWI-αFDRVYTIRQAi RI-^ 291

RIG2F protein IQS--WPKVTCT£n(NNUΦ.__TK_WnMCG_.FPE3_I_DIPim 293

RIG2G protein IGSEEWREVFKISYDMIiQDEVTKSIFIJjCAIf PEDFDIPTE__,VRYGW_UO_. IEAKTIR_-.RNRnnCTEMJ?_rniUJ. GSDDIGCVKhOIDVVRDFVL 297 R G2H protein lGS___VWREΛ/FKISYDtπ.QDEITKSIFU-_AlJP_X)FDIPT_-a_ΦYGMGUαf I__U<TlR_-UWRI_ πΕ3UJl_πtI_4_FGΞDDIGCVKHIff)VVRDFVL 289 FXG2I protein IGSES-WREVFKISYENLQDEVTKSIF _^MJ. P_-.FDIPT_-_LVRYGVCUOJ. 294

R1G2J protein IGS_-_WREVFKXSY_tnjQDEOTKSi >CA_J. PEDFDIPIEEJ-VRYG^ 289

RIG2K protein IET--IAmπ/FQ^K TΛΛQ.π__ΛQSIFi__>_GIJ. PEE^ 293

RLG2L, protein IXX--VAPKVF_nT⁽MOT.HNKI_rKSAF__«xπ.FP_X>FNIPTEϊX^ 275

RLG2M protein II_.--VAPKVFCTCTINI _--_TKSTπ_4CG__^rPEDF PT^^ 285

__B_ililι,T B.I.H'ill I. 11 βSS B-SfflBS BBS Bl!> -hi UiiiBflB _F IMl'lli B KF UliW SM„E_t ^"_£_ .|,l SB '!«___! WmB

GMFSEVE_lAS-V GN--MPGWPE_3ro-IVHS(-KRI-a_JT^ 1 1 1 1 1 1 r^ r" 1 °—r

310 320 330 340 350 360 370 380 390 400

RLG2A protein t»TCS.OTI_^S_VOT_N--_T_EWHAm--Mm_CKHI_ ^ 390

RIG2B protein CWFSEΛrt_U^IVMlGN--MI<MPDENIWIVlISCKRISLTCKGrøEIPVDUζFPK TII_^ 391

R1G2C protein G-4YSEVEQASIV_πiGN--h_?GWPDE a _Vl_-CKRISLT_KGrø_I^rPVDl_(FPKLTIl^ 389

RLG2D protein GmSEVEQASIvmGN--MIKWD-W_tCraiS<-KRISL^ 381

RIG2E protein V7ffSErølASIIrølGN--MIGWPEϊr_--_πNSCm_lT ^ 387

RIG2F protein GhB. SEVΕllAS_VrølGN--MPEWmro--.m)SC~KQISLTa^^ 389

R1G2G protein HIFS_ΛΛ2Iι7VSIVNHGN--VSEW_J__-m-εiYSCKRISLTCXG_3^^ 394

R1G2H protein HIFSEΛ/QIlAS_VMIGN--VSEWL-_am-SIYSaaUSLTCKΘ_-_3^ 386

R G2I protein HIFSEVQIIASIvroiGN--VS_>n-E_-m-SIYS<-røISLTCKaiSE^ 391

RIG2J protein JrøSEVKllAS_VrøIG -- _WPE3ND-TεNSCπRISLTCKGMSKFPro 386

RLG2K protein D F^πU^a^SL_Λ'^π^G^J3G^_-GWP_N-I_^__._3SCOT^ 392

RLG2 protein CI«SEVEIJASI NHGN--MHGmTOπ -_flIlSCJrV_aΛ^^ 371

RLG2M protein G-ffSEV-_JAS_VWG_l--MPGWPD_MMIVHSCKRI8LTC__Gra^ 383

Mil.B::-:-3l..: . « ::.:B ylt ..>: B:.> :>' ΛB' β. ,l|l' lllilfc: B' IIIBIII .. JBBWIK :. $tW SSI ailll.BliBSIt • B„L I'll, .,!,'■ τ^n-^w^^_i^-aJ^^FIx: sIG^fc--^I--V^

410 420 4J0 440 450 460 470 41)0 490

KIG2A protein VNl HV1 lllJIhC .VMl IX-SClONI .111 L/Iil Λl)_.ΛIl)Rl._ ' K_KI.KKI.RI J.l>£.TNX.YGVRlIlt. ,-VIΛKLUKI 1-.I.YMIVV DRGRKAI 479

RLG2B protβin^'imRVUO_TECSU<MFIXSSIGN_-»n:.EVl_SFANSHIt^ P 481

RIG2C protein im.3/IilLTECSI_MTCSCIGra_3 I__VI__FAN8CI_ 472

RIG2D protein TNIRVU-_TEC8__<MFIX:SSIGt-_8m-_VI^FA 8RI-^PSTTO VM 470

RIG2E protein INU*.TJI__raCSr_ΦffrcsC-G__<Uπj_VI,SFVKεσiE 471

R1G2F protein TI__WU__lEC^^^^_πX^SIG^JU^;^^^l^X FA SSI_IAPS^^ 477

RLG2G protein ^JΛ v Jι l^YC^U?MFIXεSIG^πJJΦ__V SFAN^NIEyπ_P8TIG^IUαα_R QAVSLTDE 488

RIG2H protein TNVRVLiajrYCS RMF _C8SIGmX_lMEVI_3FANSlJIEM.PSTIGin KUl_I_3LlNCKG_ΛI_ΪJGVIJ j V 472

RIG2I protein .tn_RVIjnJIECεi FIX:εSIGraJWMEV εFAIiεGIEWI,PSTrGrøja j«J_D lIXXMUIia KC H 480

RIG2J protein ItfWVIJIUIYCSIJlhff _CSSlG_πXT_<_WI-SFANSNIEMLPSTIGNIJ<K RIXJ_LT^^ QAVεLTD 479

RLG2K protein ^TΛΛ.^JD_I^QCSL-^ff_CSSIG^l _ J=^π. FANSG GRYQK 478

R1G2L protein TOLRVUD_!mC8U»ttJXSCIGNLTOUΛrc,SFANSGIERIPSAIG 465

RLG2M protein raR.^J_LTECSLK^ffrcS IG^π-3^^l_EVIJFANSXI_ra 480

ATTCTTGTTTCAAAATAAGTT-GCATCTTTATTTT-TG--TATrA_Cr^ GAAGGTG

110 120 130 Hθ 150 160 170 180 190 200

AC15-2A ATTCTTClTlGAAAGTAAGTr-GCA.CmATTrT-TG--TArrΛTCTTGTTGa GAAGGTG 187

AC15-2B ATTCT_GTTKGAAAGTAAGlT-GCATCrrrrATGTr-TG--TATTATXOT GAAGGTG 187

AC15-2C AlTCTrcTrTGAAAATAAGTr-GCATCTrTATnT-TG--TArrATCnGTrGa\TAGGAlCCT-TAGCA GAAGGTG 186

AC15-2D ATTCTTGTπGAAAATAAGTr-GCATCTTrATTTT-TGCATAπATCTTG-IT^ GAAGCTG 188

AC15-2E TCTCTTGl IGAAAAT-AATCCACATCTT-ACrrT-AAATATATCTAT- GAAGGTG 137

AC15-2G ACTCTΓGTΓTGAAAATAAGTΓ-GCATCTTTATTTT-TG--TATTATCTTGTTGCA GAAGGTG 187

AC15-2H ATTCTTGTrTGAAAATAAGTTAGCATATTTATrrT-T-TGTATTATCrrGTIGCATAGGATCCT-TAGC^ 176

AC15-2I AlTCT'rGlTTGAAAATAAGTT-GCATnTTAlGTT-TG--TATTATCCTGTrGa\TAC_IATCCT-TAGCATCT^ GAAGGTG 164

AC15-2J CCCATΓCTTGGAΓΓACCACCCCGCAATGGGAAACGATTCAAAACAGGGCGTΓAC_\'!A--ATTTG-TTG^ 194

AC15-2 TCTCTTGTTTCAAAAT-AGTTCACATCπ-AATrAAAATAl^^ 122

AC15-2N ATTCrTGTTTGAMGTAAGTr-GCAT nTrATGTT-TG--TATTATCTrGTrGa GAAGGTG 187

AC15-20 --TCT AATAA-TGCACATCTTAAATT.AAAAGTATTTAATTGTrGCATAGCAKG^ GAAGGTG 168

r 1- 1 ι T 1 i 1 1 r

210 220 230 240 250 260 270 280 290 300

AC15-2A .AAAGAτCX_VACrATrTTTAATCTGTTGGCATTTrc(_ATCATTm 286 AC15-2B .AAGATα-AACTATTTTrAATCTατiXXXΛTTTrC^ AATAαrrAAAATC_\AAATAACCATTTrCATATC<_A 28 AC15-2C AAAGATCCAACTATrrTTAATCTGTTGACGTTTTCCΛTCATTrGC^ 285 AC15-2D AAAGATCC7UlCTAGTriTGATCTGTTGG _VrrτrcC_mΛ 286 AC13-2E AGAGATCAAACTAl IX7rAATCTGTTGAC_WVTTrCAATC_AT rw_ΛATT^^ TACTT AGAATCA AAGAAATATTTTTCTAATCCA 2 3 AC1S-2G AAAGATCAAACTATTTTTTAGCIGTTGGCATTTT(-CATXaT^^ 287 AC1S-2H cττπττxϊCΛτττrcαvτcΛτr GαvA πτ_τττcτrGAA 253 AC15-2I AAAGATCCAACTATTTT-TAGCrGTTGG -ATTTrCCA CATT-GCAAC G rix:^ 263 AC15-2J -AAGATCCAACrATTTTTAATCTGTTGGCATITrCCATCATTTO^ 293 AC1S-2L CCΛAC_.CTTl rAATrTGTTG_\GAATT rCATCATATGχ__AATGTT^^ TGCCTAAAATCAA---AATATT_TTCAAATCCA 208 AC15-2N AAAGATcc__AcτAτττrτAAτcrcτrGGCAτrττcc_\τc^ττro(-^ — AATACCTAAAATCAAAATAAITCATTTΓCATATCCA 284 AC15-20 AAAGATC _ ACTACTTI-TAA7 IGTTAA ΛATTTCAATCATΓTGCAAATGTΓC^ 268

AAATTATAAGAGAGAAT GTTAATGGAC- ATGGAATCATAAATCATTAAC- - - ACAGΓTCAGTACACAAGΓΓGCTAATTACATΓTCTΓGCTG 1 1 1 1 r- 1 1 1 i r

310 320 330 340 350 360 370 380 390 400

AC15-2A AAATTATAAGAGAGAATTGTAAATGGAC-ATGGAATCATAAATCATTAAC---ACAGTTC^ 375

AC15-2B _AATTATAAGAGAGAATr nTAA∞GAC-ATGGAATK__TAAATCAπ 373

AC15-2C AMTTATAAGAGAGAATTGTAAATGGAC-ATGGAATCATAAATCATTAAC ACAGTTCAGTAAA-MGTTGCTAATTACATTrCTTGCTG 374

AC15-2D ?AATTATAACΛGAGAATOπTAATGGAC-GTGGAATCATAAATCATTAAC---A 375

AC15-2E AAATTATAAGAGAGAAT_GGGAATGGACAG'rGTAA'rTATAAATCATTAAC AC_AATTCAATATTαW GTTA(-TAATTACAT rATrGTrGGGATATAT 330

AC15-2G AAATTATAAGATAGAATTGTΓAATGGAC-ATGGAATCATAGATCATTAAC — A _\GTTC_ΛGTAAACAAGTTX3CTAATΓACATTTCTTGCΓG 376

AC15-2H AAATTATAAGAGAGAATTGTTAATGGAC-ATGGAATCATAAATC_\TTAAC---ACΛGT^ 342

AC15-2I AAATTATAAGAGAGAATTGTAAATGGAC-ATGGAAT _ΛTMATCATTAAC---ACΛGTrCAGTAAAC__AGTTXXr^ 352

AC15-2J AAATTATAAGAGAGAATTCTAAATGGAC-ATGGAATCTΓAAATC_*TΓ.*C---A(^^ 382

AC15-2L AJWTTCTAAGAGATAATTGTGAATGGACT-TCAAGTTATAAATCATTrACTACACΛ^ 307

AC15-2N AAATΓATAAGAGAGAATTGTΓAA∞GAC-ATCGAATCATAAATCATTAAC — ACΛGT CAGTACACA XΠTGCTAATTACΛTTT ΓTGCTG 373

AC15-20 AAATTATGAGACAGAATTGAGAAGGGAT-GTGAAATTATAAACCATrAAC---ACAATTα^^ 364

-TGCΛGATTGAAATT TATCAGAGAAAGAGACΛTTA(_AAGAAG(XACTGGCA- -GTATTTCTAAT- -GTTGTATT---CCCATCCTGTCTCATGCA -J-

410 420 430 440 450 446600 470 480 449900 500

AC15-2A .---TGCAGAinGAAATTCTATCAGAGAAAiC_AGACATTACAAGAAGCCACIGACj\---Gl 462

AC15-2B ^' TGCAGATTGAAATTCTATOU3ACU_*AGAGAC_ ACΛAGAA X^^ 460

AC15-2C TT_CAGATTGAAATTCTATOU_A£»AAC»GACATTA^ 461

AC15-2D TGCAGATTGAAATTCT'ATCAGAGAAAGΛGACATTACAAGAAGTCACTGATACTAATATTTCT 471

AC15-2E GTGTGCACΛCTGATACTCTGTCAGAGGAAGAGATATΓACAAGAAGTCACT^ 421

AC15-2G TGCAGATTGAAATTCTAT -AGAGAAAGAC- CATTACAAGAAGCCACTGACA GTATITX-TAAT---GTrcTATr---CCCATCCrrcTCTCATGCA 463

AC15-2H ---TGCAGATTGAAATTCTATCΛGAGAAAGAGACATTACAACUVAGCCΛ^^ 429

AC15-2I TGCAGATTGAAATTCTATCAGAGAAAGAGAC_AT ACAAGAAGC __CTGGCA---GTATT^^ 439

AC15-2J ---TGCAGATTGAMTTCTATCAGAGAAAGAGACATTACAAGtfΛGCCΛCI^ 469

AC15-2 ATCCACAGACTGATATTCTXSTCACΛGGAAGA ΛCATT^^ 398

AC15-2N TGCAGATTCAAATTCTATCAGAGAAAGAGACAT.ACAAGAAGCCACTGGCA---GTATT^^ 460

AC 15 - 2 O ATGTACAGACΓGATATITIGTCAGAGGAAGTGAAATΓACAAGAAGTCACTGATACTA - — TΠCTA ATGTro - - - TATTCACATCGTGTCTCATACA 55

_BBBBBBBC____-_B_HBBBB_BBaBBfl CTXπTITCATAAC---CT∞VTAAACTTAAATrt-AAGAGATrTGAAGGA( ^

510 520 530 540 550 560 570 580 590 600

AC15-2A CTCTTTTCATAAC CTCCAGAAACTTATATTGAACAGAGTTAAAGGAGTGGAGGTGGTGTTTGAGATAGAGAGTGAGAGTCC^ 559

AC15-2B CTCTTrTC_VTAAC---CTCCATAAACTrAACTIt_AA(_AGAGTTGAAGGAGTGGAGGT^^ 557

AC15-2C CTCTTTTCATAAC CTCCGTGTGCrTACATTGGATAATTATGAAGGA πXXlRGGTGGTGTTIXlAGATAGAGAGT^ 558

AC15-2D CTCTTTTCATAAC CTCCATAAACTTAAATTGGAAAATTATGAAGGAGTGGAGGTGGTGTTTGAGATAGAGAGTGAGAGTC ^ 568

AC15-2E CTCTTTTCCTAAC CTCCGTAGACTTGAATTGGAGAAATATAAGGGAGTGGAGGTπϊIX-TTTGAAATAGAGAGT CCCACAAGTAGAGAATTG 512

AC15-2G CrrCTTTrCATMC---CTCCATAAACTTAAATTTlAAGAGAGTTAAACX_^^ 560

AC15-2H CTCTrm VTAAC---CTCCATAAACTAAAAATCJ\AGAAGTATAAAGGAGTG^ AGTCCAACAAGTAGAGAATTG 520

AC15-2I CTCTTTTCATAAC---CTCCATAAACTTAACTTGAAC_AGAGTTGAAGG^ 536

AC15-2J CrCTTTTCATAAC---CTCCAGAAACTTATATπ_AACACΛGTTAAAGGAGTGGAGGTGGTG^ 566

AC15-2 CTCTTTTCATAAC crCCATAAACTTrACTTGAAGAAGTATGAAGGAGTGAAGGTGGTGTTTGAGATGGAGAAT CCAACAAGTAGAGAATTG 489

AC15-2N CT _TTTTCΛTAAC---CπCCΛTAAACTTAACTTGAACAGAGTTGAAGGAGTGGAGGT^ 557

AC15-20 CTCTTIΓΓATAACAACCTCCGTAAACTCAACTTGGAGAAGTATGGAGG^ AGAGTTCAACAAGTAGAGAATTG 549

610 662200 6J0 6.0 650 660 667700 680 690 700

AC15-2A GTAACAAC CACCATAACCAACAACAAC--CTAT- TATACTTXXt_AACCTCCA«_AATTGATTCTMWlAATA^ 653 AC15-2B σrAACAACTCGCAATAACCAACAACAGC—CTAT- — TATACTICCCTACCTCXΛCaϊATTTGTΛTCTAAGGW^ 651 AC15-2C GTAACAACTCACAATAACCAACAACAGC— CTAT- TATA rπXrCTAαrrCCΛGGAA ππ'ATCΗUiGGAA λT^ 652 AC15-2D GTAACAACTCACAATAACCAACAACAGC--CTAT TATACTIXXX_AACCΓCX_AGGAA1TTΠA1CTAAGGAATATGGAC__A Λ^ 662 AC15-2E GTAACAACTCAACATAGTCAACAACCAC T ACTT rπiAACXπTGAGGAATTCCATCTAAGTTITATtXXlAAGCATGA n^ 600 AC15-2Q GTAACAACTCACAATAACCAACAACAGC--CTAT TATACTTCCXrrAαrrα»GGAAOTAGTICTAAGGAATATGGACA^ 654 AC15-2H GTAACΛACTCACCATAACGAACAACATC--CTAT TATACTTOnAAαnT AGCATITGGATCTAAGGAATAraiΛC^ 614 AC15-2I GTAACAACTCACCATAACCAACAACAGC--CTGT TATATTTCCC_UVCCT »G⁽-ATTK^TCTAAGGGCTATGGAC^ 630 AC15-2J GTAACAACTCACCATAACCAACAACAGC— CTGT TATATTTCCXΛACCTTXΛGCΛ1TIGGATCT7ΛGGGGTAT^ 660 AC15-2 GTAACAACTCACCATAACCAACAACAGC --CTAT ACrTCTCAACXrrCCAGGAATTATATCTATATAATATtXlACAACAlGAGCCATGTATGGA 580 AC15-2H GTAACAACTCACCATAACCAACAACAAC— CTAT TATACTTTCCMCCTα_!λGGAATTGATTCTATGGAAT^^ 651 AC15-20 GTAACAAC_VTACCATAAACAAC_W_AAC_UK_\ACAAαn7VTATrrC^^ 649

AGT XaGCAACTGGA TA Tπ-Tr ACTπTCtaAA CA C AΕ_ GaATC ^^ 1 1 j 1 r^ 1 1 1 1 r

710 720 730 740 750 760 770 780 790 800

AC15-2A AGTGCAGCAACTGGAATAAATTCTITlACTCTrcαiAAACAAC^ 753

AC15-2B ACHTXΛGCΛACTGGAATAAATrCTTCΛCrrCTrC^^ 751

AC15-2C AG GCAGCAACΠTXIAATAAATTCTT ACT ΓTCCAAAACAACAATCAGAATCA ^ 752

AC15-2D AGTG⁽-AG _AACTtXlAATAAATrCTICACTCTrCCAAAA _MCΛATCAGAATCΛ 762

AC15-2E AGTG--- vACTGGAATAAATTCTTX_ACTCTrTCAAAACAA TCTCAATOXCATTCXΛGAACCTCACAGCCATATACCT^ 694

AC15-2G AGTGCAGC_VACTGGAATAAATTCTΓCA<_TΠTCCAAAACAACAATX_A »_\ 754

AC15-2H AGTGCACK-AACrOGAATAAATTCTTCACTCTTCCAAAACAACAATTΛGAA 714

AC15-2I AGTGCAGOVACTGGAATAAATTXπTCACTCTrCCAAAACΛACAATCAGAATCCCXAT^ 722

AC15-2J AGTGCAGCAACTGGAATAAATTCTTT_ACTCπTCC__AAACAACAATC_VGAATrc 760

AC15-2 AGTG CAACXX3GTATA∞TTCTTC_ATClTCCλAAACAλCλA^ 677

AC15-2N ACHW GCΛACTGXϊAATAAATTCTI λCTCTKXAAA^ 751

AC15-20 AGTGCAACAACTGGAATAAATΠTT ACΛACAATCλGAATσxXΛTTCCACAACCTtΛCΛACCATACACA^ 737

$ Q 0 tt iζ

RI_G3 (real R3_G3) [Strand] AATGGCAAAA GAAGTCGGAG CAAGAGCTAA GTTAGAGCAT CTATTTGACG TCATTATCAT GGTAGATGTC ACTCAAGCAC CCAACAAGAA CACAATTCAA AGTAGTATTT CAGAACAGTT GGGATTAAAA CTGCAAGAAG AGAGCTTGT GGTAAGAGCA GCTAGGGTAA GTGCGAGGTT AAAAATGCTT ACAAGGGTGC TGGTGATA T AGACGATATA TGGTCAAGGC TTGACATGGA GGAACTTGGG ATTCCCTTTG GATCAGATAG ACAACACCAC GGCTGCAAAA TCTTGTTGAC TTCAAGAAGT ATTAGTGCTT GTAACCAGAT GAGAGCTGAT AGAATCTTTA AAATACGAGA AATGCCACTG AATGAAGCAT GGCTTCTTTT CGAAAGAACA GCTAAAAAAG CTCCGAATCT GCATCAAGTA GCAAGAGATA TCGTGGAGGA GTGTGGTGGG C

secure 1 : GAATTCGGTC TTGGTAAGAC AACTCTTGCC TCTTCTGTTT ATGATGAAAT CTCTAGCAAG TITGATGGTT GCTGCTTTC? AAAAATATCT GGGAGGAATC AAGTAATAAA GACGGTATAG AAAGATTGCA AGAAAAAATC ATTTGTCATG TTITGAAACA AGAGCAAGTG GGCGTAGGGA GAGTTGAAGA AGGAAAGCGC ATGATAAAGG ATAGGTTACA ACATAGAAAG GTATTGATTG TGCTTGATGA TGTCGACAAC GTTGAGCAGC TAGCTAGAAC AGTTGGCTGG ATCACATGAT TGGTTTGGTG AAGGTAGCCG CATAATAATC ACAACTAGAG ATGAACATGT ATTAATTGCA CACAAAGTAG ATGTGATACA CAATATAAGC TTGTTAAACA ACGATGAAGC TATGCATCTC TTCTGCAAGC AAGCACCACG GGGTCACAAA CGTATACAAG ATTATGAGCA ACTTTTAAAA CATGTΞGTTT CTTATGCTGG TGGGCTTCCA CTAGCACTGT CGAC

[Strand] ATCGTAACCG TTCGTACGAG ANCGCTGTCC CTCCTTCATC TTTTGTCATA TGTCATATTC TCATONATTW i TGCCACATΪJT AATTTTGTGG TTATTTTAAA TΓAATΠTTA TΓCCACATGT CATTTTATGA GTΠTΓCTAT 41 TTTATTGAGT TTCACATAAT ATITAAATGT AATAACAATA AATGCATATT TATTΠTC T AAATAAACG 11 CATATAATAT ATAGATTAAA ATCATATAAT ACATAGGTTA AACTCATATA ATACATATGT TCATCCCCAG 81 TTTATTTATA TGTCTCATCC TTAATTTATT TATTATTTAT TTATTAGAGT AGATGATCTT TGTGATATTA 51 AAAATTTAAT TTGTTCAAAA TTTAAAATTA TTAATAATCC CACAATTTGA ATAAAATTAA AAAAAATGGN 21 CCCACCATTA GTCCATCACT TTTTCAGCTC ATCAATATCG TGAGTATTCT CXriTCGTTTC CACCCTAATC 91 AATATTTCCA GCGAATGACA GACTCCTACG GCGTTTCTGA ATTTGCGTTC CGACACTGTT CATTGAAGGA 561 GATAATAAAT CAAATGGAGC TGCTCCAATG TTCATTGCTG ATGAAAGGTG AATTGTATGT GAAGANAATG 631 TCAGCGATC. ATCTCCATCC GGAACCCACC ACATTATCAG TGTACCACCA AACCACTCAA AACGGYGGAA 701 GTAGRRAKAC WRKAAAGTCA TGAAGAATAG ATTATTTTTG TCCTCATGGG CTGACTGAGG AGCGGGTTTA 771 GTTCATCATT TTTCTTTGAN CAAAGAATTA TCGGTCCATC GAATTTTTAC ATCGACAAAG AAGTTTCACT 841 TCGCAATGTT TTGTTAAACA ATTTTTAATC TTTTTATCTT TTCGTTGAAA CTCCTCAATT GCAACTTGCA 911 ACTTGCAACT TTTGGGCCCA CAAATTTGTG GTGGGCGTTA ATTTAATCCA CATATTCACT GTAAACAATA 981 ATTCAAATCG ATCTCTGTTC ATCCAATTCA TCAACATCTC TTGATAATTG AAATCATTCA CGCTTCATCC 1051 ATTTCATCCA CATCTATACT ATATTCTCTG CTCTTATCAT ATTAAACGAT GGCTGAAATC GTTCTTTCTG 1121 CCTTCTTGAC AGTGGTGT T GAAAAGCTGG CATYTGAAGC CTTGAAGAAG ATTGTTCGCT CCAAAAGAAT 1191 TGAATCTGAG CTTAAGAAAT TGAAGGAGAC ATTAGACCAA ATCCAAGATC TGCTTAACGA TGCTTCCCAG 1261 AAGGAAGTAA CTAATGAAGC CGTTAAAAGA TGGCTGAATG ATCTCCAACA TITGGCTTAT GACATAGACG 1331 ACCTACTTGA TGATYTTGCA ACTGAAGCTG TTCAWCGTGA GTTGACCGAG GAGGGTGGAG CCTCCTCCAG 1401 TATGGTAAGA AAACTAATCC CAAGTTGTTG CACAAGTTTC TCACAAAGTA ATAGGATGCA TGCCAAGTTA 1471 GATGATATTS CCACCAGGTT ACAAGAACTG GTAGAGGCAA AAAATAATCT TGGTTTAAGT GTGATAACAT 1541 ATGAAAAGCC AAAAATTGAA AGGTATGAGG CGTCTTTGGT AGATGAAAGC GGTACTGTCG GACGTGAAGA 1611 TGATAAGAAA AAATTG TGG AGAAGCTGTT GGGGGATAAA GATGAATCAG GGAGTCAAAA CTTCAGCATC 1681 GTGCCCATAG TTGGTATGGG TGGAGTTGGT AAAACAACTC TAGCTAGACT TTTGTATGAT GAAAAGAAAG 1751 TGAAGGATCA CTTCGAACTC AGGGCTTGGG TTTGTGTITC TGATGAGTTC AGTGTTCCCA ATATAAGCAG 1821 AGTTATTTAT CAATCTGTGA CTGGGGAAAA GAAGGAGTTT GAAGACTTAA ATCTGCTTCA AGAAG TCTT 1891 AAAGAGAAA TTAGGAACCA GCTATTTCTA ATAGTTITGG ATGATGTGTG GTCTGAAAGC TATGGTGATT 1961 GGGAGAAATT AGTGGGCCCA TTCCTTGCGG GGTCTCCTGG AAGTAGAATA ATCATGACAA CTCGGAAGGA 2031 GCAATTGCI AGAAAGCTGG GCTTTTCTCΛ TCAAGACCCT CTGGAGGGTC TATCACAAGA TGATGCTTTG 2101 TCTTTGTI G CTCAACACGC ATTTGGTGTA CCAAACTTTG ATTCACΛTCC AACACTAAGG CCACATGGAG 2171 AACTGT TGT GAAGAAATGT GATGGCTTAC CTCTAGCYTT AAGAACACTT GGAAGGTTAT TAAGGACAAA 2241 AACAGACGAG GAACAATGGA AGGAGCTGTT GGATAGTGAG ATATGGAGGT TAGGAAAGAG CGATGAGATT 2311 GTTCCGGCT TTAGACTAAG CTACAATGAT CTTTCTGCCW CTTTGAAGCT RTTRTTTGCA TAYTGCTCCT 2381 TGΪTTCCCAA GGACTATGAG TTTGACAAGG AGGAGTTGAT TCTATTGTGG ATGGCAGAAG GGTTTTTGCA 2451 CCAACCAACT AYAAACAAGT CAAAGCAACG KTTGGGTCTT GAATATTTTR AAGAGTTRTT GTCAAGRTCR 2521 TTTTTTCAAC ATGCTCCTAA TRRCAAATCS TTGTTTGTGA TGCATGACCT AATGAATGAT TTGGCTACAT 2591 TTGTTGCTGG AGAATTTTTT TCAAGGTTAG ACATAGAGAT GAAGAAGGAA TTTAGGATGS AATCTTTGGA 2661 RAAGCACCΞl CATATGTCAT TTGTATGTGA GRATTACATA GGTTACAAAA RGTTCGAGCC ATTTAGAQGA 2731 GCTAAAAATT TGAGAACATT TTTAGCATTG TCTGTTGGGG TGGTAGAAGA TTGGAAGATG TTTTACTTAT 2801 CAAACAAGGT CTIGAATGAC WTACTTCARG ATTTACCATT GTTAAGGGTC CTRAKTTTGA TTRRTCTTAY 2871 AATAASYRAG GTACCARAAK TCGTSGGTAG TATGAASCAC TTGCGGTATC TTAATCTATC WGRAACTTWA 2941 ATCACMCATT TACCGGAAWA TKTCTGCAAT CTTTATAATT TACARACCCT GATTGTKTCT GGCTGTGAMT 3011 ATTTAGTTAA KTTGCCCAAR ACCTTCTCAA ASCTTAAAAA TTTGCASCAT TTTGACATGA GGGRTACTCC 3081 KAAKTTRAAR AACATGCCCT TARGGATTGG TGARTTGAAA ARTCTACAAA CTCTCTTYMG TAACATTGGC 3151 ATAGCAATAA CCGAGCTTAA GAACTTGCAM AAYCTCCATG GGAAARTTTG TATTGGCGGG CTGGGAAAAA 3221 TGGAAAATC MGTKGGATGC ACGTTAAGCG AACTTGTCTC A:AAAAAGGT T AATGARTT ANAAACTGGR 3291 WTKGGGGGTG ATRAATTTAA TGTTTTCCGA AATGGGAACA CTTGAAAAAA AAGGTCCTC AATGAATTGA 3361 ATGCCTCATA ATGGTAYTCY AAMWAARRRY YY TAR WAT TWMGKAWRRK GKGTTYATRR TKTTMYRAA 3431 WAGRGTKTT-. KARGTAGGTT TCATCCAATC ACCCAAGTGG GAAAATAGAT GATATTTTCA GGGCYTACTG 3501 ATGAGATG 3 GAGAGGTATG ATAGGGTOTC TTGGGGCGGT AGAAGAAATA AGCATCCATT CTTGTAATGA 3571 AATAAGATAT YTGTGGGAAT CAGAAGCAGA GGCAAGTAAG GTTCTTATGA ATTTAAAGAA GTTGGATTTA 3641 GGTGAATGTS AAAATTTGGT GAG1TTAGGG GAGAAAAAGG AGGATAATCA TAATATTAAT AGTGGGAGCA 3711 GCCTAACATC TTTTAGGAGG TTGAATGTAT GGAGATGTAA CAGCTTGGAG CATTGCAGGT GTCCAGATAG 3781 CATGGAGAA TTGTATATGC ACATGTGTGA TTCAATNACA TCCGTCTCCT TCCCAACAGG AGGAGGACAG 3851 AAGATCAACΓT CACTTACCAT CACTGATTGC AAGAAGCTTT CGGAAGAGGA GTTGGGAGGA CGAGAGAGGA 3921 CAAGAGTGC TATAAACTCA AAAATGCAGA TGCTTGAATC AGTAGATATA CGTAATTGGC CAAATCTGAA 3991 ATCTATCAGT GAATTGAGTT GCTTCATTCA CCTGAACAGA TTATATATAT CAAACTGTCC GAGTRTGGAG 4061 TCATTTCCT3 ACCATGAGTT GCCAAATCTC ACCTCCTTAA CAGATCGAAG GAGAGGACAG CGATTTTCGT

RD31-E169 [Strard]

4131 ACGAACGGTT ACGATTCGAC TGGCCGTCGT TTT

Further Characterization of RG2 Family Members:

Further sequencing of cloned RG2 polynucleotide sequences, as discussed above, identified additional RG2 species, listed below. Additionally, further sequencing of the 5 ' sections of RG2 sequences listed above resulted in modified and/or new sequence information, also listed below. The AC 15 sequences found in the 3' sections of RG2 family have not changed.

Listed below are: four full length species, RG2A, RG2B, RG2C and RG2S; two near complete, but with a gap in the largest intron, RG2D and RG2J; three nearly complete RG2 gene sequences, RG2K, RG2N, and RG2O. The deduced translation products (polypeptides) encoded by these RG2 species are listed below. The polynucleotide sequences do not contain any gaps (as with some of the polynucleotide sequences), because all of the gaps in the sequences are in introns, i.e., there are no gaps in exon, or coding, sequences.

They include: an RG2A polynucleotide sequence (SEQ ID NO: 87) and its deduced polypeptide sequence (SEQ ID NO:88); an RG2B polynucleotide sequence (SEQ ID NO: 89) and its deduced polypeptide sequence (SEQ ID NO: 90); an RG2C polynucleotide sequence (SEQ ID NO: 91) and its deduced polypeptide sequence (SEQ ID NO: 92); an RG2D polynucleotide sequence (SEQ ID NO:93) and (SEQ ID NO:94), and its deduced polypeptide sequence (SEQ ID NO: 95); an RG2E polynucleotide sequence (SEQ ID NO:96) and its deduced polypeptide sequence (SEQ ID NO: 97); an RG2F polynucleotide sequence (SEQ ID NO: 98) and its deduced polypeptide sequence (SEQ ID NO: 99); an RG2G polynucleotide sequence (SEQ ID NO: 100) and its deduced polypeptide sequence (SEQ ID NO: 101); an RG2H polynucleotide sequence (SEQ ID NO: 102) and its deduced polypeptide sequence (SEQ ID NO: 103); an RG2I polynucleotide sequence (SEQ ID NO: 104) and its deduced polypeptide sequence (SEQ ID NO: 105); an RG2J polynucleotide sequence (SEQ ID NO: 106) and (SEQ ID NO: 107), and its deduced polypeptide sequence (SEQ ID NO: 108); an RG2K polynucleotide sequence (SEQ ID NO: 109) and (SEQ ID NO: 110), and its deduced polypeptide sequence (SEQ ID NO: 111); an RG2L polynucleotide sequence (SEQ ID NO: 112) and its deduced polypeptide sequence (SEQ ID NO: 113); an RG2M polynucleotide sequence (SEQ ID NO: 114) and its deduced polypeptide sequence (SEQ ID NO: 115); an RG2N polynucleotide sequence (SEQ ID NO: 116) and its deduced polypeptide sequence (SEQ ID NO: 117); an RG2O polynucleotide sequence (SEQ ID NO: 118) and its deduced polypeptide sequence (SEQ ID - NO: 119); an RG2P polynucleotide sequence (SEQ ID NO: 120) and its deduced polypeptide sequence (SEQ ID NO: 121); an RG2Q polynucleotide sequence (SEQ ID NO: 122) and its deduced polypeptide sequence (SEQ ID NO: 123); RG2S polynucleotide sequence (SEQ ID NO: 124) and its deduced polypeptide sequence (SEQ ID NO: 125); an RG2T polynucleotide sequence (SEQ ID NO: 126) and its deduced polypeptide sequence (SEQ ID NO: 127); an RG2U polynucleotide sequence (SEQ ID NO: 128) and its deduced polypeptide sequence (SEQ ID NO: 129); and RG2V polynucleotide sequence (SEQ ID NO: 130) and its deduced polypeptide sequence (SEQ ID NO:131); and, an RG2W polynucleotide sequence (SEQ ID NO: 132) and its deduced polypeptide sequence (SEQ ID NO: 133).

Characterization of New RG Family Groups and RG Species:

Further BAC insert characterization and sequencing, as discussed above, identified new RG polynucleotide sequences. The new sequences were characterized as belonging to new RG families; designated RG5 and RG7. These RG polynucleotides sequences, and their predicted translation products (the polypeptides which are encoded by these sequences) are summarized and listed below.

Identified and listed below is an RG5 family member, designated as the RG5 polynucleotide sequence set forth in SEQ ID NO: 134, and its deduced polypeptide sequence (SEQ ID NO: 135). This sequence contains an NBS region sequence.

Also identified and listed below is an RG7 family member, designated as the RG7 polynucleotide sequence set forth in SEQ ID NO: 136. No deduced polypeptide sequence is given for the new RG7 family member as this sequence appears to be a pseudogene.

