CN110129340A - 寨卡病毒mr766毒株的感染性克隆及其应用 - Google Patents

寨卡病毒mr766毒株的感染性克隆及其应用 Download PDF

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CN110129340A
CN110129340A CN201810132277.8A CN201810132277A CN110129340A CN 110129340 A CN110129340 A CN 110129340A CN 201810132277 A CN201810132277 A CN 201810132277A CN 110129340 A CN110129340 A CN 110129340A
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易志刚
袁正宏
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Abstract

本发明属于基因工程和医药领域，涉及稳定的、基于寨卡病毒MR766毒株的一系列cDNA克隆。本发明的cDNA包括寨卡病毒MR766毒株的核酸序列和一个低拷贝质粒骨架；寨卡病毒MR766毒株的核酸序列包括寨卡病毒MR766毒株5′到3′正向极性序列，病毒5′及3′非编码区及一个编码病毒蛋白的开放阅读框，所述的3′非编码区不包括SEQ ID NO 13所示的序列；寨卡病毒MR766毒株的核酸序列中，5′非编码区、编码病毒蛋白的开放阅读框、3′非编码区依次排列。本发明还包括其衍生克隆、突变克隆；以及利用这些克隆产生的各种载体、重组病毒、亚单位病毒颗粒；以及这些病毒在疫苗的开发及诊断试剂方面的应用。

Description

寨卡病毒MR766毒株的感染性克隆及其应用
技术领域
本发明属于基因工程和医药领域，涉及寨卡病毒MR766毒株的感染性cDNA克隆的构建，以及利用此cDNA克隆及其衍生克隆在病毒治疗，疫苗研发，病毒诊断方面的应用。
背景技术
现有技术公开了寨卡病毒(Zika virus)为黄病毒科(Flaviviridae)黄病毒属(flavivirus)家族成员，最早于1947年在乌干达猴子身上分离鉴定，随后发现该病毒感染人类。该病毒主要集中于非洲大陆，直到1980年代在东南亚发现，随后2007年在Micronesia(密克罗尼西亚联邦)发现，2014年在美洲发现至今有全球蔓延趋势(Saiz et al.FrontMicrobiol.2016,7:496)。寨卡病毒与人类幼儿小头症(microcephaly)高度相关(Driggerset al.N Engl J Med.2016,374(22):2142)。寨卡病毒为黄病毒科(Flaviviridae)黄病毒属(flavivirus)家族成员，为单正链RNA病毒。病毒基因组编码一单一开放阅读框(Openreading frame,ORF)，两端由非编码区(non-translated region,NTR)5’-NTR及3’-NTR组成。病毒编码的开放阅读框翻译后被宿主蛋白酶和病毒自身编码的蛋白酶切割加工成单个病毒蛋白。其中包括组成病毒颗粒的结构蛋白C,prM和E及负责病毒复制的非结构蛋白NS1,NS2A,NS2B,NS3,NS4A,2K,NS4B及NS5。病毒的非结构蛋白特异性识别病毒基因组末端的非编码区，利用病毒自身编码的RNA依赖的RNA聚合酶(RNA-dependent RNA polymerase,RdRp)NS5起始病毒复制。除NS5外，其他的病毒非结构蛋白均参与在宿主内质网膜上组装成病毒的复制复合体来完成病毒复制(Lindenbach,et al.Fields Virology.2007,Fifthedition；Welsh,et al.Cell Host Microbe.2009,5:365)。病毒的结构蛋白及非结构蛋白共同参与，特异识别病毒基因组上的RNA序列，包装病毒复制产生的子代基因组，产生子代病毒颗粒并释放到胞外(Lindenbach,et al.Fields Virology.2007,Fifthedition)。
寨卡病毒MR766毒株为由1947年最早从猴子分离到的血清于老鼠传代而来(DICKet al.Trans R Soc Trop Med Hyg.1952,46(5):509；DICK et al.Trans R Soc Trop MedHyg.1952,46(5):521)。其序列最早于2007年测定并公布(Kuno G et al.ArchVirol.2007,152(4):687)。
单正链RNA病毒的感染性克隆：单正链(positive-strand)RNA病毒的基因组RNA被释放，进入宿主细胞细胞浆后可以直接作为mRNA模版进行翻译；翻译产生的病毒非结构蛋白招募病毒基因组形成复制复合物起始病毒的基因复制及生活周期。因此单正链RNA病毒的基因组RNA具有感染性，经导入到宿主细胞后，可以完全起始病毒的整个生活周期(Racaniello,et al.Science.1981,214(4523):916)。构建感染性克隆的方法通常采用病毒感染的细胞总RNA作为模版，逆转录成互补DNA(cDNA)，然后克隆病毒片段入克隆载体形成病毒的感染性克隆。构建的感染性克隆利用体外转录产生完整的病毒RNA，然后转染病毒RNA入宿主细胞来起始病毒生活周期，产生子代病毒。或者构建的感染性克隆如果带有真核细胞启动子，可以直接转染质粒，由宿主细胞的RNA聚合酶转录出病毒全长RNA，进而起始病毒生活周期，产生子代病毒。
寨卡病毒感染性克隆(infectious cDNA clone)：目前报道的多株寨卡病毒感染性克隆大多采用从病毒感染的细胞中抽提细胞总RNA，然后通过逆转录，得到病毒cDNA片段，再进行重组形成病毒全长感染性克隆(Shan,et al.Cell Host Microbe.2016,19(6):891-900；Tsetsarkin,et al.MBio.2016,7(4):e01114-16；Schwarz,et al.mSphere.2016,1(5):e00246-16；Weger-Lucarelli,et al.J Virol.2016,91(1):e01765-16；Widman,etal.MBio.2017,8(2):e02014-16；Deng,et al.J Gen Virol.2017,98(7):1739-1743；Liu,et al.J Virol.2017,JVI.00484-17)。Setoh等根据已报道的一例小头症患者中分离的寨卡病毒的序列，通过合成的从头合成的办法得到了全长的感染性克隆(Setoh,etal.mSphere.2017,2(3):e00190-17)。
RNA病毒的复制由其自身编码的RNA依赖的RNA聚合酶(RNA-dependent RNApolymerase,RdRp)进行复制。病毒RdRp在复制过程中由于缺失纠错能力，导致病毒复制过程中产生大量突变(Lauring,et al.PLoS Pathog.2010,6(7):e1001005)，因此经培养细胞传代的病毒与人体分离的母病毒(Parental virus)相比可能存在多处突变(Schwarz,etal.mSphere.
2016,1(5):e00246-16)，其中有些突变可能导致毒力的减弱(Shan,et al.CellHost Microbe.2016,19(6):891-900)。同时在利用逆转录酶构建感染性克隆的过程中由于逆转录酶的纠错能力较差，同样会引入突变。因此，得到与人体分离的母病毒(Parentalvirus)序列最接近的病毒全序列，利用其构建感染性克隆得到的子代病毒最大程度保持与母病毒一致的复制特性及致病特性。此类感染性克隆作为研究病毒复制与致病机制及研发疫苗的开发最具有价值。构建黄病毒属家族成员感染性克隆的一个挑战是病毒序列较难克隆，且构建成功的克隆可能也存在在繁殖扩增过程中不稳定等情况。构建寨卡病毒感染性克隆同样存在类似问题。目前采用的方法包括使用低拷贝质粒骨架(Shan,et al.CellHost Microbe.2016,19(6):891)或采用在病毒特定序列中加入内含子序列来降低病毒序列的毒性等办法(Schwarz,et al.
mSphere.2016,1(5):e00246-16；Liu,et al.J Virol.2017,JVI.00484-17)。
MR766毒株是寨卡病毒的原始毒株(prototype)，目前流行的毒株均由MR766毒株通过突变演化而来。MR766毒株在培养细胞中表现出比其他毒株更强的复制能力(Xu,etal.Nat Med.2016,22(10):1101)，也能感染神经组织(Qian,et al.Cell.2016,165(5):1238)及小鼠模型(Lazear,et al.Cell Host Microbe.2016,19(5):720)。
发明内容
本发明要解决的技术问题是提供稳定的、基于寨卡病毒MR766毒株的感染性cDNA克隆。
本发明要解决的另一个技术问题是提供稳定的、基于寨卡病毒MR766毒株的减毒cDNA克隆。
本发明要解决的再一个技术问题是提供针对寨卡病毒MR766毒株的cDNA克隆的应用。
本发明提供了一个稳定的、基于寨卡病毒MR766毒株的感染性cDNA克隆，包括寨卡病毒MR766毒株的核酸序列和一个低拷贝质粒骨架；寨卡病毒MR766毒株的核酸序列包括寨卡病毒MR766毒株5′到3′正向极性序列(positive-sense)，病毒5′及3′非编码区及一个编码病毒蛋白的开放阅读框，所述的3′非编码区不包括SEQ ID NO 13(CTGGA GACTA GCTGTGAATC TCCAG CAGA)所示的序列；寨卡病毒MR766毒株的核酸序列中，5′非编码区、编码病毒蛋白的开放阅读框、3′非编码区依次排列。
或者，在所述的cDNA的3′非编码区加入SEQ ID NO 13所示的序列，形成完整的寨卡病毒MR766毒株的感染性cDNA克隆。
较好的，在上述的cDNA中插入报道基因荧光素酶Gluc编码序列，并在报道基因荧光素酶Gluc编码序列中删除SEQ ID NO 13所示的序列。
也可以在上述的cDNA中插入荧光蛋白Venus编码序列，并在荧光蛋白Venus编码序列中剔除SEQ ID NO 13所示的序列。
本发明还包括全长感染性克隆序列的嵌合病毒感染性克隆及其序列，能产生全长感染性克隆序列的双链DNA(double stranded DNA)，正向cDNA(positive-sense cDNA)或负向cDNA(negative-sense cDNA)。
或者，在上述的DNA中插入报道基因荧光素酶Gluc编码序列或者荧光蛋白Venus编码序列。
本发明还包括使用上述DNA的序列构建的寨卡病毒RNA复制子，以这些克隆为基础，通过改变核酸的手段得到的突变病毒克隆(adapted virus)，减毒病毒克隆(live-attenuated virus)，复制缺陷病毒克隆(defective virus)及复制性的非感染性克隆(replication-competent non-infectious virus)等衍生物(derivative)，如包括缺失结构蛋白的亚基因组复制子。
本发明还包括使用上述DNA制备的重组病毒。
在本发明的一个优选实施例中，寨卡病毒MR766毒株的核酸序列如SEQ ID NO 2所示，低拷贝质粒骨架的序列如SEQ ID NO 3所示，开放阅读框病毒编码蛋白的序列如SEQ IDNO 4所示，报道基因荧光素酶Gluc编码序列如SEQ ID NO 5所示，荧光蛋白Venus编码序列如SEQ ID NO 6所示。相应的，寨卡病毒MR766毒株的感染性cDNA克隆的核酸序列如SEQ IDNO 1所示。
本发明提供了一种质粒，能通过体外转录产生含有全长Zika病毒MR766毒株全长感染性RNA的质粒。较好的，所述的质粒包括：
a)利用其他分离株的部分序列替换寨卡病毒全长感染克隆的部分序列得到的重组病毒克隆；
或者b)利用基因突变对寨卡病毒中的序列进行突变得到的突变病毒克隆；
或者c)由寨卡病毒经过适应性突变产生的减毒，复制非感染病毒及非复制性病毒等衍生克隆。
本发明还包括使用上述质粒制备的疫苗、病毒载体、病毒颗粒，以及检测病毒的方法。
本发明还包括使用上述述病毒制备抗寨卡病毒抗体的方法，使用减毒株免疫动物及分离抗寨卡病毒抗体的方法，使用该病毒筛选人抗体库的方法，使用该病毒进行的抗寨卡病毒药物的筛选的应用，检测寨卡病毒的试剂盒；以及，使用该病毒构建细胞系或者动物感染模型，用于药物筛选，或者感染体外培养的组织模型，用于药物筛选的方法。
本发明提供了一个稳定的、基于寨卡病毒MR766毒株的感染性cDNA克隆(核酸序列1)及其含有各类报道基因的衍生克隆(核酸序列5，核酸序列6)、及以其为母本构建的各种突变克隆(核酸序列7)。这些克隆产生的病毒RNA在细胞中能自行复制、产生子代病毒颗粒及表达报道基因；
本发明还包括利用这些克隆质粒为母本，通过分子生物学构建的各种重组病毒、亚单位病毒颗粒质粒；
本发明还包括利用这些克隆可以产生的各种重组病毒、亚单位病毒颗粒；
本发明还包括利用这些病毒或亚单位病毒颗粒用于疫苗的开发及诊断试剂；
本发明还包括利用此病毒或亚病毒单位质粒作为基因治疗载体或表达载体质粒及利用这些质粒所产生的病毒或亚病毒颗粒；
本发明还包括利用基于带有报道基因的病毒克隆产生的报道病毒用于抗病毒药物的研发等。
本发明根据公共数据库中公布的，利用高通量测序得到的寨卡病毒基因组全序列，采用化学合成的方法，分段、从头合成寨卡病毒MR766毒株的病毒基因组全序列，构建了稳定的、不依赖插入内含子序列的cDNA克隆。通过体外转录RNA、转染Vero细胞证实我们的cDNA克隆来源的病毒RNA能产生高滴度的寨卡病毒。进一步，本发明构建了含有报道基因Gluc(Gaussia luciferase)及Venus的重组病毒，并证实含有报道Gluc及Venus的重组病毒具有同野生克隆产生的病毒类似的病毒滴度。利用含有报道基因的病毒，本发明证实先前报道的能广谱调控黄病毒属家族成员的宿主蛋白DNAJC14，在过表达的情况下能抑制寨卡病毒的复制。最后发明本删除寨卡病毒MR766毒株3’UTR的一段保守序列后，其cDNA克隆产生的病毒相较与野生克隆产生的病毒，在Vero细胞中，其复制水平降低；其产生的子代病毒感染性降低。本发明还提供了所述的克隆在测试蛋白抗病毒方面效果的应用，利用本发明的寨卡病毒MR766毒株和减毒株，能够为疫苗和诊断试剂的开发提供依据；以及利用此病毒作为基因治疗载体或表达载体提供一种新的手段。