RG2A polynucleotide sequence (SEQ ID NO:87)

AAAGTTCATATCCAAGCTTGCCCTCCAACTCTAGCTCCTTCAATGGCACC TCCTTCTCTTCAAAAGCACACAAGAACACTTTCAAGCTCAACCACACTCA CACAAGCTCTAGAACGAGGGTTAGGGCACATTTAGGGTTTTGCTCTCTGG

AAATGGTGTCTAAAAGTGAGGCCATAATGTTCCTTATATAAGGCTCACTC CCACAATTAGGCTTTCAATCTGAACGTANTACGCCCAGTGTACACTATGG TACGCCCAACGTACTCGGTAGTCTCCGCGTCAANAATACACTCATGAGTA WO 98/30083 _{i Λ} . PCT/US98/00615

104

CGCGCAACGTACTTTCCCTTACGCCCAGCGTACTCAAAAGCCAAACATTC TTTTCAAGGACTAATTTTGACAACTTGAGGAAAGAAAAGGATCAAAGANA TATACTTGAATTCCGGGATGTTACAATGAAGTTGANACCTTGGCTAAAAA ATTAAATTGGTTGTGGAAGCCGTTGGCTGAGCAAGCAACAAGGGTAAAAT TCGTAATCTACAAATGGTGTTATTTTCTATTTCTTCTTATTATTTTACTT

GATTTACGGGTAGTTTTTTTTTCTTACAAAAAATATTAAAGTTGATAAAG TATAGCCACTAAAATTGACTTTTTCCAAAACATAATGTCAAATGGTGCGT ATATGTATCATGTTGTATTANATAATGAATATGATGATNCTGTTCTATTT AANCCGAAAAAATTATCTAATGATTTTATATTGGAAAACAAAGTTGTGAT TTTTNGCATAATATAATCAAATCCNCTTTTGTNTGGGAGGTGGATAAATG TGGTAAATTTANAACAAGTGTTTTNACNTTGAAGGGTNTGGAAAGGTTGA AAAAAGTTAAAATGATAAAATGTTTACACAAATGTTGTATCCGACTGAAT ATNATGTTTAAGGATNATTGTATTAAATTGTTGATATATAGTAAGCATAA ATATTTAGAATTGTGACTTAAATTTATAAGTTATNCNAACTGGATTGAAA CATTTTTGATATANATTAGGAATGAAAATGAGCAACCCTAACATACTTAT

CTTTGGTAGTTTGGTTATTATATTTTTATTANAATATAGAANCATCCCTT TATTTTAAACCCATATTGTGGACGGACTTGAATAAATGGGAAAAATGTAC CTTGCTATTTAGCACAAAAAAATTATAAAAATGTACATTGCTATTTAGCA CAAACAAAAAAAAAAAACTTATCCTTTTTGCATTAGGTCACAAAGAAATA TAAAATGGGAAATGTGTTGCTATTTAATGCACTAAAAGAAACTATTTTGC CTTTATTAAACCGGGTAAACCAATAGAAAAATGGAAGTACATTGTCATTT AGCATGAAAAAAAATAACTTTCCATTTTTTGCATCCGGTCACAATAATAG AAAAATGAAAGTACGTTGCTATTTAGCGAAACTAACTTCCTTTTTTCTTT TTGGCATCGTATCATAAAATATAGACTAAAATACGTTAGTTTTACATTTT TAATACATTGAAATGTCTAATCCACATGTTATTCTATAAAAAGGGAAATG

TAATTTACTTATTCTTTGATTCTTTGGCTTCTTTTTAGTACCCAAAACAT CCCTCTATCCATCTATTCCAACTAAAATAATGAAAACTATATTCCTTCCA TTGTAGGGATGTTATAAATTTTGTAATTGTTTTTATGCAAAAAAGTGTTT TTTGTTAACTAGATTAACGAGATTCATTTTTCAGCATTTTAGGAGAAGTT CATCCATCTTTTGGATATGAAGTGCAAGCCAAGTTCTTTAACATGGAATA TGAGGTCCCTATATGCTCAAAAAATAGCAAATGAGAAATTTTTTAAATTG GATCCCCATAAAAGAAAATTTGTTAATGGTTGTTTTAATATTGGTCAATG TGTCCACCGGATGAGCATAATACTAGTTTATAAGGGGTAAAGGTGGGTTT GGTGGGCCCATTTATCTTTATTATTTCTAAAAGTCAGAATTAAGTAAAAA AAATTATAAGATAAATACCATAAGGATAAAAAATCATTTTATTTGGACCA

AAGACCAAAGTTGTTAAGGGGCTGTTTGTTTTTTTTGTGAAGAGCTGTGC AACCACTTTTGTCTGCGCCGCACAGACAACGTGCAGACATATGCCCTCGC AGAGTGTTTGTTTTTTGAAAGTGCGCAGACCAAAAAAACGTCTGCGCGAG GTCATCCTGGCGCATATATGTGTCACTGTCTTCAAAGGTCTTCAGACCTC ATTTTAACCAAAAAAAAAAAAGACCACCGGTTTTTTTTTTTTTTTTNTTC

TTTCTCTTGTAGCTGAAAATGCATTTTTAATCTTTATGACATGAAATTAA GTTTGAAAAATTAATTTATTTCAACAGCTGTAGACGTTAAAAACAAACAG TCTTCTTGTTGCAGACTGTGGACATTTGGTCCACCTCTTCTACCGCAGAG ACTTGCAGATGTGGTCCGCAGACTGCAGACATTTTGGCTTCAAATAAACA AACATCACCTAATTTGACTACACCACACGGACCTCCAATGTAACAAAAAA AAGGTTGAAACAAAGTTGCCTATTTCTCCATATCCAGGGGCCATTTATGT AAGAGTTATCTAAATTTTAGTTCGGTAGATCAGTTCTCACATTTTAACCG GGTAAAGTGTATGTGTGTACGCGCGCACCTGAAAGGTTTGAANGTAACTT CCAAACTGAANCAANAATCGATATGAAGTATCAAGTTAGAGGTTCAATTG GTGAAGGAATCAGCTGGAGGTTGGGGAATCGAGCTTCCACTATTAAGGTA AAATCCATAACCCTAAATGTTGGTACGCTCATATATCAAATTGCGTGTTT TGTTGAATGAAAAAAGCATGCTCAAAAAACCAGTGTAAGGCACGGTATAT GACATATTTATAGTTACTGATAACAAATTATGATAATTTTGGGTTTACGT AAGTTAGGATTCGTACTTCAACCAAATGTAATAGTTTTTGTGAGTCTATC TATGTATTTGGGGAATCACATTAGCAACGGGATTGTACTAGTAATTCGAA AAAGTCTTTTAAATAATTTTTCTGTTTATAATTTATGAATAGTTTTAGCG ACATCTAATATTAAATAGAATGTATCTGATATTGAATTAATGTCCTTAAT GTGAACATAGACCTTTTCCATTTACTAATGCCTAATTATTAGTTTCTAAT

CAATAAATTTTAATTTCTGTTTTATGCTTCTAAGACAATAAAAATCCATG ATTTACCTTTAAATATTAACAAAAATGACCATAAATAAATAAAAAATTAG GATACCAAACCCCCCCGCCATGCCCAATGTCTAAATATTCTTGATGCTTT TGCTTTTCCCTCTTTTCCTTGTTAGTCTATTATTCTGGAGAGTTTGAGAG AGTTTCATACAAGAAAATTTCAAGAAGAAAGCAAAGGTCCAGGTATTCTC TTTTCTTAATTATGTATTAACTTACAAGCATTTTTTACACGATCCATGGT TTTTTGTGTATGTTTTTCAAATTGAAACTAGATTGGGACTTTTGCCCTTG ATGATTCATAAGATATTGCATGGAGTTGAGATTGTGTAAGAAAAGTGGTG AATAGAAAGAGCAAGTGAATCCAGATATAGTATTGGTAATATATGATGAT GAGATAGAGATATGTTAAAACTGGCTAGAAAATTGTTTTAATTTGAAATT TAGGTTGTTGAATTTGAAAGATACCAAGCTAATAACTAATTAGTTATGCT AAATAGTTATAAAGAACAACAAACTCGTAGTTTTTTTTTCATGATTTTCA ACCTCTTCGTACCAAACTAAATTATAACAAAATTGAATATCATTCTCTGC AATCAATTTTAACTTTTGTTATTATCATCATGTCTAAAATTGCCACAAGT TTATTTTCATAGTCATATTGGATTATGAAAGGACTATTTTTACCAATTAC ATCTTTACTTTATGGCCAAAGCTAATACAATCCGACTAAACTAAAGGATT CTAGGATGCATATAGTTTGCTCCCCGATTATAGATTTCTATCTAATTTGT CTATTGTACTAATTTAGGTGCCACCACAAGTAAATTCCTGAAATGGATGT CGTTAATGCCATTCTTAAACCAGTTGTCGAGACTCTCATGGTACCCGTTA AGAAACACATAGGGTACCTCATTTCCTGCAGGCAATATATGAGGGAAATG GGTATCAAAATGAGGGGATTGAATGCTACAAGACTTGGTGTCGAAGAGCA CGTGAACCGGAACATAAGCAACCAGCTTGAGGTTCCAGCCCAAGTCAGGG GTTGGTTTGAAGAAGTAGGAAAGATCAATGCAAAAGTGGAAAATTTCCCT AGCGATGTTGGCAGTTGTTTCAATCTTAAGGTTAGACACGGGGTCGGAAA GAGAGCCTCCAAGATAATTGAGGACATCGACAGTGTCATGAGAGAACACT

CTATCATCATTTGGAATGATCATTCCATTCCTTTAGGAAGAATTGATTCC ACGAAAGCATCCACCTCAATACCATCAACCGATCATCATGATGAGTTCCA GTCAAGAGAGCAAACTTTCACAGAAGCACTAAACGCACTCGATCCTAACC ACAAATCCCACATGATAGCCTTATGGGGAATGGGCGGAGTGGGGAAGACG ACAATGATGCATCGGCTCAAAAAGGTTGTGAAAGAAAAGAAAATGTTTAA TTTTATAATTGAGGCGGTTGTAGGGGAAAAAACAGACCCCATTGCTATTC AATCAGCTGTAGCAGATTACCTAGGTATAGAGCTCAATGAAAAAACTAAA CCAGCAAGAACTGAGAAGCTTCGGAAATGGTTTGTGGACAATTCTGGTGG TAAGAAGATCCTAGTCATACTCGACGATGTATGGCAGTTTGTGGATCTGA ATGATATTGGTTTAAGTCCTTTACCAAATCAAGGTGTCGACTTCAAGGTG TTGTTGACATCACGAGACAAAGATGTTTGCACTGAGATGGGAGCTGAAGT TAATTCAACTTTTAATGTGAAAATGTTAATAGAAACAGAAGCACAAAGTT TATTCCACCAATTTATAGAAATTTCGGATGATGTTGATCCTGAGCTCCAT AATATAGGAGTGAATATTGTAAGGAAGTGTGGGGGTCTACCCATTGCCAT AAAAACCATGGCGTGTACTCTTAGAGGAAAAAGCAAGGATGCATGGAAGA ATGCACTTCTTCGTTTAGAGCACTATGACATTGAAAATATTGTTAATGGA GTTTTTAAAATGAGTTACGACAATCTCCAAGATGAGGAGACTAAATCCAC CTTTTTGCTTTGTGGAATGTATCCCGAAGACTTTGATATTCTTACCGAGG

AGTTGGTGAGGTATGGATGGGGGTTGAAATTATTTAAAAAAGTGTATACT ATAGGAGAAGCAAGAACCAGGCTCAACACATGCATTGAGCGGCTCATTCA TACAAATTTGTTGATGGAAGTTGATGATGTTAGGTGCATCAAGATGCATG ATCTTGTTCGTGCTTTTGTTTTGGATATGTATTCTAAAGTCGAGCATGCT TCCATTGTCAACCATAGTAATACACTAGAGTGGCATGCAGATAATATGCA CGACTCTTGTAAAAGACTTTCATTAACATGCAAGGGTATGTCTAAGTTTC CTACAGACCTGAAGTTTCCAAACCTCTCCATTTTGAAACTTATGCATGAA GATATATCATTGAGGTTTCCCAAAAACTTTTATGAAGAAATGGAGAAGCT TGAGGTTATATCCTATGATAAAATGAAATATCCATTGCTTCCCTCATCAC CTCAATGTTCCGTCAACCTTCGCGTGTTTCATCTACATAAATGCTCGTTA

GTGATGTTTGACTGCTCTTGTATTGGAAATCTGTCGAATCTAGAAGTGCT TAGCTTTGCTGATTCTGCCATTGACCGGTTGCCTTCCACAATCGGAAAGT TGAAGAAGCTAAGGCTACTGGATTTGACGAATTGTTATGGTGTTCGTATA GATAATGGTGTCTTAAAAAAATTGGTCAAACTGGAGGAGCTCTATATGAC AGTGGTTGATCGAGGTCGAAAGGCGATTAGCCTCACAGATGATAACTGCA

AGGAGATGGCAGAGCGTTCAAAAGATATTTATGCATTAGAACTTGAGTTC TTTGAAAACGATGCTCAACCAAAGAATATGTCATTTGAGAAGCTACAACG ATTCCAGATCTCAGTGGGGCGCTATTTATATGGAGATTCCATAAAGAGTA GGCACTCGTATGAAAACACATTGAAGTTGGTTCTTGAAAAAGGTGAATTA TTGGAAGCTCGAATGAACGAGTTGTTTAAGAAAACAGAGGTGTTATGTTT AAGTGTGGGAGATATGAATGATCTTGAAGATATTGAGGTTAAGTCATCCT CACAACTTCTTCAATCTTCTTCGTTCAACAATTTAAGAGTCCTTGTCGTT TCAAAGTGTGCAGAGTTGAAACACTTCTTCACACCTGGTGTTGCAAACAC TTTAAAAAAGCTTGAGCATCTTGAAGTTTACAAATGTGATAATATGGAAG AACTCATACGTAGCAGGGGTAGTGAAGAAGAGACGATTACATTCCCCAAG CTGAAGTTTTTATCTTTGTGTGGGCTACCAAAGCTATCGGGTTTGTGCGA TAATGTCAAAATAATTGAGCTACCACAACTCATGGAGTTGGAACTTGACG ACATTCCAGGTTTCACAAGCATATATCCCATGAAAAAGTTTGAAACATTT AGTTTGTTGAAGGAAGAGGTAAATATAAATTTTTAATGCTAATACATTAC AAAGGATCTTTTCAGTTAAATCTTTCAAAATATATTGTAATTTGATTGTA TGGGGTATTATTGTTGGATGGGACTATTAATAAATGATTATCTTGCAGGT TCTGATTCCTAAGTTAGAGAAACTGCATGTTAGTAGTATGTGGAATCTGA AGGAGATATGGCCTTGCGAATTTAATATGAGTGAGGAAGTTAAGTTCAGA GAGATTAAAGTGAGTAACTGTGATAAGCTTGTGAATTTGTTTCCGCACAA GCCCATATCTCTGCTGCATCATCTTGAAGAGCTTAAAGTCAAGAATTGTG GTTCCATTGAATCGTTATTCAACATCCATTTGGATTGTGTTGGTGCAACT GGAGATGAATACAACAACAGTGGTGTAAGAATTATTAAAGTGATCAGTTG TGATAAGCTTGTGAATCTCTTTCCACACAATCCCATGTCTATACTGCATC ATCTTGAAGAGCTTGAAGTCGAGAATTGTGGTTCCATTGAATCGTTATTC AACATTGACTTGGATTGTGCTGGTGCAATTGGGCAAGAAGACAACAGCAT CAGCTTAAGAAACATCAAAGTGGAGAATTTAGGGAAGCTAAGAGAGGTGT GGAGGATAAAAGGTGGAGATAACTCTCGTCCCCTTGTTCATGGCTTTCAA TCTGTTGAAAGCATAAGGGTTACAAAATGTAAGAAGTTTAGAAATGTATT

CACACCTACCACCACAAATTTTAATCTGGGGGCACTTTTGGAGATTTCAA TAGATGACTGCGGAGAAAACAGGGGAAATGACGAATCGGAAGAGAGTAGC CATGAGCAAGAGCAGGTAAGGATTTCAATTTCACTGTCTTAATTAATGAT TAAGCTCCTGCTTTTTGAATAAAAAAGGGACAAACCATTTCATGACTTAA TGTAGCAATACAAGTCATGTATAAGAGTGACCAACTCTTTTTTATTTATA AAATGACTACAAAATATTTTTTTTCATTAGAGATCATGTATAAATGTGAC TAATTTTTCATCACCTAACTTTAGTTGATAAATCTTTATAAATGTCACTA GTTACTTTTCAGTAAAATAACAAATTTAATAAATTATCAACAAAAAGCAT CAACTAAAAAAATCCCACAACCCGTAATAATTTAAAATAAAAGGATTTAA CATCTAATACGAACAATTTTTTTTCTAAACATGATTTGGACCAAATATCA

CCAGCAACTCAAGTTTGGAATCGATTCAGCTTAAAACTTGACCAGCATAA TTAGATAGATGAGAGTTGAAGCTAAAGTGCCTATATAAGTTCGTTTCATC TTTTTTCTTGATCTTGATAGCAAGTTGAATGATTTTCTTCTTCAAAATTG ATAAAAATCTACATTATAAAGAGACTAGCTTGAAAAAAAATGGTCTAGGT GGGTCTTGGGTTCTGGTAGATGAAGATGGAAGGGGAGAGTAGATTTCAAA GACACAACACATCCTTCATTTTATTTATTTATTATTATTATTATTTTTTG ATATCTTGCTCATATTTGTTACAGATATGTGAGGTCTATTAATCTTTTTA AATATATAAAAAAATAAATAACATAAATGAGAAAATTAAATAAAGAATAA ATTAATAAGGGCACAATAGTCTTTTTAGGTAAGACAAGGACCAAACACGC AACAAAAATAAACAGTAGGGACCATCCGATTTAAAAAAAATAATTAGGGA

CCAAAAACATAAATTCCCCCAAACCATAGGGACCATTCATGTAATTTACT CTTACTTTTCGTTTTGTTCATATTTGGGTAACTATTTTTTTTGTACACAT CTAGGTAACGAACTTGTTGAAGTGTTCCCATTTAGGATGTGACCTACTAC AACCGATCATAATAGTCATATGTGAACACTTCCAACAACTTTATTACTTA GGTGTGTACAAAAAAACAATAGTTACCATGATGTGAACATACTGAAAAAT

TAATTACCTTAGCAAGTTATTTTCCCATTTAGGTTGTATGGAAACAGTTC CGTGAGACCGTGACTTGGATGGTAGATAAATTTAGTAAACTTAACCCTTC AATTAACCTACCTTTTTCTTATTAACTCAATTTCAACCTAAATTCTGATT lUo

CTTGTTTGAAAGTAAGTTGCATCTTTATTTTTGTATTATCTTGTTGCATA GGATCCTTAGCATCTTTTAATAATTTATTTGAAGGTGAAAGATCCAACTA TTTTTAATCTGTTGGCATTTTCCATCATTTGCAACTGTTTCTTGAAAAAA AAATACCTAAAATCAAAATAACCATTTTCAAATCCAAAATTATAAGAGAG AATTGTAAATGGACATGGAATCATAAATCATTAACACAGTTCAGTAAACA AGTTGCTAATTACATTTCTTGCTGTGCAGATTGAAATTCTATCAGAGAAA GAGACATTACAAGAAGCCACTGACAGTATTTCTAATGTTGTATTCCCATC CTGTCTCATGCACTCTTTTCATAACCTCCAGAAACTTATATTGAACAGAG TTAAAGGAGTGGAGGTGGTGTTTGAGATAGAGAGTGAGAGTCCAACAAGT AGAGAATTGGTAACAACTCACCATAACCAACAACAACCTATTATACTTCC CAACCTCCAGGAATTGATTCTATGGAATATGGACAACATGAGTCATGTGT GGAAGTGCAGCAACTGGAATAAATTCTTCACTCTTCCAAAACAACAATCA GAATCCCCATTCCACAACCTCACAACCATAAAAATTATGTATTGCAAAAG CATTAAGTACTTGTTTTCGCCTCTCATGGCAGAACTTCTTTCCAACCTAA AGCATATCAAGATAAGAGAGTGTGATGGTATTGGAGAAGTTGTTTCAAAC

AGAGATGATGAGGATGAAGAAATGACTACATTTACATCTACCCACACAAC CACCACTTTGTTCCCTAGTCTTGATTCTCTCACTCTAAGTTTCCTGGAGA ATCTGAAGTGTATTGGTGGAGGTGGTGCCAAGGATGAGGGGAGCAATGAA ATATCTTTCAATAATACCACTGCAACTACTGCTGTTCTTGATCAATTTGA GGTATGCTTTGTACATATTCAATTATTTATTTAATTTCCTTTTTTATTTG CAATATTCTATAAATAATACATTTTATACCCACTATACTAAGATAATAAT TACCTAGAGGGATGGATGCTATGACACAGCTGCTACACTTCAGAAACTCT AGTAAGGGCAGTTATGGAAGTTCAATAAAATGATAATGGCATCTTTTGAT GGGTAATATAGGCAATTTAAGTTTTATTTCTGTTAAAGCAGTATTTAGCA AGTACTGGCCAGTAGGAGAGGAGAATATCACCTTTTGTGAAAATCTGGTC ATTGTACCCAGAATTTAGTTAAATGTAACATTTTAGATATCAGGGGTCAT CAGGTGACAGATATTGTAGAATAGAACAATATATAATATCACCCAAAACT ATTTTTTCTAAGGTTATTCTGTTAAATATGTGCTTTCTTGTTTTCATNGA ATTNGCATTCGTATATTTTAGGTGTTAAAGTGATTTTNTCTTCAATAAAT CCC G AA ATTAATT AAAAAA AAAAAAAC AAAAGT AC ATTTTTGATGTGGAG

AGCACTGGTATCACTTAGTATATAAAAAGCTTGATTTTGAATTAACTTTC TTATACAAAAGTTGTGTATATAGTTTAATTAGTTTTACATCATTTTTCCA TGTGGTGTTGCAGTTGTCTGAAGCAGGTGGTGTTTCTTGGAGCTTATGCC AATACGCTAGAGAGATGAGAATAGAATTCTGCAATGCATTGTCAAGTGTA ATTCCATGTTATGCAGCAGGACAAATGCAAAAGCTTCAAGTGCTGACAGT AAGTGATTGCAAAGGGATGAAGGAGGTATTTGAAACTCAATTAAGGAGGA GCAGCAACAAAAACAACAAGAGTGGTGCAGGTGAGGAAGGAATTCCAAGA GTAAATAACAATGTTATTATGCTTTCTGGTCTGAAGATATTGGAAATCAG CTTTTGTGGGGGTTTGGAACATATATTCACATTCTCTGCACTTGAAAGCC TGAGACAGCTCCAAGAGTTAAAGATAACATTTTGCTACGGAATGAAAGTG

ATTGTGAAGAAGGAAGAAGATGAATATGGAGAGCAGTAAACAACAACAAC AACAACAATAACGAAGGGGGCATCATCATCATCATCTTCTTCATCTTCTA AGGAGGTTGTGGTCTTTCCTCGTCTCAAATCCATTGAACTAAATGATGTA CCAGAGCTGGTAGGATTCTTCTTGGGGAAGAATGAGTTCCGGTTGCCTTC ATTGGAAGAAGTTACCATCAAGTATTGCTCAAAAATGATGGTGTTTGCAG CTGGTGGGTCCACAGCTCCCCAACTCAAGTATATACACACAGAATTAGGC AGACATGCTCTTGATCAAGAATCTGGCCTTAACTTTCATCAGGTATATAT ATTTCTTTAATTGGCATCATCTAATTAAGAAAGATATCATTCCTGCCAAG TAAATTTACTTCAAACACATTCACACTGGTTTCAGTCTAAGTTTATGTTG TTCTAGGAAGGCCAAAATGGGAAAGCAAGATAGGGAAAAATAGTGTATTT CAGTGGAAAGGGTATTTTAGGTATTTTCTGTCAAAAGTTGTTATTGCAGG CTTTTTAGTACCTGGAATCGTGTGTGGGAGGAGCATTATTATTCTGATTT GCTTGTTTCTTTATCATTTTTTCTTAGCCTCTGGAACAGCTAGAAACCCT TTTAATCTTTTGATTTTCAATGACAAAATTTTTCCTGTTACTACATTTGA TTGTTGTTCTTCATGGTTCTAAGTGAGTTATTGGCTCATCTGTTACTTCT TTTGATTGTTATTTTCATATCATGTTAGTCACTTGAATCAAGCTTTTCTA TTTTCAACCAGGGCAAAAGGTCAAAAGTAACCTACTTTATGAGATCAAAA AC AGC AACCC ATCGGAT AACTTTT AGTTGGAGTTAATAGTTAC A ATT ACC

ATTGTGATTAATAATTATAATATCTTGTATTAATTCATAAAAATTGGTAC AGCACATATATGACATTTCAAAGGTTTTTGTTTGACATATATATGCCTCT GGCGTTTTCTTTATTGGACATGCAGACCTCATTCCAAAGTTTATACGGTG ACACCTTGGGCCCTGTAACTTCAGAAGGGACAACTTGTTCTTTTCATAAC TTGATCGAATTATATATGGAATTTAATGATGCTGTTAAAAAGATTATTCC

ATCCAGTGAGTTGCTGCAACTGCAAAAGCTGGAAAAGATTCATGTGACTT ATTGTAATTGGGTAGAGGAGGTATTTGAAACTGCATTGGAAGCAGCAGGG AGAAATGGAAATAGTGGAATTGGTTTTGATGAATCGTCACAAACAACTAC CACTACTCTTGTCAATCTTCCAAACCTCAGAGAAATGAAGTTATGGTATC TAAATTGTCTGAGGTATATATGGAAGAGCAATCAGTGGACAGCATTTGAG

TTTCCAAACCTAACAAGAGTCGATATATGGGGATGTGATAGGTTAGAACA TGTATTTACTAGTTCCATGGTTGGTAGTCTATTGCAACTCCAAGAGCTAC GCATATGGAACTGCAGTCAGATAGAGGTCGTGATTGTTCAGGATGCAGAT GTTTGTGTAGAAGAAGACAAAGAGAAAGAATCTGATGGCAAGACGAATAA GGAGATACTTGTGTTACCTCGTCTAAAGTCCTTGATATTAAAACACCTTC

CAWGTCTTAAGGGGTTTAGCTTGGGGAAGGAGGATTTTTCATTCCCATTA TTGGATACYTTGGAAATCTACRAATGCCCAGCAATAACCACCTTCACCAA GGGAAATTCCRCTACTCCACAGCTAAAAGAAATTGAAACAMATTTTGGCT TCTTTTATGCTGCAGGGGAAAAAGACATCAACTCCTCTATTATAAAGATC AAACAACAGGTAAACCAGATCTTTGTTGCTTNNATAATTCTTAAACNACA

TNTGAAAAGCTTCATGCAAGTTTTTTTNGTTATATNGTCAAAAACCGCAA CCTACATTTTCAGCTTTANATTTATGTACTTTATGCAGGATTTCAAACAA GACTCTGATTAATGTGAAGTGAATATTAAAGGTAAATTATATTTTCATGT TCCTAGTNGCCTATTAATTAAAGGCCTTTTAGTTCGNGATTTTTGGATGT ATTCTTCATGATGATGTCAATCTTCTAATACCCCATTCATTGTTTGGTTG

AATGTTGACTCTATGTCAGGATGAATATTCAAGGGAAGAATTGTTCATCA TATGAAGGACATTAAAGAACATGGATGCTCTGAAGATGTTGGGAACACA RG2A deduced polypeptide sequence (SEQ ID NO:88)

MD\^NAILKPVVETLMVPVKKHIGYLISCRQYMREMGIKMRGLNATRLGVEEHVN RNISNQLEVPAQVRGWFEEVGKINAKVENFPSDVGSCFNLKVRHGVGKRASKIIEDI DSVMREHSIII NDHSIPLGRIDSTKASTSIPSTDHHDEFQSREQTFTEALNALDPNHK SHMJALWGMGGVGKTTMMHRLKKVVKEKKMFNFIIEAVVGEKTDPIAIQSAVADY

LGIELNEKTKPARTEKLRKWFVDNSGGKKILVILDDVWQFVDLNDIGLSPLPNQGV DFKλ^LLTSRDKDVCTEMGAEVNSTFNVKMLIETEAQSLFHQFIEISDDVDPELHNIG VN ΕKCGGLPIAKTMACTLRGKSKDAWKNALLRLEHYDIENIVNGVFKMSYDNL QDEETKSTFLLCGMYPEDFDILTEELVRYGWGLKLFKKVYTIGEARTRLNTCIERLI HTNLLMEVDDVRCIKMHDLVRAFVLDMYSKVEHASIVNHSNTLEWHADNMHDSC IOlLSLTCKGMSKFPTDLKFPNLSILKLMHEDISLRFPK_ FYEEMEKl_EVISYDKMKY PLLPSSPQCSVNLRVFHLHKCSLVMFDCSCIGNLSNLEVLSFADSAIDRLPSTIGKLK KLRLLDLTNCYGVRIDNGVLKKLVKLEELYMTVVDRGRKAISLTDDNCKEMAERS KDIYALELEFFENDAQPKNMSFEKLQRFQISVGRYLYGDSIKSRHSYENTLKLVLEK GELLEARMNELFKKTEVLCLS VGDMNDLEDIEVKSSSQLLQSSSFNNLRVLV VSKC AEUOIFFTPGVANTLKKLEHLEVYKCDNMEELIRSRGSEEETITFPKLKFLSLCGLP KLSGLCDNVKIIELPQLMELELDDIPGFTSIYPMKKFETFSLLKEEVLIPKLEKLHVSS MW XKEIWPCEFNMSEEVKFREIKVSNCDKLVNLFPHKPISLLHHLEELKVKNCGSI ESLFNIHLDCVGATGDEYNNSGVRIIKVISCDKLVNLFPHNPMSILHHLEELEVENC GSIESLFNIDLDCAGAIGQEDNSISLRNIKVENLGKLREVWRIKGGDNSRPLVHGFQS VESIRVTKCKKFRNVFTPTTTNFNLGALLEISIDDCGENRGNDESEESSHEQEQIEILS EKETLQEATDSISNVVFPSCLMHSFHNLQKLILNRVKGVEVVFEIESESPTSRELVTT HHNQQQPIILPNLQELILWNMDNMSHVWKCSNWNKFFTLPKQQSESPFHNLTTIKI MYCKSIKYLFSPLMAELLSNLKHIKIRECDGIGEVVSNRDDEDEEMTTFTSTHTTTT LFPSLDSLTLSFLENLKCIGGGGAKDEGSNEISFNNTTATTAVLDQFELSEAGGVSW

SLCQYAREMRIEFCNALSSVIPCYAAGQMQKLQVLTVSDCKGMKEVFETQLRRSSN KNNKSGAGEEGIPRVNNNVIMLSGLKILEISFCGGLEHIFTFSALESLRQLQELKITFC YGIvIKVIVKKEEDEYGEQ . TTTTTTITKGASSSSSSSSSKEVVVFPRLKSIELNDVPELV GFFLGKNEFRLPSLEEVTIKYCSKMMVFAAGGSTAPQLKYIHTELGRHALDQESGL NFHQTSFQSLYGDTLGPVTSEGTTCSFHNLIELYMEFNDAVKKIIPSSELLQLQKLEK

IHVTYCNWVEEVFETALEAAGRNGNSGIGFDESSQTTTTTLVNLPNLREMKLWYL NCLRYIWKSNQWTAFEFPNLTRVDIWGCDRLEHVFTSSMVGSLLQLQELRIWNCSQ IEVΛTVQDADVCVEEDKEKESDGKTNKEILVLPRLKSLILKHLPCLKGFSLGKEDFSF PLLDTLEIYKCPAITTFTKGNSTTPQLKEIETHFGFFYAAGEKDINSSIIKIKQQDFKQ DSD.CEVNIK

RG2B polynucleotide sequence (SEQ ID NO:89)

TTTTTTAAGATCAGGGATTCAAATTCAGCCCTAGTGATTACAATTGTGTC TAAACTTTCCCATACCTTCACATTATTGTAAGTATACTTTCTCAGTTTCT CTC TTGG AAGCTTCCTTGGTATTTTAACTCGTGTTCTAATATTT AACTCT

GATAGTTATTTTGGCCAATCTACTATCTGCATGTCCGGTTATTGAATCCG AAGGCACTGGAATCTTGGATTCCATTCCGTTGTGTGTTTGGTTGCCAAAT GAACGGAATTGAATTATGTAAGATTCCTTCAAAATCCATGTTTAGGTATA TCGTTGTTTCTTGGGATGGATGGTAAAGAACGGAATTTCTCCTGTTCATT TTTTAATGAAAGACCAAATTGACCTTATAAACCTGTTAAAAAAATTACAT TCCAGTTTTCTTAACAAACTGAAAATGGTAAAGGAGTGTGATTGAATTCC AATCTGTTTCCTGTCCAAAACACGTGACGGAATATTACAATTCCTTCAAA TTTCATTTTCTTAAATTGTTATTCCCTTTCTTACAAAAACAAGGTAAACG AAACACCCGCTTACTTAATCATACTCCTACATGATGTAAATGAAAAGGGT ATAAATGGTATTTTATTCACAGGGATGAGTCACCATGGTCATGAAAGAAT CATTAACCGCCCTTACCCAATTCATGTTTGCCCCTAAAATATGATTTAAA GTAATATTGGCTTATGGGATTCAAGTTGACTTTTTTGTGGCGAAGAAATA ATGAAAATCTTCATTTCTAAAGTGTCTTCTACCACTGACATTTTCTAAGA AAGAACTTGCTAGAAGAAGGTGGGTTGTTTAGTCTTTTTACTCTTTAAAT GTGAAGACTGTTGAGTTATTATTATTATTTTGCCAACTATGGACAACTTG TTTAGTTTTTTTTTTTCCCCAATATCCATTTATATGCGATTTATTTCTGA A AT AATTTTATC AAAACGC AGGA AAC AATGTAGAATA AT ACTGGT AT AAT

TAATTATATAAAGTTATTAGGCTGAAATCTTGAGGCTACTATAATTTAAT TATCATAATTTGAAAATCATCAAATTGTATTCCATGTATATTTATGTTAT CAGATAATTAATAATATGTGAGCCACACAAATCCACATCATCAGACACCC CACCTTATTGTCGGCTACCTCACCACTTGCATGATCCCGACATCTTCCCA ACCCCACCGACGACTTGGGGTCTCCTTAATATATCAATTATTTTCTGTAA

GTATTTATTTGTGTAAATGTGTAATGTCATTTTACCTTTTTTCTAATATA TACAGAAACATAAATTTTAAATGAAATTCAACTGCGTTTCATTCTTGCAT TAAAAAAAAAGACTGTACTGTTGTCAATATTTTACTTATAACCTGATTAA TTAATTAAAGCGTAATTGCATAATTTGCATTAGGTTGTAATTTTGTGTTT TATAGGGAGGGTGAGGGTCACCGGGAATCAAAGCACTTATGTAAAAGCAG

GGAAATACAAAAAATTTACTCGAAACAAATTTTATTCAATTTAAGTGAGA TAATAATGTTCTGATTAGATTATGAGAACTAGGAGATTTAAGTGATATAT CCCATTTAAAAGAAATTGCATTATTAATTTTGGATCTCTTGATGATGACA AAATTAACTCGTGACAGGTTATATATCATATACAAAATGAGTGGCTATGC TTTCGCTTTCCAAAAAGCAATTATAGTTATACTACACCTACAAATTTTAA

AAGGGGTTAAACATATCAAAATACTTGATAAGTAATTATATAAATATGCA TTTAACCCTCTAAAGAAAATGCTACTAAGCTTGGACCATCTCAGAATTAC AATCATACCCTTCCCCTCAAAAAAGATTCGTATATATCATGTCATTTGGC ATTCATTTCTTTTTCACAATTCATAGTTCTATTCTCAAAAAATTCGAGTT CTCGTATTTGTAAGGAAGATCAGAAGAGACTGTTCACACAGGTACTCTCT

TTTATTTATTGATTCACATTCATATATGTTATTGTTTTCTTGCTTAATGG TTTCGTCAGTCTAACTGCGCTTGCTGATTTAAATTTCTTCACTTTCTTCC ACGGATTTTTTAAATATTAGTTTTGTGAATGAACAATTGGTGAAGGAAAG AAACATGGGAGTCTTTTCTAAAGTAAACCTAGATACTTAGGTTATAAGGG TATATGCTAAAATGAACTATGCCCATTCACCTTTGCCTTTTCTTTTACTT

TTTAGTTTTTAGAATCCAAGTTTTCATATGTATCTCGATGTGTGAGAAGA ATAGGCATTAGAAAGGTAAAGGACGTACATAAAATTGATTAATTAGTGAA TGTTCTTTGATATCATTATTTTTACTCTCATAAAAAGCATATAGATCAAA CACAAATTGCTACTTGTTAGTGTAACAACTTCGACTTAATAATGTTAATA ATCAAGATTCTCTTGATTTCAACTATTTTCTAACCGAACAAGCTCACTAA AAACTCATATTGCTTTGAGTCTGAGTGGTTTATATTTGGGGTTTTACATT TAATTTTTTGTGCATGAATGTGAAAATAGACTGCTTATTGATTCTTTGTG TTTCATTGAGTTGATTTTCATTATTACTACCTTACAAATTGCTCAGTGAT AGATTTCCATTAATTTGCTAATTCGGTTGCTTCTAAATATGTAGGAGCTA CTAAAAGCAAAAATATCGAGCAATGTCGGACCCAACGGGGATTGCTGGTG CCATTATTAACCCAATTGCTCAGACGGCCTTGGTTCCCGTTACGGACCAT GTAGGCTACATGATTTCCTGCAGAAAATATGTGAGGGTCATGCAGATGAA AATGACAGAGTTGAATACCTCAAGAATCAGTGTAGAGGAACACATTAGCC GGAACACAAGAAATCATCTTCAGATTCCATCTCAAACTAAGGAATGGTTG GACCAAGTAGAAGGGATCAGAGCAAATGTGGAAAACTTTCCGATTGATGT CATCACTTGTTGTAGTCTCAGGATCAGGCACAAGCTTGGACAGAAAGCCT TCAAGATAACTGAGCAGATTGAAAGTCTAACGAGACAACTCTCCCTGATC AGTTGGACTGATGATCC AGTTCCTCTAGGAAGAGTTGGTTCC ATGAATGC ATCCACCTCTGCATCATTAAGTGATGATTTCCCATCAAGAGAGAAAACTT TTACACAAGCACTAAAAGCACTCGAACCCAACCAAAAATTCCACATGGTA GCCTTGTGTGGGATGGGTGGAGTGGGGAAGACTAGAATGATGCAAAGGCT GAAGAAGGCTGCTGAAGAAAAGAAATTGTTTAATTATATTGTTGGGGCAG TTATAGGGGAAAAGACGGACCCCTTTGCCATTCAAGAAGCTATAGCAGAT TACCTCGGTATACAACTCAATGAAAAAACTAAGCCAGCAAGAGCTGATAA GCTTCGTGAATGGTTCAAAAAGAATTCAGATGGAGGTAAGACTAAGTTCC TCATAGTACTTGACGATGTTTGGCAATTAGTTGATCTTGAAGATATTGGG TTAAGTCCTTTTCCAAATCAAGGTGTCGACTTCAAGGTCTTGTTGACATC ACGAGACTCACAAGTTTGCACTATGATGGGGGTTGAAGCTAATTCAATTA TTAACGTGGGCCTTCTAACTGAAGCAGAAGCTCAAAGTCTGTTCCAACAA TTTGTAGAAACTTCTGAGCCCGAGCTCCAGAAGATAGGAGAGGATATCGT AAGGAAGTGTTGCGGTCTACCTATTGCCATAAAAACCATGGCATGTACTC TTAGAAATAAAAGAAAGGATGCATGGAAGGATGCACTTTCGCGCATAGAG CACTATGACATTCACAATGTTGCGCCCAAAGTCTTTGAAACGAGCTACCA CAATCTCCAAGAAGAGGAGACTAAATCCACTTTTTTAATGTGTGGTTTGT TTCCCGAAGACTTCGATATTCCTACTGAGGAGTTGATGAGGTATGGATGG GGCTTGAAGCTATTTGATAGAGTTTATACGATTAGAGAAGCAAGAACCAG GCTCAACACCTGCATTGAGCGACTGGTGCAGACAAATTTGTTAATTGAAA GTGATGATGTTGGGTGTGTCAAGATGCATGATCTGGTCCGTGCTTTTGTT

TTGGGTATGTTTTCTGAAGTCGAGCATGCTTCTATTGTCAACCATGGTAA TATGCCTGGGTGGCCTGATGAAAATGATATGATCGTGCACTCTTGCAAAA GAATTTCATTAACATGCAAGGGTATGATTGAGATTCCAGTAGACCTCAAG TTTCCTAAACTAACGATTTTGAAACTTATGCATGGAGATAAGTCGCTAAG GTTTCCTCAAGACTTTTATGAAGGAATGGAAAAGCTCCATGTTATATCAT

ACGATAAAATGAAGTACCCATTGCTTCCTTTGGCACCTCGATGCTCCACC AACATTCGGGTGCTTCATCTCACTGAATGTTCATTAAAGATGTTTGATTG CTCTTCTATCGGAAATCTATCGAATCTGGAAGTGCTGAGCTTTGCAAATT CTCACATTGAATGGTTACCTTCCACAGTCAGAAATTTAAAGAAGCTAAGG TTACTTGATCTGAGATTTTGTGATGGTCTCCGTATAGAACAGGGTGTCTT GAAAAGTTTTGTCAAACTTGAAGAATTTTATATTGGAGATGCATCTGGGT TTATAGATGATAACTGCAATGAGATGGCAGAGCGTTCTTACAACCTTTCT GCATTAGAATTCGCGTTCTTTAATAACAAGGCTGAAGTGAAAAATATGTC ATTTGAGAATCTTGAACGATTCAAGATCTCAGTGGGATGCTCTTTTGATG AAAATATCAATATGAGTAGCCACTCATACGAAAACATGTTGCAATTGGTG ACCAACAAAGGTGATGTATTAGACTCTAAACTTAATGGGTTATTTTTGAA AACAGAGGTGCTTTTTTTAAGTGTGCATGGCATGAATGATCTTGAAGATG TTGAGGTGAAGTCGACACATCCTACTCAGTCCTCTTCATTCTGCAATTTA AAAGTTCTTATTATTTCAAAGTGTGTAGAGTTGAGATACCTTTTCAAACT CAATCTTGCAAACACTTTGTCAAGACTTGAGCATCTAGAAGTTTGTGAAT GTGAGAATATGGAAGAACTCATACATACTGGAATTGGGGGTTGTGGAGAA GAGACAATTACTTTCCCTAAGCTGAAGTTTTTATCTTTGAGTCAACTACC GAAGTTATCAAGTTTGTGCCATAATGTCAACATAATTGGGCTACCACATC

TCGTAGACTTGATACTTAAGGGCATTCCAGGTTTCACAGTCATTTATCCG CAGAACAAGTTGCGAACATCTAGTTTGTTGAAGGAAGGGGTAGATATATG TTCTTTATGTTAATACAATTTAAATAATATTTTCAACCAAATTTTCATAA TATATCTGTAATTTGATTGTATGATGTGTTATTGTTTATATGTGGCTATT AAGGGATGATTATTTTGCAGGTTGTGATTCCTAAGTTGGAGACACTTCAA

ATTGATGACATGGAGAACTTAGAAGAAATATGGCCTTGTGAACTTAGTGG AGGTGAGAAAGTTAAGTTGAGAGCGATTAAAGTGAGTAGCTGTGATAAGC TTGTGAATCTATTTCCGCGCAATCCCATGTCTCTGTTGCATCATCTTGAA GAGCTTACAGTCGAGAATTGCGGTTCCATTGAGTCGTTATTCAACATTGA CTTGGATTGTGTCGGTGCAATTGGAGAAGAAGACAACAAGAGCCTCTTAA GAAGCATCAACGTGGAGAATTTAGGGAAGCTAAGAGAGGTGTGGAGGATA AAAGGTGCAGATAACTCTCATCTCATCAACGGTTTTCAAGCTGTTGAAAG CATAAAGATTGAAAAATGTAAGAGGTTTAGAAATATATTCACACCTATCA CCGCCAATTTTTATCTGGTGGCACTTTTGGAGATTCAGATAGAAGGTTGC GGAGGAAATCACGAATCAGAAGAGCAGGTAACGCTTTCAATTTCACTTTC

TTAATTAATTAAGGACTAAGCTCCTGTTTTTTGAATAATAAAGAGGTGGG ATGACTAAACTTGGGCATCACAATTGCAACAAAATGTTACAAACCATGAA ACGTTCAAACCATTTCTTGAATTAAGGTTTCAATACAAGTCATTTAAAAA TATGGCTTAAATTTTTTTTATATTTATGTATCAACATGATTTTTCATTAG AGATCATTATTATAATAGTAAGTTTAAAGCAATTTAAATCAGAACTAATT

CTAACTTTAGCTAATAAATCGTTATAAATGTAAATAATTACTTTTTAGTG AAATAAGCAACGGATTTAATAAGTTAACAACTTAAATGTCATTTCCTAAC AAAAAAAACTATTTGGTTCAGAAAAACCGTAATTCAAGATAACTAAAATA AAAATATTTGACATTCACTAAGAGCATTTTTTTTTCTAAATATGATTGCA AATGAATAAAACTTAAATTTATACAGAAAATTCTTTTATATATGTTATAC

AAAATTTACAAATTGAAATTGGATATGTTAATTAACGGTTTATAATTCTG GTATCACAAAGGGATATATAATAAAATATTATTTTCTGTAGTCATTTGTA ATTGTACTAGTTTATAACCCGTGGGAACCATGAGTTCTAAAATTAGTTAA ACTTTCATAATAAAAATTTATAATTATTATTTATTTTAAATAAATTATTA ATTAAGAGATATATCAAAAATTTAAAGTTATTATAACTTCAAATTTAACA TATAATTAGAAAATATATGATCATAACTTTCTGCAACTCTTCTTTTGTAT TAAAATGACCAGAGAAGCTCTTAGTATATTTCTAATCAAAGTCTCAAAMC TAATGAAGCATATAATTTGTGAAAATCAATTAGCATTAGGTTTTAAGAGT CACCAAATTCAAAGAATAATCCAATGCTTTCATTACCACTATGGAGAAAA TATTTTCTTAGTTTAAATGAAATGAAAACAAACATTCAAACTAATTGTTG CTTATTAAACCAAAGACCCATTACTTAGCCAAGAGTTTAACAAAAAAAAA TTACATTCATGTATCATTATTCATGACTAGATATATATGAACATGAAGGG AGTTTTTATAGAAAATATAATCATAGATATTCAACATAACTTCAGGGAAT TCCTCAAAATAACCAAGTTATTCAAGAAATTACATCCAAGTCAACCAAAG AGAAGTTTAGCCTAGCATGGCTAAACTCAAGAAACTAAAATAAGGATTAG AAGTACCAAACATGTAGTAAGAATCACAGTAAAAGATGATGTTGTTCTTG ATGTTCTTCTAAGTTCTTCAAGTCTCCAGTTGCTCCTAATAATGCAAAGG AGAGCCATTAAATTCGTATGTATTGATCCCTTCAAAAGCTGCACCAACCT

CCCTTAAATAACACTCAAAGCAAAAATGACAAAATTGCCCCTGAAGGACC CTATGTGGGTGCCTTGCGCGGGTGGAGCTGCATACGAAAGGTCTTTGGTC TTTGTGAGGGTGATGTTGTGCGGGATAGCTTGTCGCATGCTTCCGCGCGG TTCACGCACATGTGCACAGGTGATGCATGGTGTGTGCGTTCTTGAGTTTT GAGCCTCCGATGCTTAGTCCACTTGGCCCAATTCGAGTCCAATCAGCTTA TAACCCATTTTTCTTCAAGTTATCTTCAAGTTAAGCCCAATTTGCCTTCT CCAAATCATCCATAACTTCACAGAATCGCCCGTTCATCTTAATCCCGGAT GCACAATTATTCTCCCGTCTTCATTTTAAGCAAGATACCACCTTCTTCAT GCTTCATCCATCAATAGTACACTTCATGTATCATCTCTACTAGTTATTTA GTCCACAATCCTTGTTGTCCTCCAAATTTAATTATCTCATTTAGTTCCCG TTCCGCTAGTTTCCTTAAAATTTGCAATTAAGCTCAGAGAAATATTAAGT ACCCGAAATGGTCATAAAATAACAAAAAGGAAAATATGCATGAAGATTAA CTAAATGATGAACGAAATATGCTAAAATAGACTATAAAATGAAGTAAATA AAATGAAATTATCGCACTCCGACCACCCTTATAGGCTTGTAGTCCACCCA CCCTTCATTCCTTGTACCAATATGGGATGGAAACATCATTAATTAAGCCA