附图说明
图1:寨卡病毒MR766毒株的感染性cDNA克隆的构建
(A)感染性克隆构建策略；寨卡病毒全基因组模式图，两端黑色柱子分别表示5’-NTR及3’-NTR。病毒结构蛋白区域及非结构蛋白区域如图所示；病毒全长序列分成5段分别合成，其中第一段F1中含有SP6序列，第五段F5含有HDVr序列；合成的序列通过限制性内切酶依图所示依次连接入pACNR载体，得到全长克隆；(B)合成序列(上)与高通量序列比较(C7)；Insertion,插入突变；deletion，缺失突变；点突变用箭头表示；数字表示病毒基因组核酸位置；(C)含有报告基因的感染性克隆；报告基因：Gluc或Venus；黑色表示FMDV 2A片段；Ub表示泛素序列；C25表示通过突变的C基因末端序列。
图2:寨卡病毒MR766毒株感染性cDNA克隆产生病毒的复制能力及感染能力
(A)感染性克隆C7，含有报道基因Gluc的感染性克隆C7-Gluc及含有报道基因Venus的感染性克隆C7-Venus经体外转录后，病毒RNA通过电转导入到Vero细胞；在电转导后不同天数(dpe)，观察细胞的细胞病变情况及荧光蛋白Venus的表达情况；由于野生病毒(C7)电转后3天细胞出现明显病变，因此只有3dpe数据；(B)电转导后不同天数(dpe)收集细胞上清，利用空斑形成实验，在Vero细胞中对上清中的病毒进行滴度滴定。病毒感染产生的空斑如图所示。图中所示的细胞为不同病毒样品的同一稀释度感染所得；(C)利用空斑形成实验对来自电转导后不同天数(dpe)收集的细胞上清中病毒的滴定情况。
图3:含有报道基因Venus的重组病毒表达Venus的稳定性
(A)含有报道基因Venus的重组病毒C7-Venus的细胞上清(P1)以1:10稀释度重新感染新的Vero细胞，感染三天后细胞用荧光显微镜观察；新的含有C7-Venus重组病毒的细胞上清(P2)同上以1:10稀释度重新感染新的Vero细胞，感染三天后细胞用荧光显微镜观察；同上依次传代感染，观察感染细胞中Venus的表达情况；(B)利用流式细胞仪对(A)中病毒感染细胞进行分析。
图4:寨卡病毒MR766毒株减毒株感染性克隆的构建
(A)登革热病毒4(Dengue virus 4)的3’-NTR的预测二级结构；在减毒病毒中被删除的区域用虚线括出；(B)寨卡病毒MR766毒株的3’-NTR的预测二级结构；在相似于登革热病毒的结构中删除相似的长29nt的区域(用虚线括出)(delta29)；(C)C7-Gluc，C7-Gluc-GNN(NS5区域RdRp活性位点突变)及C7-Gluc去除3’-NTR的29nt的区域的质粒C7-Gluc-delta29体外转录后产生的RNA转染Vero细胞，在转染后不同时间点收集细胞，测定细胞中Gluc的表达水平来反映病毒复制能力；(D)或在转染后不同时间点收集细胞上清，重新感染新的Vero细胞，感染后3天测定细胞中Gluc的表达水平来反映分泌到细胞上清中病毒的感染能力。
图5:过表达宿主蛋白DNAJC14抑制寨卡病毒MR766的复制
(A)HEK293T细胞中分别转染HA-RFP(RFP)、HA-RFP-DNAJC14-NT1(RFP-NT1)及HA-RFP-DNAJC14-NT1CT1(RFP-NT1CT1)表达质粒，两天后感染寨卡病毒C7-Venus(MOI，1)，感染三天后收取细胞，用流式细胞仪检测细胞中的RFP及Venus信号；(B)计算在RFP细胞中感染有寨卡病毒(Venus)的细胞比例(Q2/(Q2+Q3)；(C)利用针对HA的抗体检测蛋白的表达情况；星号所指为目的蛋白条带。
具体实施方式
本发明的感染性克隆(SEQ ID NO 1)为一个由DNA序列构成的一个完整质粒(plasmid)。其中包含一个全长的寨卡病毒MR766毒株的核酸序列(SEQ ID NO 2)及一个低拷贝质粒骨架序列(SEQ ID NO 3)。质粒(plasmid)是以共价键结合的闭合双链DNA(doublestranded DNA)。其中包含一条与mRNA序列一致的一条有义链(positive-sense strand)及一条与之互补的反义链或负义链(negative-sense strand)。
本发明的感染性克隆(核酸序列1)中所包含的寨卡病毒MR766毒株的全长核酸序列(SEQ ID NO 2)包括病毒正链(positive sense)序列的5’末端的非翻译区(non-translated region,NTR)、一个开放阅读框(open reading frame,ORF)和3’末端非翻译区(3’-NTR)。在此感染性克隆中，病毒全长核酸序列5’末端含有一个SP6启动子(ATTTA GGTGACACTA TAGA)(SEQ ID NO 10)(图1A)，可以在体外由商品化的SP6转录试剂盒来转录病毒全长RNA；在病毒全长核酸序列3’末端含有一个具有自动剪切活性的核酶(Ribozyme)HDVr(Michael,et al.Eur.J.Biochem.1997,247:741)的序列(GGCCG GCATG GTCCC AGCCTCCTCG CTGGC GCCGG CTGGG CAACA TGCTT CGGC ATGGC GAATG GGAC)(SEQ ID NO 11)来转录后剪切产生精确的病毒3’末端(图1A)。此感染性克隆在体外经AfeI线性化后，由SP6转录试剂盒来转录出含有病毒全长RNA及其3’末端的HDVr RNA，后经HDVr RNA自身切割产生完整的与病毒全序列一致的病毒全长RNA。该体外产生的病毒RNA经电转或转染的方法导入到宿主细胞如Vero细胞后，病毒的RNA作为翻译模版，翻译其ORF，产生病毒多肽(蛋白序列4)；该病毒多肽经加工形成病毒结构蛋白及非结构蛋白，起始整个病毒生活周期，产生子代病毒。
由于基于编码的兼并性，通过改变密码子而不改变蛋白序列仍可以得到相同功能蛋白产物。本发明包括编码与“蛋白序列4”相同的其他核酸序列和感染性克隆。
MR766毒株在培养细胞中表现出比其他毒株更强的复制能力(Xu,et al.NatMed.2016,22(10):1101)，也能感染神经组织(Qian,et al.Cell.2016,165(5):1238)及小鼠模型(Lazear,et al.Cell Host Microbe.2016,19(5):720)。本发明的感染性克隆(核酸序列1)所产生的病毒在细胞中表现出很强的复制能力(图2)，可以用于感染体外培养的细胞系、神经组织、小鼠或猴等建立病毒感染的细胞模型及动物感染模型，用于药物的研发。