AAAAGCTAACATATAAGGGTTTAGTGACAAAGGTAAGTACTAAAGATGAA AATAATCCATTTTTCTTGTATATACACAACACACACATAGGGGCAGACGT AGGATTTCAAAGTACAGATTGTTGGTGGCACATAAGTGTTGCTGGTGACA TTTTTTTTTTTTTTTTACGTAGTGGCACAACAGTAGGAAAAACGAAAAAT TCGAAATTTTTTACAATTTGTCTAAAAAAAACAGTGGTTGTTGGTGCCAC

TATGGACACCAAAGTTGAACTGCCCCCACGCGCGCACACACACACACACA CATAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAAAGAAAGAAAGAGAGA GAGAGTTTGGGATGTGATACTTCTTTTAGGAAAATGGAGTTATATCTTTG ATATTGTATTTTTTTAATGTAATTTATATATTTAATCATTTTAGTTTATA AGTTTTATTTATTTTGATATGAAAAAAAAAGTCTTTTATACATTGGATTT

AACATAAAAATCCAACAATATTAATCAAAAAGACCAMACATGTGGACAMW

TATGTATATAAWTAATTCACAATAGTCTTTAGGAATAGNATTATATATAT

AATTAATTCTCAATGGTCTTAGGAATAGTAAGTTCTTATATTTCAAACTT TNGCCACAATTCTTTGKTTACTTWGACACTTYCCTCTCTCTAATTATATA TATATATATATATATATATATATATATACACACACACACACACACACTAG ATGTGTGCCCGCGCAAAGCAGTGACGTNNNGGAGAANACTTTCTTAAGCA TAAATAATTATTATATTTTTTATTGGGTATTATATAATAAAAAATTACAA CTTTTAAATAAAATATTTATGTTTATACTTTATATTTATATTGCTTGTAT ACTATTAATATAATAAATTAATATTTATGTCTAATTTATGAAATGTAAAT TAATTTAAATACATGAATTTAATATTTTTAAAATTTTCAGTTTGCTTCAA ATTGAGTTTCTTAATTATTTTTTTTAATTCANGTATTCAAACTTTTGGTA AGTATTAAAGAATTATTTATGCATAATTGATTTATACAAAAAACTTTGTA ACTTATACATCTTAAAATTCAAGATATAACTAACATGTTTTACAATATAT ATATATATATATATATATATATATATATATATATATATATATATATATAT TAAAGCGCAAAGGTCATAGGAATAGAATATTTTCTATTATTCTACGTTTT GCCACAAAAGTTTGAACACTTTGCCACTTTTTGTCCCTCCTTAACCTTTT CAATGTTTTGCGACAAAAGTTCCAAAACTTTGCCACTTTGATCATTCCTC AACTTTTCACCGC AATTAGTTTGTGGAGTTGGC AGTTTTGATCCCCCTAA CTTCGATATTCTCTACTGCTAGCCAAAAAGGGTTCCAGAGTTTCACACTT TTGGTCCCTGACAGTAACCAAATGTGAGATGTCAAATTTTTGCCACATTA GTTTGTGGAGTTGTCCCTTTTGGTCCCCCCACATTCGATATTCTANTATA CGACCTTATTTTTNTCAAATAACAACACGTATATTTAATTACCAATTATA GAAATAGATATCAAATAAAGTATTTGTAACACTGTGTAAGAACGGTGCTA CTATAGGTAAAAATAAACATTTCAAAGTACGATATCCTAATTGGAAAAAG AGTTTTAAAAAAATAACGACTAGGGGCGAGTTTTTTTTACAAGTTTGTAT CAAATCATATCAAAATTTAAGGTGGAACGGTGACCACATTAACCAGAAAT GTAATTTATTCTTTGATTTTGATAATTTTTAATATTTTGTTGTGATCTAT GTATTTAAAAGTAAACAACAAAGAACATAATCCAAAACCCTAAATTGCAA

GTCTCGCCCAATTTCTCTATCACTAGTCCTCACTTACGATGGCGTTACGT CGCTCTCTCACTGCTTACAACCCTTTGTTGCTACTCATTACAATAACGAA AAGTTGAATATCCATATATTTATTTGGATGTGGAATTGAACGAATCTCGT CAAAATTTTGATTTTGTTGATGGATTTGAGTAGAAGTTTGGGCAGAACGG GAATGATGGTCTGCAAGTGGTTATAAACTTGATTCTGAGTTATTACTATA

TATGTAGCCTCTTTACAACGACCAAGGTTTCTTCCAGGTACCATTTGATC TTTTTAGAACTTAGTTTTCTGAAACACCCTGATTTGGATCAAATATCACC AACAACTCTTAAAAACTTGATTAATCAATTGTTTTCTTCATCTTGATAAC AAGTGGAATGATTTTCTACTTAGATTAACTTGAAAAAAAAGGTCCATGTG CGTCTGGTGGATCTGGTAAATGAAGATGGAAGGGAGAGCTGACTTTAAAG

ACACAAACACGTCACCATATCTCTTATTTTATTTTAAATTTGCTTTTGGT GTATTTTCTTTTTTCCTATTTCTTTCTTTCTTGATCTCCAGATGGTATGT GGTGTGGATAATTTACACCTAGAGATTGGGAACGATGGGAAGGGGTCTGT GATTTATGGCTGGCCGAGTTTTACTTATTAACTCAATTTCAACCTAAATT CTGATTCTTGTTTGAAAATAAGTTGCATCTTTATTTTTGTATTATCTTGT

TGCATAGGATCCTTAGCATCTTTTAATAATTTATTTGAAGGTGAAAGATC CAACTATTTTTTAGCTGTTGGCATTTTCCATCATTTGCAACTGTTTCTTG AAAAAAAAATACCTAAAATAAAAATAACCATTTTCAAATCCAAAATTATA AGAGAGAATTGTAAATGGACATGGAATCATAAATCATTAACACAGTTCAG TAAACAAGTTGCTAATTACATTTCTTGCTGTGCAGATTGAAATTCTATCA GAGAAAGAGACATTACAAGAAGCCACTGGCAGTATTTCAAATCTTGTATT CCCATCCTGTCTCATGCACTCTTTTCATAACCTCCGTGTGCTTACATTGG ATAATTATGAAGGAGTGGAGGTGGTATTTGAGATAGAGAGTGAGAGTCCA ACATGTAGAGAATTGGTAACAACTCGCAATAACCAACAACAGCCTATTAT ACTTCCCTACCTCCAGGATTTGTATCTAAGGAATATGGACAACACGAGTC ATGTGTGGAAGTGCAGCAACTGGAATAAATTCTTCACTCTTCCAAAACAA CAATCAGAATCCCCATTCCACAACCTCACAACCATAAATATTCTTAAATG CAAAAGCATTAAGTACTTGTTTTCGCCTCTCATGGCAGAACTTCTTTCCA ACCTAAAGGATATCCGGATAAGTGAGTGTGATGGTATTAAAGAAGTTGTT TCAAACAGAGATGATGAGGATGAAGAAATGACTACATTTACATCTACCCA CACAACCACCACTTTGTTCCCTAGTCTTGATTCTCTCACTCTAAGTTTCC TGGAGAATCTGAAGTGTATTGGTGGAGGTGGTGCCAAGGATGAGGGGAGC AATGAAATATCTTTCAATAATACCACTGCAACTACTGCTGTTCTTGATCA

ATTTGAGGTATGCTTTGTACATATTCAATTATTTATTTAATTTCCTTTTT TATTTGCAATATTCTATAAATAATACATTTTATACCCACTATACTAAGAT AATAATTACCTAGAGGGATGGATGCTATGACACAGCTGCTACACTTCAGA AACTCTAGTAAGGGCAGTTATGGAAGTTCAATAAAATGATAATGGCATCT TTTGATGGGTAATATAGGCAATTTAAGTTTTATTTCTGTTAAAGCAGTAT TTAGCAAGTACTGGCCAGTAGGAGAGGAGAATATCACCTTTTGTGAAAAT CTGGTCATTGTACCCAGAATTTAGTTAAATGTAACATTTTAGATATTAGG GGACATCAGGTGACAGATATTGTAGAATAGAACAATATATAATATTACCC AAAACTATTTTTTCTAAGGTTATTCTGTTAAATATGTGCTTTCTTGATTT CATTGAATTTGCATTCCTATATTTTAGGTGGTAAAGTGATTGTCTCTTCA

ATAAATCCCGAAATTAATTAAAAAAGAAAAAAACAAAAGTAAATTTTTGA TATGGAGAGCACTGGTATCATTTAGTATATAAAAAAACTAGATTTTGAAT TAAGTTTCTTATATAAAAGCTGTGTATATAGTTTAATTAGTTTTACATCA TTTTTCCATGTGGTGTTGCAGTTGTCTGAAGCAGGTGGTGTTTCTTGGAG TTTATGCCAATACGCTAGAGAGATARAAATAGKTGGATGCTATGCATTGT CAAGTGTGATTCCATGTTATGCAGCAGGACAAATGCAAAAGCTTCAAGTG CTGAGAATAGAGTCTTGTGATGGCATGAAGGAGGTATTTGAAACTCAATT AGGGACGAGCAGCAACAAAAACAACGAGAAGAGTGGTTGCGAGGAAGGAA TTCCAAGAGTAAATAACAATGTTATTATGCTTCCCAATCTAAAGATATTA AGTATTGGAAATTGTGGGGGTTTGGAACATATATTCACATTCTCTGCACT

TGAAAGCCTGAGACAGCTCCAAGAGTTAAAGATAAAATTTTGCTACGGAA TGAAAGTGATTGTGAAGAAGGAAGAAGATGAATATGGAGAGCAGCAAACA ACAACAACAACAACGAAGGGGGCATCTTCTTCTTCTTCTTCTTCTTCTTC TTCTTCTTCTAAGAAGGTTGTGGTCTTTCCTTGTCTAAAGTCCATTGTAT TGGTCAATCTACCAGAGCTGGTAGGATTCTTCTTGGGGATGAATGAGTTC

CGGTTGCCTTCATTAGATAAACTTAAGATCAAGAAATGCCCAAAAATGAT GGTGTTTACAGCTGGTGGGTCCACAGCTCCCCAACTCAAGTATATACACA CAAGATTAGGCAAACATACTCTTGATCAAGAATCTGGCCTTAACTTTCAT CAGGTATATATATATTTCTTTAATTGGCATCATCTAATTAAGAAAGATAT CATTCCTGCCAAGTAAATTTACTTCAAACACATTCACACTGGTTTCAGTC TAAGTTTATGTTGTTCTAAGAAGGCCAAAATGGGAAAGCAAGATAGGGAA AAATAGTGTATTTCAGTGGAAAGGGTATTTTAGGCATTTTCTGTCAAAAG TTGTTATTGCAGGCTTTTTAGTACCTGGAATCGTGTGTGGGAGGAGCATT ATTATTCTGATTTGCTTGTTTCTTTATCATTTTTTCTTAGCCTCTCGAAC AGCTAGAAACCCTTTTAATCTTTTGATTTTCAATGACGAAATTTTTCCCT GTTACTCCATTTGATTGTTGTTCTTCATGGTTCTAAGTGAGTTATTGGCT CATCTGTTACTTCTTTTGATTGTTATTTTCATATCATGTTGTCCTTTGAA TCAAGCTTTTCCATTTTCAACCAGGGCAAAAGGTCAAAAGTAACCTACTT TATGAGATCAAAAACAGCAACCCATCGGATAACTTTTAGTTGGAGTTAAT AGTTACAATTACCATTGTGATTAATAATTATAATATCTTGTATTAATTCA TAAAAATTGGTACAGCACATATATGACATTTCAAAGGTTTTTGTTTGACA TATATATGCCTCTGGCGTTTTCTTTATTGGACTTGCAGACCTCATTCCAA AGTTTATACGGTGACACCTTGGGCCCTGCTACTTCAGAAGGGACAACTTG GTCTTTTCATAACTTTATCGAATTAGATGTGGAAGGTAATCATGATGTTA AAAAGATTATTCCATCCAGTGAGTTGCTGCAACTGCAAAAGCTGGAAAAG ATT.AATGTAAGGTGGTGTAAAAGGGTAGAGGAGGTATTTGAAACTGCATT GGAAGCAGCAGGGAGAAATGGAAATAGTGGAATTGGTTTTGATGAATCGT CACAAACAACTACCACTACTCTTGTCAATCTTCCAAACCTTAGAGAAATG

AACTTATGGGGTCTAGATTGTCTGAGGTATATATGGAAGAGCAATCAGTG GACAGCATTTGAGTTTCCAAACCTAACAAGAGTTGATATCTATAAATGTA AAAGGTTAGAACATGTATTTACTAGTTCCATGGTTGGTAGTCTATCGCAA CTCCAAGAGCTACATATATCCAACTGCAGTGAGATGGAGGAGGTGATTGT TAAGGATGCAGATGATTCTGTAGAAGAAGACAAAGAGAAAGAATCTGATG GGGAGACGAATAAGGAGATACTTGTGTTACCTCGTCTAAACTCCTTGATA TTAAGAGAACTTCCATGTCTTAAGGGGTTTAGCTTGGGGAAGGAGGATTT TTCATTCCCATTATTGGATACTTTAAGAATTGAGGAATGCCCAGCAATAA CCACCTTCACCAAGGGAAATTCCGCTACTCCACAGCTAAAAGAAATTGAA ACACATTTTGGCTCGTTTTGTGCTGCAGGGGAAAAAGACATCAACTCTCT

TATAAAGATCAAACAACAGGTAAATCAGATCTTTGTTGCTTTAATAATTC TTAAACTACATTTGAAAAGCTTCATGCAAGTTTTTTTTGTTATATTGTCA AAAACCGCAACCTACATTTTCAGCTTTATATTTATGTACTTTATGCAGGA GTTCAAACAAGACTCTGATTAATGTGAAGTAAATACTAAAGGTAAATTAT ATTTTCATGTTCCTAGTTGCCTATTAATTAATTGCCTTTTAGTTCATGAT TTTTGGATGCATTCTTCATGATGATGTCAATCTTCTAATACCCCATTCAT TGTTTGGTTGAATGTTGACTCTATGTCTTGATGAATATTCAAGGGAAGAA TTGTTCATCATATGAAGGACATTAAAGAAGAACATGGATGCTATGAAGAT GTGGGAAAACAA RG2B deduced polypeptide sequence (SEQ ID NO:90)

MSDPTGIAGAIINPIAQTALVPVTDHVGYMISCRKYVRVMQMKMTELNTSRISVEE HISR TRNHLQIPSQTKEWLDQVEGIRANVENFPIDVITCCSLRIRHKLGQKAFKITE QIESLTRQLSLISWTDDPVPLGRVGSMNASTSASLSDDFPSREKTFTQALKALEPNQK FHMVALCGMGGVGKTRMMQRLKKAAEEKKLFNYIVGAVIGEKTDPFAIQEAIADY LGIQLNEKTKPARADKLREWFKKNSDGGKTKFLIVLDDVWQLVDLEDIGLSPFPNQ GVDFKVLLTSRDSQVCTMMGVEANSIINVGLLTEAEAQSLFQQFVETSEPELQKIGE DIVRKCCGLPIAIKTMACTLRNKRKDAWKDALSRIEHYDIHNVAPKVFETSYHNLQ EEETKSTFLMCGLFPEDFDIPTEELMRYGWGLKLFDRVYTIREARTRLNTCIERLVQ TNLLIESDDVGCVKMHDLVRAFVLGMFSEVEHASIVNHGNMPGWPDENDMIVHSC KRISLTCKGMIEIPVDLKFPKLTILKLMHGDKSLRFPQDFYEGMEKLHVISYDKMKY PLLPLAPRCSTNIRVLHLTECSLKMFDCSSIGNLSNLEVLSFANSHIEWLPSTVRNLK KLRLLDLRFCDGLRIEQGVLKSFVKLEEFYIGDASGFIDDNCNEMAERSYNLSALEF AFFNNKAEVKNMSFENLERFKISVGCSFDENINMSSHSYENMLQLVTNKGDVLDSK LNGLFLKTEVLFLS VHGMNDLED VEVKSTHPTQSSSFCNLKVLIISKC VELRYLFKL NLANTLSRLEHLEVCECENMEELIHTGIGGCGEETITFPKLKFLSLSQLPKLSSLCHN VNΠGLPHLVDLILKGIPGFTVIYPQNKLRTSSLLKEGVVIPKLETLQIDDMENLEEI PCELSGGEKVKLRAIKVSSCDKLVNLFPRNPMSLLHHLEELTVENCGSIESLFNIDLD CVGAIGEEDNKSLLRSINVENLGKLREVWRIKGADNSHLINGFQAVESIKIEKCKRFR NIFTPITANFYLVALLEIQIEGCGGNHESEEQIEILSEKETLQEATGSISNLVFPSCLMH SFH LRVLTLDNYEGVEVVFEIESESPTCRELVTTRNNQQQPIILPYLQDLYLRNMD NTSHVWKCSNWNKFFTLPKQQSESPFHNLTTINILKCKSIKYLFSPLMAELLSNLKDI RISECDGKEVVSNRDDEDEEMTTFTSTHTTTTLFPSLDSLTLSFLENLKCIGGGGAK DEGSNEISFNNTTATTAVLDQFELSEAGGVSWSLCQYAREIEIVGCYALSSVIPCYAA GQMQKL

RG2C polynucleotide sequence (SEQ ID NO:91)

ATAATATTACACAAAGGTAACGTCATTAATTAATTACGATACGAGACAGA CTTTTTCACTCGGACATNAACGGTCTATTCCTAACTTNANNTAATTNAAT GAATTTAGGATGTGCTAATATGCATGTAANATTCGCTACCGTCATCTTTC

AAATGACCATATTTTTATGTATTTATAATGAATCAATGAAAAACCGGATT TCTATTTAAAATTCTTAAAACTTCATCTTTTAAGCCAGGGTGAATACAAT TGCTAGATCCACTGTTAATTTCCATCGAATTATGCCTGATCAATTGTTGG CTGCCTACGATGCAGGTGCTACCACAAGAATATGGCCATGGAAACTGCTA ATGAAATTATAAAACAAGTTGTTCCAGTTCTCATGGTTCCTATTAACGAT TACCTACGCTACCTCGTTTCCTGCAGAAAGTACATCAGTGACATGGATTT GAAAATGAAGGAATTAAAAGAAGCAAAAGACAATGTTGAAGAGCACAAGA ATCATAACATTAGTAATCGTCTTGAGGTTCCAGCAGCTCAAGTCCAGAGC TGGTTGGAAGATGTAGAAAAGATCAATGCAAAAGTGGAAACTGTTCCTAA AGATGTCGGCTGTTGCTTCAATCTAAAGATTAGGTACAGGGCCGGAAGGG

ATGCCTTCAATATAATTGAGGAGATCGACAGTGTCATGAGACGACACTCT CTGATCACTTGGACCGATCATCCCATTCCTTTGGGAAGAGTTGATTCCGT GATGGCATCCACCTCTACGCTTTCAACTGAACACAATGACTTCCAGTCAA GAGAGGTAAGGTTTAGTGAAGCACTCAAAGCACTTGAGGCCAACCACATG ATAGCCTTATGTGGAATGGGGGGAGTGGGGAAGACCCACATGATGCAAAG GCTGAAGAAGGTTGCCAAAGAAAAGAGGAAGTTTGGTTATATCATCGAGG CGGTTATAGGGGAAATATCGGACCCCATTGCTATTCAGCAAGTTGTAGCA GATTACCTATGCATAGAACTGAAAGAAAGCGATAAGAAAACAAGAGCTGA GAAGCTTCGTCAAGGGTTCAAGGCCAAATCAGATGGAGGTAACACTAAGT TCCTCATAATATTGGATGATGTCTGGCAGTCCGTTGATCTAGAAGATATT GGTTTAAGCCCTTCTCCCAATCAAGGTGTCGACTTCAAGGTCTTGTTGAC TTCACGAGACGAACATGTTTGCTCAGTGATGGGGGTTGAAGCTAATTCAA TTATTAACGTGGGACTTCTAATTGAAGCAGAAGCACAAAGATTGTTCCAG CAATTTGTAGAAACTTCTGAGCCCGAGCTCCACAAGATAGGAGAAGATAT TGTTAGGAGGTGTTGCGGTCTACCCATTGCCATCAAAACCATGGCGTGTA CTCTAAGAAATAAAAGAAAGGATGCATGGAAGGATGCACTTTCTCGTTTA CAACACCATGACATTGGTAATGTTGCTACTGCAGTTTTTAGAACCAGCTA

TGAGAATCTCCCGGACAAGGAGACAAAATCTGTTTTTTTGATGTGTGGTT TGTTTCCCGAAGACTTCAATATTCCTACCGAGGAGTTGATGAGGTATGGA TGGGGCTTAAAGTTATTTGATAGAGTTTATACAATTATAGAAGCAAGAAA CAGGCTCAACACCTGCATTGACCGACTGGTGCAGACAAATTTACTAATTG GAAGTGATAATGGTGTACATGTCAAGATGCATGATCTGGTCCGTGCTTTT GTTTTGGGTATGTATTCTGAAGTCGAGCAAGCTTCAATTGTCAACCATGG TAATATGCCTGGGTGGCCTGATGAAAATGATATGATCGTGCACTCTTGCA AAAGAATTTCATTAACATGCAAGGGTATGATTGAGTTTCCAGTAGACCTC AAGTTTCCTAAACTAACGATTTTGAAACTTATGCATGGAGATAAATCGCT AAAGTTTCCTCAAGAATTTTATGAAGGAATGGAAAAGCTCCGGGTTATAT

CATACCATAAAATGAAGTACCCATTGCTTCCTTTGGCACCTCAATGCTCC ACCAACATTCGGGTGCTTCATCTCACGGAATGTTCATTAAAGATGTTTGA TTGCTCGTGTATTGGAAATCTATCGAATCTGGAAGTGCTGAGCTTTGCTA ATTCTTGCATTGAGTGGTTACCTTCCACGGTCAGAAATTTAAAAAAGCTA AGGTTACTTGATTTGAGATTGTGTTATGGTCTCCGTATAGAACAGGGTGT CTTGAAAAGTTTGGTCAAACTTGAAGAATTTTATATTGGAAATGCATATG GGTTTATAGATGATAACTGCAAGGAGATGGCAGAGCGTTCTTACAACCTT TCTGCATTAGAATTCGCGTTCTTTAATAACAAGGCTGAAGTGAAAAATAT GTCATTTGAGAATCTTGAACGATTTAAGATCTCAGTGGGATGCTCTTTTG ATGGAAATATCAATATGAGTAGCCACTCATACGAAAACATGTTGCGATTG

GTGACCAACAAAGGTGATGTATTAGACTCTAAACTTAATGGGTTATTTTT GAAAACAGAGGTGCTTTTTTTAAGTGTGCATGGCATGAATGATCTTGAAG ATGTTGAGGTGAAGTCGACACATCCTACTCAGTCCTCTTCATTCTGCAAT TTAAAAGTCCTTATTATTTCAAAGTGTGTAGAGTTGAGATACCTTTTCAA ACTCAATGTTGCAAACACTTTGTCAAGACTTGAGCATCTAGAAGTTTGTA

AATGCAAGAATATGGAAGAACTCATACATACTGGGATTGGGGGTTGTGGA GAAGAGACAATTACTTTCCCCAAGCTGAAGTTTTTATCTTTGAGTCAACT ACCGAAGTTATCAGGTTTGTGCCATAATGTCAACATAATTGGGCTACCAC ATCTCGTAGACTTGAAACTTAAGGGCATTCCAGGTTTCACAGTCATTTAT CCGCAGAACAAGTTGCGAACATCTAGTTTGTTGAAGGAAGAGGTAGATAT ATGTTCTTTATGTTAATACAATTTAAACAATATTTTCAACCAAATTTTCA TAATATATCTGTAATTTGATTGTATGATGTGTTATTGTTTATATGTGGCT ATTAAGGGATGATAATTTTGCAGGTTGTGATTCCTAAGTTGGAGACACTT CAAATTGATGACATGGAGAACTTAGAAGAAATATGGCCTTGTGAACTTAG TGGAGGTGAGAAAGTTAAGTTGAGAGAGATTAAAGTGAGTAGCTGTGATA AGCTTGTGAATCTATTTCCGCGCAATCCCATGTCTCTGTTGCATCATCTT GAAGAGCTTACAGTCGAGAATTGCGGTTCCATTGAGTCGTTATTCAACAT TGACTTGGATTGTGTCGGTGCAATTGGAGAAGAAGACAACAAGAGCCTCT TAAGAAGCATCAACGTGGAGAATTTAGGGAAGCTAAGAGAGGTGTGGAGG ATAAAAGGTGCAGATAACTCTCATCTCATCAATGGTTTTCAAGCTGTTGA AAGCATAAAGATTGAAAAATGTAAGAGGTTTAGAAATATATTCACACCTA TCACCGCCAATTTTTATCTGGTGGCACTTTTGGAGATTCAGATAGAAGGT TGCGGAGGAAATCACGAATCAGAAGAGCAGGTAACGCTTTCAATTTCACT TTCTTAATTAATTANGGACTAAGCTCCTGTTTTTTGAATAATAAAGAGGT GGGATGACTAAACTTGGGCATCACAATTGCAACAAAATGTTACAAACCAT GAAACGCTCAAACCATTTCTTGAATTAAGGTTTCAATACAAGTCATTTAA AAATATGGCTTAAATTTTTTTATATTTATGTATCAACATGATTTTTCATT AGAGATCATTATTATAATAGTAAGTTTAAAGCAATTTAAATTAGAACTAA TTCTAACTTTAGCTAATAAATCGTTATAAATGTAAATAATTACTTTTTAG TGAAATAAGCAACGGATTTAATAAGTTAACAACTTAAATGTCATTTCCTA ACAAAAAAAACTATTTGGTTCAGAAAAACTGTAATTCAAGATAACTAAAA TAAAAATATTTGACATTCACTAAGAGCATTTTTTTCTAAATATGATTGCA AATGAATAAAACTTAAATTTATACAGAAAAGATTTTTATATATGTTATAC AAAATTTACAAATTGAAATTGGATATGTTAATTAACGGTTTATAATTCTG GTATCACAAAGGGATATATAATAAAATATTATTTTTCTGTAGTCATTTAT AATTGTACTAGTTTATAACCCGTGGGAACCATGAGTTCTAAAATTAGTTA AACTTTCATAATAAAAATTTATAATTATTATTTATTTTAAATAAATTATT AATTAAGAGATATATCAAAAATTTAAAGTTATTATAACTTCAAATTTAAC ATATAATTAAAAAATATATGATCATAACTTTCCGCAACTCTTCTTTTGTA TTAAAATGACCAGAGAAGCTCTTAGTATATTTTCTAAATCAAAGTCACAA AACTAATGAAGCATATAATTTTGTGAAAATCAATTAGCATTAGGTTTTAA GAGTCACCAAATTCAAAGAGTAATCCAATGCTTTCATTACCACTATGGAG AAAATATTTTCTTAGTTTAAATGAAATGAAAACAAACATTCAAACTAATT

GTTGCTTATTAAACCAAAGACCCATTACTTAGCCAAGAGTTTAACCAAAA AAAATTACATTCATGTATCATTATTAATGACTAGATATATATGAATATGA AGGGAGTTTTTATAGAAAATATAATCATAGATATTCAACATAACTTCATG GAATTCCTCAAAATAACCAAGTTATTCAAGAAATTACATCCAAGTCAACC AAAGAGAAGTTTAGCCTAGCATGGCTAAACTCAAGAAAATAAAATAAGGA

TTAGAAGTACCAAACATGTAGTAAGAATCACAGTAAAAGATGATGTTGTT CTTGATGTTCTTCTAAGTTCTTCAAGTCTCCAGTTGCTCCTAATAATGCA AAGGAGAGCCATTAAATTCGTATGTATTGATCCCTTCAAAAGCTGCACCA ACCTCCCTTAAATAACACTCAAAGCAAAAATGACAAAATTGCCCCTGAAG GACCCTATGCGGGTGCCTTGCGCGGGTGGAGCTGAATATGAAAGGTCTTT GGTCTTTGTGAGGGTGATGTTGTGCGGGTTAGCTTGTCGCATGCTTCCGC GCGGTTCGCGCACATGTGCACAGGTGATGCATGGTGTGTACGTTCTTGAC TTTTGAGCCTCCGATGCTTAGTCCACTTGGCCCAATTCGAGTCCAATCAA CTTATGACCCATTTTTCTTCAAGTTATCTTCAAGTTAAGCCCAATTTGCC TTCTCCAAATCATCCATAACTTCACAGAATCGCCCGTTCATCTTAATCCC GAATGAACAATTATTCTCCCGTCTTCATTTTAAGCAAGATACCACCTTCT TCATGCTTCATCCATCAATAGTACACTTCATGTATCATCTCTACTAGTTA TTTAGTCCACAGTCCTTGTTGTCCTCCAAATTTAATTATCTCATTTAGTT CCCGTTCCGCTAGTTTCCTTAAAATTTGCAATTAAGCTCACAGAAATATT AAGTACCCGAAATGGTCATAAAATAACAGAAAGGAAAATATGCATGAAGA TTAACTAAATGATGAACGAAATATGCTAAAATAGACTATAAAATGAAGTA AATAAAATGAAATTATCGCACTCCGACCACCCTTATAGGCTTGTAGTCCA CCCACCCTTCATTCCTTGTACCAATATGGGATGGAAACATCATTAATTAA

GCCAAAAAACTAACATATAAGGGGTGAGTGACAAAGGTAAGTACTAAAGA TGAAAAAAATCCATTTTTCTTGTATATACACAACACACACATAGGGGCAG ACGTAGGATTTCATAGTACAGATTGTTGGTGGCACATAAGTGTTGCTAGT GACATTTTTTTTTTCTTTTACGTAGTGGCACAACAGTARAAAAAACRAAA AATTCGAAATTTTTTACAATGTGCCTAAAAAAAACAGTGGTTGTTGGTGC CACTATGGACACCAAAGTTGAACTGCCCCTGCGCGCGCACACACACACAC ACATAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGTTTG GGATGTGATACTTCTTTTGGGAAAATGGAGTTATATCTTTGATATTGTAT TTTTTTAATGTAATTTATATATTTAATCATTTTAGTTTATAAGTTTTATT TATTTKGATATGAAAAAAAAAGTCTTTTATACATTGGATTTAACATAAAA ATCCAACAATATTAATCAAAAAGACCAAACATGTGGACAATTATGTATAT AATTAATTCACAATAGTCTTTAGGAATAGNATTATATATATAATTAATTC TCAATGGTCTTAGGAATAGTAAGTTCTTATATTTCAAACNTTTGCCACAN TTCTTTGNTTACTTNGACACTTTYCTCTMWNNANWMWWTWATATATATAT ATATATATATATAHAHAHAHAVACACACACACTAGATGTGTGCCMGCGCA AAGCAGTGACGTNNNGGAGAANACTTTCTTAAGCATAAATAATTATTATA TTTTTTATTGGGTATTATATAATAAAAAATTACAACTTTTAAATAAAATA TTTATGTTTATACTTTATATTTATATTGCTTGTATACTATTAATATAATA AATTAATATTTATGTCTAATTTATGAAATGTAAATTAATTTAAATACATG AATTTAATATTTTTAAAATTTTCAGTTTGCTTCAAATTGAGTTTCTTAAT

TATTGACCAAACATGTGGACAATTATGTATATAATTAATTCACAATAGTC TTTAGGAATAGTATTATATATATAATTAATTCTCAATGGTCTTAGGAATA GTAAGTTCTTATATTTCAAACTTTTGCCACAATTCTTTGCTTACTTTGAC ACTTTTCCTTCCTAACTTTACATATATATATATATTAAAGCGCAAAGGTC ATAGGAATATAATATTTTCTATTATTCTACGTTTTGCCACAAAAGTTTGA

ACACTTTGCCACTTTTTGTCCCTCCTTAACCTTTTCAATGTTTTGCGACA AAAGTTCCAAAACTTTGCCACTTTGATCATTCCTCAACTTTTCACCGCAT TAGTTTGTGGAGTTGGCAGTTTTGGTCCCTCTAACTTCGATATTCTCTAC TGCTAGCCAAAAAGGGTTCCAGAGTTTCACACTTTTGGTCCCTGACAGTA ACCAAATGTGAGATGTCAAATTTTTGCCACATTAGTTTGTGGAGTTGTCC CTTTTGGTCCCCCCACATTCGATATTCTACTATACGATCTTATTTTTCTC AAATAACAACACGTATATTTAATTACTAATGATAGAAATAGATATCAAAT AAAGTATTTGTAACACTGTGTAGAGTTTTTTTTTACAAGTTTGTATCAAA TCATATCAAAATTTAAGGTGGAACGGTGACCACATTAACCAGAAATGTAA TTTATTCTTTGATTTTGATAATTTTTAATATTTTGTTGTGATCTATGTAT TTAAAAGTAAACAACAAAGAACATAATCCAAAACCCTAAATTGCAAGTCT CGCCCAATTTCTCTATCACTAGTCCTCACTTACGATGGCGTTACGTCGCT CTCTCACTGCTTACAACCCTTTGTTGCTACTCATTACAATAACGAAAAGT TGAATATCCATATATTTATTTGGATGTGGAATTGAACGAATCTCGTCAAA TTTTTGATTTAGTTGATGGATTTGAGTAGAAGTTTGGGCAGAACGGGAAT GATGGTCTGCAAGTGGTTATAAACTTGATTCTGAGTTATTACTATATATG TAGCCTCTTTACAACGACCAAGGTTTCTTCCAGGTACCATTTGATCTTTT T AG AACTT AGTTTTCTGAAAC ACCCTGATTTGGATC AAAT ATC ACC AAC A

ACTCTTAAAAACTTGATTAATCAATTGTTTACTTCATCTTGATAACAAGT GGAATGATTTTCTACTTGAAAAAAAAGGTCCATGTGCGTCTGGTGGATCT GGTAAATGAAGATGGAAGGGAGAGCTGACTTTAAAGACACAAACACGTCA CCATATCTTTTATTTTATTTTAAATTTTCTTTTTTCCTATTTCTTTCTTT CTTGATCTCCAGATGGTATGTGGTGTGGATAATTTACACATAGAGATTGG

GAACGACTGTGATTTAGAGAGGACGTGGCTTGGGGTTGAGGATGGTTTAT

GGCTGGCCGAGTTTCATTTATATAAACAAACAAATATATAAAACAAGGGG

TAAAATGGCCATCTTATATGTATTTAACCGTCCTCTTTTTTTTTTTTTTT _{ττττττττττττττττχττGTAATTTAAGAAGGGGT} CTCTTATTCCCAACCAGTCAAATAGGGACTTAGGTTGTTTGGAAACAGTT

CCGTGAGACCGTGACTTGGATGGTAGATAAATTTAGTAAACTTAACCCTT CAATTAACCTACCTTTTTCTTATTAACTCAATTTCAACCTAAATTCTGAT TCTTGTTTGAAAATAAGTTGCATCTTTATTTTTGTATTATCTTGTTGCAT AGGATCCTTAGCATCTTTTAATAATTTATTTGAAGGTGAAAGATCCAACT ATTTTTAATCTGTTGACGTTTTCCATCATTTGCAACTGTTTCTTGAAAAA

AAAATACCTAAAATCAAAATAACCATTTTCAAATCCAAAATTATAAGAGA GAATTGTAAATGGACATGGAATCATAAATCATTAACACAGTTCAGTAAAC AAGTTGCTAATTACATTTCTTGCTGTGCAGATTGAAATTCTATCAGAGAA AGAGACATTACAAGAAGCCACTGGCAGTATTTCAAATCTTGTATTCCCAT CCTGTCTCATGCACTCTTTTCATAACCTCCGTGTGCTTACATTGGATAAT

TATGAAGGAGTGGAGGTGGTGTTTGAGATAGAGAGTGAGAGTCCAACAAG TAGAGAATTGGTAACAACTCACAATAACCAACAACAGCCTATTATACTTC CCTACCTCCAGGAATTGTATCTAAGGAATATGGACAACACGAGTCATGTG TGGAAGTGCAGCAACTGGAATAAATTCTTCACTCTTCCAAAACAACAATC AGAATCACCATTCCACAACCTCACAACCATAGAAATGAGATGGTGTCATG

GCTTTAGGTACTTGTTTTCGCCTCTCATGGCAGAACTTCTTTCCAACCTA AAGAAAGTCAAGATACTTGGGTGTGATGGTATTAAAGAAGTTGTTTCAAA CAGAGATGATGAGGATGAAGAAATGACTACATTTACATCTACCCACAAAA CCACCAACTTGTTCCCTCATCTTGATTCTCTCACTCTAAACCAACTGAAG AATCTGAAGTGTATTGGTGGAGGTGGTGCCAAGGATGAGGGGAGCAATGA AATATCTTTCAATAATACCACTGCAACGACTGCTGTTCTTGATCAATTTG AGGTATGCTTTGTACATATTCAATTATTTATTTAATTTCCTTTTTTATTT GCAATATTCTATAAATAATACATTTTATACCCACTATACTAAGATAATAA TTACCTAGAGGGATGGATGCTATGACACAGCTGCTACACTTCAGAAACTC TAGTAAGGGCAGTTATGGAAGTTCAATAAAATGATAATGGCATCTTTTGA TGGGTAATATAGGCAATTTAAGTTTTATTTCTGTTAAAGCAGTATTTAGC AAGTACTGGCCAGTAGGAGAGGAGAATATCACCTTTTGTGAAAATCTGGT CATTGTACCCAGAATTTAGTTAAATGTAACATTTTAGATATTAGGGGTTA TCAGGTGACAGATATTGTAGAATAGAACAATATGTAATATTACCCAAAAC TATTTTTTCTAAGGTTGCTCTGTTAAATATGTGCTTTCTTGATTTCATTG AATTTGCATTCCTATATTTTAGGTGGTAAAGTGATTGTCTCTTCAATAAA TCCCGAAATTAATTAAAAAAAAAAAAACAAAAGTAAATTTTTGATATGGA GAGCACTGGTATCATTTAGTATATAAAAAAACTAGATTTTGAATTAAGTT TCTTATATAAAAGCTGTGTATATAGTTTAATTAGTTTTACATCATTTTTC CATGTGGTGTTGCAGTTGTCTGAAGCAGGTGGTGTTTCTTGGAGCTTATG CCAATACGCTAGAGAGATAAAAATAGGCAACTGCCATGCATTGTCAAGTG TGATTCCATGTTATGCAGCAGGACAAATGCAAAAGCTTCAAGTGCTGAGA GTAATGGCTTGCAATGGGATGAAGGAGGTATTTGAAACTCAATTAGGGAC GAGCAGCAACAAAAACAACGAGAAGAGTGGTTGTGAGGAAGGAATTCCAA GAGTAAATAACAATGTTATTATGCTTCCCAATCTAAAGATATTAAGTATT GGAAATTGTGGGGGTTTGGAACATATATTCACATTCTCTGCACTTGAAAG CCTGAGACAGCTCCAAGAGTTAACGATTAAGGGTTGCTACAGAATGAAAG TGATTGTGAAGAAGGAAGAAGATGAATATGGAGAGCAGCAAACAACAACA ACAACAACGAAGGGGGCATCTTCTTCTTCTTCTTCTTCTAAGAAGGTGGT GGTCTTTCCTTGTCTAAAGTCCATTGTATTGGTCAATCTACCAGAGCTGG TAGGATTCTTCTTGGGGATGAATGAGTTCCGGTTGCCTTCATTAGATAAA CTTATCATCGAGAAATGCCCAAAAATGATGGTGTTTACAGCTGGTGGGTC CACAGCTCCCCAACTCAAGTATATACACACAAGATTAGGCAAACATACTC

TTGATCAAGAATCTGGCCTTAACTTTCATCAGGTACATATATATTCCTTT AATTGGCATCATCTAATTAAGAAAGATATCATTCCTGCCAAGTAAATTTA CTTCAAACACATTCACACTAGTTTCAGTCCAAGTTTATGTTGTTCTAGGA AGGCCAAAATGGGAAAGCAAGATAGGGAAAAATAGAGTATTTCAGTGGAA AGGGTATTTTAGGTATTTTCTGTCAAAAATTGTTATTGCAGGCTTTTTAG

TACCTGGAAGAGCATGATTATTCTCGATTTGCTTGTTTCTTTATCATTTT TCTTAGCCTAGCATGATTTTCAATGAAATCTTTCCCTGTTACTCCATTTG ATTGTTGTTCTTCATGGTTCTAAGTGAGTTAGTGGCTCATCTGTTACTTC TTTTGATTGTTATTTTCATAGCATGTTGTCACTTGAATCAAGCTTTTCCA TTTTCAACAAGGACAAAAGGTCAAAACTAACCTACTTTATGAGATCAAAA ATAGCAACCCATCGGATAACTTTTAGTTGGAGTTAATACTTACAATTACC ATTGTGATTAATAATTATAATATCTTGTATTAATTCATAAAAATTGGTAC AGCACATATATGACATTTCAAAGGTTTTTGTTTGACATATATATGCCTCT GGCGTTTTCTTTATTGGACATGCAGACTTCATTCCAAAGTTTATACGGTG ACACCTTGGGCCCTGCTACTTCAGAAGGGACAACTTGGTCTTTTCATAAC TTTATCGAATTAGATGTGAAATCTAATCATGATGTTAAAAAGATTATTCC ATCCAGTGAGTTGCTGCAACTGCAAAAGCTGGTAAAGATTAATGTAATGT GGTGTAAAAGGGTAGAGGAGGTATTTGAAACTGCATTGGAAGCAGCAGGG AGAAATGGAAATAGTGGAATTGGTTTTGATGAATCGTCACAAACAACTAC CACTACTCTTGTCAATCTTCCAAACCTTGGAGAAATGAAGTTACGGGGTC TCGATTGTCTGAGGTATATATGGAAGAGCAATCAGTGGACAGCATTTGAG TTTCCAAACCTAACAAGAGTTGAAATTTATGAATGTAATTCATTAGAACA TGTATTTACTAGTTCCATGGTTGGTAGTCTATTGCAACTCCAAGAGCTAG AGATTGGTTTGTGCAACCATATGGAGGTCGTGCATGTTCAGGATGCAGAT GTTTCTGTAGAAGAAGACAAAGAGAAAGAATCTGATGGCAAGATGAATAA GGAGATACTTGTGTTACCTCATCTAAAGTCATTGAAATTACTACTTCTTC AAAGTCTTAAGGGGTTTAGCTTGGGGAAGGAGGATTTTTCATTCCCATTA TTGGATACTTTGGAAATCTACGAATGCCCAGCAATAACCACCTTCACCAA

GGGAAATTCCGCTACTCCACAGCTAAAAGAAATGGAAACAAATTTTGGCT TCTTTTATGCTGCAGGGGAAAAAGACATCAACTCCTCTATTATAAAGATC AAACAACAGGTAAACCAGATCTTTGTTGCTTTAATAATTCTTAAACTACA TTTGAAAAGCTTCATGCAAGTTTTTTTTGTTATATTGTCAAAAACCGCAA CCTACATTTTCAGCTTTATATTTATGTACTTTATGCAGGATTTCAAACAA GACTCTGATTAATGTGAAGTGAATATTAAAGGTAAATTATATTTTCATGT TCCTAGTTGCCTATTAATTAAAGGCCTTTTAGTTCGTGATTTTTGGATGT ATTCTTCATGATGATGTCAATCTTCTAATACCCCATTCATTGTTTGGTTG AATGTTGACTCTATGTCAGGATGAATATTCAAGGGAAGAATTGTTCATCA TATGAAGGACATTAAAGAACATGGTGCTAT

RG2C deduced polypeptide sequence (SEQ ID NO:92)

MAJNIETANEIIKQVVPVLMVPINDYLRYLVSCRKYISDMDLKMKELKEAKDNVEEH KNH ISNRLEVPAAQVQSWLEDVEKINAKVETVPKDVGCCFNLKIRYRAGRDAFNI IEEIDSVMRRHSLITWTDHPIPLGRVDSVMASTSTLSTEHNDFQSREVRFSEALKALE ANHMIALCGMGGVGKTHMMQRLKKVAKEKRKFGYIIEAVIGEISDPIAIQQVVADY LCELKESDKKTRAEKLRQGFKAKSDGGNTKFLIILDDVWQSVDLEDIGLSPSPNQG VDFKVLLTSRDEHVCSVMGVEANSIINVGLLIEAEAQRLFQQFVETSEPELHKIGEDI VRRCCGLPIAIKTMACTLRNKRKDAWKDALSRLQHHDIGNVATAVFRTSYENLPD KETKSVFLMCGLFPEDFNIPTEELMRYGWGLKLFDRVYTIIEARNRLNTCIDRLVQT

NLUGSDNGVHVKMHDLVRAFVLGMYSEVEQASIVNHGNMPGWPDENDMIVHSC KWSLTCKGMIEFPVDLKFPKLTILKLMHGDKSLKFPQEFYEGMEKLRVISYHKMKY PLLPLAPQCSTNIRVLHLTECSLKMFDCSCIGNLSNLEVLSFANSCIEWLPSTVRNLK KLRLLDLRLCYGLRIEQGVLKSLVKLEEFYIGNAYGFIDDNCKEMAERSYNLSALEF AFFNNKAEVKNMSFENLERFKISVGCSFDGNINMSSHSYENMLRLVTNKGDVLDSK LNGLFLKTEVLFLSVHGMNDLEDVEVKSTHPTQSSSFCNLKVLIISKCVELRYLFKL NVANTLSRLEHLEVCKCKNMEELIHTGIGGCGEETITFPKLKFLSLSQLPKLSGLCH NVNΠGLPHLVDLKLKGIPGFTVIYPQNKLRTSSLLKEEVVIPKLETLQIDDMENLEEI. WTCELSGGEKVKLREIKVSSCDKLVNLFPRNPMSLLHHLEELTVENCGSIESLFNID LDCVGAIGEEDNKSLLRSINVENLGKLREVWRΠ GADNSHLINGFQAVESIKIEKCK RFR IFTPITANFYLVALLEIQIEGCGGNHESEEQIEILSEKETLQEATGSISNLVFPSC LMHSFHNLRVLTLDNYEGVEVVFEIESESPTSRELVTTHNNQQQPΠLPYLQELYLR NMDNTSHVWKCSNWNKFFTLPKQQSESPFHNLTTIEMRWCHGFRYLFSPLMAELL SNUA VKILGCDGIKΕVVSNW_)DEDEEMTTFTSTHKTTNLFPHLDSLTLNQLKNLK CIGGGGAKDEGSNEISFNNTTATTAVLDQFELSEAGGVSWSLCQYAREIKIGNCHAL SSVIPCYAAGQMQKLQVLRVMACNGMKEVFETQLGTSSNKNNEKSGCEEGIPRVN NNΛLMLPNLKILSIGNCGGLEHIFTFSALESLRQLQELTIKGCYRMKVIVKKEEDEYG EQQTTTTTTKGASSSSSSSKKVVVFPCLKSIVLVNLPELVGFFLGMNEFRLPSLDKLII EKCPKMMVFTAGGSTAPQLKYIHTRLGKHTLDQESGLNFHQTSFQSLYGDTLGPAT SEGTTWSFHNFIELDVKSNHDVKKIIPSSELLQLQKLVKINVMWCKRVEEVFETALE AAGRNGNSGIGFDESSQTTTTTLVNLPNLGEMKLRGLDCLRYI KSNQWTAFEFPN LTRVEIYECNSLEH VFTSSM VGSLLQLQELEIGLCNHMEVVHVQD AD VS VEEDKEK ESDGKMNKEILVLPHLKSLKLLLLQSLKGFSLGKEDFSFPLLDTLEIYECPAITTFTK GNSATPQLKEMETNFGFFYAAGEKDINSSIIKIKQQDFKQDSD.

RG2D polynucleotide sequence (SEQ ID NO:93) and (SEQ ID NO:94) ACGACCACTATAGGGCGAATTGGGCCCGACGTCGCATGCTCCCGGCCGCC ATGGCCGCGGGATGTAAAACGACGGCCAGTCGAATCGTAACCGTTCGTAC GAGAATCGCTGTCCTCTCCTTCAACCATTTAATGTATATGAGCTAAATTG AAACATCTACTATCATGTTTAAATTTATAAACTTTTTCCTTTAGATTCAC TTGTCTGGATGTGTTTAATAAAACCCAATTTCCCACATGCGTAGAGATCA TAGATGTAACTATTGTTAATCAATTTTGCCTGCCAAGTTTTAATAATTAT

ACTTGGATATTAACAAAACTTTATCTAACGACCAAGGTAATATTAAAAAT AGGTTATTATTCTTCATGCTAATTAAAAGATGGGTTGCAAAAGTGAGACC ATGAAAACATTAACACGTTGATATTTTCAACTTTTATTCTTTCATATTCA CCATATTTTTTACTTTCGTATTGATTAATCATCTTTCAATCACAGGCTCC TTGGCAAAAAGTCAGATCTATTAACAAATACTTCCATGTGGTTGCAAATT

ACAAGGATTTCAACATAATTACCAAAACATAGCATTATCATAAGATCGAA TAATAATCAAATTCTTCTATAATATTACACAAAGGTAACGTCATTAATTA ATTACGATACGAGACAGACTTTTTCACTCGTGACATCAACGGTCTATTCT AACTTTACTTAATTAAATGAATCTAGGATGTGCTCATATGCATGTAATAT TTGCTACCGTCATCTTTCAAATGACCATATTTTTATGTATTTATAATGAA TCAATGAAAAACCGGATTTCTATTTAAAATTCTTAAAACTTCATCTTTTA AGCCAGGGTGAATACAATTGTAGATCCACTGTTAATTTCCATCGATTATG CGTGATCAATTGTTGGCTGCATACGATGCAGGTGCTACCACAAGAATATG GCCATGGAAACTGCTAATGAAATTATAAAACAAGTTGTTCCAGTTCTCAT GGTTCCTATTAACGATTACCTACGCTACGTCGTTTCCTGCAGAAAGTACA TCAGTGACATGGATTTGAAAATGAAGGAATTAAAAGAAGCAAAAGACAAT GTTGAAGAGCACAAGAATCATAACATTAGTAATCGTCTTGAGGTTCCAGC WO 98/30083 _{< Λ}, PCT/US98/00615

126

AGCTCAAGTCCAGAGCTGGTTGGAAGATGTAGAAAAGATCAATGCAAAAG TGGAAACTGTTCCTAAAGATGTCGGCTGTTGCTTCAATCTAAAGATTAGG TACAGGGCCGGAAGGGATGCCTTCAATATAATTGAGGAGATCGACAGTGT CATGAGACGACACTCTCTGATCACTTGGACCGATCATCCCATTCCTTTGG GAAGAGTTGATTCCGTGATGGCATCCACCTCTACGCTTTCAACTGAACAC AATGACTTCCAGTCAAGAGAGGTAAGGTTTAGTGAAGCACTCAAAGCACT TGAGGCCAACCACATGATAGCATTATGTGGAATGGGGAGAGTGGGGAAGA CCCACATGATGCAAAGGCTGAAGAAGGTTGCCAAAGAAAAGAGGAAGTTT GGTTATATCATCGAGGCAGTTATAGGGGAAATATCGGACCCCATTGCTAT TCAGCAAGTTGTAGCAGATTACCTATGCATAGAGCTGAAAGAAAGCGATA AGAAAACAAGAGCTGAGAAGCTTCGTCAAGGGTTCAAGGCCAAATCAGAT GGAGGTAACACTAAGTTCCTCATAATATTGGATGATGTCTGGCAGTCCGT TGATCTAGAAGATATTGGTTTAAGCCCTTCTCCCAATCAAGGTGTCGACT TCAAGGTCTTGTTGACTTCACGAGACGAACATGTTTGCTCAGTGATGGGG GTTG AAGCT AATTC AATT ATTAACGTGGGACTTCT AATTGAAGC AGAAGC ACAAAGATTGTTCCAGCAATTTGTAGAAACTTCTGAGCCCGAGCTCCACA AGATAGGAGAAGATATTGTTAGGAGGTGTTGCGGTCTACCCATTGCCATC AAAACCATGGCGTGTACTCTAAGAAATAAAAGAAAGGATGCATGGAAGGA TGCACTTTCTCGTTTACAACACCATGACATTGGTAATGTTGCTACTGCAG TTTTTAGAACCAGCTATGAGAATCTCCCGGACAAGGAGACAAAATCTGTT TTTTTGATGTGTGGTTTGTTTCCCGAAGACTTCAATATTCCTACCGAGGA GTTGATGAGGTATGGATGGGGCTTAAAGTTATTTGATAGAGTTTATACAA TTATAGAAGCAAGAAACAGGCTCAACACCTGCATTGAGCGACTGGTGCAG GCAAATTTACTAATTGGAAGTGATAATGGTGTACACGTCAAGATGCATGA TCTGGTCCGTGCTTTTGTTTTGGGTATGTATTCTGAAGTCGAGCAAGCTT CAATTGTCAACCATGGTAATATGCCTGGGTGGCCTGATGAAAATGATATG ATCGTGCACTCTTGCAAAAGAATTTCATTAACATGCAAGGGTATGATTGA GATTCCAGTAGACCTCAAGTTTCCTAAACTAACGATTTTGAAACTTATGC ATGGAGATAAGTCTCTAAAGTTTCCTCAAGAATTTTATGAAGGAATGGAA AAGCTCCAGGTTATATCATACGATAAAATGAAGTACCCATTGCTTCCTTT GGCACCTCAATGCTCCACCAACATTCGGGTGCTTCATCTCACTGAATGTT CATTAAAGATGTTTGATTGCTCTTCTATCGGAAATCTATCGAATCTGGAA GTGCTGAGCTTTGCTAATTCTCGCATTGAATGGTTACCTTCCACAGTCAG AAATTTAAAGAAGCTAAGGTTACTTGATCTGAGATTTTGTGATGGTCTCC GTATAGAACAGGGTGTCTTGAAAAGTTTGGTCAAACTTGAAGAATTTTAT

ATTGGAAATGCATATGGGTTTATAGATGATAACTGCAAGGACATGGCAGA GCGTTCTTACAACCTTTCTGCATTAGAATTCGCGTTCTTTAATAACAAGG CTGAAGTGAAAAATATGTCATTTGAGAATCTTGAACGATTCAAGATCTCA GTGGGGTGCTCTTTTGATGGAAATATCAGTATGAGTAGCCACTCATACGA AAACATGTTGCAATTGGTGACCAACAAAGGTGATGTATTAGACTCTAAAC

TTAATGGGTTATTTTTGAAAACAGAGGTGCTTTTTTTAAGTGTGCATGGC ATGAATGATCTTGAAGATGTTGAGGTGAAGTCGACACATCCTACTCAGTC CTCTTCATTCTGCAATTTAAAAGTCCGTATTATTTCAAAGTGTGTAGAGT TGAGATACCTTTTCAAACTCCATGTTGCAAACACTTTGTCAAGCCTTGAG CATCTAGAAGTTTGTGGATGCGAAAATATGGAAGAACTCATACATACTGG GATTGGGGGTTGTGGAGAAGAGACAATTACTTTCCCCAAGCTGAAGTCTT TATCTTTGAGTCAACTACCGAAGTTATCAGGTTTGTGCCATAATGTCAAC ATAATTGGGCTACCACATCTCGTAGACTTGAAACTTAAGGGCATTCCAGG TTTCACAGTCATTTATCCGCAGAACAAGTTGCGAACATCTAGTTTGTTGA AGGAAGAGGTAGATATATGTTCTTTATGTTAATACAATTTAAATAATATT TTCAACCAAAATTTCATAATATATCTGTAATTTGATTGTATGATGTGTTA TTGTTTATATGTGGCTATTAAGGGATGATTATTTTGCAGGTTGTGATTCC TAAGTTGGAGACACTTCAAATTGATGGCATGGAGAACTTAGAAGAAATAT

GGCCTTGTGAGCTTAGTGGAGGTGAGAAAGTTAAGTTGAGAGAGATTAAA GTGAGTAGCTGTGATAAGCTTGTGAATCTATTTCCGCACAATCCCATGTC TCTGTTGCATCATCTTGAAGAGCTTAAAGTCAAAAATTGTCGTTCCATTG AGTCGTTATTCAACATCGACTTGGATTGTGTCAGTGCAATTGGAGAAGAA GACAACAAGAGCATCTTAAGAAGAATCAAAGTGAAGAATTTAGGGAAGCT AAGAGAGGTGTGGAGGATAAAAGGTGCAGATAACTCTCGTCCCCTCATCC ATGGCTTTCCAGCTGTTGAAAGCATAAGTATCTGGGGATGTAAGCGGTTT AGAAATATATTCACACCTATCACCGCCAATTTTGATCTGGTGGCACTTTT GGAGATTCACATAGGAAATTACAGAGAAAATCATGAATCGGAAGAGCAGG TAACGCTTTCAATTTCACTTTCTTACTTAATTAAGGACTAAGCTCTTGTT TTTTGAATAATAAAGAGGTGGGATGACTAAACTTGGGCATCACAATTGTA ACAAAATGTTACAAACCATGAACGTACAAACCATTTCTTGAATTAAGGTT TCAATACAAGTCATTTACAAATATGGCTTAAGTTTTTTTATATTTATGTA TCAACATTATTTTTCATTAGAGGTCATTATTATAATAGTAAGTTTAAAGC AATTTAAATTAGCACTAATTTTTCATCATCTAACTTTAGCTAATAAATCG

TTATAAATGTCAATAGCTAAAATAAAAATATTTGACATTCACTGAGAGCA ATTTTTTCTAAACATGATTGCAAATGATTAAAACTTAAATTTAAACTAAA AAGATTTTTATATATGTTATACAAAATTTACAAATTGAAATTGGATATGT TAATTAACAGTTTATAATTATTGTATTACAAAGCGATATATAATAAAATA TTATTTTTCTGTAGTCATGTATAATTGTATATGTAAATGATTTTTTAAGA

TGGTAGAAGTGGAAACTAGTCAATCTCACTTAACTCATTGTCACACCAGT TTTATATCCGTTTCTCTCTCTCTCTCTTCTTGCCTCCATCTTTTTTCAAC TCATAACACATAAAAATAACATATTTTCCAACACATTTAAGTCACTACCA CATCATTATTTTTAATTTAATTAAATTAGAAAATATAAAATTAAATAAAA CATAACATTTTTTTATTAAAAGGCACTAATACAAATAAAAAGATACACGG

TAAATAAAAAAACGATAATTAGAAAAAAAACATAATAAAAAAAGACAACA TTAAAAATAWAAAGCGACAACTAAAATTAACTAATGATCAAGAAAATTCT AAAACTCCCACCATATTTTTCTGCAATTTGTCATTTATGTTCAAACACCA TTCGCAGAATCCCTCCTATCAAGTGATCATGTTGATTGAGAAAAAACTGT ATGTCTCTCTCATGTATCTCCAAGTCCAACAAGTTAGCTTTCATTTCTTC

ATTTTCTCATGTAAGACGCAAATTTTCATCCCGATATTGTTTTCTATCTT CCACCTCTACTTTATTCACAGTGTGGATGAAGGAGAGGACAGCGATTCTC GTACGAACGGTTACGATTCGACTGGCCGTCGTTTTACAATCCCGCGGCCA TGGCGGCCGGGAGCATGCGACGTCGGGCCCATTCGCCCTATAGTGGTCGT AATACA (SEQ ID NO:93)

Sequence gap TGAGCCTCCGATGCTTAGTCCACTTGGCACAGTTCAAGTCCAATCAACTT ATAACCCATTTTTCTTCAAGTTGTCTTCAAGTTAAGCCCAATTTGCCTTC TCCAAATCATCCATAACTTCATGGAATCGCCCCTTCATCTTAATCCCGAA TGCACAATTATTCTCCCATCTTCATTTTAAGCAAGAGGCCACCTTCTTCA TGCTTCATCCATCAATAGTCTGTTGGAATAGTGTCTAAGGCTGCAACTAT ATTAGACAAGTATTTGACCCGGTTGTGCATGGTCCTTTTGGGTTGCCTTC ACCATAGCAACTTGATAGGATGATTTATTAAGAGAGAGTAAATATTATTA ATATATTATGAGAATAATATAATGAATAATATATTTGTTATTTGATTAAT ATAAGTCATAGAATTAATTAGAATTAATTTGGTGACTTAAAGAGATTAAT TAAATAAAGGGGTATAAACTGTCAATTGTTTGATAGTTAAGCTTTAGACT GTAAATCCATTTGGATATGGTATGGACGAATCCTAAGGGATTTAGGATAG CTAAAATCGTCCATATGAGTTATCTAAGAAGGATTTGGATAGCCTTAAGA

GAAGATTATCTGATAGGGACTTATCTGTAATCCTTAAGGAGTCTACAAGT ATAAATAGACCCTATGGCTGATGGAATTCGACACATCTCCTAAAGTAAGA GAGCCTTGGCCGAATTCCTCCCCTCACCTCTCTCCTAAATCATTCTTCTT GCTATTGGTGTTTGTAAGCCATTAGAGGAGTGACATTTGTGACTCTAGAA TCTCCAAGACCTCAAGATCAACAAGGAATTCAAAGGTATGATTCTAGATC TGTTTCAATGTTGTTATTTGTCCTAATTAGTCATTAGAAGACTTGGATTC AAAGCATGTTTATTAGAAAGCCTAGATCYGAGCAATAGGGTTTTGCATGC GCACATAGGAAAGTTCTTATGGCTAAAACCCATCATAGTCCACTTCATGT ATCATCTCTACTAGTTATTTAGTCCATAATCCTTGTTGTCCTCCAAGTTT AATTACCTCCCTTAGTTCCTGTTCTGCTAGTTTCCTTAAAATTTGCTATT

AAGATCACAGAACTAGAGAGTACCCAAAATGGTTATAAAATAACAAAAAG GAAAATATGCATGAAGATTAACTAAATTATAAATGTAATATGCTAAAATA AACTATAAAAAAAAAGTAAATAAAATGAAACTATCACACTCCGACCACCC TTATAGGCTTGTACTGCACCCACCCTTCATTCCTTGTACCAATATGGGAT GGAAACATTATTCATTAAGCCAAAAAACTAACATTTAAGGGGTGAGTGAC AAAGGTAAGTACTAAAGACAACAATAATCCATTTTTCTTGTACATACACA ACACACACATAGGGGCGGACGTAGGATTTGTAGTATGTGTTGTGGGTGAC ACATTTTTTCTTTTACGTAGTGACACAATAGTAGAGAAAACGAGAAATTC CAATTTTTTACATTGTGTTCGAAAAAATATACAGGGGTTGCTGGTGCTAC TCTGGGCACCAAAGTGGAACCGCCCCTGCACACACACACACATAGAGGGA GAGAGAGAGGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGATTT TGGGATGTGATACTTCTTTTGGGAAAATGGAGCAATATCTTTAATATTGT ATTTTTTTAATGTAATTTATATATTTAATCATTTTAGTTTATAACTTTTA GTTTTTTTTATTTTAATCTGTATATTTAATCATTTCAGTTTATAAGTTTT ATTTATTTTGGTATACCAGAAAAAAAAGTCTTTTATGTGTTGGATTTAAC

ATAAAAATCTAACAATATTAATCAAAAAGACCAAACATGTGGACAATTAT GTATATAATTAATTCTCAATGGTCTTAGTGTAACGATATAAATTTCAAAA CAATTTTTCACATTAAAAAAAACACTTTCAGTCATAATTGTTATAAATTA TCATTGTATCACAAAATCAGTTCATAACATCACATCCCAAGATCAATAAA GTGTAAATACTCCTCATGTGTGTACTAATCAAGCCGACGCCTTCCCGCGA TTCTCACTGGTACCTGAAACACGTAACATAACAACTGTAAGCATAAATGC TTAGTGAGTTCCCCAAAATACCACATACCACATATATGCCTTTCCAGGCC ATAACTCTGTAGGATCTTCCGACCCAAGTGTCTCAGGGGACTTCCGTCCC GAATCCCGGTAGACCTTCCGGTCCTACCCGTATTGACCTTCCGGTCCGTA TCATACATAACATACATAACACATACATATCACATAACAACATATAGCAC ATACATCTCATAACATAAAAGACCTTCCGGTCACATAAAGGTACCCTTCC AGGTACAGTATAGTGAGAANACTCACCTCGTATGATGTCTAATACCTCAC GTGCTCGATATCCCTGAATCTCGAAACAATGACCTAGCCCCGCCTACTCA CATAAAGTAATTATTTCAAATCATTAACGGCTCTCAAGGCTAGACTACAT CCCTTTCTATAAATCCACAGAAGGGTAAAAGACCATTTTACCCCTCCTTG ACCCAAAAGTCCAAATGTTGATCAAAACCCCAAAAGTCAACGAAAGACAA TGGTCAACTTTGACCCTACTCGTGGAGTGCACAAAGGTGACTCGGCAAGT AC ATGCGGGTCCTCTGAATCCTTTC AGTCTCTCTTGGCTCGTCGAGTCTT TCTTCCACCCGACGAGTTACACCTGTCATGAATCGCGGGGCAACCCCGAC TCGACTTGTCGAGTCCGCTCATGGACTCAACGAGTTCATTCCATGCTCAC ACTCAAATGACCTCCTGAGGTCAGATCTGTTCCTCTAATCCATAGATCTG ACCTTCCCAAGCTCAATAAACACGTAAAGGTTCGAACTTGATACTCATGC AACGTCCAAATGATTCTACTTGATGATTTAGCCCCAAATACAACATCCTA AGTCCATACGACCTTATTTTTCTCAAATAACAACACATATATTTAATTAC CAATGACAGTAATAGATATCATATAAAGTATTTGTAACACTTTGTAAGAA CCTTGCTACTATAGGTAAAAAGAAACATTTCAAAGTACATGCCCTAATTA GAAAAAAAGTTATAAAAAAATAATGACTAGGGGCGTGTTTTTTTTACTAG TTTGTATCAAATTATATCAAAATTTAAGGTGGAAAAGAATGACGACCACA TTAACCAGAAATGTAATTATTTTTTTATTTGGTAATTTTTAATATTTGTT GTGATCTATGTATTTAAAAGTAAATATCAAACAAGAACATAATCCAAACC CTAAATTGCAAGTCTCGCCCAATTTCTCTATCACTAGTCCTCACTTACGA TGGCGTTACGTCGCTCTCTCACTTCCTACAACCCATTGTTGCTACTAATT ACACTAACGAAAAGTTGAATATCCATATATTTATTTGGATGTGAAATTGA ACGAATCTCGTCAAATTTTTTATTTTGTTGATGGATTTGAGTGGAAGTTT AGGCAGAACGGGAATGATGGTCTGCAAGTGGTTATAAACATGGGTGAAGA TAAAATGGAGTTGTCGCCGTTGTATTATAGATCTCTTAGGGGTTTGATTC TGAGTTATTACTGTATACGTAGCCTCTTTACAACGACCATTCTTCCAAGT ACCATTTGATCTTTTTAGAATCCAGTTGTCTGAAACACCCTGATTTGGAT CAAATATCACCAACAACTCTTAAGAACTGGACTAATTAATTGTTTTCTTG ATCTTGATAACAAGAGGAAACACGTCACCATATCTTTTATTTTAAATTTG CTTTTGGTGTATTTTCTTTCTTCCCATTTCTTTCTTGATCTGTTCCAGAT GGTATTTGGTGTGGATAATTTACACCTGGAGATTGTGAACGATGGGAAGG GGTATGTGATTTACAGAGGATGTGGCTTGTGGTTGAGGATGGTTTATGGC

TGGCCGAGTCTAATTTATATTTATATAAACAAATAAATATATAAAACAAG GGTAAAATATGTATTTAAGCGTCCTCTTTTAATGGTGACAATTTTTACAG TTTACTCTCTTTGTTTTTTAATTGTGATGCCCACGATCGAACTCATTCAT CCCCCCCCCTTTTTTTTTTAAAATAAAAAATTAAGAAGGGGTACCACCAT ATACCCGTGTCAGCTTCTTATTCCCAAGCAGTCAAATAGGGACTTAGGTT GTATGGAAACAGTTCCGTGACTTGGATGGCAGATAAATTTAGTAAACTTA ACCCTTCAATTAACCTACCTTTTTCTTATTAACTCAATTTCAAGCTAAAT TCTGATTCTTGTTTGAAAATAAGTTGCATCTTTATTTTTGCATATTATCT

TGTTGCATAGGATCCTTAGCATCTTTTAATAGTTTATTTGAAGCTGAAAG ATCCAACTAGTTTTGATCTGTTGGCATTTTCCATCATTTGCAACTGTTTC TTGAAAAAAAATACCTAAAATCAAAATAACCATTTTCAAATCCAAAATTA TAAGAGAGAATTGTTAATGGACGTGGAATCATAAATCATTAACACAGTTC AGTACACAAGTTGCTAATTACATTTCTTGCTGTGCAGATTGAAATTCTAT CAGAGAAAGAGACATTACAAGAAGTCACTGATACTAATATTTCTAATGAT GTTGTATTATTCCCATCCTGTCTCATGCACTCTTTTCATAACCTCCATAA ACTTAAATTGGAAAATTATGAAGGAGTGGAGGTGGTGTTTGAGATAGAGA GTGAGAGTCCAACATGTAGAGAATTGGTAACAACTCACAATAACCAACAA C AGCCTATTATACTTCCCAACCTCCAGGAATTGTATCTAAGGAATATGGA CAACACGAGTCATGTGTGGAAGTGCAGCAACTGGAATAAATTCTTCACTC TTCCAAAACAACAATCAGAATCACCATTCCACAACCTCACAACCATAGAA ATGAGATGGTGTCATGGCTTTAGGTACTTGTTTTCGCCTCTCATGGCAGA ACTTCTTTCCAACCTAAAGAAAGTCAAGATACTTGGGTGTGATGGTATTG AAGAAGTTGTTTCAAACAGAGATGATGAGGATGAAGAAATGACTACATTT

ACATCTACCCACACAACCACCAACTTGTTCCCTCATCTTGATTCTCTCAC TCTAAAATACATGCACTGTCTGAAGTGTATTGGTGGAGGTGGTGCCAAGG ATGAGGGGAGCAATGAAATATCTTTCAATAATACCACTACAACTACCGAT CAATTTAAGGTATGTTTGTACATATTTAATTATATATTTAATTTCCTTGT TAATTTCCTTTTCTTTGCAATATTCTATGCGAACTCAAGAATGGGATTTG

GAGGCATATAAAGTTACATTCATTTGAACAAGTATTACCTTTTATTTGTT ATTTATCATTTTCATATCAAGTACCTATAACATTTCTTTTTTATTTTTCT AATTAGAAGAGGTCCACATGTCTAATTAGGTTTTCCATTCTATGTGTAAC CTCTATTCTCTCTGTAATCAAGCATCTTAGATTATTTATCCATTTTCATA ATTGTGTTTATTTTTACAGTTTTTTTTTTTATTTAATTTTAATAATTTAA TTTTAATTTATTTATTATTTTTTTTTTGGTAATTGCAACCTGTCATATAT TCAAGTCTTAATGTAACATAATAATACATTTTATACCCACTATACTAAGA TAATAATTACCTAAAGGGATGGATGCCATGACACTGCTACACTTCAGNAA CTCTAGTAAGGGCAGTTATGGAAGTTCAATAAAATGATAATGGCATCTTT TGATGGGTAATATAGGCAATTTAAGTTTTATTTCTGTTAAAGCAGTATTT

AGCTAGTAGTGGCCAGTAGGAGAGGAGAATATCACCTTTTGTCAAAATCT GGTCATTGTACCCAGAATTTAGTTAAATGTAACATTTTAGATATTAGGGG TCATCAGGTGACAGATATTGTAGAATAGAACAATATGTAATATTACCCAA AACTATTTTTTCTAAGGTTGCTCTGTTAAATATGTGCTTTCTTGATTTCA TTGAATTTGCATTCGTATATTTTAGGTGGTAAACTGATTGTCTCTTCAAT AAATCCTGAAATTAATTAAAAAAAAAAAAACAAAAGTACATTTTTGATTT GGAGAGCACTGGTATCATTTAGTATAGAAAAAAACTAGATTTTGAATTAY CTTTCTTATATAAAAGTTGTGTATATAGTTTAATTAGTTTTACATCATTT TTCTATGTGTTGTTGCAGTTGTCTGAAGCAGGTGGTGTTTGTTGGAGCTT ATGCCAATACTCTAGAGAGATAGAGATATATAGGTGTGATGCACTGTCAA GTGTAATTCCATGTTACGCAGCAGGACAAATGCAAAAGCTGCAAGTGCTG ACAGTCAGTTCTTGTAATGGTCTGAAGGAGGTATTTGAAACTCAATTAGG GACGAGCAGCAACAAAAACAACGAGAAGAGTGGTTGTGAGGAAGGAATTC CAAGAGTAAATAACAATGTTATTATGCTTCCCAATCTAAAGATATTGGAA ATCTACGGTTGTGGGGGTTTGGAACATATATTCACATTCTCTGCACTTGA AAGCCTGAGACAGCTCCAAGAGTTAACGATTAAGGGTTACTACTCTTGTC AATCTTCCAAACCTCAAAGAAATGAGGTTGGAGTGGCTAAGTAATCTGAG GTATATATGGAAGAGCAATCAGTGGACAGCATTTGAGTTTCCAAACCTAA CAAGAGTTGAAATTTGTGAATGTAATTCATTAGAACATGTATTTACTAGT TCCATGGTTGGTAGTCTATTGCAACTCCAAGAGCTACATATATTTAACTG CAGTCTGATGGAGGAGGTAATTGTTAAGGATGCAGATGTTTCTGTAGAAG AAGACAAAGAGAAAGAATCTGATGGCAAGACGAATAAGGAGATACTTGTG TT ACCTC ATCT AAAGTCCTTG AAATTAC AACTTCTTCGAAGTCTTAAGGG

GTTTAGCTTGGGGAAGGAGGATTTTTCATTCCCATTATTGGATACTTTAG AAATCAAAAGATGCCCAACAATAACCACCTTCACCAAAGGAAATTCCGCT ACTCCACAACTAAAAGAAATACAAACAAATTTTGGCTTCTTTTATGCTGC AGGGGAAAAAGACATCAACTCTCTTATAAAGATCAAACAACAGGTAAATC AGATCTTTGTTGCTTTAATAATTCTTAAACTACATTTGAAAAGCTTCATG

CAAGTTTTTTTGTTATATTGTCAAAAACCGCAACCTACATTCAGCTTTAT ATTTATGTACTTTATGCAGGATTTCAAACAAGACTCAGATTAATGTGAAG TGAATATTAAAGGTAAATTATATTTTCATGTTCCTAGTTGCCTATTAATT AATGGCCTTTTAGTTCATGATTTTTGGATGTATTCTTCATGATGATGTGA ATCTTCTAATACCCCATTCATTGTTTGGTTGAATGTTGACTCTATGTCAG

GATGAATATTCAAGGGAAGAATTGTTCATCAWATGAAGGACATTAAAGAA CATGGATGCTATGAAGATGTTGGGAAAACATATGTATCAAGTGGCAARCT GCTTAATGATCTAAGTTTGTTGGTTGANGATGTTGATTTTAATATTTCAA ATTCATTGGTTATATGGGCTTATCAATAGTGTTAATGGGATAATGAGTGA CTTAACCTAAATTATGTTGTTGGTAAATGTTGGACAAGTATGGAAAATTA GGAATGACTTGTGAAAAAAAAATAAAAAAAAA (SEQ ID NO:94)

RG2D deduced polypeptide sequence (SEQ ID NO:95)

MA 1ETANEIIKQVVPVLMVPINDYLRYVVSCRKYISDMDLKMKELKEAKDNVEE HKNHNISNRLEVPAAQVQSWLEDVEKINAKVETVPKDVGCCFNLKIRYRAGRDAF NΠEEIDSVMRRHSLITWTDHPIPLGRVDSVMASTSTLSTEHNDFQSREVRFSEALKA LEANHMIALCGMGRVGKTHMMQRLKKVAKEKRKFGYIIEAVIGEISDPIAIQQVVA DYLCIELKESDKKTRAEKLRQGFKAKSDGGNTKFLIILDDVWQSVDLEDIGLSPSPN QG\ ⁾FKVLLTSRDEHVCSVMGVEANSIINVGLLIEAEAQRLFQQFVETSEPELHKIG EDIΛTIRCCGLPIAIKTMACTLRNKRKDAWKDALSRLQHHDIGNVATAVFRTSYENL PDKETKSVFLMCGLFPEDFNIPTEELMRYGWGLKLFDRVYTIIEARNRLNTCIERLV QANXLIGSDNGVHVKMHDLVRAFVLGMYSEVEQASIVNHGNMPGWPDENDMIVH SCKRISLTCKGMIEIPVDLKFPKLTILKLMHGDKSLKFPQEFYEGMEKLQVISYDKM . KYPLLPLAPQCSTNIRVLHLTECSLKMFDCSSIGNLSNLEVLSFANSRIEWLPSTVRN LKKLRLLDLRFCDGLRIEQGVLKSLVKLEEFYIGNAYGFIDDNCKDMAERSYNLSA LEFAFFNNKAEVKNMSFENLERFKISVGCSFDGNISMSSHSYENMLQLVTNKGDVL DSKLNGLFLKTEVLFLSVHGMNDLEDVEVKSTHPTQSSSFCNLKVRIISKCVELRYL FKLHVANTLSSLEHLEVCGCENMEELIHTGIGGCGEETITFPKLKSLSLSQLPKLSGL CHNVNIIGLPHLVDLKLKGIPGFTVIYPQNKLRTSSLLKEEVVIPKLETLQIDGMENL EEΓVVPCELSGGEKVKLREIKVSSCDKLVNLFPHNPMSLLHHLEELKVKNCRSIESLF NIDLDCVSAIGEEDNKSILRRIKVKNLGKLREVWRIKGADNSRPLIHGFPAVESISI GCKRFRNIFTPITANFDLVALLEIHIGNYRENHESEEQIEILSEKETLQEVTDTNISND WLFPSCLMHSFHNLHKLKLENYEGVEVVFEIESESPTCRELVTTHNNQQQPIILPN LQELYLRNMDNTSHVWKCSNWNKFFTLPKQQSESPFHNLTTIEMRWCHGFRYLFS PLMAELLSNLKKVKILGCDGIEEVVSNRDDEDEEMTTFTSTHTTTNLFPHLDSLTLK YMHCLKCIGGGGAKDEGSNEISFNNTTTTTDQFKLSEAGGVCWSLCQYSREIEIYRC DALSSVIPCYAAGQMQKLQVLTVSSCNGLKEVFETQLGTSSNKNNEKSGCEEGIPR VNNNVIMLPNLKILEIYGCGGLEHIFTFSALESLRQLQELTIKGYYTLVNLPNLKEM RLEWLSNLRYIWKSNQWTAFEFPNLTRVEICECNSLEHVFTSSMVGSLLQLQELHIF NCSLMEEVIVKDADVSVEEDKEKESDGKTNKEILVLPHLKSLKLQLLRSLKGFSLGK EDFSFPLLDTLEIKRCPTITTFTKGNSATPQLKEIQTNFGFFYAAGEKDINSLIKIKQQ DFKQDSD.CEVNIK

RG2E polynucleotide sequence (SEQ ID NO:96)

TGGGAAGACACAATGATGCAAAGGTTGAAGAAGGTTGCTAAAGAAAATAGAAT GTTCAATTATATGGTTGAGGCAGTTATAGGGGAAAAGACAGACCCACTTGCTAT TCAACAAGCTGTAGCGGATTACCTTTGTATAGAGTTAAAAGAAAGCACTAAACC

AGCAAGAGCTGATAAGCTTCGTGAATGGTTTAAGGCCAACTCTGGAGAAGGTA AGAATAAGTTCCTTGTAATATTTGATGATGTTTGGCAGTCCGTTGATCTGGAAG ACATTGGTTTAAGTCATTTTCCAAATCAAGGTGTCGACTTCAAGGTCTTGTTGA CTTCACGAGACGAACATGTTTGCACAGTAATGGGGGTTGAAGCTAATTCAATTC TTAATGTGGGACTTCTAGTAGAAGCAGAAGCACAAAGTTTGTTCCAGCAATTTG

TAGAAACTTTTGAGCCCGAGCTCCATAAGATAGGAGAAGATATCGTAAGGAAG TGTTGTGGTTTACCTATTGCCATTAAAACCATGGCATGTACTCTAAGAAATAAA AGAAAGGATGCATGGAAGGATGCACTTTTGCATTTAGAGTACCATGACATTAGC AGTGTTGCGCCCAAAGTCTTTGAAACGAGCTACCATAATCTCCACAACAAGGAG ACTAAATCTGTGTTTTTGATGTGTGGTTTTTTTCCTGAAGACTTCAATATTCCAA

TCGAGGAGTTGATGAGGTATGGATGGGGCTTAAAGATATTTGATAGAGTTTATA CTATTAGACAAGCAAGAATCAGGCTCAACACCTGCATTGAGCGACTGGTGCAG ACAAATTTGTTAATAGAAAGTGATGATGGTGTGCACGTCAAGATGCATGATCTG GTCCGTGCTTTCGTTTTGGTTATGTTTTCTGAAGTTGAACATGCTTCAATTATCA ACCATGGTAATATGCTTGGATGGCCTGAAAATTATATGACCAACTCTTGCAAAA

CAATTTCATTAACATGCAAGAGTATGTCTGAATTTCCGGGAGATCTCAAGTTTC CAAACCTAACGATTTTGAAACTCATGCATGGAGATAAGTTGCTAAGATATCCTC AAGACTTTTATGAAGGAATGGAAAAGCTCTGGGTTATATCATATGATGAAATGA. AGTATCCATTGCTTCCCTCGTTACCTCAATGCTCCATCAACCTTCGAGTGCTTCA CCTCCATCGATGCTCATTAATGATGTTTGATTGCTCTTGTATTGGAAATATGTTG AATCTGGAAGTGCTTAGCTTTGTTAAATCTGGCATTGAATGGTTACCTTCCACA ATAGGAAATTTAAAGAAGCTAAGGTTACTTGATCTGAGAGATTGTTATGGTCTT CGTATAGAAAAAGGTGTCTTGAAAAATTTGGTGAAAATTGGAGGAATTTATATT GGTAGAGCAGATATTTTATAGAT

RG2E deduced polypeptide sequence (SEQ ID NO:97) WEDTMMQRLKKVAKENRMFNYMVEAVIGEKTDPLAIQQAVADYLCIELKESTKP ARADKLREWFKANSGEGKNKFLVIFDDVWQSVDLEDIGLSHFPNQGVDFKVLLTS RDEHVCTVMGVEANSILNVGLLVEAEAQSLFQQFVETFEPELHKIGEDIVRKCCGL PIAIKTMACTLRNKRKDAWKDALLHLEYHDISSVAPKVFETSYHNLHNKETKSVFL MCGFFPEDFNIPIEELMRYGWGLKIFDRVYTIRQARIRLNTCIERLVQTNLLIESDDG VH\T MHDLVRAFVLVMFSEVEHASIINHGNMLGWPENYMTNSCKTISLTCKSMSE

FPGDLKFPNLTILKLMHGDKLLRYPQDFYEGMEKLWVISYDEMKYPLLPSLPQCSI NLRVLHLHRCSLMMFDCSCIGNMLNLEVLSFVKSGIEWLPSTIGNLKKLRLLDLRD CYGLRIEKGVLKNLVKIGGIYIGRADIL.