通过对感染性克隆(SEQ ID NO 1)进行改造，在病毒的特定区域(C区域，病毒基因组序列第181nt位置，包括C蛋白前25氨基酸)插入报道基因，可以构建带有报道基因的感染性克隆。该插入外源基因的区域被证实在黄病毒属的其他家族成员中可以成功被利用插入外源基因片段而不引起病毒致死突变(Schoggins,et al.Proc Natl Acad Sci.2012,109(36):14610)。本发明在此感染性克隆(SEQ ID NO 1)中插入报道基因荧光素酶Gluc及荧光蛋白Venus，分别构成带有Gluc的感染性克隆(SEQ ID NO 5)及带有Venus的感染性克隆(SEQ ID NO 6)(图1C)。报道基因Gluc或Venus首先与FMDV 2A片段及Ub泛素序列融合。其中FMDV 2A片段及Ub序列在翻译后可以自动切除(Schoggins,et al.Proc Natl AcadSci.2012,109(36):14610)。另外重复C基因的编码前25个氨基酸的核酸序列，并通过兼并原则对其进行突变(ATGAA gAACC CAAAG AAaAA ATCaG GAGGA tTtCG GATaG TCAAc ATGCTAAAAC GCGGc GTAGC CCGTG TtAAC)(SEQ ID NO 12)。带有报道基因的感染性克隆同上，在体外转录后，导入宿主细胞如Vero细胞后，可以起始病毒生活周期，产生子代病毒(图3)。病毒在复制过程中表达报道基因Gluc及Venus。Gluc可以利用商品化的荧光素酶活性检测试剂盒进行检测。Venus的表达可以利用荧光显微镜进行观察或利用流式细胞仪进行检测(图4，5)。产生的含有报道基因片段的子代病毒重新感染新细胞，在新细胞中可以有效复制。报道基因由于与病毒蛋白处于同一个开放阅读框，其表达水平反应病毒蛋白水平，亦可反应病毒复制水平。且含有报道基因的重组病毒在相当长的时间内连续传代报道基因无丢失(图3)。利用此含有报道基因的重组病毒，可以快速、方便的检测病毒复制及包装水平，可以用于研究病毒的生活周期、病毒－宿主相互作用、病毒的免疫学及抗病毒药物的开发等。如果把报道基因替换成其他目的基因，可以利用此携带目的基因的重组病毒作为病毒载体(Viral vector)来在某些细胞中或组织中表达目的基因，作为基因治疗的某种手段。该病毒载体(Viral vector)可以是以寨卡病毒MR766毒株(SEQ ID NO 1、5或6)为母本，通过对病毒基因组进行改造，比如替换SEQ ID NO 5或6中的报道基因为某种有治疗功能的目的基因；或进一步通过改造使携带有目的基因的重组寨卡病毒MR766毒株失去致病功能从而降低其细胞毒性来达到治疗某种疾病的目的。
本发明对感染性克隆(SEQ ID NO 1)进行改造，参照黄病毒属其他病毒，比如剔除病毒的结构蛋白C-prM-E区域，可以构成病毒的亚基因组复制子(subgenomic replicon)(Christopher,et al.Virology.2005,331)等复制非感染性病毒(replication competentnon-infectious)。该亚基因组复制子能进行病毒基因复制，但由于缺少病毒的结构蛋白不能包装出子代病毒。该亚基因组复制子可以用于研究病毒的基因复制周期等。参照黄病毒属其他病毒，共表达病毒结构蛋白E与prM能产生重组的亚病毒颗粒(recombinantsubviral particles,RSPs)(Ferlenghi,et al.Mol Cell.2001,7(3):593；Konishi,etal.J Virol.2001,5(5):2204)等非复制性病毒(defective variants)颗粒。这些非复制性病毒颗粒可以作为一种型式的疫苗(Konishi,et al.Virology.1992,188(2):714)。
对感染性克隆(SEQ ID NO 1)进行改造，可以构成减毒(live-attenuated)病毒，此减毒病毒可以作为疫苗。在黄病毒属病毒成员登革热病毒(Dengue virus)中删除病毒3’-NTR一段长30nt的RNA的发夹结构(stem loop)LT2序列导致病毒复制水平的降低，此重组病毒在动物体内表现为减毒并能诱生免疫保护(Whitehead,et al.J Virol.2003,77(2):1653；Men,et al.J Virol.1996,70(6):3930；Blaney,et al.Vaccine.2008,26(6):817)，因此可以作为减毒疫苗。在一株寨卡病毒毒株(Cambodian strain FSS13025)中，利用类似的策略得到了在小鼠中减毒的病毒。我们参照登革热病毒，在我们的寨卡病毒MR766毒株感染性克隆(SEQ ID NO 1)中删除与登革热病毒高度类似的区域，得到了缺失3’-NTR中一段29nt序列(CTGGA GACTA GCTGT GAATC TCCAG CAGA)(SEQ ID NO 13)的感染性克隆(SEQ ID NO 7)。同时我们在带有报道基因Gluc及Venus的的感染性克隆该感染性克隆中分别删除相同的区段，得到带有报道基因Gluc并减毒的感染性克隆(SEQ ID NO 8)及带有报道基因Venus并减毒的感染性克隆(SEQ ID NO 9)。利用带有报道基因Gluc并减毒的感染性克隆(SEQ ID NO 8)产生的病毒与相应的野生型感染性克隆(SEQ ID NO 5)病毒相比较，减毒病毒表现为复制动力学的延迟及产生的子代病毒的感染性的降低。该减毒的MR766可以作为疫苗；或以此为骨架，通过与其他病毒的结构蛋白嵌合(比如其他寨卡病毒毒株或黄病毒属其他病毒成员的结构蛋白)，构建嵌合病毒，作为疫苗。减毒后的重组病毒也可以作为母本，通过类似于SEQ ID NO 5或者6所描述的策略加入目的基因，成为病毒载体。
本发明所用的方法均为常规的分子生物学方法，许多具体的操作细节不再赘述。
实施例1:寨卡病毒MR766毒株的感染性cDNA克隆的构建
如图1A所示，我们采取从头合成病毒全基因组序列的策略。根据公共数据库中发表的寨卡病毒MR766毒株的序列信息，我们首先分成5段分别合成了寨卡病毒MR766毒株的序列(AY632535.2)(Kuno G et al.Arch Virol.2007,152(4):687-96)。首先合成的F3片段经限制性内切酶NotI/AfeI消化后，与经同样限制性内切酶消化的pACNR载体连接，得到pACNR-F3质粒。体外合成的F1片段经限制性内切酶NotI/AgeI消化后与经限制性内切酶AgeI/SbfI消化F2片段进行体外连接，通过琼脂糖胶电泳回收连接成功的F1+F2片段。然后对pACNR-F3质粒进行NotI/SbfI消化，与脂糖胶电泳回收连接成功的F1+F2片段进行连接，得到pACNR-F1+2+3质粒。通过类似对策略，利用RsRII/AfeI把F4片段连接入pACNR-F1+2+3质粒得到pACNR-F1+2+3+4质粒。最后通过KpnI/AfeI把F5片段连接入pACNR-F1+2+3+4质粒得到含有全长寨卡病毒MR766毒株序列的质粒，命名为pZikaMR766。