RG2F polynucleotide sequence (SEQ ID NO:98)

CTGTGGAAGACACAATGATGCAAAGGCTGAAAAAGGTTGTGCATGAAAAGAAA ATGTTTAACTTTATTGTTGAAGCAGTTATAGGGGAAAAGACAGACCCCGTTGCC ATTCAGGATGCTATAGCAGATTACCTAGGTGTAGAGCTCAATGAAAAATCTAAG CAAGCAAGAGCTGATAAGCTCCGTCAAGGATTCAAGGACAAATCAGATGGAGG CAAAAATAAGTTCTTTGTAATACTTGACGATGTTTGGCAGTCTGTTGATCTGGA

AGATATTGGTTTAAGTCCTTTTCCAAATCAAGGCGTCGACTTCAAGGTCTTGTT GACATCACGAGACAGACATGTTTGCACAGTGATGGGGGTTGAAGCCAAATTAA TTCTAAACGTGGGACTTCTAATTGAAGCTGAAGCACAAAGTTTGTTCCACCAAT TTGTTGTCACTTCTGAGCCCGAGCTCCATAAGATAGGAGAAGATATTGTAAAGA AGTGTTTCGGTCTGCCAATTGCCATCAAAACCATGGCATGTACTCTACGACATA AAAGAAAGGATGCATGGAAGGATGCACTTTCACGTTTAGAGCACCATGACATT CAAAGTGTTGTGCCTAAAGTATTTGAAACGAGCTACAACAATCTCAAAGACAA GGAGACTAAATCCGTATTTTTGATGTGTGGTTTGTTTCCTGAAGACTTGGATAT ACCTATCGAGGAGTTGATGAGGTATGGATGGGGCTTAAGATTATTTGATAGAGT TAATACTATTACACAAGCAAGAAACAGGCTCAACACCTGCATTGAGCGACTGG

TGCACACAAATTTGTTAATTGAAAGTGTTGATGGTGTGCATGTCAAGATGCATG ATCTGGTTCGTGCTTTTGTTTTGGGAATGTTTTCTGAAGTGGAGCATGCTTCAAT TGTCAACCATGGTAATATGCCCGAGTGGACTGAAAATGATATGACTGACTCTTG CAAACAAATTTCATTAACATGCAAGAGTATGTTGGAGTTTCCTGGAGACCTCAA GTTTCCAAACCTAAAGATTTTGAAACTTATGCATGGAGGTAAGTCACTAAGGTA TCCTCAAGACTTTTATCAAGGAATGGAAAAGCTGGAGGTTATATCATACGATGA AATGAAGTATCCATTGCTTCCCTCGTTGCCTCAATGTTCCACCATCCTTCGAGTG CTTCATCTCCATGAATGTTCATTAAGGATGTTTGATTGCTCTTCAATCGGTAATC . TTTTCAACATGGAAGTGCTCAGCTTTGCTAATTCTAGCATTGAATTGTTACCTTC CGTAATTGGAAATTTGAAGAAGTTGCGGCTGCTAGATTTGACAAACTGTTATGG TGTTCGTATAGAAAAGGATGTCTTGAAAAATTTGGTGAAACTTGAAGAGCTTTA TATTAGGAATGGTCTACCAGTTTACAGAGGAT

RG2F deduced polypeptide sequence (SEQ ID NO:99)

VEDTMMQRLKKVVHEKKMFNFIVEAVIGEKTDPVAIQDAIADYLGVELNEKSKQA RADKLRQGFKDKSDGGKNKFFVILDDVWQSVDLEDIGLSPFPNQGVDFKVLLTSRD RHVCTVMGVEAKLILNVGLLIEAEAQSLFHQFVVTSEPELHKIGEDIVKKCFGLPIAI KTMACTLi iGN DAWKDALSRLEHHDIQSVVPKVFETSYNNLKDKETKSVFLMCG LFPEDLDIPIEELMRYGWGLRLFDRVNTITQARNRLNTCIERLVHTNLLIESVDGVH VKMHDLVRAFVLGMFSEVEHASIVNHGNMPEWTENDMTDSCKQISLTCKSMLEFP GDLKFPNLKILKLMHGGKSLRYPQDFYQGMEKLEVISYDEMKYPLLPSLPQCSTILR VLHLHECSLRMFDCSSIGNLFNMEVLSFANSSIELLPSVIGNLKKLRLLDLTNCYGV

RIEKDVLKNLVKLEELYIRNGLPVYRG

RG2G polynucleotide sequence (SEQ ID NO: 100)

GAAGACACGATGATGAAGAACTGAAGGAGGTCGTGGGACAAAAGAAATCATTC AATATTATTATTCAAGTGGTCATAGGAGAGAAGACAAACCCTATTGCAATTCAG

CAAGCTGTAGCAGATTACCTCTCTATAGAGCTGAAAGAAAACACTAAAGAAGC AAGAGCTGATAAGCTTCGTAAACGGTTTGAAGCCGATGGAGGAAAGAATAAGT TCCTTGTAATACTTGACGATGTATGGCAGTTTGTCGATCTTGAAGATATTGGTTT AAGTCCTCTGCCAAATAAAGGTGTCAACTTCAAGGTCTTGTTGACGTCAAGAGA TTCACATGTTTGCACTCTGATGGGAGCTGAAGCAAATTCAATTCTTAATATAAA AGTTTTAAAAGATGTAGAAGGACAAAGTTTGTTCCGCCAGTTTGCTAAAAATGC GGGTGATGATGACCTGGATCCTGCTTTCAATGGGATAGCAGATAGTATTGCAAG TAGATGTCAAGGTTTGCCCATTGCCATCAAAACCATTGCCTTAAGTCTTAAAGG TAGAAGCAAGTCTGCATGGGACGTTGCACTTTCTCGTCTGGAGAATCATAAGAT TGGTAGTGAAGAAGTTGTGCGTGAAGTTTTTAAAATTAGCTACGACAATCTCCA AGATGAGGTTACTAAATCTATTTTTTTACTTTGTGCTTTATTTCCTGAAGATTTT GATATTCCTACTGAGGAGTTGGTGAGGTATGGGTGGGGCTTGAAATTATTTATA GAAGCAAAAACTATAAGAGAAGCAAGAAACAGGCTCAACACCTGCACTGAGCG GCTTAGGGAGACAAATTTGTTATTTGGAAGTGATGACATTGGATGTGTCAAGAT GCACGATGTGGTGCGTGATTTTGTTTTGCATATATTCTCAGAAGTCCAACACGC TTCAATTGTCAACCATGGTAACGTGTCAGAGTGGCTAGAGGAAAATCATAGCAT CTACTCTTGTAAAAGAATTTCATTAACATGCAAGGGTATGTCTCAGTTTCCCAA AGACCTCAAATTTCCAAACCTTTCAATTTTGAAACTTATGCATGGAGATAAGTC ACTGAGCTTTCCTGAAAACTTTTATGGAAAGATGGAAAAGGTTCAGGTAATATC ATATGATAAATTGATGTATCCATTGCTTCCCTCATCACTTGAATGCTCCACCAA CGTTCGAGTGCTTCATCTTCATTACTGTTCATTAAGGATGTTTGATTGCTCTTCA ATTGGTAATCTTCTCAACATGGAAGTGCTCAGCTTTGCTAATTCTAACATTGAA TGGTTACCATCTACAATTGGAAATTTGAAGAAGCTAAGGCTACTAGATTTGACA . AATTGTAAAGGTCTTCGTATAGATAATGGTGTCTTAAAAAATTTGGTCAAACTT GAAGAGCTTTATATGGGTGTTAATCGTCCGTATGGACAGGCCGTTAGCTTGACA GATGAAAA

RG2G deduced polypeptide sequence (SEQ ID NO:101)

RHDDEELKEVVGQKKSFNIIIQVVIGEKTNPIAIQQAVADYLSIELKENTKEARADKL

RKRFEADGGKNKFLVILDDVWQFVDLEDIGLSPLPNKGVNFKVLLTSRDSHVCTL

MGAEANSILNIKVLKDVEGQSLFRQFAKNAGDDDLDPAFNGIADSIASRCQGLPIAI KTIALSLKGRSKSAWDVALSRLENHKIGSEEVVREVFKISYDNLQDEVTKSIFLLCAL FPEDFDIPTEELVRYGWGLKLFIEAKTIREARNRLNTCTERLRETNLLFGSDDIGCVK MHDVVRDFVLHIFSEVQHASIVNHGNVSEWLEENHSIYSCKRISLTCKGMSQFPKDL KFPNLSILKLMHGDKSLSFPENFYGKMEKVQVISYDKLMYPLLPSSLECSTNVRVLH LHYCSLRMFDCSSIGNLLNMEVLSFANSNIEWLPSTIGNLKKLRLLDLTNCKGLRID NG\XKNLVKLEELYMGVNRPYGQAVSLTDE

RG2H polynucleotide sequence (SEQ ID NO: 102)

TGAAGGAGGTTGTGGAACGAAAGAAAATGTTCAGTATTATTGTTCAAGTG GTCATAGGAGAGAAGACAAACCCTATTGCTATTCAGCAAGCTGTAGCAGA TTACCTCTCTATAGAGCTGAAAGAAAACACTAAAGAAGCAAGAGCTGATA AGCTTCGTAAATGGTTCGAGGCCGATGGAGGAAAGAATAAGTTCCTTGTA ATACTTGACGATGTATGGCAGTTTGTCGATCTTGAAGATATTGGTTTAAG TCCTCTGCCAAATAAAGGTGTCAACTTCAAGGTCTTGTTGACGTCAAGAG ATTCACATGTTTGCACTCTGATGGGAGCCGAAGCCAATTCAATTCTCAAT ATAAAAGTTTTAACAGCTGTAGAAGGACAAAGTTTGTTCCGCCAGTTTGC

TAAAAATGCGGGTGATGATGACCTGGATCCTGCTTTCAATAGGATAGCAG ATAGTATTGCAAGTAGATGTCAAGGTTTGCCCATTGCCATCAAAACCATT GCCTTAAGTCTTAAAGGTAGAAGCAAGCCTGCGTGGGACCATGCGCTTTC TCGTTTGGAGAACCATAAGATTGGTAGTGAAGAAGTTGTGCGTGAAGTTT TTAAAATTAGCTATGACAATCTCCAAGATGAGATTACTAAATCTATTTTT TTACTTTGTGCTTTATTTCCTGAAGATTTTGATATTCCTACTGAGGAGTT GATGAGGTATGGATGGGGCTTGAAATTATTTATAGAAGCAAAAACTATAA GAGAAGCAAGAAACAGGCTCAACACCTGCACTGAGCGGCTTAGGGAGACA AATTTGTTATTTGGAAGCGATGACATTGGATGCGTCAAGATGCACGATGT GGTGCGTGATTTTGTTTTGCATATATTCTCAGAAGTCCAGCACGCTTCAA

TTGTCAACCATGGTAACGTGTCAGAGTGGCTAGAGGAAAATCATAGCATC TACTCTTGTAAAAGAATTTCATTAACATGCAAGGGTATGTCTGAGTTTCC CAAAGACCTCAAATTTCCAAACCTTTCAATTTTGAAACTTATGCATGGAG ATAAGTCGCTGAGCTTTCCTGAAAACTTTTATGGAAAGATGGAAAAGGTT CAGGTAATATCATATGATAAATTGATGTATCCATTGCTTCCCTCATCACT

TGAATGCTCCACTAACGTTCGAGTGCTTCATCTCCATTATTGTTCATTAA GGATGTTTGATTGCTCTTCAATTGGTAATCTTCTCAACATGGAAGTGCTC AGCTTTGCTAATTCTAACATTGAATGGTTACCATCTACAATTGGAAATTT GAAGAAGCTAAGGCTACTAGATTTGACAAATTGTAAAGGTCTTCGTATAG ATAATGGTGTCTTAAAAAATTTGGTCAAACTTGAAGAGCTTTATATGGGT GTTAATCATCCGTATGGAC

RG2H deduced polypeptide sequence (SEQ ID NO: 103)

KEVVERKKMFSIIVQVVIGEKTNPIAIQQAVADYLSIELKENTKEARADKLRKWFEA DGGKNKFLVILDDVWQFVDLEDIGLSPLPNKGVNFKVLLTSRDSHVCTLMGAEAN SILNIKVLTAVEGQSLFRQFAKNAGDDDLDPAFNRIADSIASRCQGLPIAIKTIALSLK GRSKPAWDHALSRLENHKIGSEEVVREVFKISYDNLQDEITKSIFLLCALFPEDFDIP TEELMRYGWGLKLFIEAKTIREARNRLNTCTERLRETNLLFGSDDIGCVKMHDVVR DFVLHIFSEVQHASIVNHGNVSEWLEENHSIYSCKRISLTCKGMSEFPKDLKFPNLSI LKLMHGDKSLSFPENFYGKMEKVQVISYDKLMYPLLPSSLECSTNVRVLHLHYCSL RMFDCSSIGNLLNMEVLSFANSNIEWLPSTIGNLKKLRLLDLTNCKGLRIDNGVLKN LVKLEELYMGVNHPYG

RG2I polynucleotide sequence (SEQ ID NO: 104)

AAGAAGAGCTGAAGGAGGTTGTGGAACAAAAGAAAACGTTCAATATTATT GTTCAAGTGGTCATAGGAGAGAAGACAAACCCTATTGCTATTCAGCAAGC TGTAGCAGATTCCCTCTCTATAGAGCTGAAAGAAAACACTAAAGAAGCAA GAGCTGATAAGCTTCGTAAATGGTTCGAGGCTGATGGAGGAAAGAATAAG TTCCTCGTNATACTTGACGATGTATGGCNGTTTGTTGATCTTGAAGATAT TGGTTTAAGTCCTCATCCAAATAAAGGTGTCANCTTCAAGGTCTTGTTGA CGTCAAGAGATTCACATGTTTGCACTCTGATGGGAGCTGAAGCCAATTCA ATTCTCAATATAAAAGTTTTAAAAGATGTAGAAGGAAAAAGTTTGTTCCG

CCAGTTTGCTAAAAATGCGGGTGATGATGACCTGGATCCTGCTTTCATTG GGATAGCAGATAGTATTGCAAGTAGATGTCAAGGTTTGCCCATTGCCATC AAAACCATTGCCTTAAGTCTTAAAGGTAGAAGCAAGTCTGCATGGGACGT TGCACTTTCTCGTCTGGAGAATCATAAGATTGGTAGTGAAGAAGTTGTGC GTGAAGTTTTTAAAATTAGCTATGACAATCTCCAAGATGAGGTTACTAAA

TCTATTTTTTTACTTTGTGCTTTATTTCCTGAAGATTTTGATATTCCTAC TGAGGAGTTGGTGAGGTATGGGTGGGGCTTGAAATTATTTATAGAAGCAA AAACTATAAGAGAAGCAAGAAACAGGCTCAACACCTGCACTGAGCGGCTT AGGGAGACAAATTTGTTATTTGGAAGTGATGACATTGGATGCGTCAAGAT GCACGATGTGGTGCGTGATTTTGTTTTGCATATATTCTCAGAAGTCCAGC

ACGCTTCAATTGTCAACCATGGTAATGTGTCAGAGTGGCTAGAGGAAAAT CATAGCATCTACTCTTGTAAAAGAATTTCATTAACATGCAAGGGTATGTC TGAGTTTCCCAAAGACCTCAAATTTCCAAACCTTTCAATTTTGAAACTTA TGCATGGAGATAAGTCGCTGAGCTTTCCTGAAAACTTTTATGGAAAGATG GAAAAGGTTCAGGTAATATCATATGATAAATTGATGTATCCATTGCTTCC

CTCATCACTTGAATGCTCCACCAACCTTCGAGTGCTTCATCTCCATGAAT GTTCATTAAGGATGTTTGATTGCTCTTCAATTGGTAATCTTCTCAACATG GAAGTGCTCAGCTTTGCTAATTCTGGCATTGAATGGTTACCATCTACAAT TGGAAATTTGAAGAAGCTAAGGCTACTGGATCTGACAGATTGTGGAGGTC TTCATATAGATAATGGCGTCTTAAAAAATTTGGTCAAACTTGAAGAGCTT TATATGGGTGCTAATCGTCTGTTTGGAAAGTGCCAT

RG2I deduced polypeptide sequence (SEQ ID NO: 105)

EELKEVVEQKKTFNIIVQVVIGEKTNPIAIQQAVADSLSIELKENTKEARADKLRKWF

EADGGKNKFLVILDDVW?FVDLEDIGLSPHPNKGV?FKVLLTSRDSHVCTLMGAEA

NSILNΠ VLKDVEGKSLFRQFAKNAGDDDLDPAFIGIADSIASRCQGLPIAΠ TIALSL KGRSKSAWDVALSRLENHKIGSEEVVREVFKISYDNLQDEVTKSIFLLCALFPEDFDI PTEELVRYGWGLKLFIEAKTIREARNRLNTCTERLRETNLLFGSDDIGCVKMHDVV RDFΛ'LHIFSEVQHASIVNHGNVSEWLEENHSIYSCKRISLTCKGMSEFPKDLKFPNLS ILKLMHGDKSLSFPENFYGKMEKVQVISYDKLMYPLLPSSLECSTNLRVLHLHECSL RMFDCSSIGNLLNMEVLSFANSGIEWLPSTIGNLKKLRLLDLTDCGGLHIDNGVLKN LVKLEELYMGANRLFGKCH

RG2J polynucleotide sequence (SEQ ID NO: 106) and (SEQ ID NO: 107)

ATGTCCGACCCAACAGGGATTGTTGGTGCCATTATTAACCCAATTGCTCA AACGGCCTTGGTTCCCCTTACAGACCATGTAGGCTACATGATTTCCTGCA GAAAATATGTGAGGGACATGCAAATGAAAATGACAGAGTTAAATACCTCA

AGAATCAGTGCAGAGGAACACATTAGCCGGAACACAAGAAATCATCTTCA GATTCCATCTCAAATTAAGGATTGGTTGGACCAAGTAGAAGGGATCAGAG CGAATGTTGCAAACTTTCCAATTGATGTCATCAGTTGTTGTAGTCTCAGG ATCAGGCACAAGCTTGGACAGAAAGCCTTCAAGATAACTGAGCAGATCGA AAGTCTAACGAGACAAAATTCGCTGATTATCTGGACTGATGAACCTGTTC

CCCTGGGAAGAGTTGGTTCCATGATTGCATCCACCTCTGCAGCATCAAGT GATCATCATGATGTCTTCCCTTCAAGAGAGCAAATTTTTAGGAAAGCACT AGAAGCACTTGAACCCGTCCAAAAATCCCACATAATAGCCTTATGGGGGA TGGGCGGAGTGGGGAAGACCACGATGATGAAGAAGCTGAAAGAGGTCGTG GAACAAAAGAAAACGTGCAATATTATTGTTCAAGTGGTCATAGGAGAGAA

GACAAACCCTATTGCTATCCAGCAAGCTGTAGCAGATTACCTCTCTATAG AGCTGAAAGAAAACACTAAAGAAGCAAGAGCTGATAAGCTTCGTAAACGG TTCGAAGCCGATGGAGGAAAGAATAAGTTCCTTGTAATACTTGACGATGT ATGGCAGTTTTTCGATCTTGAAGATATTGGTTTAAGTCCTCTGCCAAATA AAGGTGTCAACTTCAAGGTCTTGTTGACGTCAAGAGATTCACATGTTTGC ACTCTGATGGGAGCTGAAGCCAATTCTATTCTCAATATAAAAGTTTTAAA AGATGTAGAAGGAAAAAGTTTGTTCCGCCAGTTTGCTAAAAATGCGGGTG ATGATGACCTGGATCCTGCTTTCATTGGGATAGCAGATAGTATTGCAAGT AGATGTCAAGGTTTGCCCATTGCCATCAAAACCATTGCCTTAAGTCTTAA AGGTAGAAGCAAGTCTGCATGGGACGTCGCACTTTCTCGTCTGGAGAATC

ATAAGATTGGTAGTGAAGAAGTTGTGCGTGAAGTTTTTAAAATTAGCTAT GACAATCTCCAAGATGAGGTTACTAAATCTATTTTTTTACTCTGTGCTTT ATTTCCTGAAGATTTTGATATTCCTATTGAGGAGTTGGTGAGGTATGGGT GGGGCTTGAAATTATTTATAGAAGCAAAAACTATAAGAGAAGCAAGAAAC AGGCTCAACAACTGCACTGAGCGGCTTAGGGAGACAAATTTGTTATTTGG AAGTCATGACTTTGGGTGCGTCAAGATGCACGATGTGGTGCGTGATTTTG TTTTGCATATGTTTTCAGAAGTCAAGCATGCTTCAATTGTCAACCATGGT AACATGTCAGAGTGGCCAGAGAAAAATGATACCAGCAACTCTTGTAAAAG AATTTCATTAACATGCAAGGGTATGTCTAAGTTTCCTAAAGACATCAACT ATCCAAACCTTTTGATTTTGAAACTTATGCATGGAGATAAGTCGCTGTGC TTTCCTGAAAACTTTTATGGAAAGATGGAAAAGGTTCAGGTAATATCATA TGATAAATTGATGTATCCATTGCTTCCCTCATCACTTGAATGCTCCACTA ACGTTCGAGTGCTTCATCTCCATTATTGTTCATTAAGGATGTTTGATTGC TCTTCAATTGGTAATCTTCTCAACATGGAAGTGCTCAGCTTTGCTAATTC TAACATTGAATGGTTACCATCTACAATTGGAAATTTGAAGAAGCTAAGGC TACTAGATTTGACAAATTGTAAAGGTCTTCGTATAGATAATGGTGTCTTA AAAAATTTGGTC A AACTTGAAGAGCTTTATATGGGTGTT AATCGTCCGT A TGGACAGGCCGTTAGCTTGACAGATGAAAACTGCAATGAAATGGTAGAAG GTTCCAAAAAACTTCTTGCACTAGAATATGAGTTGTTTAAATACAATGCT CAAGTGAAGAATATATCCTTCGAGAATCTTAAACGATTCAAGATCTCAGT GGGATGTTCTTTACATGGATCTTTCAGTAAAAGCAGGCACTCATACGAAA ACACGTTGAAGTTGGCCATTGACAAAGGCGAACTATTGGAATCCCGAATG AACGGGTTGTTTGAGAAAACGGAGGTTCTTTGTTTAAGTGTGGGGGATAT GTATCATCTTTCAGATGTTAAGGTGAAGTCCTCTTCGTTCTACAATTTAA GAGTCCTTGTCGTTTCAGAGTGTGCAGAGTTGAAACACCTCTTCACACTT GGTGTTGCAAATACTTTGTCAAAGCTTGAGCATCTTAAAGTCTACAAATG CGATAATATGGAAGAACTCATACATACCGGGGGTAGTGAAGGAGATACAA TTACATTCCCCAAGCTGAAGCTTTTATATTTGCATGGGCTGCCAAACCTA TTGGGTTTGTGTCTTAATGTCAACGCAATTGAGCTACCAAAACTTGTGCA AATGAAGCTTTACAGCATTCCGGGTTTCACAAGCATTTATCCGCGGAACA AGTTGGAAGCATCTAGTTTGTTGAAAGAAGAGGTACATATACATATAGTT TATGTTAATACATTTTAAACAATCTTTTCAACTAAAAGTTTCAGAATATA TCTGTATTTTGATTGTATGATGTGTTAGTGTTTGGATGTGGCTATTAAAG GATAATTATTTGGCAGGTTGTGATTCCTAAGTTGGATATACTTGAAATTC ATGACATGGAGAATTTAAAGGAAATATGGCCTAGTGAGCTTAGTAGAGGT GAGAAAGTTAAGTTGAGAAAGATTAAAGTGAGAAATTGTGATAAACTTGT GAATCTATTTCCACACAATCCCATGTCTCTGCTGCATCATCTTGAAGAGC TTATAGTCGAGAAATGTGGTTCCATTGAAGAGTTGTTCAACATCGACTTG GATTGTGCCAGTGTAATTGGAGAAGAAGACAACAACAGCAGCTTAAGAAA CATCAATGTGGAGAATTCAATGAAGCTAAGAGAGGTGTGGAGGATAAAAG GTGCAGATAACTCTCGTCCCCTCTTTCGTGGCTTTCAAGTTGTTGAAAAG ATAATCATTACGAGATGTAAGAGGTTTACAAATGTATTCACACCTATCAC

CACAAATTTTGATCTGGGGGCACTTTTGGAGATTTCAGTTGATTGTAGAG GAAATGATGAATCAGACCAAAGTAACCAAGAGCAAGAGCAGGTATGGATT TCAATTTTACTCTTTTACTTAATTAATGATTAAGCCCCTGCTTTTTAATA AAAAGGGGACAAACCATTTCTTGACTTAATGTTGCAATACAAGTCATGTA TAAGAGTGATTAACTTTTTTTTATTTATAAAATAACTACAAAACATGTTT TTTCATTATAGATCATGTATAAATGTGACTAATTTTTTTCATCGCCTAAC TTTTGTTGATAAATCATTAGAAATGTCACTAATTACTTTTTAGTATTTAT AAAATAACTACAAAACATGTTTTTTCATTATAGATCATGTATATATCAAC TAAAAATATTATTCCCTTACACAAAAAAAAAAGGTTCAAGAAAGCCTGTA TTTCGAAATAACTAAAAAGAAAATATTTGATATTCACTAAGAGAAATTTT TTTCTAAACATGATCGCAAATGATTAAAACTTAAATTAAAACTAAAAAGA TTTTTATATATGTTATNCAAAATTAAAATTTGAAATTAAGTTTATAATTC TNGTNTCACAAAGGGATATATATAGTAAAATATTATTTTTTTGCAGTCAT GCATAGTTGTATTTTTAAATGATTTATTAACGTGGTAGGAGTGGAAACCA CTCAATCTAGTAGACCCACTATCACATGTCACATCAGCTTTACATCTATT TTTCTTTCTCCTTTTTTCATCTTTTTAAACTCATAACACNTAAAANTANC ATATTTTCCAACACACTNAACTCATTGTCACATTATTATTTTTAATTTAA TTAAATTNGAAAATTAAAATTAANTAAANCNTAACATTTTTTAATTAAAA

AATATTAATCCAAATAAAAANTNCACGATAAATTAAAAANGTTTANTTTG GAAAAAAANCC (SEQ ID NO:106) Sequence gap ATAACCCTTTCAAGGGTCAACTCAAGTCCAAGTTAAAGTCAAGGTCAAAA CCTTGGTTAAAGTCAACTTTGGTCAAAGTCAACATCTACTTGACTCACCT CACCGAGTTGGTCCACCAACTTGTCGAGTCCCTTAATCCACAAACTTCAA GAACTTCGATCCTACTCGTCGAGTCTTTCAAGAACTCTTCGAGTTTCCAT TACACAGAATCGGGACCTTTTGCTCATGACTCGCCGAGTTCATCCTTGAA CTTGTCGAGTCTAGCTTCATACGAGTTCGAGTGTTTAGTCCTTGACTCGT CGAGTTCTTCCTTGAACTCGTCGAGTCCATCTTCGTATAGTTGGGACATT

GCCTTGAACTCACCGAGTTCATCATTGAACTCATCGAGTCCTTCGATCTT CAAGTCCATAATCCTGTCCATCTTGTTGAGTCCTCTTCTAGACTCAACCA GATTCCTCAGAAACAGAAAAGGTTAGGGAACCATTACCTGACTCGCCGAG TCCCAAGAACGAATCCCCGAGTCCCCCAATGTCCATGACCATACAATCGA TTTTCGTTGGGCTCATTGCATCCAAAGCATAGATCTAACCTCCTAGGGTC CATATTACACGTAAAGCTACGAACTTGACGTCCATGCATGGGGGATTTGG CTCAAATGGCATTAAAATGGGGTTTATCTGATGCATGGGACTCCCATGGC CATAAAGTTAACACCTTTATGCCATGGGAATCCTCAATGGTTCCATATCT GAAGTTAACACTCTACAATATGTTCTAAACCCGAAGGTGGCTTAGAAATG CCCCAAAATGGCAAGATTCAAGCCTTAAAGGAGATCTAACAAATGATAAG

TCAAGGTTCAAGCTTTTTACCTTGAATAAGCTGGAAATGAAGCAAAATCT CTGGATCCACTTGCTTCTTCAAGAACCCCCAAGCTTCCACTTCTTCCTTC AAGTTTCAAACAACTTTAAACACTCAAAAATGGCTCAAGAACACTCAAAA AGCTTTAGGGTTTCGAGTTAGGGCTTTTTGGAAGCGAGAGGGACGATGGG GGCTGAAATGAGGCTAGAAAAAGTGTTTAAATAGGGGGCAAACCCTAAAT

ATTAGGGTTTCATCCAGGCAGCCCTACTCGTCGAGTCGGGCTCCCGACTC GTCGAGTAGGTCACTTAAAACCCGCGTCCATAATCCAGTCTACTCGACGA GTTGGGCCTCCAACTCGTCGATTCCGAGTGCAAAACGTTCAATTACTTAA ATTTAAATATGTACCAGGAACCGGGTGTTACAGTTGAGACTTTATACCTC CATAAGATAGATCTAGGTGCACATAGCCTGGATCCACAAGCTCCATGTCA ACAAGCGACTCTTCAAGAAGTTCATTCTTCCTCCTTAAGCACCAAAAAAC ACACAAAATCACCATGAAGCTCAAGAAATACTCAAATAGAGGATAGGGTT TCGTTCGTAGGGTTAGAGAGGATGGAGGCTAGAGGAAATGAGGGATAGAG GCGAGTTAAGGTCTTTAAATAGGGTCCAAGACCCTAAATTAGGGTTTTAA TCTGGCCAGACGAACGCAGGGTGTTCCCAAATGCATATGTGTCCAAATTC TCGTGTGCGCCATGCGTACCTCCCTTGTACGCCATGTGTACCGGGTTTGG TCCAAACCCTTCTAACTTCAAATGATCATAACTTGCACCCCTTATCTGTT TTCGATGTTCTTTATATCCACGGAAAGGTAACAAGAAGCCCTATACTTCT ATAAACTTTATTTAATCTGAAAACCAACCGAAATTAAATCCAAAATTCAT AAAAGTCCCGAACCAACACATTTACCGATACCCTTGGGCTCCAAAACACA AATTGAAAACCCGGATCATCCAAACTACATCATCCACCTCCAAATGAGCC CAAACTCAATTATTCAAGGGTTCTAAGCCTGTTAATGCCCACTCCTCGAT TACCACCCCGCAATGGGAAACGATTCAAAACAGGGCGTTACATAATTTGT

TGTGGTTTTGTATTTTTTATTTCCGGTGAAGGTGAAAGATCCAACTATTT TTAATCTGTTGGCATTTTCCATCATTTGCAACTGTTTCTTGAAAAAAAAA TACCTAAAATCAAAATAACCATTTTCAAATCCAAAATTATAAGAGAGAAT TGTAAATGGACATGGAATCTTAAATCATTAACACAGTTCAGTACACAAGT TGCTAATTACATTTCTTGCTGTGCAGATTGAAATTCTATCAGAGAAAGAG ACATTACAAGAAGCCACTGACAGTATTTCTAATGTTGTATTCCCATCCTG TCTCATGCACTCTTTTCATAACCTCCAGAAACTTATATTGAACAGAGTTA AAGGAGTGGAGGTGGTGTTTGAGATAGAGAGTGAGAGTCCAACAAGTAGA GAATTGGTAACAACTCACCATAACCAACAACAGCCTGTTATATTTCCCAA CCTCCAGCATTTGGATCTAAGGGGTATGGACAACATGATTCGCGTGTGGA

AGTGCAGCAACTGGAATAAATTCTTCACTCTTCCAAAACAACAATCAGAA TCCCCATTCCACAACCTCACAACCATAAATATTGATTTTTGCAGAAGCAT TAAGTACTTGTTTTCACCTCTCATGGCAGAACTTCTTTCCAACCTAAAGA AAGTCAATATAAAATGGTGTTATGGTATTGAAGAAGTTGTTTCAAACAGA GATGATGAGGATGAAGAAATGACTACATTTACATCTACCCACACAACCAC

CATCTTGTTCCCTCATCTTGATTCTCTCACTCTAAGTTTCCTGGAGAATC TGAAGTGTATTGGTGGAGGTGGTGCCAAGGATGAGGGGAGCAATGAAATA TCTTTCAATAATACCACTGCAACTACTGCTGTTCTTGATCAATTTGAGGT ATGCTTTGTTCATATTCAATTATTTATTTAATTTCCTTTTTTATTTGCAA TATTCTATAAATAATACATTTTATACCCACTATACTAAGATAATAATTAC CTAGAGGGATGGATGCTATGACACAGCTGCTACACTTCAGAAACTCTAGT AAGGGCAGTTATGGAAGTTCAATAAAATGATAATGGCATCTTTTGATGGG TAATATAGGCAATTTAAGTTTTATTTCTGTTAAAGCAGTATTTAGCAAGT ACTGGCCAGTAGGAGAGGAGAATATCACCTTTTGTGAAAATCTGGTCATT GTACCCAGAATTTAGTTAAATGTAACATTTTAGATATCAGGGGACATCAG

GTGACAGATATTGTAGAATAGAACAATATATAATATTACCCAAAACTATT TTTTCTAAGGTTTTTCTGTTAAATATGTGCTTTCTTGATTTCATTGAATT TGCATTCCTATATTTTAGGTGGTAAAGTGATTGTCTCTTCAATAAATCCC WO 98/30083 , , . PCT/US98/00615

141

GAAATTAATTAAAAAAAAAAAAAAACAAAAGTAAATTTTTGATATGGAGA GCACTGGTATCATTTAGTATATAAAAAAACTAGATTTTGAATTAAGTTTC TTATATAAAAGCTGTGTATATAGTTTAATTAGTTTTACATCATTTTTCCA TGTGGTGTTGCAGTTGTCTGAAGCAGGTGGTGTTTCTTGGAGCTTATGCC AATACGCTAGAGAGATAAGTATAGAATTCTGCAATGCATTGTCAAGTGTG ATTCCATGTTATGCAGCAGGACAAATGCAAAAGCTTCAAGTGCTGACAGT CAGTTCTTGTAATGGTCTGAAGGAGGTATTTGAAACTCAATTAAGGAGGA GCAGCAACAAAAACAACGAGAAGAGTGGTTGTGATGAAGGAAATGGTGGA ATTCCAAGAGTAAATAACAATGTTATTATGCTTTCTGGTCTGAAGATATT GGAAATCAGCTTTTGTGGGGGTTTGGAACATATATTCACATTCTCTGCAC TTGAAAGCCTGAGACAGCTCGAAGAGTTAACGATAATGAATTGCTGGTCA ATGAAAGTGATTGTGAAGAAGGAAGAAGATGAATATGGAGAGCAGCAAAC AACAACAACAACGAAGGGGACTTCTTCTTCTTCTTCTTCTTCTTCTTCTT CTTCTTCTTCTTCTTCTTCTCCTCCTTCTTCTTCTAAGAAGGTTGTGGTC TTTCCTTGTCTAAAGTCCATTGTATTGGTCAATCTACCAGAGCTGGTAGG ATTCTTCTTGGGGATGAATGAGTTCCGGTTGCCTTCATTAGATGAACTTA TCATCGAGAAATGCCCAAAAATGATGGTGTTTACAGCTGGTGGGTCCACA GCTCCCCAACTCAAGTATATACACACAAGATTAGGCAAACATACTATTGA TCAAGAATCTGGCCTTAACTTTCATCAGGTATATATGTTTCTTTAATTGG CATCATCTAATTAAGAAAGATATCATTCCTGCCAAGTAAATTTACTTCAA

ACACATTCACACTGGTTTCAGTCTAAGTTTATGTTGTTCTAGGAAGGCCA AAATGGGAAAGCAAGATAGGGAAAAATAGTGTATTTCAGTGGAAAGGGTA TTTTAGGTATTTTCTGTCAAAAGTTGTTATTGCAGGCTTTTTAGTACCTG GAATCGTGTGTGGGAGGAGCATTATTATTCTGATTTGCTTGTTTCTTTAT CATTTTTTCTTAGCCTCTCGAACAGCTAGAAACCCTTTTAATCTTTTGAT TTT.AAATGACAAAATTTTTCCCTGTTACTCTATTTGATTGTTGTTCTTCA TGGTTCTAAGTGAGTTATTGGCTCATCTGTTACTTCTTTTGATTGTTATT TTCATAGCATGTTAGTCACTTGAATCAAGCTTTTTCATTTTCAACCAGGG CAAAAGGTCAAAAGTAACCTACTTTATGAGATCAAAAACAGCAACCCATC GGATAACTTTTAGTTGGAGTTAATAGTTACAATTACCATTGTGATTAATA

ATTATAATATCCTGTATTAATTCATAAAAATTGGTACAGCACATATATGA CATTTCAAAGGTTTTTGTTTGACATATATATGCCTCTGGCGTTTTCTTTA TTGGACTTGCAGACCTCATTCCAAAGTTTATACGGTGACACCTTGGGCCC TGCTACTTCAGAAGGGACAACTTGGTCTTTTCATAACTTGATTGAATTAG ATGTGAAATTTAATAAGGATGTTAAAAAGATTATTCCATCCAGTGAGTTG

CTGCAACTGCAAAAGCTGGAAAAGATAAATATAAACAGTTGTGTTGGGGT AGAGGAGGTATTTGAAACTGCATTGGAAGCAGCAGGGAGAAATGGAAATA GTGGAATTGGTTTTGATGAATCGTCACAAACAACTACCACTACTCTTGTC AATCTTCCAAACCTTAGAGAAATGAACTTATGGGGTCTAGATTGTCTGAG GTATATATGGAAGAGCAATCAGTGGACAGCATTTGAGTTTCCAAAACTAA

CAAGAGTTGAAATTAGTAATTGCAACAGTTTAGAACATGTATTTACTAGT TCCATGGTTGGTAGTCTATCGCAACTCCAAGAGCTACATATAAGTCAGTG CAAACTTATGGAGGAGGTGATTGTTAAGGATGCAGATGTTTCTGTAGAAG WO 98/30083 . .. PCT/US98/00615

AAGACAAAGAGAAAGAATCTGATGGCAAGATGAATAAGGAGATACTTGCG TTACCTAGTCTAAAGTCCCTGAAATTAGAAAGCTTACCATCTCTTGAGGG GTTTAGCTTGGGGAAGGAGGATTTTTCATTCCCATTATTGGATACTTTAA GAATTGAGGAATGCCCAGCAATAACCACCTTCACCAAGGGAAATTCCGCT ACTCCACAACTAAGAGAAATAGAAACAAGATTTGGCTCGGTTTATGCAGG GGAAGACATCAAATCCTCTATTATAAAGATCAAACAACAGGTAAATCAGA TCATTGTTGGTTTAATAATTCTTAAACTACATTTGAAAAGTTTCATGTAA GTTTTTTATTATTGTCAAAAGCCGCAACCTATATTTTCAACTTTATATTT ATGTACTTTATGCAGGATTTCAAAAAAGCCCAGGACTCTATTTAATGTGA AGTAAATACTAGAAGAGGTAAATTCTATTTACATGTCTCCTGATTGCCTA TTAATTAATGGCCTTTCAGTTCATGGTTTTTGGATGTATTCTTCATGATG ACGTGAATGTTTAAATACCCCACTAGTTAATTGTTAGGTTGAATGTTGAT GACCAAAGGACTATATGTCGGGAAGAATATTCAAGGAAAGAATTGTTCAT CATATGAAGGGCATTAAATTAAGAAGAACATGGATGCTATGAAGATGTTG GGAAAATATATGAATCAAATAACAAGCTACTCACTTATCTAAGTTTGTTG GTTGAGGATGTTGATTTTAATATTTCAAATTCATTGGTATCATTATATGG GTTTATCAGTAGTGTTAATGGGATAATGAGCAACTTAACCTTAAATTATG CTGTTGGTAAATGTTGGACTCAAGTATGGAAAATTAGGAATAACTTGTGA AAAATATATGCAAAAGTAGGATTGAGATTTTCAATGAAAAAAATTATGAA ACTATACTACTATAGTATATAAATAAATTCAACTTACTGTTGGGTATATT

GGAAGCACATATCATGAAAGTAACTAGAAGCAGAATTTGTTCCCATCTTC ATCTACTTATAGTTTCCATTTCTTACTTGTAAAAATCTGATTAAACTTTA GAGTTATTTCTATTTTTTACCAACCAAAATTTTCATATAAAGGCCACAAG T (SEQ ID NO: 107)

RG2J deduced polypeptide sequence (SEQ ID NO: 108)

MSDPTGIVGAIINPIAQTALVPLTDHVGYMISCRKYVRDMQMKMTELNTSRISAEEH

ISRNTRNHLQIPSQIKDWLDQVEGIRANVANFPIDVISCCSLRIRHKLGQKAFKITEQI

ESLTRQNSLII TDEPVPLGRVGSMIASTSAASSDHHDVFPSREQIFRKALEALEPVQ KSHΠALWGMGGVGKTTMMKKLKEVVEQKKTCNΠVQVVIGEKTNPIAIQQAVADY LSIELKENTKEARADIO-RKRFEADGGKNKFLVILDDVWQFFDLEDIGLSPLPNKGV NFKVLLTSRDSHVCTLMGAEANSILNIKVLKDVEGKSLFRQFAKNAGDDDLDPAFI GIADSIASRCQGLPIAIKTIALSLKGRSKSAWDVALSRLENHKIGSEEVVREVFKISYD NLQDEVTKSIFLLCALFPEDFDIPIEELVRYGWGLKLFIEAKTIREARNRLNNCTERL RET LLFGSHDFGCVKMHDVVRDFVLHMFSEVKHASIVNHGNMSEWPEKNDTSN SCKRISLTCKGMSKFPKDINYPNLLILKLMHGDKSLCFPENFYGKMEKVQVISYDKL MYPLLPSSLECSTNVRVLHLHYCSLRMFDCSSIGNLLNMEVLSFANSNIEWLPSTIG NLKKLRLLDLTNCKGLRIDNGVLKNLVKLEELYMGVNRPYGQAVSLTDENCNEM VEGSKKLLALEYELFKYNAQVKNISFENLKRFKISVGCSLHGSFSKSRHSYENTLKL AIDKGELLESRMNGLFEKTEVLCLSVGDMYHLSDVKVKSSSFYNLRVLVVSECAEL KHLFTLGVANTLSKLEHLKVYKCDNMEELIHTGGSEGDTITFPKLKLLYLHGLPNL LGLCLNVNAIELPKLVQMKLYSIPGFTSIYPRNKLEASSLLKEEVVIPEELIVEKCGSI EELPNIDLDCASVIGEEDNNSSLRNINVENSMKLREVWRIKGADNSRPLFRGFQVVE KIΠTRCKRFTNVFTPITTNFDLGALLEISVDCRGNDESDQSNQEQEQIEILSEKETLQE ATDSISNVVFPSCLMHSFHNLQKLILNRVKGVEVVFEIESESPTSRELVTTHHNQQQP VIFPNLQHLDLRGMDNMIRVWKCSNWNKFFTLPKQQSESPFHNLTTINIDFCRSΠ Y LFSPLMAELLSNLKKVNIKWCYGIEEVVSNRDDEDEEMTTFTSTHTTTILFPHLDSL TLSFLENLKCIGGGGAKDEGSNEISFNNTTATTAVLDQFELSEAGGVSWSLCQYAR EISIEFCNALSSVIPCYAAGQMQKLQVLTVSSCNGLKEVFETQLRRSSNKNNEKSGC DEGNGGIPRVNNNVIMLSGLKILEISFCGGLEHIFTFSALESLRQLEELTIMNCWSMK VIVKKEEDEYGEQQTTTTTKGTSSSSSSSSSSSSSSSSPPSSSKKVVVFPCLKSIVLVNLP ELVGFFLGMNEFRLPSLDELIIEKCPKMMVFTAGGSTAPQLKYIHTRLGKHTIDQES GLNFHQDIYMPLAFSLLDLQTSFQSLYGDTLGPATSEGTTWSFHNLIELDVKFNKD \T K__PSSELLQLQKLEKININSCVGVEEVFETALEAAGRNGNSGIGFDESSQTTTTTL VNLPNLREMNLWGLDCLRYIWKSNQWTAFEFPKLTRVEISNCNSLEHVFTSSMVGS LSQLQELHISQCKLMEEVIVKDADVSVEEDKEKESDGKMNKEILALPSLKSLKLESL PSLEGFSLGKEDFSFPLLDTLRIEECPAITTFTKGNSATPQLREIETRFGSVYAGEDIKS SIIKIKQQDFKKAQDSI.CEVNTR

RG2K polynucleotide sequence (SEQ ID NO:109) and (SEQ ID NO:110)

TGGGATTCCATATATAAAAACATATATTTTTATAAAGTGGGATTCCATTG TTTATATAGATTTTTATTCACCAATAGACAATAGATTAAAAAAAGATATA AAAACATGTCGGCTTTTGACTAAAAATATAGATTTTTATGAATAGAATAT TCAATTTGCTTAACTCGTTTAAAAAAAATGAAAAAGATGTCGATATAAAA TCTCATATGGGCCTTCTTTACCATTCAAATAGTAAAATAGTAAAAGATAC TTGTTTGGGGCATGAACTGACCATAGTCAAACCCATACAAAATCAAACGA ATCCCACATGGATGATGACGATGGGGTCGCAGTAAATGTGTTTTGGTCCT TTTTTTTCGAGAGAACAGAAGCTTCTGCTCTTCATCTTCTTTAGATTTTG GGGATTTTCTGGTTTCAGGGGTTTGTGAGTGGAAACTAAATTGAAGCAAA AAAGTATGGTATAATTGGTTGCTAGTGAAATTGATGCTTTCTATTACTAT CATCTTTAAAATTGTCAAAACATTATGTATTAAATTATGAGATCGAAAGT GGTCTATGGGCCAAAGGTAATACAAGCTTACTCAATGAAATGAATCTAGG ATGCATCATGCATGTATTGGTTAGATTAAAGATTTTCATCAAATTTCCTT

TATCAAATTGTTGTATACCATGTTATGTAGGTGCTACCACAAGCCATAAC ATCGAGCAATGGAGTGTATTACTGGCATCTTTAGCAACCCGTTTGCTCAG TGTCTCATCGCTCCTGTGAAAGAACACCTTTGCCTTCTGATTTTCTATAC ACAATATGTAGGGGATATGCTTACTGCAATGACGGAGTTGAATGCTGCAA AAGACATTGTTGAAGAGCGGAAGAATCAAAACGTAGAAAAATGTTTTGAG

GTTCCAAACCATGTCAACCGTTGGTTGGAAGATGTTCAAACAATCAACAG AAAAGTGGAACGTGTTCTTAACGATAATTGCAATTGGTTCAATCTATGTA ATAGGTACATGCTCGCAGTGAAAGCCTTGGAGATAACTCAGGAGATCGAT CATGCCATGAAACAACTCTCTCGGATAGAATGGACTGATGATTCAGTTCC TTTGGGAAGAAATGATTCCACAAAGGCATCCACCTCTACACCATCAAGTG ATTACAATGACTTCGAGTCAAGAGAACACACTTTTAGGAAAGCACTTGAA GCACTTGGATCCAACCACACATCCCACATGGTAGCCTTATGGGGGATGGG TGGAGTTGGGAAGACCACGATGATGAAGAGGCTGAAAAATATTATTAAAG AAAAGAGGACGTTTCATTATATTGTTTTGGTGGTTATAAAGGAAAATATG GATCTCATTTCCATCCAGGATGCTGTAGCAGATTATCTGGATATGAAGCT AACAGAAAGCAATGAATCAGAAAGAGCCGATAAACTTCGTGAAGGGTTTC AGGCCAAATCAGATGGAGGTAAGAATAGGTTCCTCATAATACTGGATGAT GTATGGCAATCTGTTAATATGGAAGATATTGGTTTAAGTCCTTTTCCGAA TCAAGGTGTCGACTTCAAGGTCTTGTTGACCTCGGAAAACAAAGATGTTT GTGCAAAAATGGGAGTTGAAGCTAATTTAATTTTCGACGTGAAATTCTTA ACAGAAGAAGAAGCACAAAGTTTGTTTTATCAATTTGTAAAAGTTTCTGA TACCCACCTTGATAAGATTGGAAAAGCTATTGTAAGAAACTGTGGTGGTC TACCCATTGCCATCAAAACCATAGCCAATACTCTTAAAAATAGAAACAAG GATGTATGGAAGGATGCACTTTCTCGTATAGAGCATCATGACATTGAGAC AATTGCACATGTTGTTTTTCAAATGAGCTACGACAATCTCCAAAACGAAG AAGCTCAATCCATTTTTTTGCTTTGTGGATTGTTTCCTGAAGACTTTGAT ATTCCTACTGAGGAATTGGTGAGGTATGGATGGGGATTGAGAGTATTTAA TGGAGTGTATACTATAGGAGAAGCAAGACACAGGTTGAACGCCTACATCG AGCTGCTCAAGGATTCTAATTTATTGATTGAAAGTGATGATGTTCACTGC ATCAAGATGCATGATTTAGTTCGTGCTTTTGTTTTGGATACGTTTAATAG ATTCAAGCATTCTTTGATTGTTAACCATGGTAATGGTGGTATGTTAGGGT GGCCTGAAAATGATATGAGTGCCTCATCTTGCAAAAGAATTTCATTAATA

TGCAAGGGCATGTCCGATTTTCCTAGAGACGTAAAGTTTCCAAATCTCTT GATTTTGAAACTTATGCATGCAGATAAGTCTTTGAAGTTTCCTCAAGACT TTTATGGAGAAATGAAGAAGCTTCAGGTTATATCATACGATCACATGAAG TATCCCTTGCTTCCAACATCACCTCAATGCTCCACCAACCTTCGTGTGCT TCATCTTCATCAATGCTCATTGATGTTTGATTGCTCTTCTATTGGAAATC TGTTGAATCTGGAAGTGCTCAGCTTTGCTAATTCTGGTATTGAGTGGTTG CCTTCCACAATCGGAAATTTGAAGGAGCTAAGGGTACTAGATTTGACAAA TTGTGATGGTCTTCGTATAGATAATGGTGTCCTAAAGAAATTGGTGAAAC TTGAAGAGCTTTATATGAGAGTTGGTGGTCGATATCAAAAGGCCATTAGC TTCACTGATGAAAACTGCAATGAAATGGCAGAGCGTTCAAAAAATCTTTC

TGCATTAGAATTTGAGTTCTTCAAAAACAATGCTCAACCAAAGAATATGT CATTTGAGAATCTTGAACGATTCAAGATCTCAGTGGGATGTTATTTTAAG GGAGATTTCGGTAAGATCTTTCACTCTTTTGAAAACACGTTGCGGTTGGT CACCAACAGAACTGAAGTTCTTGAATCTAGGCTTAATGAGTTGTTTGAGA AAACAGATGTTCTTTATTTAAGTGTGGGAGATATGAATGATCTTGAAGAT

GTTGAGGTAAAGTTGGCACATCTTCCTAAATCCTCTTCCTTCCACAATTT AAGAGTCCTTATCATTTCTGAGTGTATAGAGTTGAGATACCTTTTCACAC TTGATGTTGCAAACACTTTGTCAAAGCTTGAGCATCTTCAAGTTTACGAA TGCGATAATATGGAAGAAATCATACATACAGAGGGTAGAGGAGAAGTGAC AATTACATTCCCAAAGCTGAAGTTTTTATCATTGTGTGGGCTACCAAATC

TGTTGGGTTTGTGTGGTAATGTGCACATAATTAATCTACCACAACTCACA GAGTTGAAACTTAATGGCATTCCAGGTTTCACAAGCATATATCCTGAAAA AGATGTTGAAACATCTAGTTTGTTGAATAAAGAGGTAAATGTGTTTTATG WO 98/30083 . . , PCT/US98/00615

145

TTAATACAATACAATCTTTTCAATTAACCGTTTCAAAATATATTGTATGA TTTATTTTTGTTTGGATGGGGTTATTAATGGGTGATTATTTCTCAGGTTG TAATTCCTAATTTGGAGAAACTTGATATTAGTTATATGAAGGATTTGAAA GAGATATGGCCTTGTGAATTAGGGATGAGTCAGGAAGTTGATGTTTCTAC GTTGAGAGTGATTAAAGTAAGCAGTTGTGATAATCTTGTGAATCTATTCC CGTGCAATCCTATGCCATTGATACATCACCTTGAAGAGCTTCAAGTGATA TTTTGTGGTTCCATTGAAGTGTTATTCAACATTGAGTTGGATTCTATTGG TCAAATTGGAGAAGGCATCAACAATAGCAGCTTGAGAATCATCCAATTGC AGAACTTAGGGAAGCTAAGTGAGGTGTGGAGGATAAAAGGTGCGGATAAC TCTAGTCTTCTCATCAGTGGCTTTCAAGGTGTTGAAAGCATTATCGTTAA CAAATGCAAGATGTTTAGAAATGTATTCACACCTACCACCACCAATTTTG ATCTGGGGGCACTTATGGAGATTCGGATACAAGATTGTGGAGAAAAGAGG AGAAACAACGAATTGGTAGAGAGTAGCCAAGAGCAAGAGCAGGTATGGCT TTCAATTTCACTTTCTTACTTAATGAAGGATTAAGCTCCTGCTTTTTGAA T AAAAAGTGGATG AATG ACTAAATTCGGG AATGCC ACCCGGAAAGTT ATC

AACCATTTAGCTACACCATTTTTTGAACTAATGTTGCAATAAATGCATAA TATAATTAAAAAATGGTCATTGATAAATGTAAACCAACCTTTTTTATTTA TTAAAATGTCTACAATAAATGATTTTCTTTATTATATATCATTTTATAAC AATAAGCTTAAAGATGTTTAAATAGCCAATGTCAGTTATAGATCGTAACT AATTTTTTATTAACTAGTTTTAGTTAAGATATCACTCATTATTATTTTTA

TAGAAAAAAGACAAGATTGGCTAATCCTCATAAGAATTTGGAAGATTTAA GCAAAATATAGAGCTTTTCCAAACATAGCCAATAGTTTCTTTTGCAGGTC CCATCTACGAAATTATCAATAGATTTGCGATTTTTTTTTGGCACCCGGGA AATTTCCATTAATTAAAAAAAAGTTCAAGCCATTTTGTAGTTGGCACCTG CAAAATGGTAGTTTGCACCTGCGGAAATCACCTTTCACCATTTCGCATCT

ATGACTTGTGAAAATGTTAATTTGTGAAATGGTCATGTGCACCTCATGAG AAATACGAAATGGTCAGTAATATGACTTTTTTATATAAATATGATGGTGG CATATATTTATAGGAAAATATAGCTGCACGATATTAATTAATAGTGAAAT TAGTTAACTGTATACGATAAGTATACAAAATTTATATGTATGAAGTATAC TCAATTTAGGACGACTCGGGCAATGAAATCATCATTTAATAGGAGCAATG AAATCATTTTCGAAAAATGTTTACAAATGAATAAAATATTAAATTAAACT TAAAACATTTTGTTAGTAGTTTGAAATTTACAAACTGAAATTTGTTGTAT TTATTAACATTTATAAATGTTGTACTATGATTTTTTCCTTGTTTGCAAAT ATTCCTTAAAAATCCACCTAAAATCAAAATAATTAATCTTTTTCAAGTTG AAAAATGAAAATCGTATGATATAACCGTGTATGGATGTGGAATTATATAT

CAGTTACTAATTACATTTTTTGTTGGGATATATGTGCGCAGATTGATATT GCAATCCCATTCACTCTCACACACTCTTTCCAAAACCTCCGTAAACTTGC TTTGGAAAAGTATGAAGGAGTGGAGGTGGTGTTTGAGATAGAGAGTCCAA CAAGTAGAGAATTGATAACAATTCACCATAATCAACAACCACTACTTCCC AACCTTGAGTTATTGGATATAAGTTTTATGGACAGCATGAGTCATGTATG

GAAGTGCAACTGGAATAAATTCTTCATTCTTCAAAAACAACAGTCAGAAT CCCCATTCTGTAATCTCACAACCATACATATTCAATATTGCCAAAGCATT AAGTACTTGTTTTCAACTCTCATGGCAAAACTTCTTTCCAACCTAAAGAA WO 98/30083 . . . PCT/US98/00615

140

GGTCGAGGTAAGAGAGTGTCATGGTATTGAAGAAGTTGTTTCGAACAGAG ATGATGAAGATGAGGAAAAGACTACATTTACATCTACATCTTCTGAAAAA AGCACTAATTTGTTCCCTCGTCTTGAATCTCTCGCTCTTTATCAACTTCC AAATCTCAAGTGTATTGGTGGTGGTGGTTCTGCCAACAGTGGGAACAATG AAATATCTCTTGATAATTCCACTACTACTACTTCTTTTGTTGATCAATCT

AAGGTATGTTTTTTTTTTTNGTTNCCCTT (SEQ ID NO: 109) Sequence gap

CCTCCCTAATAATACATGTTATGCACACTATACTAACATATTAGACACGT AAAGGATAAATGCTATGCCTCATATAATACGTTATATTTATAATCTTTAA ACAATCAAATTTATTAAACAAATAACTAAGTGTGAGCAAAGGCAGGTACC CGACTAAATTGCCCAAAACCAGTCTGGTGGTTCGTGGAATGTTGGGCCAG GTCGTTAAAACGTCTACACACCGGTTCTTTAAATCACAGATCCGCTTCTC ATACTGTGAACCCGGTTTTAATTTTAAAAGAAAATTTCATTATAAAGTAA ATGACTTAAACCATTACAAACAACAAAAATTTACCATTACAATGTTGGAC T ATC ATTATTTGC AAC ATAAAACTGAAAATAC ACATATTTCCTTCTGATA

TCAGCATGAGTGGCTGGTTGGCTAACCCAAAAATCCATGCATTGTAGATG TGTGTTACAACACATAGTATCAATGAAAGGCATATTTTTAGGCTAGAATT TAACAATCTGTAATAATATTCCCTAAAACTAATATCATCATCAACCAACT AATATAAAACCATTGGGTTCGTCATTTTAGGTACAAAACATAGATTTTTC TAAGCTTGTTGTATTTAAACATATGCTTTCTAAACTTAATTGATTTTGCA TTCCAAAATTTTAGGTTGTAAAGTGGTATGTCATTTGTTGTCTTTTCAAC ATTAATTGTACAAAAACCAAAACTACATAATTGATGTAGATATCATAACA ATTGTGTTATTTAGTATATAAAAACTAAATTTTGAATTGAATTTCTTATA CAAAAGTTGTGTCTATGTATACATGTTTATGTAGGTAATAGACAATTAGT CTCTGTTAAGTATATGGAGTTTAATTTTTAGACTAATTTTTCATGTGTTG CAGTTTTATCAGGCAGGTGGCGTTTTTTGGACGTTATGCCAATACTCCAG AGAGATAAATATAAGGGAGTGTTATGCATTGTCAAGTGTAATTCCATGTT ATGCAGCAGGACAGATGCAAAATGTTCAAGTGCTGAATATATACAGGTGC AACTCAATGAAGGAGTTATTTGAAACTCAAGGGATGAACAACAACAATGG TGACAGTGGTTGTGATGAAGGAAATGGTTGTATACCAGCAATTCCAAGAC TAAATAACGTTATTATGCTACCCAATCTAAAGATATTGAAGATTGAAGAT TGTGGTCATCTGGAACATGTATTCACATTCTCTGCACTTGGAAGCCTGAG ACAGCTCGAAGAGTTAACGATAGAGAAATGCAAGGCAATGAAAGTGATAG TGAAGGAAGAAGATGAATATGGAGAGCAAACAACAAAGGCATCTTCGAAG GAGGTTGTGGTCTTTCCTCGTCTCAAGTCCATTGAACTGGAAAATCTACA

AGAGCTCATGGGTTTCTACTTAGGGAAGAATGAGATTCAGTGGCCTTCAT TGGATAAGGTTATGATCAAGAATTGCCCAGAAATGATGGTGTTTGCACCT GGTGAGTCCACAGTTCCCAAGCGCAAGTATATAAATACAAGCTTTGGCAT ATATGGGATGGAGGAGGTACTTGAAACTCAAGGGATGAACAACAATAATG ATGACAATTGTTGTGATGATGGAAATGGTGGAATTCCAAGACTAAATAAC

GTTATTATGTTTCCAAATATAAAGATATTGCAAATCAGCAATTGTGGCAG TTTGGAACATATATTCACATTCTCTGCACTTGAAAGCCTGATGCAGCTCA AAGAGTTAACAATAGCGGATTGCAAGGCAATGAAAGTGATTGTGAAGGAG GAATATGATGTAGAGCAAACAAGGGTATTGAAGGCTGTGGTATTTTCTTG TCTAAAGTCCATTACACTATGCCATCTACCAGAGTTGGTGGGTTTCTTCT TGGGGAAGAATGAGTTCTGGTGGCCTTCATTGGATAAGGTTACCATCATT GATTGCCCACAAATGATGGGGTTCACACCTGGTGGGTCAACAACTTCCCA CCTCAAGTACATACACTCAAGCTTAGGCAAACATACTCTTGAATGTGGCC TTAATTTCAAGTCACAACTACTGCATATCATCAGGTATAATTATTATTCT TTNACACCATCTAATTATGGAATCATGACGCTAATTACAGTATTAAACAC (SEQ ID NO: 110)

RG2K deduced polypeptide sequence (SEQ ID NO:lll)

MECITGIFSNPFAQCLIAPVKEHLCLLIFYTQYVGDMLTAMTELNAAKDIVEERK NQNVEKCFEVPNHVNRWLEDVQTINRKVERVLNDNCNWFNLCNRYMLAVKAL EITQEIDHAMKQLSRIEWTDDSVPLGRNDSTKASTSTPSSDYNDFESREHTFRKAL EALGSNHTSHMVALWGMGGVGKTTMMKRLKNIIKEKRTFHYIVLVVIKENMDL ISIQDAVADYLDMKLTESNESERADKLREGFQAKSDGGKNRFLIILDDVWQSVN

MEDIGLSPFPNQGVDFKVLLTSENKDVCAKMGVEANLIFDVKFLTEEEAQSLFY QFVKVSDTHLDi GKAIVRNCGGLPIAIKTIANTLKNRNKDVWKDALSRIEHHD IETLAHVVFQMSYDNLQNEEAQSIFLLCGLFPEDFDIPTEELVRYGWGLRVFNGV YTIGEARHRLNAYIELLKDSNLLIESDDVHCIKMHDLVRAFVLDTFNRFKHSLIV NHGNGGMLGWPENDMSASSCKRISLICKGMSDFPRDVKFPNLLILKLMHADKS

LKFPQDFYGEMKKLQVISYDHMKYPLLPTSPQCSTNLRVLHLHQCSLMFDCSSI GNLLNLEVLSFANSGIEWLPSTIGNLKELRVLDLTNCDGLRIDNGVLKKLVKLEELY MRYGGRYQKAISFTDENCNEMAERSKNLSALEFEFFKNNAQPKNMSFENLERFKIS VGCYFKGDFGKIFHSFENTLRLVTNRTEVLESRLNELFEKTDVLYLSVGDMNDLED VE\Ε AHLPKSSSFHNLRVLIISECIELRYLFTLDVANTLSKLEHLQVYECDNMEEII

HTEGRGEVTITFPKLKFLSLCGLPNLLGLCGNVHIINLPQLTELKLNGIPGFTSIYPEK DVETSSLLNKEVVIPNLEKLDISYMKDLKEI PCELGMSQEVDVSTLRVIKVSSCDN LVNLFPCNPMPLIHHLEELQVIFCGSIEVLFNIELDSIGQIGEGINNSSLRIIQLQNLGK LSEλ^RIKGADNSSLLISGFQGVESIIVNKCKMFRNVFTPTTTNFDLGALMEIRIQDC GEKRRNNELVESSQEQEQ

RG2L polynucleotide sequence (SEQ ID NO: 112)

GGAAGACACAATGATGCAAAGACTGAAGAAGGTTGCCAAAGAAAATAGAA TGTTCAGTTACATGGTCGAGGCAGTTATAGGGGAAAAGACAGACCCAATT GCTATTCAACAAGCTGTAGCCGATTACCTTCGTATACAGTTCAAAGAAAG CACTAAACCAGCAAGAGCTGATAAGCTTCGTGAATGGTTCAAGGCCCACT CTGNAGACGGTAAGAATAAGTTCCTCGTAATATTTGATGACGTCTGGCAG TCCGTTGATCTGGAAGATATTGGNTTAAGTCCTTTTCCAAATCAAGGTGT CGACTTCAAGGTCTTGTTGACTTCACGAGACGAACACGTTTGCACAATGA TGGGGGTTGAAGCTAATTCAGTTATTAATGTGGGACTTCTAACTGAAGTA GAAGCACAAAGTCTGTTCCAGCAATTTGTAGAAACTTTTGAGCCCGAGCT CTGTAAGATAGGAGAAGTTATCGTAAGAAAGTGTTGCGGTCTACCTATTG WO 98/30083 _{Λ Λ O} PCT/US98/00615

14o

CCATCAAAACCATGGCGTGTACTCTAAGAAATAAAAGAAAGGATGCATGG AAGGATGCACTTTCACGTATAGAGCACTATGACATTCGTAGTGTTGCGCC TAAAGTCTTTGAAACAAGCTATCACAATCTCCAAGACAGGGAGACTAAAT CCGTGTTTTTGATGTGTGGTTTGTTTCCTGAAGACTTCAATATTCCTACC GAGGAGTTGATGAGGTATGGATGGGGCTTAAAGCTATTTGACAGAGTTTA TACAATTAGAGAAGCAAGAACCAGGCTCAACACCTGCATTGAGCGACTTG TGCAGACAAATTTGTTAATTGAAAGTGATGATGTTGGGTGTGTCAAGATG CATGATCTGGTGCGTGCTTTTGTTTTGGGTATGTATTCTGAAGTCGAGCA TGCTTCAATTGTCAACCATGGTAATATGCATGGGTGGACTAAAAATGATA TGAACGACTCTTGCAAAACAGTTTCTTTAACATGCGAGAGTGTGTCTGAG TTTCCAGGAGACCTCAAGTTTCCAAACCTAAAGCTTTTGAAACTTATGCA TGGAGATAAGATGCTAAGGTTTTCTCAAGACTTTTATGAAGGAATGGAAA AGCTCCAGGTAATATCATACCATAAAATGAAGTATCCATTGCTTCCCTCG TCACCTCAATGCTCCACCAACCTTCGAGTGCTTCATCTTCATCGGTGTTC ATTACGGATGCTTGATTGCTCTTGTATCGGAAATTTGACGAATCTGGAAG TGTTGAGCTTCGCTAATTCTGGCATTGAACGGATACCTTCAGCAATCGGA AATTTGAAGAAGCTTAGGCAACTTGATCTGAGAGGTCGTTATGGTCTTTG TATAGAACAGGGTGTCTTGAAAAATTTGGTCGAACTTGAAGAACTTTATA TTGGAAATGCATCTGCGTTTAGAGATTATAACTGCAATGAGATGGCAG

RG2L deduced polypeptide sequence (SEQ ID NO: 113)

EDTMMQRLKKVAKENRMFSYMVEAVIGEKTDPIAIQQAVADYLRIQFKESTKPAR

ADKLREWFKAHS7DGKNKFLVIFDDVWQSVDLEDIGLSPFPNQGVDFKVLLTSRDE

HVCTMMGVEANSVINVGLLTEVEAQSLFQQFVETFEPELCKIGEVIVRKCCGLPIAI KTNIACTLIWKRKDAWKDALSRIEHYDIRSVAPKVFETSYHNLQDRETKSVFLMCG

LFPEDFNIPTEELMRYGWGLKLFDRVYTIREARTRLNTCIERLVQTNLLIESDDVGC VKIvIHDLVRAFVLGMYSEVEHASIVNHGNMHGWTKNDMNDSCKTVSLTCESVSEF PGDLKFPNLKLLKLMHGDKMLRFSQDFYEGMEKLQVISYHKMKYPLLPSSPQCST NLRVLHLHRCSLRMLDCSCIGNLTNLEVLSFANSGIERIPSAIGNLKKLRQLDLRGR YGLCIEQGVLKNLVELEELYIGNASAFRDYNCNEMA

RG2M polynucleotide sequence (SEQ ID NO:114)

GGGGAAGACACAATAGATGCAAAGGCTGAAGAAGTTGCCAAAGAAAAGAG AATGTTCAGTTATATCATTGAGGCGGTTATAGGGGAAAAGACAGACCCCA TTTCCATTCAGGAAGCTATATCATATTACCTTGGTGTAGAGCTCAATGCA AATACTAAGTCAGTAAGAGCTGATATGCTTCGTCAAGGGTTCAAGGCCAA ATCTGATGTAGGTAAGGATAAATTCTTAATAATACTCGACGATGTATGGC AGTCTGTTGATTTGGAAGATATTGGATTAAGTCCATTTCCAAATCAAGGT GTTAACTTCAAGGTCCTGTTAACATCACGAGACCGACATATTTGCACTGT GATGGGGGTTGAAGGTCATTCGATTTTTAATGTGGGACTTCTCACAGAAG

CAGAATCAAAAAGATTGTTCTGGCAGTTTGTAGAAGGTTCTGATCCTGAG CTCCATAAGATAGGAGAAGATATTGTAAGTAAGTGTTGTGGTCTACCCAT TGCCATTAAAACCATGGCATGTACACTTAGAGATAAAAGTACGGATGCAT GGAAGGATGCACTGTCTCGTTTAGAGCATCATGACATTGAAAATGTTGCC TCTAAAGTTTTTAGAGCGAGCTATGACCATCTCCAAGACGAGGAGACTAA ATCCACTTTTTTTCTATGTGGATTGTTTCCAGAAGATTCCAATATTCCTA TGGAGGAGTTGGTGAGGTATGGGTGGGGATTGAAATTATTTAAAAAAGTG

TATACCATAAGAGAAGCAAGAACTAGGCTCAACACTTGCATTGAGCGGCT CATCTATACCAATTTGTTGATAAAAGTTGATGATGTTCAGTGCATCAAGA TGCATGATCTCATCCGTTCTTTTGTTTTGGATATGTTTTCTAAAGTTGAG CATGCTTCGATTGTCAACCATGGTAATACGCTAGAGTGGCCTGCAGATNA TNTGCACGACTCTTGTAAAGGGCTTTCATTAACATGCAAGGGTANATGTG AGTTTTGTGGAGACCTNAANTTTCCAACCCTAATGATTTTAAAACTTATG CATGGAGATAAATCGCTAAGGTTT

RG2M deduced polypeptide sequence (SEQ ID NO:115) GEDTIDAKAEEVAKEKRMFSYIIEAVIGEKTDPISIQEAISYYLGVELNANTKSVRAD

MLRQGFKAKSDVGKDKFLIILDDVWQSVDLEDIGLSPFPNQGVNFKVLLTSRDRHI CTVMGVEGHSIFNVGLLTEAESKRLFWQFVEGSDPELHKIGEDIVSKCCGLPIAIKT MACTLRDKSTDAWKDALSRLEHHDIENVASKVFRASYDHLQDEETKSTFFLCGLFP EDSNIPMEELVRYGWGLKLFKKVYTIREARTRLNTCIERLIYTNLLIKVDDVQCIKM HDLIRSFVLDMFSKVEHASIVNHGNTLEWPAD??HDSCKGLSLTCKG?CEFCGDL?F PTLMILKLMHGDKSLRF

RG2N polynucleotide sequence (SEQ ID NO:116)

AGGTAAAATCCATAACCCTAAATGTTGGTACGCTCATATATCAAATTGCG TGTTTTGTTGAATGAAAAAAGCATGCTCAAAAAACCAGTGTAAGGCACGG

TATATGACATATTTATAGTTACTGATAACAAATTATGATAATTTTGGGTT TACRTAAGTTAGGATTCGTACTTCAACCAAATGTAATAGTTTTTGTGAGT CTATCTATGTATTTGGGGAATCACATTAGCAACGGGATTGTACTAGTAAT TCGAAAAAGTCTTTTAAATAATTTTTCTGTTTATAATTTATGAATAGTTT TAGCGACATCTAATATTAAATAGAATGTATCTGATATTGAATTAATGTCC TTAATGTGAACATAGACCTTTTCCATTTACTAATGCCTAATTATTAGTTT CTAATCAATAAATTTTAATTTCTGTTTTATGCTTCTAAGACAATAAAAAT CCATGATTTACCTTTAAATATTAACAAAAATGACCATAAATAAATAAAAA ATTAGGATACCAAACCCCCCCGCCATGCCCAATGTCTAAATATTCTTGAT GCTTTTGCTTTTCCCTCTTTTCCTTGTTAGTCTATTATTCTGGAGAGTTT

GAGAGAGTTTCATACAAGAAAATTTCAAGAAGAAAGCAAAGGTCCAGGTA TTCTCTTTTCTTAATTATGTATTAACTTACAAGCATTTTTTACACGATCC ATGGTTTTTTGTGTATGTTTTTCAAATTGAAACTAGATTGGGACTTTTGC CCTTGATGATTCATAAGATATTGCATGGAGTTGAGATTGTGTAAGAAAAG TGGTGAATAGAAAGAGCAAGTGAATCCAGATATAGTATTGGTAATATATG

ATGATGAGATAGAGATATGTTAAAACTGGCTAGAAAATTGTTTTAATTTG AAATTTAGGTKGTTGAATTTGAAAGATACCAAGCTAATAACTAATTAGTT ATGCTAAWTAGTTATAAAGAACAACAAACTCTTAGTTTTTTTTTTCATGA TTTTCAACCTCTTTGTACCAAACTAAATTATAGCAAAATTGAATATCATT CTCTGCAATCAATCTTAACTTTTGTTATTATCATCATGTCTAAAATTGCC ACAAGTTTATTTTCAAAGTCATATTGGATTATGAAAGGACTATTTTTACC AATTACATCTTTACTTTATGGGCCAAAGCTAATACAATCCGACTAAACTA AAGGAATATGGGATGCATATAGTTTGCTTCCCGATTATAGATTTCTATCT AATTTGTCTATTGTACTAATTTAGGTGCCACCACAAGTAAATTTGTTAAA TGGATATCGTTAATGCCATTCTTAAACCAGTTGTCGAGACTCTCATGGTA CCCGTTAAGAAACACATAGGGTACCTCATTTCCTGCAGGCAATATATGAG GGAAATGGGTATCAAAATGAGGGGATTGAATGCTACTAGACTTGGTGTCG

AAGAGCATGTGAACCGGAACATAAGCAACCAGCTTGAGGTTCCAGCCCAA GGCAGGGGTTGGTATGAAGAAGTAGGAAAGATCAATGCAAAAGTGGAAAA TTTTCCTAGCGATGTTGGCAGTTGTTTCAATCTTAAGGTTAGACACGGGG TCGGAAAGAGAGCCTCCAAGATAATTGAGGACATCGACAGTGTCATGAGA GAACACTCTATCATCATCTGGAATGATCATTCCATTCTTCTAGGAAGAAT

TGATTCCACGAAAGCATCCACCTCAATACCATCAACCGATCATCATGATG AGTTCCAGTCAAGAGAGCAAACTTTCACAGAAGCACTAAACGCACTCGAT CCTAACCACAAATCCCACATGATAGCCTTATGGGGAATGGGCGGAGTGGG GAAGACGACAATGATGCATCGGCTGAAAAAGGTTGTGAAAGAAAAGAAAA TGTTTAATTTTATTGTTGAGGCGGTTGTAGGGGAAAAAACAGACCCCATT GCTATTCAATCAGCTGTGGCAGATTACCTAGGTATAGAGCTCAATGAAAA AACTAAACCAGCAAGAACTGAGAAGCTTCGTAAATGGTTTGTGGACAATT CTGCTGGTAAGAAGATCCTAGTCATACTCGACGATGTATGGCAGTTTGTA GATCTGAATGATATTGGTTTAAGTCCTTTACCAAATCAAGGTGTCGACTT CAAGGTGTTGTTGACATCACGAGACAAAGATGTTTGCACTGAGATGGGAG

CTGAAGTTAATTCAACTTTTAATGTGAAAATGTTAATAGAAACAGAAGCA CAAAGTTTATTCCACCAATTTGTAGAAATTTCGGATGATGTTGATCGTGA GCTCCATAATATAGGAGTGAATATTGTAAGGAAGTGTGGCGGTCTACCCA TTGTCATCAAAACCATGGCGTGTACTCTTAGAGGAAAAAGCAAGGATGCA TGGAAGAATGCACTTCTTCGTTTAGTGAACTACAACATTGAAAATATAGT GAATGGAGTTTTTAAAATGAGTTACGACAATCTCCAAGATGAGGAGACTA AATCCACCTTTTTGCTTTGTGGAATGTTTCCCGAAGACTTTAATATTCCT ACCGAGGAGTTGGTGAGGTATGGATGGGGGTTGAAATTATTTAAAAAAGT GTATACTATAGGAGAAGCAAGAATCAGGCTCAACACATGCATTGAGCGGC TCATTCATACAAATTTGTTGATTGAAGTTGATGATGTTAGGTGCATCAAG

ATGCATGATCTTGTCCGTGCTTTTGTTTTGGATATGTATTCTAAAGTCGA GCATGCTTCCATTGTCAACCATGGTAATACACTAGAGTGGCATGTGGATA ATATGCACAACTCTTGTAAAAGACTTTCATTAACATGCAAGGGTATGTCT AAGTTTCCTACAGACCTCAAGTTTCCAAACCTCTCGATTTTGAAACTTAT GCATGAAGATATATCATTGAGGTTTCCCAAAAACTTTTATGAAGAAATGG

AGAAGCTTGAGGTTATATCCTATGATAAAATGAAATATCCATTGCTTCCC TCATCACCGCAATGCTCCGTCAACCTTTGCGTGTTTCATCTCCATAAATG CTCGTTAGTGATGTTTGACTGCTCTTGTATTGGAAATCTGTCGAATCTAG AAGTGCTTAGCTTTGCTGATTCTGCCATTGACCTGTTGCCTTCCACAATC GGAATTTTGAAGAAGCTAAGGCTACTGGATTTGACAAATTGTTATGGTCT TTGTATAGCTAATGGTGTCTTTAAAAAATTGGTCAAACTTGAAGAGCTCT ATATGACAGTGGTTAATGGAGGAGTTCGAAAGGCGATCAGCCTCACTGAG GATAACTGCAATGAGATGGCAGAACGTTCAAAAGACCTTTCTGCATTAGA ACTTGAGTTCTTTGAAAACAATGCTCAGCCAAAGAATATGTCATTTGAGA AGCTACAACGATTCCAGATCTCAGTGGGGTGCTATTTATATGGAGCTTCC ATAAAGAGCAGGCACTCGTATGAAAACACATTGAAGTTGGTTATTGACAA AGGTGAATTATTTGAATCTTGAATGAACGGCCTGTTTAAGAAAACAGAGG TGTTATGTTTAAGTGTGGGAGATATGAATGATCTTGAAGATRTTGAGGTT AAGTCATCCTCACAACYTCTTCAATCTTCTTCGTTCAACAATTTAAGAGT CCTTGTCGTTTCAAAGTGTGCAGAGTTGAAACACTTCTTCACACCTGGTG TTGCAAACACTTTAAAAAAGCTTGAGCATCTTGAAGTTTACAAATGTGAT AATATGGAAGAACTCATACGTAGCAGGGGTAGTGAAGAAGAGACGATTAC ATTCCCC AAGCTGAAGTTTTTATCTTTGTGTGGGCT ACCAAAGCTATCGG GTTTGTGCGATAATGTCAAAATAATTGAGCTACCACAACTCATGGAGTTG GAACTTGACGACATTCCAGGTTTCACAAGCATATATCCCATGAAAAAGTT TGAAACATTTAGTTTGTTGAAGGAAGAGGTAAATATAAATTTTTAATGCT AATACATTACAAAGGATCTTTTCAGTTAAATCTTTCAAAATATATTGTAA TTTGATTGTATGGGGTATTATTGTTGGATGGGACTATTAATAAATGATTA TCTTGCAGGTTCTGATTCCTAAGTTAGAGAAACTGCATGTTAGTAGTATG TGGAATCTGAAGGAGATATGGCCTTGCGAATTTAATATGAGTGAGGAAGT TAAGTTCAGAGAGATTAAAGTGAGTAACTGTGATAAGCTTGTGAATTTGT TTCCGCACAAGCCCATATCTCTGCTGCGTCATCTTGAAGAGCTTAAAGTC AAGAATTGTGGTTCCATTGAATCGTTATTCAACATCCATTTGGATTGTGC

TGGTGCAACTGGAGATGAATACAACAACAGTGGTGTAAGAATTATTAAAG TGATCAGTTGTGATAAGCTTGTGAATCTCTTTCCACACAATCCCATGTCT ATACTGCATCATCTTGAAGAGCTTGAAGTCGAGAATTGTGGTTCCATTGA ATCGTTATTCAACATTGACTTGGATTGTGCTGGTGCAATTGGGCAAGAAG ACAACAGAAGCAGCTTAAGAAACATCAAAGTGGAGAATTTAGGGAAGCTA AGAGAGGTGTGGAGGATAAAAGGTGGAGATAACTCTCGTCCCCTTGTTCA TGGCTTTCAATCTGTTGAAAGCATAAGGGTTACAAAATGTAAGAGGTTTA GAAATGTATTCACACCTACCACCACAAATTTTAATCTGGGGGCACTTTTG GAGATTTCAATAGATGACTGCGGAGAAAACAGGGAAAATGACGAATCGGA AGAGAGTAGCCATGAGCAAGAGCAGGTAAGGATTTCAATTTCACTTTCKT ACTTAATTAATGATTAAGCTCCTGCTTTTTRAATAAAAAAGGGACAAACC ATTTCATGACTTAATGTAGCAATACAAGTCATGTATAAGAGTGACCAACT CTTTTTTATTTATAAAATGACTACAAAATATTTTTTTTCATTAGAGATCA TGTATAAATGTGACTAATTTTTCATCACCTAACTTTAGTTGATAAATCTT TATAAATGTCACTAGTTACTTTTCAGTAAAATAACAAATTTAATAAATTA TCAACAAAAAGCATCAACTAAAAAAATCCCACAACCCGTAATAATTTAAA ATAAAAGGATTTAACATCTAATACGAACAATTTTTTTTCTAAACATGATT TGGACCAAATATCACCAGCAACTCAAGTTTGGAATCGATTCAGCTTAAAA CTTGACCARCATAATTAGATAGATGAGAGTTGAAGCTAAAGTGCCTATAT AAGTTCGTTTCATCTTTTTTCTTGATCTTGATAGCAAGTTGAATSATTTT CTTCTTCAAAATTGATAAAAATCTACATTATAAAGAGACTAGCTTGAAAA AAAATGGTCTAGGTGGGTCTTGGGTCTGGTAGATGAAGATGGAAGGGAGA GTAGATTTCAAAGACACAAACACATCTTCATTTTATTTATTTATTTATTA

TTATTATTTTTTGATATCTTGCTCATATTTGTTACAGATATGTGAGGTCT ATTAATCTTTTTAAATATATAAAAAATAAATACATAAATGAGAAAATTAA ATAAAGAATAAATTAATAAGGGCACAATAGTCTTTTTTGGTAAGACAAGG ACCAAAAGCGCAACAAAAGTAAACAGTAGGGACCATCCGATTTAAAAAAT TAATTAGGGACCAAAAACATAAATTCCCCCAAACCATAGGGACCATTCGT GTAATTTACTCTTGCTTTTCGTTTTGTTCATATTTGGGTAACTATTTTTT TTGTACATATCTAGGTAACGAACTTGTTGAAAGTGTTCACATCTACGATG TGACCTACTACAACCGATCATAATGGTCATATATGAACACTTCCAACAAG TTTGTTATCTAGGTGTGTACAAAAAAACGATAGTTACCATGATGTGAACA TACCAAAAAATTAATTACCTTAGCAAGTTATTTTCCCATTTAGGTTGTAT GGAAACAGTTCCGTGAGACCGTGACTTGGATGGTAGATAAATTTAGTAAA CTTAACCCTTCAATTAACCTACCTTTTTCTTATTAACTCAATTTCAAGCT AAATTCTGATTCTTGTTTGAAAGTAAGTTGCATCTTTATGTTTGTATTAT CTTGTTGCATAGGATCCTTAGCATCTTTTAATAATTTATTTGAAGGTGAA AGATCCAACTATTTTTAATCTGTTGGCATTTTCCATCATTTGCAACTGTT TCTTGAAAAAAA: :TACCTAAAATCAAAATAACCATTTTCATATCCAAAA TTATAAGAGAGAATTGTTAACGGACATGGAATCATAAATCATTAACACAG TTCAGTACACAGGTTGCTAATTACATTTCTTGCTGTGCAGATTGAAATTC TATCAGAGAAAGAGACATTACAAGAAGCCACTGGCAGTATTTCAAATATT GTATTCCCATCCTGTCTCATGCACTCTTTTCATAACCTCCATAAACTTAA

CTTGAACAGAGTTGAAGGAGTGGAGGTGGTGTTTGAGATAGAGAGTGAGA GTCCAACAAGTAGAGAATTGGTAACAACTCACCATAACCAACAACAACCT ATTATACTTCCCAACCTCCAGGAATTGATTCTATGGAATATGGACAACAT GAGTCATGTGTGGAAGTGCGGCAACTGGAATAAATTCTTCACTCTTCCAA AAGAACAATCAGAATCCCCATTCCACAACCTCAGTAACATACATATTTAT GAATGCAAAAGCATTAAGTACTTGTTTTCACCTCTCATGGCAGAACTTCT TTCCAACCTAAAGCATATCGAGATAAGAGAGTGTGATGGTATTGAAGAAG TTGTTTC AAAAAGAGATGGTGAGGATGAAGAC ATGACTAC ATCTAC : : : : : : :GCACACAACCACCACTTTTTCCCTCATCTTGATTCTCTCACTCTAAA GCAACTGAAGAATCTGAAGTGTATTGGTGGAGGTGGTGCCAAGGATGAGG

GGAGCAATGAAATATCTTTCAATAATACCACTGCAACTACTGCTGTTCTT GATCAATTTGAGGTATGCTTTGTACATATTCAATTATTTATTTAATTTCC TTGTTAATTTCCTTTTTTCTTTGCAATATTCTATGAAAAAAATCACCAAA TCACAAATAAGAGATTTAAACTTTTATTTCACACCCATGCGGACTCAAGA ATGGGATTTGGAGGCATATAAAGTTACATTCATTTGAACAAGTATTACCA

TTTATTTGTTATTTATCATTTTCATATCATTTACTGATAACATTTCTTTT TTACTTTTCTAATTAGAAAAGGTCCACATGTCTAATTAGGTTTTCCATTC TATGTGAATCCTCTATTCTGTCTGTAATCAAGCATCTTAGATTATTTATC CATTTTCATAATTGTGTTTATATTGACAGTTTTTTTCTTTTTATAGTTGT

AATTGCAACCTGTCATATWTTMWWKKCWWWATKYWMWWARTAATACATTT

TATACCCWCTATACTAAGATA

RG2N deduced polypeptide sequence (SEQ ID NO: 117)

LGKTTMMHRLKXVVKEKKMFNFIVEAVVGEKTDPIAIQSAVADYLGIELNEKTKPA RTEKLRKWFVDNSAGKKILVILDDVWQFVDLNDIGLSPLPNQGVDFKVLLTSRDKD VCTEMGAEVNSTFNVKMLIETEAQSLFHQFVEISDDVDRELHNIGVNIVRKCGGLPI VIKTMACTLRGKSKDAWKNALLRLVNYNIENIVNGVFKMSYDNLQDEETKSTFLL CGMFPEDFNIPTEELVRYGWGLKLFKKVYTIGEARIRLNTCIERLIHTNLLIEVDDVR