为构建带有报道基因的感染性克隆，如图1C所示，以质粒pZikaMR766为模版，首先利用融合PCR，拼接包含有Gluc/或Venus，FMDV 2A片段、Ub泛素序列及通过兼并原则重编的C基因的编码前25个氨基酸的核酸序列(C25)，然后进一步利用融合PCR连接入如图所示的C基因区域，分别得到pZikaMR766-Gluc与pZikaMR766-Venus质粒。
对质粒pZikaMR766，pZikaMR766-Gluc与pZikaMR766-Venus用AfeI进行酶切，线性化，然后利用体外转录试剂盒(mMESSAGE mMACHINE，Ambion,cat:AM1340)。体外转录的3gRNA利用电转导的方法转入Vero细胞。电转导的方法的方法如下：Vero细胞经胰酶消化后，用冰冷的DPBS洗两遍，然后重悬于DPBS中，使细胞终浓度为2×107细胞/ml。取400 l细胞悬液与3g RNA混合，用ECM830(BTX)电穿孔仪进行电转导(电转导参数：125V,pulse length10ms,3pulses)。电转后观察，未发现Vero细胞有明显细胞病变(CPE)出现；pZikaMR766-Venus电转导的细胞亦未见荧光蛋白表达。提示没有病毒复制信号。
通过对比pZikaMR766中Zika MR766序列与最近公布的另一个用高通量测序策略(Illumina)得到的MR766的序列(KU955594.1)，发现pZikaMR766中的病毒序列相较于高通量测序得到的MR766的序列有多处点突变及移码突变(图1B)。随后，利用融合PCR的方法，对pZikaMR766，pZikaMR766-Gluc与pZikaMR766-Venus中的与KU955594.1序列不一致的序列进行逐步的修正，最终得到与KU955594.1一致的序列。对这些修正过的质粒重新命名为pZikaMR766-C7(SEQ ID NO 1)，pZikaMR766-C7-Gluc(SEQ ID NO 5)与pZikaMR766-C7-Venus(SEQ ID NO 6)。
实施例2:寨卡病毒MR766毒株感染性cDNA克隆产生病毒的复制能力及感染能力
与上述方法类似，对质粒pZikaMR766-C7，pZikaMR766-C7-Gluc与pZikaMR766-C7-Venus用AfeI进行酶切，线性化，然后利用体外转录试剂盒。体外转录的RNA 3 g利用电转导的方法转入Vero细胞。电转后不同时间点观察细胞病变情况。如图2A所示，pZikaMR766-C7(C7)，pZikaMR766-C7-Gluc(C7-Gluc)与pZikaMR766-C7-Venus(C7-Venus)转录的RNA转导Vero细胞后细胞均出现明显细胞病变(CPE)。其中C7在电转后第3天(3dpe)即出现明显CPE；C7-Gluc与C7-Venus在第5天出现明显CPE。C7-Venus在电转后第3天可见有绿色荧光蛋白表达的细胞，随后增加。分别收集C7电转后3天、C7-Gluc与C7-Venus电转后第6天及第7天的细胞上清，利用0.45m的滤膜过滤。利用空斑形成实验(plague assay)对上清中的病毒在Vero细胞中进行病毒滴度的测定。各细胞上清按1:10梯度稀释，取200 l稀释液感染Vero，1小时后，覆盖0.6％琼脂糖。培养7天后用7％甲醛溶液固定，然后用结晶紫溶液进行染色。如图2B所示，C7病毒形成较大的空斑。C7-Gluc与C7-Venus形成的空斑较小。对空斑计数计算得到病毒梯度，以PFU/ml表示。如图1C所示，虽然C7-Gluc与C7-Venus形成的空斑相较C7较小，但病毒滴度与C7接近，均达到1-2×107PFU/ml。
实施例3:含报道基因的重组病毒表达报道基因的稳定性
有报道在黄病毒属病毒的基因组中插入的外源基因片段容易在病毒复制过程中被剔除(Schoggins,et al.Proc Natl Acad Sci.2012,109(36):14610)。如图3所示，为验证我们构建的带有报道基因的病毒表达报道基因的稳定性，我们以含有报道基因Venus的重组病毒C7-Venus为例，对电转导C7-Venus RNA的细胞上清(P1)以1:10稀释度重新感染新的Vero细胞，感染三天后细胞用荧光显微镜观察；新的含有C7-Venus重组病毒的细胞上清(P2)同上以1:10稀释度重新感染新的Vero细胞，感染三天后细胞用荧光显微镜观察。同上依次传代感染，观察感染细胞中Venus的表达情况。C7-Venus病毒经过12天，4次传代，其表达Venus的水平没有明显变化，直到第5代出现C7-Venus表达的丢失。该结果证明在一般的研究或药物筛选的条件下(一般没有传代要求)，带有报道基因的重组寨卡病毒有相当的稳定性。
实施例4:寨卡病毒MR766毒株减毒株感染性克隆的构建
在黄病毒属病毒成员登革热病毒(Dengue virus)中删除病毒3’-NTR一段长30nt的RNA序列导致病毒复制水平的降低，此重组病毒在动物体内表现为减毒并能诱生免疫保护(Whitehead,et al.J Virol.2003,77(2):1653；Men,et al.J Virol.1996,70(6):3930；Blaney,et al.Vaccine.2008,26(6):817)。采用类似的策略，我们首先分析了已经报道的通过删除3’-NTR一发夹结构LT2的登革热病毒4(Dengue virus 4)的3’-NTR的预测二级结构(图4A)，利用相同的RNA二级结构预测软件(http://rna.urmc.rochester.edu/RNAstructureWeb)对寨卡病毒MR766毒株的3’-NTR的预测二级结构，可以得到与登革热病毒4类似的发夹结构LT2。根据文献报道的删除策略，我们在质粒pZikaMR766-C7中删除相似于登革热病毒中的序列(用虚线括出)。此序列包括一长29nt的序列(CTGGA GACTA GCTGTGAATC TCCAG CAGA)，得到的质粒命名为pZikaMR766-C7-delta29(SEQ ID NO 7)。同时我们在带有报道基因Gluc及Venus的的感染性克隆该感染性克隆中分别删除相同的区段，得到带有报道基因Gluc并减毒的感染性克隆(核酸序列8)及带有报道基因Venus并减毒的感染性克隆(SEQ ID NO 9)。利用带有报道基因Gluc并减毒的感染性克隆(SEQ ID NO 8)产生的病毒与相应的野生型感染性克隆(SEQ ID NO 5)产生的病毒相比较，减毒病毒表现为复制动力学的延迟及产生的子代病毒的感染性的降低；而含有病毒RdRp NS5活性位点突变(GDD突变为GNN)的克隆pZikaMR766-C7-Gluc-GNN(C7-Gluc-GNN)产生的RNA转染后只能在转染前10小时内检测到RNA翻译所产生的信号(图4C)。转染后不同时间点收集细胞上清，重新感染新的Vero细胞，感染后3天测定细胞中Gluc的表达水平来可以反映分泌到细胞上清中病毒的感染能力。减毒病毒的感染能力相较与野生病毒同样表现为降低(图4D)。