CIKλlHDLVRAFVLDMYSKVEHASIVNHGNTLEWHVDNMHNSCKRLSLTCKGMSK FPTDLKFPNLSILKLMHEDISLRFPKNFYEEMEKLEVISYDKMKYPLLPSSPQCSVNL CVFHLHKCSLVMFDCSCIGNLSNLEVLSFADSAIDLLPSTIGILKKLRLLDLTNCYGL CIANGVFKKLVKLEELYMTVVNGGVRKAISL

RG20 polynucleotide sequence (SEQ ID NO: 118)

TTGTAAAACGACGGCCAGTCGAATCGTAACCGTTCGTACGAGAATCGCTG

TCCTCTCCTTCATTTGAATCATGATATTTGAATATCGATACTTTTGACTG

TAGCTTTTGGGTCGATTTTTTAGCAAGATACATAACTGGCCAAACCCATT GGCTATTTTAGCCCAAAATATGAAATGGACTGGATTGTTTTTTTCCTTTC TAACACGCACACATCTGGCGATCAGTATCACTCCATTATGAAGACCTAGT CAAATTCATTAACGTTCAGTCGTTCCTTCAAAGTTTCAAAGTTCCAACTT CCA CTTCCCTCTTTTTTTTTTCTTTCCTCGATTCTGATTTGAA.TCCGAT TCTGCGACGAAGGAGAGCTTGGTCAGAGGGCTGTGATTCTTGAGTCTTGA CCTCCGAATCTAGCTGGATTATTTTCGACACACCAGACCACGTATCAGGT

TGCTCATCCCGAAATACTGCTTTGCAAACTGTTGTATCATCGCCTAGGAA ATTAAGTTTCTTTTTTGGCTCTGTTACTGAATCAGTAGCTTTGCAACTTG CTCATTATAAGCTGATCCATATTTTACATATCTTTTGAAGAATAATAGGT ACTGACTTTACCTTTCTGATGAGAGCGATTTAAGAGATACCTCTGTAAAA TCCATTTTTGTGAAGGGATCTGGGTTAGTTTTTAAAGGATTTGCTACAAC AGTATCCCACAAACGATCTATTTCCCATTTNACTCATCCGCTCAAGATCT ATCCACCTTTATATATGTTAATTGGGAGTCTTCCATGGTGCAATGAATCT AGGATGCATTTAGAAGCCCAATCCATTACAAGTTTTCATCCAATTTCATG TGACAAGTTGTTGGTTACTATGTAGGTACTTCCACAATTAAGAATTTCCA GCAATGGATGTTGTTAATGCCATTCTTAAACCAGTTGCCGAGACACTTAT

GGAACCTGTTAAGAAACATCTAGGCTACATCATTTCCAGCACAAAACATG TGAGGGATATGAGTAACAAAATGAGGGAGTTGAACGCTGCAAGACATGCT GAAGAAGACCACTTGGACAGGAACATAAGAACTCGTCTTGAGATTTCAAA TCAAGTTAGGAGTTGGTTAGAAGAAGTAGAAAAGATCGATGCAAAAGTAA AAGCCCTTCCTAGTGATGTCACCGCTTGTTGCAGTCTCAAGATCAAACAT

GAAGTCGGAAGGGAAGCCTTGAAGCTAATTGTGGAGATTGAAAGTGCCAC AAGACAACACTCTTTGATCACCTGGACTGATCATCCCATTCCTCTGGGAA AAGTTGATTCCATGAAGGCATCGATGTCCACAGCATCAACCGATTACAAT GACTTTCAGTCAAGAGAAAAAACTTTTACTCAAGCATTGAAAGCACTTGA ACCAAACAACGCTTCCCACATGATAGCGTTATGTGGGATGGGTGGAGTGG GGAAGACCACAATGATGCAAAGACTAAAAAAAGTTGCTAAACAAAATAGA ATGTTCAGTTATATGGTTGAGGCAGTTATAGGGGAAAAGACGGACCCAAT TGCTATTCAACAAGCTGTAGCGGATTACCTTCGTATAGAGTTAAAAGAAA GCACTAAACCAGCAAGAGCTGATAAGCTTCGTGAATGGTTCAAGGCCAAC TCTGGAGAAGGTAAGAATAAATTCCTTGTAATACTTGATGACGTCTGGCA GTCTGTTGATCTAGAAGATATTGGTTTAAGTCCTTTTCCAAATCAAGGTG TCGACTTCAAGGTCTTATTGACTTCACGAGACGAACATGTTTGCACAGTA ATGGGAGTTGGATCTAATTCAATTCTTAATGTGGGACTTCTAATAGAAGC AGAAGCACAAAGTTTGTTCCAACAATTTGTAGAAACTTCTGAGCCCGAGC TCCATAAGATAGGAGAAGATATTGTAAGGAAGTGTTGCGGTCTACCTATT GCCATCAAAACCATGGCATGTACTCTTAGAAATAAAAGAAAGGATGCTTG G AAGG ATGC ACTTTCGCGT AT AGAGC ACTATGACCTTCGC A ATGTTGCGC CTAAAGTCTTTGAAACGAGCTACCACAATCTCCATGACAAAGAGACTAAA TCAGTGTTTTTGATGTGTGGTTTGTTTCCGGAAGACTTCAATATTCCTAC TGAGGAGTTGATGAGGTATGGATGGGGATTAAAGATATTTGATAGAGTCT ATACATTTATAGAAGCAAGAAACAGGATCAACACCTGCATTGAGCGACTG GTGCAGACAAATTTGTTAATTGAAAGTGATGATGTTGGGTGTGTCAAGAT

GCATGATCTGGTCCGTGCTTTTGTTTTAGGTATGTATTCTGAAGTAGAGC ATGCTTCAGTTGTCAACCATGGTAATATACCTGGATGGACTGAAAATGAT CCGACTGACTCTTGTAAAGCAATTTCATTAACATGCGAGAGTATGTCTGG AAACATTCCAGGAGACTTCAAGTTTCCAAACCTAACGATTTTGAAACTTA TGCATGGAGATAAGTCGCTAAGATTTCCACAAGACTTTTATGAAGGAATG

GAAAAGCTCCAGGTTATATCATACGATAAAATGAAGTATCCAATGCTTCC CTTGTCTCCTCAATGCTCCACCAACCTTCGAGTGCTTCATCTCCATGAAT GTTCATTAAAGATGTTTGATTGCTCTTGTATTGGAAATATGGCGAATGTG GAAGTGTTGAGCTTTGCTAATTCTGGCATTGAAATGTTACCTTCCACTAT CGGAAATTTAAAGAAGCTAAGGTTACTTGATTTAACAGATTGTCATGGTC

TTCATATAACACACGGTGTCTTTAACAATTTGGTCAAACTTGAAGAGTTG TATATGGGATTTTCTGATCGACCTGATCAAACTCGTGGTAATATTAGCAT GACAGATGTCAGCTACAATGAATTAGCAGAACGTTCAAAAGGCCTTTCTG CATTAGAGTTCCAGTTCTTTGAAAACAATGCCCAACCAAATAATATGTCG TTTGGGAAACTTAAACGATTCAAGATCTCAATGGGATGCACTTTATATGG AGGATCAGATTACTTTAAGAAAACGTATGCTGTCCAAAACACATTGAAGT TGGTTACTAACAAAGGTGAACTATTGGACTCTAGAATGAACGAGTTGTTT GTTGAAACAGAAATGCTTTGTTTAAGTGTTGATGATATGAATGATCTTGG TGATGTTTGTGTGAAGTCCTCACGTTCTCCTCAACCTTCTGTGTTCAAAA TTC T AAGAGTCTTTGTCGTTTCC AAGTGTGTTGAGTTGAGAT ACCTTTTC

ACAATTGGTGTAGCCAAGGATTTGTCAAATCTTGAGCATCTTGAAGTTGA TTCATGTAATAATATGGAACAACTCATATGTATTGAGAATGCTGGAAAAG AGACAATTACATTCCTAAAGCTGAAGATTTTATCTTTGAGTGGGCTACCA AAGCTTTCGGGTTTGTGCCAAAATGTCAACAAACTTGAGCTACCACAACT CATAGAGTTGAAACTTAAGGGCATTCCAGGGTTCACATGCATTTATCCGC AAAACAAGTTGGAAACATCTAGTTTGTTGAAGGAAGAGGTAGATATATGT TTTATGTTAATACAAGTTAAAAAATCTTTTTAACTAAAAGTTTCAGTATA TATATCTATATGTCTATAATTTGATTATATGATGTATTAGTGTTTGGATG

TGGCTATTAAGGGATGATTATTTTGCAGGTTGTGATTCCTAAGTTGGAGA CACTTCAAATTGATGAGATGGAGAATTTAAAGGAAATATGGCATTATAAA GTTAGTAATGGTGAGAGAGTTAAGTTGAGAAAGATTGAAGTGAGTAACTG TGATAAGCTTGTGAATCTATTTCCACACAACCCCATGTCTCTGCTGCATC ATCTTGAAGAGCTTGAAGTCAAGAAATGTGGTTCCATTGAATCGTTATTC AACATCGACTTGGATTGTGTTGATGCCATAGGAGAAGAAGACAACATGAG GAGCTTAAGAAACATTAAAGTGAAGAATTCATGGAAGTTAAGAGAAGTGT GGTGTATAAAAGGTGAAAATAACTCTTGCCCCCTTGTTTCTGGCTTTCAA GCTGTTGAAAGCATAAGCATTGAAAGTTGTAAGAGGTTTAGAAATGTATT CACACCTACCACCACCAATTTTAATATGGGGGCACTTTTGGAGATATCAA TAGATGACTGTGGAGAATACATGGAAAATGAAAAATCGGAAAAGAGTAGC CAAGAGCAAGAGCAGGTATGGATTTCAATTTCACTTTCTTACTTACTTAA GGATTAAGCTTCTGTTTTTTTGAATAAAAAAGGGACATCTTCTAATAATG CACATCTTAAATTAAAAAGTATTTAATTGTTGCATAGCAGCGTATAACAT CTTCTAATAATTTATCTGAAGGTGAAAGATCCAACTACTTCTAATTTGTT AACAATTTCAATCATTTGCAAATGTTCCTTAAAAAATTAATTACCTGAAA TCAAAACAATCTTCTTCAAATCCAAAATTATGAGACAGAATTGAGAAGGG ATGTGAAATTATAAACCATTAACACAATTCCATGCTCACGTTACTAATTA CATTTCTTGTTGGGATATATATGTACAGACTGATATTTTGTCAGAGGAAG TGAAATTACAAGAAGTCACTGATACTATTTCTAATGTTGTATTCACATCG

TGTCTCATACACTCTTTTTATAACAACCTCCGTAAACTCAACTTGGAGAA GTATGGAGGAGTTGAGGTTGTGTTTGAGATAGAGAGTTCAACAAGTAGAG AATTGGTAACAACATACCATAAACAACAACAACAACAACAACCTATATTT CCCAACCTTGAGGAATTATATCTATATTATATGGACAACATGAGTCATGT ATGGAAGTGCAACAACTGGAATAAATTTTTACAACAATCAGAATCCCCAT TCCACAACCTCACAACCATACACATGTCCGATTGCAAAAGCATTAAGTAC TTGTTTTCACCTCTCATGGCAGAACTTCTTTCCAACCTAAAGAGAATCAA TATTGACGAGTGTGATGGTATTGAAGAAATTGTTTCAAAAAGAGATGATG TGGATGAAGAA

RG20 deduced polypeptide sequence (SEQ ID NO:119)

MD\ ^NAIL_ VAETLMEPViα_HLGYIISSTKΗVRDMSNKMRELNAARHAEEDHLD RNI TRLEISNQVRSWLEEVEKIDAKVKALPSDVTACCSLKIKHEVGREALKLIVEIE SATRQHSLITWTDHPIPLGKVDSMKASMSTASTDYNDFQSREKTFTQALKALEPNN ASHMIALCGMGGVGKTTMMQRLKKVAKQNRMFSYMVEAVIGEKTDPIAIQQAVA

DYLRIELKESTKPARADKLREWFKANSGEGKNKFLVILDDVWQSVDLEDIGLSPFP NQGVDFKVLLTSRDEHVCTVMGVGSNSILNVGLLIEAEAQSLFQQFVETSEPELHKI GEDIVRKCCGLPIAIKTMACTLRNKRKDAWKDALSRIEHYDLRNVAPKVFETSYHN LHDKETKSVFLMCGLFPEDFNIPTEELMRYGWGLKIFDRVYTFIEARNRINTCIERL VQTNLLIESDDVGCVKMHDLVRAFVLGMYSEVEHASVVNHGNIPGWTENDPTDSC KAISLTCESMSGNIPGDFKFPNLTILKLMHGDKSLRFPQDFYEGMEKLQVISYDKMK YPMLPLSPQCSTNLRVLHLHECSLKMFDCSCIGNMANVEVLSFANSGIEMLPSTIGN

LKKLRLLDLTDCHGLHITHGVFNNLVKLEELYMGFSDRPDQTRGNISMTDVSYNE LAERSKGLSALEFQFFENNAQPNNMSFGKLKRFKISMGCTLYGGSDYFKKTYAVQ NTLKLVTNKGELLDSRMNELFVETEMLCLSVDDMNDLGDVCVKSSRSPQPSVFKIL RVFVVSKCVELRYLFTIGVAKDLSNLEHLEVDSCNNMEQLICIENAGKETITFLKLKI LSLSGLPKLSGLCQNVNKLELPQLIELKLKGIPGFTCIYPQNKLETSSLLKEEVVIPKL ETLQIDEMENLKEI HYKVSNGERVKLRKIEVSNCDKLVNLFPHNPMSLLHHLEEL EVKKCGSIESLFNIDLDCVDAIGEEDNMRSLRNIKVKNSWKLREVWCIKGENNSCPL VSGFQAVESISIESCKRFRNVFTPTTTNFNMGALLEISIDDCGEYMENEKSEKSSQEQ EQTDILSEEVKLQEVTDTISNVVFTSCLIHSFYNNLRKLNLEKYGGVEVVFEIESSTS RELVTTYHKQQQQQQPIFPNLEELYLYYMDNMSHVWKCNNWNKFLQQSESPFHN LTTIHMSDCKSIKYLFSPLMAELLSNLKRINIDECDGI

RG2P polynucleotide sequence (SEQ ID NO: 120)

CCCATTGCTATTCAGGAAGCAGTAGCAGATTACCTCNGTATAGAGCTCAA AGAAAAAACTAAATCNGCAAGAGCTGATATGCTTCGTAAAATGTTAGTTG CCAAGTCCGATGGTGGTAAAAATAAGTTCCTAGTAATACTTGACGATGTA TGGCAGTTTGTTGATTTAGAAGATATCGGTTTAAGTCCTTTGCCAAATCA AGGTGTTAACTTCAAGGTCTTGCTAACATCACGGGATGTAGATGTTTGCA CTATGATGGGAGTCGAAGCCAATTCAATTCTCAACATGAAAATCTTACTA GATGAAGAAGCACAAAGTTTGTTCATGGAGTTTGTACAAATTTCGAGTGA

TGTTGATCCCAAGCTTCATAAGATAGGAGAAGATATTGTAAGAAAGTGTT GTGGTTTGCCTATTGCCATCAAAACCATGGCCCTTACTCTTAGAAATAAA AGCAAGGATGCATGGAGTGATGCACTTTCTCGTTTAGAGCATCATGACCT TCACAATTTTGTGAATGAAGTTTTTGGAATTAGCTACGACTATCTTCAAG ACCAGGAGACTAAATATATCTTTTTGCTTTGTGGATTGTTTCCCGAAGAC

TACAATATTCCTCCTGAGGAGTTAATGAGGTATGGATGGGGCTTAAATTT ATTTAAAAAAGTGTATACTATAAGAGAAGCAAGAGCCAGACTCAACACCT GCATTGAGCGGCTTATCCATACCAATTTGTTGATGGAAGGAGATGTTGTT GGGTGTGTAAAGATGCATGATCTAGCACTTGCTTTTGTTATGGATATGTT TTCTAAAGTGCAGGATGCTTCAATTGTCAACCATGGTAGCATGTCAGGGT GGCCTGAAAATGATGTGAGTGGCTCTTGCCAAAGAATTTCATTAACATGC AAGGGTATGTCTGGGTTTCCTATAGACCTCAACTTTCCAAACCTCACAAT TTTAAAACTTATGCATGGAGATAAGTTTCTCAAGTTTCCTCCAGACTTTT ATGAACAAATGGAAAAGCTTCAAGTTGTATCGTTTCATGAAATGAAATAT CCGTTTCTTCCCTCGTCTCCTCAATATTGCTCCACCAACCTTCGAGTTCT

TCATCTCCATCAATGCTCATTGATGTTTGATTGCTCTTGTATTGGAAATC TGTTTAATCTGGAAGTGTTGAGCTTTGCTAATTCTGGCATTGAATGGTTA CCTTCCAGAATTGGAAATTTGAAGAAGCTAAGGCTACTAGATTTGACAGA TTGTTTTGGTCTTCGTATAGATAAGGGTGTCTTAAAAAATTTGGTCAAAC TTGAAGAGGTTTATATGAGAGTTGCTGTTCGAAGCAAAAAAGCCGGAAAT AGAAAAGCCATTAGCTTCACAGATGATAACTGCAATGAGATGGCAGAGCG TTC

RG2P deduced polypeptide sequence (SEQ ID NO: 121)

PIAIQEAVADYL7IELKEKTKSARADMLRKMLVAKSDGGKNKFLVILDDVWQFVDL EDIGLSPLPNQGVNFKVLLTSRDVDVCTMMGVEANSILNMKILLDEEAQSLFMEFV QISSDVDPKLHKIGEDIVRKCCGLPIAIKTMALTLRNKSKDAWSDALSRLEHHDLHN FVNEVFGISYDYLQDQETKYIFLLCGLFPEDYNIPPEELMRYGWGLNLFKKVYTIRE ARARLNTCIERLIHTNLLMEGDVVGCVKMHDLALAFVMDMFSKVQDASIVNHGS MSGWPENDVSGSCQRISLTCKGMSGFPIDLNFPNLTILKLMHGDKFLKFPPDFYEQ MEKLQVVSFHEMKYPFLPSSPQYCSTNLRVLHLHQCSLMFDCSCIGNLFNLEVLSF ANSGIEWLPSRIGNLKKLRLLDLTDCFGLRIDKGVLKNLVKLEEVYMRVAVRSKKA

GNRKAISFTDDNCNEMAERS

RG2Q polynucleotide sequence (SEQ ID NO:122)

TGGGGAAGACACAGTGATAGAAAARAAAAAGAATGTTGTGGAAAAGAGGA AAATGTTTGATTATGCTGTTGTGGCGGTTATAGGGGAAAAGACGGACCCT ATTGCTCTTCAGAAAACTGTTGCGGATTACTTGCATATTGAGCTAAATGA AAGCACTAAACTAGCAAGAGCAGATAAACTTTGCAAATGGTTCAAGGACA ACTCGGATGGAGGTAAGAAAAAGTTCCTCGTAATACTCGACGATGTTTGG CAATCTGTTGATTTGGAAGATATTGGTTTAAGTACTCCTTTTCCAAATCA AGGTGTCAACTTCAAGGTTTTGTTGACATCACGAAAGAGAGAAATTTGCA

CAATGATGGGAGTTGAAGCTGATTTAATTCTCAATGTCAAAGTCTTAGAA GAAGAAGAAGCACAAAAGTTGTTCCTCCAGTTTGTAGAAATTGGTGACCA ATACCACGAGCTTCATCAGATAGGGGTACATATAGTAAAGAAGTGTTATG GTTTACCCATTGCCATTAAAACCATGGCTCTTACTTTAAGAAATAAAAGA AAGGATTCATGGAAGGACGCACTCTCTCGTTTAGAGGACCATGACACTGA AAATGTTGCAAATGCAGTTTTCGAGATGAACTACCGCAATCTACAAGATG AGGAGACCAAAGCCATTTTTTTGCTTTGCGGTTTGTTCCCCGAAGACTTT GATATTCCTACTGAGGAGTTGGTGAGGTATGGATGGGGCTTAAATCTATT TAAAAAAGTGTATACCATAAGAAAGGCAAGAACGAGATCGCATACATGTA TTGAGCGACTCTTGGATTCAAATTTGTTGATTGAAAGTAACGATATTCGG

TGCGTCAAGATACACGATCTGGTGCGCGCTTTTGTTTTGGATATGTATTG TAAAGTTGAGCATGCTTCAATTGTCAACCATGGTAATATGCGGACCGAAT ATAATATGGCTGACTCTTGCAAAACAATTTCATTAACATACAAGAGTATG TCTGGGTTTGAGTTTCCAGGAGACCTCAAGTTTCCAAACCTAACAGTTTT GAAACTTATGCANGGAGATAAGTCTCTAAGGTTTCCTCAAGACTTTTATC

AATCAATGGAAAAACTTCGGGTTATATCATATGATAAAATGAAGTATCCA TTGCTTCCCTCATCACCTCAATGCTCCACTAACATCCGAGTGCTTCGTCT CCATGAATGTTCATTAAGGATGTTTGATTGCTCTTGTATTGGAAAGCTAT TGAATTTGGAAGTCCTCAGCTTTTTTAATTCTAACATTGAATGGTTACCT TCCACAATCAGAAATTTAAAAAAGCTAAGGCTACTAGATTTGAGATATTG TGATCGTCTTCGTATAGAACAAGGTGTCTTGAAAAATTTGGTCAAACTTG AAGAACTTTATACTGGATATACATCAGCGTTTACAGA

RG2Q deduced polypeptide sequence (SEQ ID NO:123)

GEDTVIEKKKNVVEKRKMFDYAVVAVIGEKTDPIALQKTVADYLHIELNESTKLAR ADK CKWFKDNSDGGKKKFLVILDDVWQSVDLEDIGLSTPFPNQGVNFKVLLTSR KREICTMMGVEADLILNVKVLEEEEAQKLFLQFVEIGDQYHELHQIGVHIYKKCYG LPIAIKTMALTLRNKRKDSWKDALSRLEDHDTENVANAVFEMNYRNLQDEETKAI FLLCGLFPEDFDIPTEELVRYGWGLNLFKKVYTIRKARTRSHTCIERLLDSNLLIESN DIRCVKIHDLVRAFVLDMYCKVEHASIVNHGNMRTEYNMADSCKTISLTYKSMSG FEFPGDLKFPNLTVLKLM7GDKSLRFPQDFYQSMEKLRVISYDKMKYPLLPSSPQCS TNIRVLRLHECSLRMFDCSCIGKLLNLEVLSFFNSNIEWLPSTIRNLKKLRLLDLRYC DRLRIEQGVLKNLVKLEELYTGYTSAFTE

RG2S polynucleotide sequence (SEQ ID NO:124)

ATTTGGGGTTTTACATTTAATTTTTTGTGCATGAATGTGAAAATAGACTG CTTATTGATTCTTTGTGTTTCATTGAGTTGATTTTCATTATTACTACCTT ACAAATTGCTCAGTGATAGATTTCCATTAATTTGCTAATTCGGTTGCTTC TAAATATGTAGGAGCTACTAAAAGCAAAAATATCGAGCAATGTCGGACCC AACGGGGATTGCTGGTGCCATTATTAACCCAATTGCTCAGAGGGCCTTGG TTCCCGTTACAGACCATGTAGGCTACATGATTTCCTGCAGAAAATATGTG AGGGTCATGCAGACGAAAATGACAGAGTTGAATACCTCAAGAATCAGTGT AGAGGAACACATTAGCCGGAACACAAGAAATCATCTTCAGATTCCATCTC AAATTAAGGATTGGTTGGACCAAGTAGAAGGGATCAGAGCAAATGTGGAA AACTTTCCGATTGATGTCATCACTTGTTGTAGTCTCAGGATCAGGCACAA GCTTGGACAGAAAGCCTTCAAGATAACTGAGCAGATTGAAAGTCTAACAA GACAGCTCTCCCTGATCAGTTGGACTGATGATCCAGTTCCTCTAGGAAGA GTTGGTTCCATGAATGCATCCACCTCTGCATCATCAAGTGATGATTTCCC ATCAAGAGAGAAAACTTTTACACAAGCACTAAAAGCACTCGAACCCAACC AACAATTCCACATGGTAGCCTTGTGTGGGATGGGTGGAGTAGGGAAGACT AGAATGATGCAAAGGCTGAAGAAGGCCGCTGAAGAAAAGAAATTGTTTAA TTATATTGTTAGGGCAGTTATAGGGGAAAAGACGGACCCCTTTGCCATTC

AAGAAGCTATAGCAGATTACCTCGGTATACAACTCAATGAAAAAACTAAG CCAGCAAGAGCTGATAAGCTTCGTGAATGGTTCAAAAAGAATTCAGATGG AGGTAAGACTAAGTTCCTCATAGTACTTGACGATGTTTGGCAATTAGTTG ATCTTGAAGATATTGGGTTAAGTCCTTTTCCAAATCAAGGTGTCGACTTC AAGGTCTTGTTGACATCACGAGACTCACAAGTTTGCACTATGATGGGGGT

TGAAGCTAATTCAATTATTAACGTGGGCCTTCTAACTGAAGCAGAAGCTC AAAGTCTGTTCCAGCAATTTGTAGAAACTTCTGAGCCCGAGCTCCAGAAG ATAGGAGAGGATATCGTAAGGAAGTGTTGCGGTCTACCTATTGCCATAAA AACCATGGCATGTACTCTTAGAAATAAAAGAAAGGATGCATGGAAGGATG CACTTTCGCGCATAGAGCACTATGACATTCACAATGTTGCGCCCAAAGTC TTTGAAACGAGCTACCACAATCTCCAAGAAGAGGAGACTAAATCCACTTT TTTAATGTGTGGTTTGTTTCCCGAAGACTTCGATATTCCTACTGAGGAGT TGATGAGGTATGGATGGGGCTTGAAGCTATTTGATAGAGTTTATACGATT AGAGAAGCAAGAACCAGGCTCAACACCTGCATTGAGCGACTGGTGCAGAC AAATTTGTTAATTGAAAGTGATGATGTTGGGTGTGTCAAGATGCATGATC TGGTCCGTGCTTTTGTTTTGGGTATGTTTTCTGAAGTCGAGCATGCTTCT ATTGTCAACCATGGTAATATGCCCGAGTGGACTGAAAATGATATAACTGA CTCTTGCAAAAGAATTTCATTAACATGCAAGAGTATGTCTAAGTTTCCAG GAGATTTCAAGTTTCCAAACCTAATGATTTTGAAACTTATGCATGGAGAT AAGTCGCTAAGGTTTCCTCAAGACTTTTATGAAGGAATGGAAAAGCTCCA TGTTATATCATACGATAAAATGAAGTACCCATTGCTTCCTTTGGCACCTC G ATGCTCCACCAAC ATTCGGGTGCTTC ATCTCACTAAATGTTCATTAAAG

ATGTTTGATTGCTCTTGTATTGGAAATCTATCGAATCTGGAAGTGCTGAG CTTTGCTAATTCTCGCATTGAATGGTTACCTTCCACAGTCAGAAATTTAA AGAAGCTAAGGTTACTTGATCTGAGATTTTGTGATGGTCTCCGTATAGAA CAGGGTGTCTTGAAAAGTTTAGTCAAACTTGAAGAATTTTATATTGGAAA TGCATCTGGGTTTATAGATGATAACTGCAATGAGATGGCAGAGCGTTCTG ACAACCTTTCTGCATTAGAATTCGCGTTCTTTAATAACAAGGCTGAAGTG AAAAATATGTCATTTGAGAATCTTGAACGATTCAAGATCTCAGTGGGACG CTCTTTTGATGGAAATATCAATATGAGTAGCCACTCATACGAAAACATGT TGCAATTGGTGACCAACAAAGGTGATGTATTAGACTCTAAACTTAATGGG TTATTTTTGAAAACAAAGGTGCTTTTTTTAAGTGTGCATGGCATGAATGA

TCTTGAAGATGTTGAGGTGAAGTCGACACATCCTACTCAGTCCTCTTCAT TCTGCAATTTAAAAGTTCTTATTATTTCAAAGTGTGTAGAGTTGAGATAC CTTTTCAAACTCAATCTTGCAAACACTTTGTCAAGACTTGAGCATCTAGA AGTTTGTGAATGCGAGAATATGGAAGAACTCATACATACTGGAATTTGTG GAGAAGAGACAATTACTTTCCCTAAGCTGAAGTTTTTATCTTTGAGTCAA CTACCGAAGTTATCAAGTTTGTGCCATAATGTCAACATAATTGGGCTACC ACATCTCGTAGACTTGATACTTAAGGGCATTCCAGGTTTCACAGTCATTT ATCCGCAGAACAAGTTGCGAACATCTAGTTTGTTGAAGGAAGAGGTAGAT ATATGTTCTTTATGTTAATACAATTTAAATAATATTTTCAACCAAATTTT CATAATATATCTGTAATTTGATTGTATGATGTGTTATTGTTTATATGTGG CTATTAAGGGATGATTATTTTGCAGGTTGTGATTCCTAAGTTGGAGACAC TTCAAATTGATGACATGGAGAACTTAGAAGAAATATGGCCTTGTGAACTT AGTGGAGGTGAGAAAGTTAAGTTGAGAGAGATTAAAGTGAGTAGCTGTGA TAAGCTTGTGAATCTATTTCCGCGCAATCCCATGTCTCTGTTGCATCATC TTGAAGAGCTTAAAGTCAAGAATTGCGGTTCCATTGAATCGTTATTCAAC ATTGACTTGGATTGTGTCGGTGCAATTGGAGAAGAAGACAACAAGAGCCT CTTAAGAAGCATCAACATGGAGAATTTAGGGAAGCTAAGAGAGGTGTGGA GGATAAAAGGTGCAGATAACTCTCATCTCATCAACGGTTTTCAAGCTGTT GAAAGCATAAAGATTGAAAAATGTAAGAGGTTTAGCAATATATTCACACC TATCACCGCCAATTTTTATCTGGTGGCACTTTTGGAGATTCAGATAGAAG GTTGCGGAGGAAATCACGAATCAGAAGAGCAGGTAACGCTTTCAATTTAA CTTTCTTAAGTAATTAAGGACTAACCTCCTGTTTTTTGAATAATAAAGAG GTGGGATGACTAAACTTGGGCATCACAATTGCAACAAAATGTTACAAACC ATGAAACGTTCAAACCATTTCTTGAATTAAGGTTTCAATACAAGTCATTT AAAAATATGGCTTAAATTTTTTTATATTTATGTATCAACATGATTTTTCA TTAGAGATCATTATTATAATAGTAAGTTTAAAGCAATTTAAATTAGAACT AATTCTAACTTTAGCTAATAAATCGTTATAAATGTAAATAATTACTTTTT AGTGAAATAAGCAACGGATTTAATAAGTTAACAACTTAAATGTCATTTCC TAACAAAAAAAACTATTTGGTTCAGAAGAACCGTAATTCAAGATAACTAA AATAAAAATATTTGACATTCACTAAGAGCATTTTTTTTTCTAAATATGAT TGCAAATGAATAAAACTTAAATTTATACAGAAAAGATTTTTATATATGTT ATACAAAATTTACAAATTGAAACTGGATATGTTAATTAACGGTTTATAAT TCTGGTATCACAAAGGGATATATAATAAAATATTATTTTCTGTAGTCATT TATAATTGTACTAGTTTATAACCCGTGGGAACCATGAGTTCTAAAATTAG TTAAACTTTCATAATAAAAATTTATAATTATTATTTATTTTAAATAAATT ATTAATTAAGAGATGTATCAAAAATTTAAAGTTATTATAACTTCAAATTT AACATATAATTAGAAAATATATGATCATAACTTTCCGCAACTCTTCTTTT GTATTAAAATGCCCAGAGAAGCTCTTAGTAYATTTTCTAAATCAAAGTCA

CAAAACTAATGAAGCATATAATTTTGTGAAAATCAATTAGCATTAGGTTT TAAGAGTCACCAAATTCAAAGAGTAATCCAATGCTTTCATTACCACTATG GAGAAAATATTTTCTTAGTTTAAATGAAATGAAAACAAACATTCAAACTA ATTGTTGCTTACTAAACCAAAGACCCATTACTTAGCCAAGAGTTTAACCA AAAAAAATTACATTCATGTATCATTATTCATGACTAGATATATATGAACA TGAAGGGAGTTTTTATAGAAAATATAATCATAGATATTCAACATAACTTC ATGGAATTCCTCAAAATAACCAAGTTATTCAAGAAATTACATCCAAGTCA ACCAAAGAGAAGTTTAGCCTAGCATGGCTAAACTCAAGAAAATAAAATAA GGATTAGAAGTACCAAACATGTAGTAAGAATCACAGTAAAAGATGATGTT GTTCTTGATGTTCTTCTAAGTTCTTCAAGTCTCCAGTTGCTCCTAATAAT

GCAAAGGAGAGCCATTAAATTCGTATGTATTGATCCCTTCAAAAGCTGCA CCAACCTCCCTTAAATAACACTCAAAGCAAAAATGACAAAATTGCCCCTG AAGGACCCTATGCGGGTGCCTTGCGCGGGTGGAGCTGAATACGAAAGGTC TTTGGTCTTTGTGAGGGTGATGCTGTGCGGGTTAGCTTGTCGCATGCTTC CGCGCGGTTCGCGCACATGTGCACAAGTGATGCATGGTGTGTACGTTCTT GAGTTTTGAGCCTCCGATGCTTAGTCCATTTGGCCCAATTCGAGTCCAAT CAGCTTATGACCCATTTTTCTTCAAGTTATCTTCAAGTTATCTTCAAGTT AAGCCCAAATTGCCTTCTCCAAATCATCCATAACTTCACAAAATCGCCCG TTCATCTTAATCCCGAATGCACAATTATTCTCCTGTCTTCCTTTTAAGCA AGATACCACCTTCTTCATGCTTCATCCATCAATAGTACACTTCATGTATC

ATCTCTACTAGTTATTTAGTCCACAATCCTTATTGTCCTCCAAATTTAAT TATCTCATTTAGTTCCCGTTCCACTAGTTTCCTTAAAATTTGCAATTAAG CTCACACAAATATTAAGTACCTGAAATGGTCATAAAATAACAAAAAGGAA AATATGCATGAAGATTAACTAAATGATGAACGAAATATGCTAAAATAGAC TATAAAATGAAGTAAATAAAATGAAATTATCGCACTCCGACCACCCTTAT AGGCTTGTAGTCCATCCACCCTTCATTCCTTGTACCAATATGGGATGGAA ACATCATTAATTAAGCCAAAAAACTAACATATAAGGGGTGAGTGACAAAG GTAAGTACTAAAGATGAAAATAATCCATTTTTYTTGTATATACACAACAC ACACATAGGGGCAGACGTAGGATTTCATAGTACAGATTGTTGGTGGCACA TAAGTGTTGCTGGTGACACTTTTTTTTTCTTTTACGTAGTGGCACAACAG TAGAAAAAACGARAAATTCGAAATTTTTTACAATGTGTSTAAAAAAAAYA GTGGTTGTTGGTGCCACTATGGACACCAAAGTTGAACTGCCCCTGCGCGC RCACACACACACACATAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAG ARAGWAWGRRRGAKAKARMCSMSYTTGGGATGTGATACTTCTTTTAGGAA AATGGAGTTATATCTTTGATATTGTATTTTTTTAATGTAATTTATATATT TAATCATTTTAGTTTATAAGTTTTATTTATTTTGATATGAAAAAAAAAGT CTTTTATACATTGGATTTAACATAAAAATCCAACAATATTAATCAAAAAG ACCAMACATGTGGACAMWTATGTATATAAWTAATTCACAATAGTCTTTAG

GAATAGNATTATATATATAATTAATTCTCAATGGTCTTAGGAATAGTAAG TTCTTATATTTCAAACTTTNGCCACAATTCTTTGKTTACTTWGACACTTY CCTCTCTCTAATTATATATATATATATATATATATATATATATATACACA CACACACACACACACTAGATGTGTGCCCGCGCAAAGCAGTGACGTNNNGG AGAANACTTTCTTAAGCATAAATAATTATTATATTTTTTATTGGGTATTA TATAATAAAAAATTACAACTTTTAAATAAAATATTTATGTTTATACTTTA TATTTATATTGCTTGTATACTATTAATATAATAAATTAATATTTATGTCT AATTTATGAAATGTAAATTAATTTAAATACATGAATTTAATATTTTTAAA ATTTTCAGTTTGCTTCAAATTGAGTTTCTTAATTATTTTTTTTAATTCAN GTATTCAAACTTTTGGTAAGTATTAAAGAATTATTTATGCACAATTGATT

TATACAAAAAACTTTGTAACTTATACATCTTAAAATTCAAGATATAACTA ACATGTTTTACAATATATATATATATANATATATATATATATATATATAT ATATATATATATATATAGTAAAGCGCANAGGTCATAGGNANAGANTATTT TCTATTATTCTACGTTTTGCCACAAAAGTTTGAACACTTTGCCACTTTTT GTC CCTCCTT AACCTTTTC AATGTTTTGCGAC AAA AGTTCC A AAACTTTG

CCACTTTGATCATTCCTCAACTTTTCACCGCATTAGTTTGTGGAGTTGGC AGTTTTGGTCCCCCTAACTTCGATATTTTCTCCTGCTAGCCAAAAAGGGT TCCAGAGTTTCACANTTTTGGTCCCTGACAATAACCAAATGTGAGATGTC AAATTTTTGCCACATTAGTTTGTGGAGTTGTCCCTTTTGGTCCCCCCACA TTCGATATTCTACTATACGACCTTATTTTTCTCAAATAACAACACGTATA

TTTAATTACCAATGATAGAAATAGATATCAAATAAAGTATTTGTAACACC GTGTAAGAACGGTGCTACTATAGGTAAAAATAAACATTTCAAAGTACGAT GTCCTAATTGGAAAAAGAGTTTTAAAAAAATAACAACTAGGGGCGAGTTT TTTTTACAAGTTTGTATCAAATCATATCAAAATTTAAGGTGGAACGGTGA CCACATTAACCAGAAATGTAATTTATTCTTTGATTTTGATAATTTTTAAT

ATTTTGTTGTGATCTATGTATTTAAAAGTAAACAACAAAGAACATAATCC AAAACCCTAAATTGCAAGTCTCGCCCAATTTCTCTATCACTAGTCGTCAC TTACGATGGCGTTACGTCGCTCTCTCACTTCTTACAACCCTTTGTTGCTA CTCATTACAATAACGAAAAGTTGAATATCCATATATTTATTTGGATGTGG AATTGAACAAATCTCGTCAAATTTTTGATTTTGTTGATGGATTTGAGTAG AAGTTTGGGCAGAACGGGAATGATGGTCTGCAAGTGGTTATAAACTTGAT TCTGAGTTATTACTATATATGTAGCCTCTTTACAACGACCAAGGTTTCTT CCAGGTACCATTTGATCTTTTTAGAACCCAGTTGTCTGAAACACCCTGAT TTGGATCAAATATCACCAACAACTCTTAAAAACTTGATTAATCAATTGTT TTCTTCATCTTGATAACAAGTGGAATGATTTTCTACTTAGATTAACTTGA AAAAAAAGGTCCATGTGCGTCTGGTGGATCTGGTAAATGAAGATGGAAGG GAGAGCTGACTTTAAAGACACAAACACGTCACCATATCTTTTATTTTATT TTAAATTTGCTTTTTTCCTATTTCTTTCTTTCTTGATCTCCAGATGGTAT

GTGGTGTGGATAATTTACACATAGAGATTGGGAACGACTGTGTTTTAGAG AGGACGTGGCTTGGGGTTGAGGATGGTTTATGGCTGGCCGAGTTTCATTT ATATAAACAAACAAATATATAAAACAAGGGGTAAAATGGCCATCTTATAT GTATTTAACCGTCCTTTTTTATTTTTTTTTTATTTTTAAATTTAAGAAGG GGTATACCAGTGTCAGCCTCTTATTCCCAACCAGGCAACCAGTCAAATAG

GGACTTAGGTTGTTTGGAAACAGTTCCGTGAGACCGTGACTTGGATGGTA GATAAATTTAGTAAACTTAACCCTTCAATTAACCTACCTTTTTCTTATTA ACTCAATTTCAACCTAAATTCTGATTCTTGTTTGAAAATAAGTTGCATCT TTATGTTTGTATTATCCTGTTGCATAGGATCCTTAGCATCTTTTAATAAT TTATTTGAAGGTGAAAGATCCAACTATTTTTTAGCTGTTGGCATTTTCCA TCATTTGCAACTGTTTCTTGAAAAAAAAATACCTAAAATCAAAATAACCA TTTTCAAATCCAAAATTATAAGAGAGAATTGTTAATGGACGTGGAATCGT AAATCATTAACACAGTTCAGTACACAAGTTGCTAATTACATTTCTTGCTG TGCAGATTGAAATTCTATCAGAGAAAGAGACATTACAAGAAGTCACTGAT ACT.AATATTTCTAATGATGTTGTATTATTCCCATCCTGTCTCATGCACTC

TTTTCATAACCTCCATAAACTTAAATTGGAGAGAGTTAAAGGAGTGGAGG TGGTGTTTGAGATAGAGAGTGAGAGTCCAACAAGTAGAGAATTGGTAACA ACTCACCATAACCAACAACATCCTATTATACTTCCCAACCTCCAGGAATT GGATCTAAGTTTTATGGACAACATGAGTCATGTGTGGAAGTGCAGCAACT GGAATAAATTCTTCACTCTTCCAAAACAACAATCAGAATCCCCATTCCAC

AACCTCACAACCATACACATGTTCAGCTGCAGAAGCATTAAGTACTTGTT TTCGCCTCTCATGGCAGAACTTCTTTCCAACCTAAAGGATATCTGGATAA GTGGGTGTAATGGTATTAAAGAAGTTGTTTCAAAGAGAGATGATGAGGAT GAAGAAATGACTACATTTACATCTACCCACACAACCACCATCTTGTTCCC TCATCTTGATTCTCTCACTCTAAGACTACTGGAGAATCTGAAGTGTATTG GTGGAGGTGGTGCCAAGGATGAGGGGAGCAATGAAATATCTTTCAATAAT ACCACTGCAACTACTGCTGTTCTTGATCAATTTGAGGTATGCTTTGTACA TATTCAATTATTTATTTAATTTCCTTTTTTCTTTGCAATATTCTATAAAT AATACATTTTATACCCACTATACTAAGATAATAATTACCTAGAGGGATGG ATGCTATGACACAGCTGCTACACTTCAGAAACTCTAGTAAGGGCAGTTAT

GGAAGTTCAATAAAATGATAATGGCATCTTTTGATGGGTAATATAGGCAA TTTAAGTTTTATTTCTGTTAAAGCAGTATTTAGCAAGTACTGGCCAGTAG GAGAGGAGAATATCACCTTTTGTGAAAATCTGGTCATTGTACCCAAGAAT TTAGTTAAATGTAACATTTTAGATATCAGGGGACATCAGGTGACAGATAT TGTAGAATAGAACAATATATAATATTACCCAAAACTATTTTTTCTAAGGT TATTCTGTTAAATATGTGCTTTCTTGATTTCATTGAATTTGCATTCCTAT ATTTTAGGTGGTAAAGTGATTGTCTCTTCAATAAATCCCGAAATTAATTA AAAAAAAAAAAAACAAAAGTAAATTTTTGATATGGAGAGCACTGGTATCA TTTAGTATATAAAAAAACTAGATTTTGAATTAAGTTTCTTATATAAAAGC TGTGTATATAGTTTAATTAGTTTTACATCATTTTTCCATGTGGTGTTGCA GTTGTCTGAAGCAGGTGGTGTTTCTTGGAGTTTATGCCAATACGCTAGAG AGATAGAGATATCTAAGTGTAATGTATTGTCAAGTGTGATTCCATGTTAT GCAGCAGGACAAATGCAAAAGCTTCAAGTGCTGAGAGTAACGGGTTGTGA TGGCATGAAGGAGGTATTTGAAACTCAATTAGGGACGAGCAGCAACAAAA ACAGAAAGGGTGGTGGTGATGAAGGAAATGGTGGAATTCCAAGAGTAAAT AACAATGTTATTATGCTTCCCAATCTAAAGACATTGAAAATCTACATGTG CGGGGGTTTGGAACATATATTCACATTCTCTGCACTTGAAAGCCTGACAC AGCTCCAAGAGTTAAAGATAGTGGGTTGCTACGGAATGAAAGTGATTGTG AAGAAGGAAGAAGATGAATATGGAGAGCAGCAAACAACAACAACAACAAC AACGAAGGGGGCATCTTCTTCTTCTTCTTCTTCTTCTTCTAAGAAGGTTG TGGTCTTTCCCCGTCTAAAGTCCATTGAACTATTCAATCTACCAGAGCTG GTAGGATTCTTCTTGGGGATGAATGAGTTCCGGTTGCCTTCATTGGAAGA AGTTACCATCAAGTATTGCTCAAAAATGATGGTGTTTGCAGCTGGTGGGT CCACAGCTCCCCAACTCAAGTATATACACACAAGATTAGGCAAACATACT CTTGATCAAGAATCTGGCCTTAACTTTCATCAGGTATATATATATTCCTT TAATTGGCATGATCTAATTAAGAAAGATATCATTCCTGCCAAGTAAATTT ACTTCAAACACATTCACACTGGTTTCAGTCTAAGTTTATGTTGTTCTAGG AAGGCCAAAATGGGAAAGCAAGATAGGGAAAAATAGTGTATTTCAGTGGA AAGGGTATTTTAGGTATTTTCTGTCAAAAGTTGTTATTGCAGGCTTTTTA GTACCTGGAATCGTGTGTGGGAGGAGCGTTATTATTCTGATTTGCTTGTT TCTTTATCATTTTTTCTTAGCCTCTCGAACAGCTAGAAACCCTTTTAATC TTTTGATTTTAAATGACAAAATTTTTCCCTGTTACTCTATTTGATTGTTG TTCTTCATGGTTCTAAGTGAGTTATTGGCTCATCTGTTACTTCTTTTGAT

TGTTATTTTCATATCATGTTGTCCTTTGAATCAAGCTTTTCCATTTTCAA CCAGGGCAAAAGGTCAAAAGTAACCTACTTTATGAGATCAAAAACAGCAA CCCATCGGATAACTTTTAGTTGGAGTTAATAGTTACAATTACCATTGTGA TTAATAATTATAATATCTTGTATTAATTCATTAAAATTGGTACAGCACAT ATATGACATTTTAAAGGTTTGTTTTTGTTWGACATATATATGCCTCTGGC GTTTTCTTTATTGGACATGCAGACCTCATTCCAAAGTTTATACGGTGACA CCTCGGGCCCTGCTACTTCAGAAGGGACAACTTGGTCTTTTCATAACTTG ATCGAATTAGATATGGAATTAAATTATGATGTTAAAAAGATTATTCCATC CAGTGAGTTGCTGCAACTGCAAAAGCTGGAAAAGATTCATGTGAGTAGTT GTTATTGGGTAGAGGAGGTATTTGAAACTGCATTGGAAGCAGCAGGGAGA

AATGGAAATAGTGGAATTGGTTTTGATGAATCGTCACAAACTACTACTAC TACTACTCTTTTCAATCTTCGAAACCTCAGAGAAATGAAGTTGCATTTTC TACGTGGTCTGAGGTATATATGGAAGAGCAATCAGTGGACAGCATTTGAG TTTCCAAACCTAACAAGAGTTCATATAAGTAGGTGTAGAAGGTTAGAACA TGTATTTACTAGTTCCATGGTTGGTAGTCTATTGCAACTCCAAGAGCTAG ATATTAGTTGGTGCAACCATATGGAGGAGGTGATTGTTAAGGATGCAGAT GTTTCTGTTGAAGAAGACAAAGAGAGAGAATCTGATGGCAAGACGAATAA GGAGATACTTGTGTTACCTCGTCTAAAATCCTTGAAATTAAAATGCCTTC CATGTCTTAAGGGGTTTAGCTTGGGGAAGGAGGATTTTTCATTCCCATTA TTGGATACTTTAGAAATCTACAAATGCCCAGCAATAACGACCTTCACCAA GGGAAATTCTGCTACTCCACAGCTAAAAGAAATAGAAACAAGATTTGGCT CGTTTTATGCAGGGGAAGACATCAACTCCTCTATTATAAAAAGATCAAAC AACAGGTAAATCAGATCTTTGTTGCTTTAATAATTCTTAAACTACATTTG AAAAGCTTCATGCAAGTTTTTTTTGTTATATTGTCAAAAACCGCAACCTA CATTTTCAGCTTTATATTTATGTACTTTATGCAGGAGTTCAAACAAAACT CTGATTAATGTGAAGTGAATATTAAAGGTAAATTATATTTTCATGTTCCT AGTTGCCTATTAATTAATGGCCTTTTAGTTCRTGATTTTTGGATGTAGTY WTCATGATGATGTGAATCTTCTAATACCCCATTCATTGTTTGGTTGAATG TTGACTCTATGTCAGGATGAATATTCAAGGGAAGAATTGTTCATCATATG AAGGACATTAAAGAACATGGATGCTATGAAGATGTTGGAARAC

RG2S deduced polypeptide sequence (SEQ ID NO: 125) MSDPTGIAGAIINPIAQRALVPVTDHVGYMISCRKYVRVMQTKMTELNTSRISVEEH ISRNTRNHLQIPSQIKDWLDQVEGIRANVENFPIDVITCCSLRIRHKLGQKAFKITEQI ESLTRQLSLISWTDDPVPLGRVGSMNASTSASSSDDFPSREKTFTQALKALEPNQQF HMVALCGMGGVGKTRMMQRLIO AAEEKKLFNYIVRAVIGEKTDPFAIQEAIADYL GIQLNEKTKPARADKLREWFKKNSDGGKTKFLIVLDDVWQLVDLEDIGLSPFPNQG VDFKVLLTSRDSQVCTMMGVEANSIINVGLLTEAEAQSLFQQFVETSEPELQKIGED IVRKCCGLPIAIKTMACTLRNKRKDAWKDALSRIEHYDIHNVAPKVFETSYHNLQE EETKSTFLMCGLFPEDFDIPTEELMRYGWGLKLFDRVYTIREARTRLNTCIERLVQT NLUESDDVGCVKMHDLVRAFVLGMFSEVEHASIVNHGNMPEWTENDITDSCKRIS LTCKSMSKFPGDFKFPNLMILKLMHGDKSLRFPQDFYEGMEKLHVISYDKMKYPLL PLAPRCSTNIRVLHLTKCSLKMFDCSCIGNLSNLEVLSFANSRIEWLPSTVRNLKKLR LLDLRFCDGLRIEQGVLKSLVKLEEFYIGNASGFIDDNCNEMAERSDNLSALEFAFF NNKAEVKNMSFENLERFKISVGRSFDGNINMSSHSYENMLQLVTNKGDVLDSKLN GLFLKTKVLFLSVHGMNDLEDVEVKSTHPTQSSSFCNLKVLIISKCVELRYLFKLNL ANTLSRLEHLEVCECENMEELIHTGICGEETITFPKLKFLSLSQLPKLSSLCHNVNIIG LPHLVDLILKGIPGFTVIYPQNKLRTSSLLKEEVVIPKLETLQIDDMENLEEI PCELS GGEKVK_LREIKVSSCDKLVNLFPRNPMSLLHHLEELKVKNCGSIESLFNIDLDCVGA IGEEDNKSLLRSINMENLGKLREVWRIKGADNSHLINGFQAVESIKIEKCKRFSNIFT PITANFYLVALLEIQIEGCGGNHESEEQIEILSEKETLQEVTDTNISNDVVLFPSCLMH SFHNLHKLKLERVKGVEVVFEIESESPTSRELVTTHHNQQHPIILPNLQELDLSFMD NMSHVWKCSNWNKFFTLPKQQSESPFHNLTTIHMFSCRSIKYLFSPLMAELLSNLK DΓVMSGCNGIKEVVSKRDDEDEEMTTFTSTHTTTILFPHLDSLTLRLLENLKCIGGGG AKDEGSNEISFNNTTATTAVLDQFELSEAGGVSWSLCQYAREIEISKCNVLSSVIPCY AAGQMQKLQVLRVTGCDGMKEVFETQLGTSSNKNRKGGGDEGNGGIPRVNNNVI

MLPNLKTLKIYMCGGLEHIFTFSALESLTQLQELKIVGCYGMKVIVKKEEDEYGEQ

QTTTTTTTKGASSSSSSSSSKKVVVFPRLKSIELFNLPELVGFFLGMNEFRLPSLEEVT

IKYCSKMMVFAAGGSTAPQLKYIHTRLGKHTLDQESGLNFHQTSFQSLYGDTSGPA

TSEGTTWSFHNLIELDMELNYDVKKIIPSSELLQLQKLEKIHVSSCYWVEEVFETAL

EAAGRNGNSGIGFDESSQTTTTTTLFNLRNLREMKLHFLRGLRYI KSNQWTAFEF

PNLTRVHISRCRRLEHVFTSSMVGSLLQLQELDISWCNHMEEVIVKDADVSVEEDK

ERESDGKTNKEILVLPRLKSLKLKCLPCLKGFSLGKEDFSFPLLDTLEIYKCPAITTFT

KGNSATPQLKEIETRFGSFYAGEDINSSIIKRSNNRSSNKTLINVK.ILK

RG2T polynucleotide sequence (SEQ ID NO: 126)

GGAAGACGACAATGGTGCAACGGTTGAAGAAGGTTGTGAAAGATAAGAAG

ATGTTCCATTATATTGTCGAGGTGGTTGTAGGGGCAAACACTGACCCCAT

TGCTATCCAGGATACTGTTGCAGATTACCTCAGCATAGAACTGAAAGGAA ATACGAGAGATGCAAGGGCTTATAAGCTTCGTGAATGCTTTAAGGCCCTC TCTGGTGGAGGTAAGATGAAGTTCCTAGTAATTCTTGACGATGTATGGAG CCCTGTTGATCTGGATGATATCGGTTTAAGTTCTTTGCCAAATCAAGGTG TTGACTTCAAGGTCTTGCTGACATCACGCAACAGTGATATCTGCATGATG ATGGGAGCTAGTTTAATTTTCAACCTCAATATGTTAACAGACGAGGAAGC ACATAATTTTTTCCGTCGATACGCAGAAATTTCTTATGATGCTGATCCCG AGCTTATTAAGATAGGAGAAGCTATTGTAGAGAAATGTGGTGGTTTACCC ATTGCCATCAAAACTATGGCCGTTACTCTTAGAAATAAACGCAAAGATGC ATGGAAAGATGCACTTTCTCGTTTAGAGCACCGTGACACTCATAATGTTG TGGCTGATGTTCTTAAATTGAGCTACAGCAATATCCAAGACGAGGAGACT CGGTCGATTTTTTTGCTATGTGGTTTGTTTCCTGAAGACTTTGATATTCC

TACCGAAGACTTAGTGAGGTATGGATGGGGATTGAAAATATTTACCAGAG TGTATACTATGAGACATGCAAGAAAAAGGTTGGACACGTGCATTGAGCGG CTTATGCATGCCAACATGTTGATAAAAAGTGATAATGTTGGATTTGTCAA GATGCATGATCTGGTTCGTGCTTTTGTTTTGGGCATGTTATCTGAAGTCG AGCATGCATCAATTGTCAACCATGGGGATATGCCAGGGTGGTTTGAAACT GCAAATGATAAGAACAGCTTGTGCAAAAGAATTTCATTAACATGCAAAGG TATGTCTGCGATTCCTGAAGACCTCACGTTTCCAAACCTCTCGATCCTGA AATTAATGGATGGAGACGAGTCACTGAGGTTTCCTGAAGGCTTTTATGGA GAAATGGAAAACCTTCAGGTTATATCATATGATAACATGAAGCAGCCATT TCTTCCACAATCACTTCAATGCTCCAATGTTCGAGTGCTTCATCTCCATC ACTGCTCATTAATGTTTGATTGCTCTTCTATTGGAAATCTTTTGAATCTC GAGGTGCTCAGCATTGCTAATTCTGCCATTAAATTGTTACCCTCCACTAT TGGAGATCTGAAGAAGCTAAGGCTCCTGGATTTGACAAATTGTGTTGGTC TCTGTATAGCTAATGGCGTCTTTAGAAATTTGGTCAAACTTGAAGAGCTT TATATGAGAGTTGATGATCGAGATTCGTTTTTTGTGAAAGCTGATGACAG CAAGACCATTACCT RG2T deduced polypeptide sequence (SEQ ID NO: 127)

KTTMVQI .KKVVKDKKMFHYIVEVVVGANTDPIAIQDTVADYLSIELKGNTRDAR AYKXRECFKALSGGGKMKFLVILDDVWSPVDLDDIGLSSLPNQGVDFKVLLTSRNS DICMMMGASLIFNLNMLTDEEAHNFFRRYAEISYDADPELIKIGEAIVEKCGGLPIAI KTMAVTLRNKRKDAWKDALSRLEHRDTHNVVADVLKLSYSNIQDEETRSIFLLCG LFPEDFDIPTEDLVRYGWGLKIFTRVYTMRHARKRLDTCIERLMHANMLIKSDNVG FVKMHDLVRAFVLGMLSEVEHASIVNHGDMPGWFETANDKNSLCKRISLTCKGMS AIPEDLTFPNLSILKLMDGDESLRFPEGFYGEMENLQVISYDNMKQPFLPQSLQCSN VRVLHLHHCSLMFDCSSIGNLLNLEVLSIANSAIKLLPSTIGDLKKLRLLDLTNCVGL CIANGVFRNLVKLEELYMRVDDRDSFFVKADDSKTIT

RG2U polynucleotide sequence (SEQ ID NO: 128)

GCCTTGTGTGGGATGGGTGGAGTGGGAAAGACCACTGTGATGAAGAAGCT GAAGGAGGTTGTGGTAGGAAAGAAACTGTTTAATCATTATGTTGAGGCGG TTATAGGGGAAAAGACAGACCCCATTGCTATTCAACAAGCTGTTGCCGAG

TACCTTGGTATAAGTCTAACCGAAACCACTAAACCAGCAAGAACTGATAA GCTCCGTACATGGTTTGCAAACAACTCAAATGGAGGAAAGAAGAAGTTCC TGGTAATACTAGACGATGTATGGCAACCAGTTGATTTGGAAGATATTGGT TTAAGTCGTTTTCCAAATCAAGATGTTGACTTCAAGGTCTTGATTACATC ACGGGACCAATCAGTTTGCACTGAGATGGGAGTTAAAGCTGATTTAGTTC TCAAGGTGAGTGTCCTGGAGGAAGCGGAAGCACACAGTTTGTTCCTCCAA TTTTTAGAACCTTCTGATGATGTCGATCCTGAGCTCAATAAAATCGGAGA AGAAATTGTAAAGAAGTGTTGCAGACTACCCATTGCTATCAAAACCATGG CCTGAACTCTTAGAAGTAAAAGTAAGGATACATGGAAGAATGCCCTTTCT CGTTTACAACACCATGACATTAACACAATTGCGTCTACTGTTTTCCAAAC

TAGCTATGACAATCTCGAAGACGAGGTGACTAAAGCTACTTTTTTGCTTT GTGGTTTATTTCCGGAGGACTTCAATATTCCTACCGAGGACCTATTGAGG TATGGATGGGGATTGAAGTTATTCAAGGAAGTAGATACTATACGAGAAGC AAGATCCAAGTTGAAAGCCTGCATTGAGCGGCTCATGCATACCAATTTGT TGATCGAAGGTGATGATGTTAGGTACGTTAAGATGCATGATCTGGTGCGT GCTTTTGTTTTGGATATGTTTTCTAAAGCCGAGCATGCATCTATTGTCAA CCATGGTAGTAGTAAGCCAAGGTGGCCTGAAACTGAAAGTGATGTGAGCT CCTCTTGCAAAAGAATTTCATTAACATGCAAGGGTNTG

RG2U deduced polypeptide sequence (SEQ ID NO: 129)

ALCGMGGVGKTTVMKKLKEVVVGKKLFNHYVEAVIGEKTDPIAIQQAVAEYLGIS LTETTKPARTDKLRTWFANNSNGGKKKFLVILDDVWQPVDLEDIGLSRFPNQDVD FK\XITSRDQSVCTEMGVKADLVLKVSVLEEAEAHSLFLQFLEPSDDVDPELNKIGE EIVKKCCRLPIAIKTMA.TLRSKSKDTWKNALSRLQHHDINTIASTVFQTSYDNLEDE VTKATFLLCGLFPEDFNIPTEDLLRYGWGLKLFKEVDTIREARSKLKACIERLMHTN LLIEGDDVRYVKMHDLVRAFVLDMFSKAEHASIVNHGSSKPRWPETESDVSSSCKR- ISLTCKG?

RG2V polynucleotide sequence (SEQ ID NO: 130) CTGTGGAAGACACGAATGATSAAGAAGCTGAAGGAGGTCGTGGAACAAAA GAAAATGTTCAATATTATTGTTCAAGTGGTCATAGGAGAGAAGACAAACC CTATTGCTATTCAGCAAGCTGTAGCAGATTACCTCTCTATTGAGCTGAAA GAAAACACTAAAGAAGCAAGAGCTGATAAGCTTCGTNAATGGTTCGAGGA CGATGGAGGAAAGAATAAGTTCCTTGTAATACTTGATGATGTATGGCAGT TTGTCGATCTTGAAGATATTGGTTTAAGTCCTCTGCCAAATAAAGGTGTC AACTTCAAGGTCTTGTTGACGTTAAGAGATTCACATGTTTGCACTCTGAT GGGAGCTGAAGCCAATTCAATTCTCAATATAAAAGTTTTAAAAGATGTTN AAGGACAAAGTTTGTTCCGCCAGTTTGCTAAAAATGCAGGTGATGATGAC CTGGATCCTGCTTTCAATGGGATAGCAGATAGTATTGCAAGTAGATGTCA AGGTTTGCCCATTGCCATCAAAACCATTGCCTTAAGTCTTAAAGGTAGAA

GCAAGCCTGCGTGGGACCATGCGCTTTCTCGTTTGGAGAACCATAAGATT GGTAGTGAAGAAGTTGTGCGTGAAGTTTTTAAAATTAGCTATGACAATCT CCAAGATGAGGTTACTAAATCTATTTTTWTACTTTGTGCTTTATTTCCTG AAGATTTTGATATTCCTATTGAGGAGTTGGTGAGGTATGGGTGGGGCTTG AAATTATTTATAGAAGCAAAAACTATAAGAGAAGCAAGAAACAGGCTCAA CACCTGCACTGAGCGGCTTAGGGAGACAAATTTGTTATTTGGAAGTGATG ACATTGGATGCGTCAAGATGCACGATGTGGTGCGTGATTTTGTTTGGTAT ATATTCTCAGAAGTCCAGCACGCTTCAATTGTCAACCATGGTAATGTGTC AGAGTGGCTAGAGGAAAATCATAGCATCTACTCTTGTAAAAGAATTTCAT TAACATGCAAGGGTATGTCTGAGTTTCCCAAAGACCTCAAATTTCCAAAC

CTTTCAATTTTGAAACTTATGCATGGAGATAAGTCGNTGAGCTTTCCTGA AGACTTTTATGGAAAGATGGAAAAGGTTCAGGTAATATCATATGATAAAT TGATGTATCCATTGCTTCCCTCATCACTTGAATGCTCCACTAACGTTCGA GTGCTTCATCTCCATTATTGTTCATTAAGGATGTTTGATTGCTCTTCAAT TGGTAATCTTCTCAACATGGAAGTGCTCAGCTTTGCTAATTCTAACATTG AATGGTTACCATCTACAATTGGAAATTTGAAGAAGCTAAGGCTACTAGAT TTGACAAATTGTAAAGGTCTTCGTATAGATAATGGTGTCTTAAAAAATTT GGTCAAACTTGAAGAGCTTTATATGGGTGTTAATGTCCGTATGGACCAGG CCGT

RG2V deduced polypeptide sequence (SEQ ID NO:131)

LWKTRM?iαXKEVVEQIv_KMFNIIVQVVIGEKTNPIAIQQAVADYLSIELKENTKEAR ADKLR7WFEDDGGKNKFLVILDDVWQFVDLEDIGLSPLPNKGVNFKVLLTLRDSH VCTLMGAEANSILNIKVLKDV7GQSLFRQFAKNAGDDDLDPAFNGIADSIASRCQGL PIAIKTIALSLKGRSKPAWDHALSRLENHKIGSEEVVREVFKISYDNLQDEVTKSIF7L

CALFPEDFDIPIEELVRYGWGLKLFIEAKTIREARNRLNTCTERLRETNLLFGSDDIG CVKMHDVVRDFVWYIFSEVQHASIVNHGNVSEWLEENHSIYSCKRISLTCKGMSEF - PKDLKFPNLSILKLMHGDKS7SFPEDFYGKMEKVQVISYDKLMYPLLPSSLECSTNV RVLHLHYCSLRMFDCSSIGNLLNMEVLSFANSNIEWLPSTIGNLKKLRLLDLTNCKG LRIDNGVLKNLVKLEELYMGVNVRMDQAV

RG2W polynucleotide sequence (SEQ ID NO: 132)

TTGGGAAAGAGACAATGATGAAGAATTGAAAGAGGTTGTGGTTGAAAAGA

AAATGTTTAATCATTATGTGGAGGCGGTTATAGGGGAGAAGACGGACCCC

ATTGCTATTCAGCAAGCCGTTGCAGAGTACCTTGGTATAATTCTAACAGA AACCACTAAGGCAGCAAGAACCGATAAGCTACGTGCATGGCTTTCTGACA ATTCAGATGGAGGAAGAAAGAAGTTCCTAGTAATACTAGACGATGTATGG CATCCGGTTGATATGGAAGATATTGGTTTAAGTCGTTTCCCAAATCAAGG TGTCGACTTCAAGGTCTTGATTACATCACGGGACCAAGCTGTTTGCACTG AGATGGGAGTTAAAGCTGATTCAGTTATCAAGGTGAGTGTCCTAGAGGAA GCTGAAGC AC AAAGCTTATTCTGCCAACTTTGGGAACCTTCTGATGATGT

CGATCCTGAGCTCCATCAGATTGGAGAAGAAATTGTAAGGAAGTGTTGTG GTTTACCCATTGCAATAAAAACCATGGCCTGCACTCTTAGAAGTAAAAGC AAGGATACATGGAAGAATGCACTTTCTCGTTTACAACACCATGACATTAA CACAGTCGCGCCTACTGTTTTTCAAACCAGCTATGACAATCTCCAAGATG AGGTGACTGGAGATACTTTTTTGCTATGTGGTTTGTTTCCGGAGGACTTC

GATATTCCTACTGAAGACTTATTGAAGTATGGATGGGGCTTAAAATTATT CAAGGGAGTGGATTCTGTAAGAGAAGCAAGATACCAGTTGAACGCCTGCA TTGAGCGGCTCGTGCATACCAATTTGTTGATTGAAAGTGATGTTGTTGGG TGCGTCAAGTTGCACGATCTGGTGCGTGCTTTTATTTTGGATATGTTTTG TAAAGCGGAGCATGCTTCGATTGTCAACCATGGTAGTAGTAAGCCTGGGT GGCCTGAAACTGAAAATGATGTGATCAGGACCTCCTGCAAAAGAATCTCA TTAACATGCAAGGGTATGATTGAGTTTTCTAGTGACCTCAAGTTTCCAAA TGTCTTGATTTTAAAACTTATGCATGGAGATAAGTCGCTAAGGTTT

RG2W deduced polypeptide sequence (SEQ ID NO: 133)

WERDNDEELKEVVVEKKMFNHYVEAVIGEKTDPIAIQQAVAEYLGIILTETTKAAR TDKLRAWLSDNSDGGRKKFLVILDDVWHPVDMEDIGLSRFPNQGVDFKVLITSRD QAYCTEMGVKADSVIKVSVLEEAEAQSLFCQLWEPSDDVDPELHQIGEEIVRKCCG LPLAIKTMACTLRSKSKDTWKNALSRLQHHDINTVAPTVFQTSYDNLQDEVTGDTF LLCGLFPEDFDIPTEDLLKYGWGLKLFKGVDSVREARYQLNACIERLVHTNLLIESD WGCVKLHDLVRAFILDMFCKAEHASIVNHGSSKPGWPETENDVIRTSCKRISLTCK GMTEFSSDLKFPNVLILKLMHGDKSLRF

RG5 polynucleotide sequence (SEQ ID NO: 134) GGGGGGGTGGGGAAGNCGACTCTAGCCCAGAAGNTCTATAATGACCATAA AATAAAAGGAAGCTTTAGTAAACAAGCATGGATCTGTGTTTCTCAACAAT ATTCTGATATTTCAGTTTTGAAAGAAGTCCTTCGGAACATCGGTGTTGAT

TATAAGCATGATGAAACTGTTGGAGAACTTAGCAGAAGGCTTGCAATAGC

TGTCGAAAATGCAAGTTTCTTTCTTGTGTTGGATGATATTTGGCAACATG

AGGTGTGGACTAATTTACTCAGAGCCCCATTAAACACTGCAGCTACAGGA

ATAATTCTAGTAACAACTCGTAATGATACAGTTGCACGAGCAATTGGGGT

GGAAGATATTCATCGAGTAGAATTGATGTCAGATGAAGTAGGATGGAAAT

TGCTTTTGAAGAGTATGAACATTAGCAAAGAAAGTGAAGTAGAAAACCTA

CGAGTTTTAGGGGTTGACATTGTTCGTTTGTGTGGTGGCCTCCCCCTAGC

CTT

RG5 deduced polypeptide sequence (SEQ ID NO: 135)

GGVGKTTLAQK7YNDHKIKGSFSKQAWICVSQQYSDISVLKEVLRNIGVDYKHDET VGELSRRLAIAVENASFFLVLDDIWQHEVWTNLLRAPLNTAATGIILVTTRNDTVA RAIGVEDIHRVELMSDEVGWKLLLKSMNISKESEVENLRVLGVDIVRLCGGLPLAL

RG7 polynucleotide sequence (SEQ ID NO: 136)

GGTGGGGTTGGGAAGACAACGGGCACAAGGAGGCGACTGCCAATACTTCC

GACTTTTATTCATAGAGATGACGAGTCTTATTTTCCTACTACTATAGGGA

GGATATTTGGTTGCGCGAGACGATTCATTGCGCGAAGGGATTCTATCCTT CTTTTTTTCCGCGAAGACTTCGTTCCGGAGGACGGGCTATATTCCCTTTA ATATTAGTCTAGCCCAGTCTAGGCCAACCATATGGCGATGCGGTAGACCT CCCAGAGATAGATACTTGATCTTAGAGGATTCACACGTTCAATGGTGGAA ACTTAAGGAACCGGCTAAGAGTGACTAAACGGAAAAACCCTATTCATTCC ATAGCCTCATCCGGTCGAGGCATTAAACAATCCATCCCAATCCTCTTTCC TTTGGTCTACTCTAATGATGTGCCCGTTCGTTGGTGGAATATCTCTTTAT ACCGACGATTTATATGGGGATTGCCACTAGCGTTG

The above examples are provided to illustrate the invention but not to limit its scope. Other variants of the invention will be readily apparent to one of ordinary skill in the art and are encompassed by the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference.

Claims

WHAT TS CLAIMED IS:

1. An isolated nucleic acid construct comprising an RG polynucleotide which encodes an RG polypeptide having at least 60% sequence identity to an RG polypeptide from an RG family selected from the group consisting of: an RG1 polypeptide, an RG2 polypeptide, an RG3 polypeptide, an RG4 polypeptide, an RG5 polypeptide, and an RG7 polypeptide.

2. The nucleic acid construct of claim 1, wherein the RG polynucleotide encodes an RG polypeptide comprising an leucine rich region (LRR).

3. The nucleic acid construct of claim 1 , wherein the RG polynucleotide encodes an RG polypeptide comprising a nucleotide binding site (NBS).

4. The nucleic acid construct of claim 1, wherein the polynucleotide is a full length gene.

5. The nucleic acid construct of claim 1, wherein the further encodes a fusion protein.

6. The nucleic acid construct of claim 1, wherein the RG1 polypeptide is encoded by an RG1 polynucleotide sequence.

7. The nucleic acid construct of claim 6, wherein the RG1 polypeptide is encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NO: l (RGIA), SEQ ID NO:2 (RGIB), SEQ ID NO: 3 (RGIC), SEQ ID NO:4 (RGID), SEQ ID NO:5 (RGIE), SEQ ID NO:6 (RGIF), SEQ ID NO:7 (RGIG), SEQ ID NO:8 (RGIH), SEQ ID

NO:9 (RG1I), and SEQ ID NO: 10 (RGIJ).

8. The nucleic acid construct of claim 1, wherein the RG2 polypeptide is encoded by an RG2 polynucleotide sequence.

9. The nucleic acid construct of claim 8, wherein the RG2 polypeptide is encoded by a polynucleotide sequence selected from the group consisting of: SEQ ID NO:21 (RG2A); SEQ ID NO:23 (RG2B); SEQ ID NO:25 (RG2C); SEQ ID NO:27 (RG2D); SEQ ID NO:29 (RG2E); SEQ ID NO:31 (RG2F); SEQ ID NO:33 (RG2G); SEQ ID NO:35 (RG2H); SEQ ID NO:37 (RG2I); SEQ ID NO:39 (RG2J); SEQ ID NO:41 (RG2K); SEQ ID NO:43 (RG2L); SEQ ID NO:45 (RG2M); SEQ ID NO:87 (RG2A); SEQ ID NO:89 (RG2B); SEQ ID NO:91 (RG2C); SEQ ID NO:93 (RG2D) and SEQ ID NO:94 (RG2D);

SEQ ID NO:96 ( RG2E); SEQ ID NO:98 (RG2F); SEQ ID NO:100 (RG2G); SEQ ID NO: 102 (RG2H); SEQ ID NO: 104 (RG2I); SEQ ID NO: 106 (RG2J) and SEQ ID NO: 107 (RG2J); SEQ ID NO:109 (RG2K) and (SEQ ID NO:l 10 (RG2K); SEQ ID NO:l 12 (RG2L); SEQ ID NO:l 14 (RG2M); SEQ ID NO:l 16 (RG2N); SEQ ID NO:l 18 (RG2O); SEQ ID NO:120 (RG2P); SEQ ID NO:122 (RG2Q); SEQ ID NO:124 (RG2S); SEQ ID NO:126 (RG2T); SEQ ID NO:128 (RG2U); SEQ ID NO:130 (RG2V); and, SEQ ID NO:132 (RG2W).

10. The nucleic acid construct of claim 1, wherein the RG3 polypeptide is encoded by an RG3 polynucleotide sequence.

11. The nucleic acid construct of claim 10, wherein the RG3 polypeptide is encoded by a polynucleotide sequence as set forth in SEQ ID NO: 68.

12. The nucleic acid construct of claim 1, wherein the RG4 polypeptide is encoded by an RG4 polynucleotide sequence.

13. The nucleic acid construct of claim 12, wherein the RG4 polypeptide is encoded by a pol nucleotide sequence as set forth in SEQ ID NO: 69.

14. The nucleic acid construct of claim 1, wherein the RG5 polypeptide is encoded by an RG5 polynucleotide sequence.

15. The nucleic acid construct of claim 14, wherein the RG5 polypeptide is encoded by a polynucleotide sequence as set forth in SEQ ID NO: 134.

16. The nucleic acid construct of claim 1, wherein the RG7 polypeptide is encoded by ^ΓÇó an RG7 polynucleotide sequence.

17. The nucleic acid construct of claim 16, wherein the RG7 polypeptide is encoded by a polynucleotide sequence as set forth in SEQ ID NO: 136.

18. The nucleic acid construct of claim 1, further comprising a promoter operably linked to the RG polynucleotide.

19. The nucleic acid construct of claim 18, wherein the promoter is a plant promoter.

20. The nucleic acid construct of of claim 19, wherein the plant promoter is a disease resistance promoter.

21. The nucleic acid construct of claim 19, wherein the plant promoter is a lettuce promoter.

22. The nucleic acid construct of claim 18, wherein the promoter is a constitutive promoter.

23. The nucleic acid construct of claim 18, wherein the promoter is an inducible promoter.

24. The nucleic acid construct of claim 18, wherein the promoter is a tissue-specific promoter.

25. A nucleic acid construct comprising a promoter sequence from an RG gene linked to a heterologous polynucleotide.

26. A transgenic plant comprising a recombinant expression cassette comprising a promoter operably linked to an RG polynucleotide.

27. The transgenic plant of claim 26, wherein the plant promoter is a plant promoter. -

28. The transgenic plant of claim 26, wherein the plant promoter is a viral promoter.

29. The transgenic plant of claim 26, wherein the plant promoter is a heterologous promoter.

30. The transgenic plant of claim 26, wherein the plant is lettuce.

31. The transgenic plant of claim 26, wherein the RG polynucleotide is selected from the group consisting of SEQ ID NO: l (RGIA), SEQ ID NO:2 (RGIB), SEQ ID NO: 3 (RGIC), SEQ ID NO:4 (RGID), SEQ ID NO:5 (RGIE), SEQ ID NO:6 (RGIF), SEQ ID NO:7 (RGIG), SEQ ID NO:8 (RGIH), SEQ ID NO:9 (RG1I), and SEQ ID NO: 10 (RGIJ).

32. The transgenic plant of claim 26, wherein the RG polynucleotide is selected from the group consisting of SEQ ID NO:21 (RG2A); SEQ ID NO:23 (RG2B); SEQ ID NO:25 (RG2C); SEQ ID NO:27 (RG2D); SEQ ID NO:29 (RG2E); SEQ ID NO:31 (RG2F); SEQ ID NO:33 (RG2G); SEQ ID NO:35 (RG2H); SEQ ID NO:37 (RG2I); SEQ ID NO:39 (RG2J); SEQ ID NO:41 (RG2K); SEQ ID NO:43 (RG2L); SEQ ID NO:45 (RG2M); SEQ

ID NO:87 (RG2A); SEQ ID NO:89 (RG2B); SEQ ID NO:91 (RG2C); SEQ ID NO:93 (RG2D) and SEQ ID NO:94 (RG2D); SEQ ID NO:96 ( RG2E); SEQ ID NO:98 (RG2F); SEQ ID NO:100 (RG2G); SEQ ID NO:102 (RG2H); SEQ ID NO:104 (RG2I); SEQ ID NO: 106 (RG2J) and SEQ ID NO: 107 (RG2J); SEQ ID NO: 109 (RG2K) and (SEQ ID NO:l 10 (RG2K); SEQ ID NO:112 (RG2L); SEQ ID NO:114 (RG2M); SEQ ID NO:l 16 (RG2N); SEQ ID NO:l 18 (RG2O); SEQ ID NO: 120 (RG2P); SEQ ID NO: 122 (RG2Q); SEQ ID NO: 124 (RG2S); SEQ ID NO: 126 (RG2T); SEQ ID NO: 128 (RG2U); SEQ ID NO: 130 (RG2V); and, SEQ ID NO: 132 (RG2W).

33. The transgenic plant of claim 26, wherein the RG polynucleotide is selected from the group consisting of SEQ ID NO:68 (RG3) and SEQ ID NO:69 (RG4).

34. The transgenic plant of claim 26, wherein the RG polynucleotide comprises a sequence as set forth in SEQ ID NO: 134 (RG5).

35. The transgenic plant of claim 26, wherein the RG polynucleotide comprises a sequence as set forth in SEQ ID NO: 136 (RG7).

36. The transgenic plant of claim 26, wherein the RG polynucleotide encodes an RG1 polypeptide selected from the group consisting of SEQ ID NO: 11 (RGIA), SEQ ID NO: 12 (RGIB), SEQ ID NO: 13 (RGIC), SEQ ID NO: 14 (RGID), SEQ ID NO: 15 (RGIE), SEQ ID NO: 16 (RGIF), SEQ ID NO: 17 (RGIG), SEQ ID NO: 18 (RGIH), SEQ ID NO: 19 (RG1I), and SEQ ID NO:20 (RGIJ).

37. The transgenic plant of claim 26, wherein the RG polynucleotide encodes an RG2 polypeptide selected from the group consisting of SEQ ID NO:22 and SEQ ID NO:41 (RG2A); SEQ ID NO:24 and SEQ ID NO:42 (RG2B); SEQ ID NO:43 (RG2C); SEQ ID

NO:44 (RG2D); SEQ ID NO:45 (RG2E); SEQ ID NO:46 (RG2F); SEQ ID NO:47 (RG2G); SEQ ID NO:48 (RG2H); SEQ ID NO:49 (RG2I); SEQ ID NO:50 (RG2J); SEQ ID NO:51 (RG2K); SEQ ID NO:52 (RG2L); SEQ ID NO:53 (RG2M); SEQ ID NO:88 (RG2A); SEQ ID NO:90 (RG2B); SEQ ID NO:92 (RG2C); SEQ ID NO:95 (RG2D); SEQ ID NO:97 (RG2E); SEQ ID NO:99 (RG2F); SEQ ID NO:101 (RG2G); SEQ ID NO:103

(RG2H); SEQ ID NO: 105 (RG2I); SEQ ID NO: 108 (RG2J); SEQ ID NO:l 11 (RG2K); SEQ ID NO:l 13 (RG2L); SEQ ID NO:l 15 (RG2M); SEQ ID NO:l 17 (RG2N); SEQ ID NO:l 19 (RG2O); SEQ ID NO:121 (RG2P); SEQ ID NO:123 (RG2Q); SEQ ID NO:125 (RG2S); SEQ ID NO: 127 (RG2T); SEQ ID NO: 129 (RG2U); SEQ ID NO:131 (RG2V); and, SEQ ID NO:133 (RG2W).

38. The transgenic plant of claim 26, wherein the RG polynucleotide encodes an RG3 polypeptide with a sequence as set forth by SEQ ID NO: 138.

39. The transgenic plant of claim 26, wherein the RG polynucleotide encodes an RG4 polypeptide with a sequence as set forth by SEQ ID NO: 139.

40. The transgenic plant of claim 26, wherein the RG polynucleotide encodes an RG5 ^' polypeptide with a sequence as set forth by SEQ ID NO: 135.

41. A method of enhancing disease resistance in a plant, the method comprising introducing into the plant a recombinant expression cassette comprising a promoter functional in the plant and operably linked to an RG polynucleotide sequence.

42. The method of claim 41 , wherein the plant is a lettuce plant.

43. The method of claim 41, wherein the RG polynucleotide encodes an RG polypeptide selected from the group consisting of SEQ ID NO:22 and SEQ ID NO:41 (RG2A); SEQ ID NO:24 and SEQ ID NO:42 (RG2B); SEQ ID NO:43 (RG2C); SEQ ID NO:44 (RG2D); SEQ ID NO:45 (RG2E); SEQ ID NO:46 (RG2F); SEQ ID NO:47 (RG2G); SEQ ID NO:48 (RG2H); SEQ ID NO:49 (RG2I); SEQ ID NO:50 (RG2J); SEQ ID NO:51 (RG2K); SEQ ID NO:52 (RG2L); SEQ ID NO:53 (RG2M); SEQ ID NO:88 (RG2A); SEQ

ID NO:90 (RG2B); SEQ ID NO:92 (RG2C); SEQ ID NO:95 (RG2D); SEQ ID NO:97 (RG2E); SEQ ID NO:99 (RG2F); SEQ ID NO: 101 (RG2G); SEQ ID NO: 103 (RG2H); SEQ ID NO:105 (RG2I); SEQ ID NO:108 (RG2J); SEQ ID NO:l 11 (RG2K); SEQ ID NO:l 13 (RG2L); SEQ ID NO:l 15 (RG2M); SEQ ID NO:l 17 (RG2N); SEQ ID NO:l 19 (RG2O); SEQ ID NO:121 (RG2P); SEQ ID NO:123 (RG2Q); SEQ ID NO:125 (RG2S); SEQ ID

NO: 127 (RG2T); SEQ ID NO:129 (RG2U); SEQ ID NO:131 (RG2V); and, SEQ ID NO:133 (RG2W).

44. The method of claim 41 , wherein the RG polynucleotide encodes an RG polypeptide selected from the group consisting of SEQ ID NO: 138 (RG3); SEQ ID NO: 139 (RG4); and

SEQ ID NO: 135 (RG5).

45. The method of claim 41, wherein the promoter is a tissue-specific promoter or a plant disease resistance promoter.

46. The method of claim 41 , wherein the promoter is a constitutive promoter or an inducible promoter.

47. A method of detecting RG resistance genes in a nucleic acid sample, the method comprising: contacting the nucleic acid sample with an RG polynucleotide to form a hybridization complex; and, wherein the formation of the hybridization complex is used to detect the RG resistance gene in the nucleic acid sample.

48. The method of claim 47, wherein the RG polynucleotide is an RGl polynucleotide.

49. The method of claim 47, wherein the RG polynucleotide is an RG2 polynucleotide.

50. The method of claim 47, wherein the RG polynucleotide is an RG3 polynucleotide, an RG4 polynucleotide, an RG5 polynucleotide or an RG7 polynucleotide.

51. The method of claim 47, wherein the RG resistance gene is amplified prior to the step of contacting the nucleic acid sample with the RG polynucleotide.

52. The method of claim 51, where the RG resistance gene is amplified by the polymerase chain reaction.

53. The method of claim 47, wherein the RG polynucleotide is labeled.

54. An RG polypeptide having at least 60% sequence identity to a polypeptide selected from the group consisting of: an RGl polypeptide, an RG2 polypeptide, an RG3 polypeptide, an RG4 polypeptide, an RG5 polypeptide, and an RG7 polypeptide.