实施例5:利用含有报道基因的寨卡病毒感染性克隆研究宿主蛋白DNAJC14在过表达情况下的抗病毒作用
之前有报道宿主蛋白DNAJC14作为黄病毒属病毒的广谱的复制调控因子，在过表达的情况下通过影响病毒蛋白的切割来抑制病毒复制(Yi,et al.PLoS Pathog.2011,7(1):e1001255；Bozzacco,et al.J Virol.2016,90(6):3212)。为验证DNAJC14过表达是否也影响寨卡病毒的复制，在HEK293T细胞中分别转染HA-RFP(RFP)、HA-RFP-DNAJC14-NT1(RFP-NT1)及HA-RFP-DNAJC14-NT1CT1(RFP-NT1CT1)表达质粒。DNAJC14-NT1为DNAJC14的N端截短突变体，其过表达与全长蛋白一样能抑制黄热病病毒(yellow fever virus)的复制；而DNAJC14-NT1CT1为DNAJC14N端及C端同时截短的突变体，其过表达后不能抑制病毒复制(Yi,et al.PLoS Pathog.2011,7(1):e1001255)。转染两天后，利用寨卡病毒C7-Venus(MOI，1)感染转染的细胞，感染三天后收取细胞，用流式细胞仪检测细胞中的RFP及Venus信号(图5A)。计算在RFP细胞中感染有寨卡病毒(Venus)的细胞比例(Q2/(Q2+Q3)，得出与黄热病病毒类似，过表达DNAJC14-NT1能显著抑制寨卡病毒的复制，而DNAJC14-NT1CT1不能抑制病毒复制(图5B)。
序列表
<110> 复旦大学
<120> 寨卡病毒MR766毒株的感染性克隆及其应用
<130> 201802
<160> 13
<170> SIPOSequenceListing 1.0
<210> 1
<211> 12879
<212> DNA
<213> Artificial
<400> 1
agcgctagcg gagtgtatac tggcttacta tgttggcact gatgagggtg tcagtgaagt 60
gcttcatgtg gcaggagaaa aaaggctgca ccggtgcgtc agcagaatat gtgatacagg 120
atatattccg cttcctcgct cactgactcg ctacgctcgg tcgttcgact gcggcgagcg 180
gaaatggctt acgaacgggg cggagatttc ctggaagatg ccaggaagat acttaacagg 240
gaagtgagag ggccgcggca aagccgtttt tccataggct ccgcccccct gacaagcatc 300
acgaaatctg acgctcaaat cagtggtggc gaaacccgac aggactataa agataccagg 360
cgtttcccct ggcggctccc tcgtgcgctc tcctgttcct gcctttcggt ttaccggtgt 420
cattccgctg ttatggccgc gtttgtctca ttccacgcct gacactcagt tccgggtagg 480
cagttcgctc caagctggac tgtatgcacg aaccccccgt tcagtccgac cgctgcgcct 540
tatccggtaa ctatcgtctt gagtccaacc cggaaagaca tgcaaaagca ccactggcag 600
cagccactgg taattgattt agaggagtta gtcttgaagt catgcgccgg ttaaggctaa 660
actgaaagga caagttttgg tgactgcgct cctccaagcc agttacctcg gttcaaagag 720
ttggtagctc agagaacctt cgaaaaaccg ccctgcaagg cggttttttc gttttcagag 780
caagagatta cgcgcagacc aaaacgatct caagaagatc atcttattaa ggggtctgac 840
gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc 900
ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag 960
taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt 1020
ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac gatacgggag 1080
ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc accggctcca 1140
gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg tcctgcaact 1200
ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag tagttcgcca 1260
gttaatagtt tgcgcaacgt tgttgccatt gctgcaggca tcgtggtgtc acgctcgtcg 1320
tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac atgatccccc 1380
atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag aagtaagttg 1440
gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac tgtcatgcca 1500
tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg agaatagtgt 1560
atgcggcgac cgagttgctc ttgcccggcg tcaacacggg ataataccgc gccacatagc 1620
agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc 1680
ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg atcttcagca 1740
tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa 1800
aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt tcaatattat 1860
tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg tatttagaaa 1920
aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga cgtgtcgacg 1980
cggccgcgct agcgatgatt taggtgacac tatagaagtt gttgatctgt gtgagtcaga 2040
ctgcgacagt tcgagtctga agcgagagct aacaacagta tcaacaggtt taatttggat 2100
ttggaaacga gagtttctgg tcatgaaaaa cccaaagaag aaatccggag gattccggat 2160
tgtcaatatg ctaaaacgcg gagtagcccg tgtaaacccc ttgggaggtt tgaagaggtt 2220
gccagccgga cttctgctgg gtcatggacc catcagaatg gttttggcga tactagcctt 2280
tttgagattt acagcaatca agccatcact gggccttatc aacagatggg gttccgtggg 2340
gaaaaaagag gctatggaaa taataaagaa gttcaagaaa gatcttgctg ccatgttgag 2400
aataatcaat gctaggaaag agaggaagag acgtggcgca gacaccagca tcggaatcat 2460
tggcctcctg ctgactacag ccatggcagc agagatcact agacgcggga gtgcatacta 2520
catgtacttg gataggagcg atgccgggaa ggccatttcg tttgctacca cattgggagt 2580
gaacaagtgc cacgtacaga tcatggacct cgggcacatg tgtgacgcca ccatgagtta 2640
tgagtgccct atgctggatg agggagtgga accagatgat gtcgattgct ggtgcaacac 2700
gacatcaact tgggttgtgt acggaacctg tcatcacaaa aaaggtgagg cacggcgatc 2760
tagaagagcc gtgacgctcc cttctcactc tacaaggaag ttgcaaacgc ggtcgcagac 2820
ctggttagaa tcaagagaat acacgaagca cttgatcaag gttgaaaact ggatattcag 2880
gaaccccggg tttgcgctag tggccgttgc cattgcctgg cttttgggaa gctcgacgag 2940
ccaaaaagtc atatacttgg tcatgatact gctgattgcc ccggcataca gtatcaggtg 3000
cattggagtc agcaatagag acttcgtgga gggcatgtca ggtgggacct gggttgatgt 3060
tgtcttggaa catggaggct gcgttaccgt gatggcacag gacaagccaa cagtcgacat 3120
agagttggtc acgacgacgg ttagtaacat ggccgaggta agatcctatt gctacgaggc 3180
atcgatatcg gacatggctt cggacagtcg ttgcccaaca caaggtgaag cctaccttga 3240
caagcaatca gacactcaat atgtctgcaa aagaacatta gtggacagag gttggggaaa 3300
cggttgtgga ctttttggca aagggagctt ggtgacatgt gccaagttta cgtgttctaa 3360
gaagatgacc gggaagagca ttcaaccgga aaatctggag tatcggataa tgctatcagt 3420
gcatggctcc cagcatagcg ggatgattgg atatgaaact gacgaaaata gagcgaaagt 3480
cgaggttacg cctaattcac caagagcgga agcaaccttg ggaggctttg gaagcttagg 3540
acttgactgt gaaccaagga caggccttga cttttcagat ctgtattacc tgaccatgaa 3600
caataagcat tggttggtgc acaaagagtg gtttcatgac atcccattgc cttggcatgc 3660
tggggcagac accggaactc cacactggaa caacaaagag gcattggtag aattcaagga 3720
tgcccacgcc aagaggcaaa ccgtcgtcgt tctggggagc caggaaggag ccgttcacac 3780
ggctctcgct ggagctctag aggctgagat ggatggtgca aagggaaggc tgttctctgg 3840
ccatttgaaa tgccgcctaa aaatggacaa gcttagattg aagggcgtgt catattcctt 3900
gtgcactgcg gcattcacat tcaccaaggt cccagctgaa acactgcatg gaacagtcac 3960
agtggaggtg cagtatgcag ggacagatgg accctgcaag atcccagtcc agatggcggt 4020
ggacatgcag accctgaccc cagttggaag gctgataacc gccaaccccg tgattactga 4080
aagcactgag aactcaaaga tgatgttgga gcttgaccca ccatttgggg attcttacat 4140
tgtcatagga gttggggaca agaaaatcac ccaccactgg cataggagtg gtagcaccat 4200
cggaaaggca tttgaggcca ctgtgagagg cgccaagaga atggcagtcc tgggggatac 4260
agcctgggac ttcggatcag tcgggggtgt gttcaactca ctgggtaagg gcattcacca 4320
gatttttgga gcagccttca aatcactgtt tggaggaatg tcctggttct cacagatcct 4380
cataggcacg ctgctagtgt ggttaggttt gaacacaaag aatggatcta tctccctcac 4440
atgcttggcc ctggggggag tgatgatctt cctctccacg gctgtttctg ctgacgtggg 4500
gtgctcagtg gacttctcaa aaaaggaaac gagatgtggc acgggggtat tcatctataa 4560
tgatgttgaa gcctggaggg accggtacaa gtaccatcct gactcccccc gcagattggc 4620
agcagcagtc aagcaggcct gggaagaggg gatctgtggg atctcatccg tttcaagaat 4680
ggaaaacatc atgtggaaat cagtagaagg ggagctcaat gctatcctag aggagaatgg 4740
agttcaactg acagttgttg tgggatctgt aaaaaacccc atgtggagag gtccacaaag 4800
attgccagtg cctgtgaatg agctgcccca tggctggaaa gcctggggga aatcgtattt 4860
tgttagggcg gcaaagacca acaacagttt tgttgtcgac ggtgacacac tgaaggaatg 4920
tccgcttgag cacagagcat ggaatagttt tcttgtggag gatcacgggt ttggagtctt 4980
ccacaccagt gtctggctta aggtcagaga agattactca ttagaatgtg acccagccgt 5040
cataggaaca gctgttaagg gaagggaggc cgcgcacagt gatctgggct attggattga 5100
aagtgaaaag aatgacacat ggaggctgaa gagggcccac ctgattgaga tgaaaacatg 5160
tgaatggcca aagtctcaca cattgtggac agatggagta gaagaaagtg atcttatcat 5220
acccaagtct ttagctggtc cactcagcca ccacaacacc agagagggtt acagaaccca 5280
agtgaaaggg ccatggcaca gtgaagagct tgaaatccgg tttgaggaat gtccaggcac 5340
caaggtttac gtggaggaga catgcggaac tagaggacca tctctgagat caactactgc 5400
aagtggaagg gtcattgagg aatggtgctg tagggaatgc acaatgcccc cactatcgtt 5460
tcgagcaaaa gacggctgct ggtatggaat ggagataagg cccaggaaag aaccagagag 5520
caacttagtg aggtcaatgg tgacagcggg gtcaaccgat catatggacc acttctctct 5580
tggagtgctt gtgattctac tcatggtgca ggaggggttg aagaagagaa tgaccacaaa 5640
gatcatcatg agcacatcaa tggcagtgct ggtagtcatg atcttgggag gattttcaat 5700
gagtgacctg gccaagcttg tgatcctgat gggtgctact ttcgcagaaa tgaacactgg 5760
aggagatgta gctcacttgg cattggtagc ggcatttaaa gtcagaccag ccttgctggt 5820
ctccttcatt ttcagagcca attggacacc ccgtgagagc atgctgctag ccctggcttc 5880
gtgtcttctg caaactgcga tctctgctct tgaaggtgac ttgatggtcc tcattaatgg 5940
atttgctttg gcctggttgg caattcgagc aatggccgtg ccacgcactg acaacatcgc 6000
tctaccaatc ttggctgctc taacaccact agctcgaggc acactgctcg tggcatggag 6060
agcgggcctg gctacttgtg gagggatcat gctcctctcc ctgaaaggga aaggtagtgt 6120
gaagaagaac ctgccatttg tcatggccct gggattgaca gctgtgaggg tagtagaccc 6180
tattaatgtg gtaggactac tgttactcac aaggagtggg aagcggagct ggccccctag 6240
tgaagttctc acagccgttg gcctgatatg tgcactggcc ggagggtttg ccaaggcaga 6300
cattgagatg gctggaccca tggctgcagt aggcttgcta attgtcagct atgtggtctc 6360
gggaaagagt gtggacatgt acattgaaag agcaggtgac atcacatggg aaaaggacgc 6420
ggaagtcact ggaaacagtc ctcggcttga cgtggcactg gatgagagtg gtgacttctc 6480
cttggtagag gaagatggtc cacccatgag agagatcata ctcaaggtgg tcctgatggc 6540
catctgtggc atgaacccaa tagctatacc ttttgctgca ggagcgtggt atgtgtatgt 6600
gaagactggg aaaaggagtg gcgccctctg ggacgtgcct gctcccaaag aagtgaagaa 6660
aggagagacc acagatggag tgtacagagt gatgactcgc agactgctag gttcaacaca 6720
ggttggagtg ggagtcatgc aagagggagt cttccacacc atgtggcacg ttacaaaagg 6780
agccgcactg aggagcggtg agggaagact tgatccatac tggggggatg tcaagcagga 6840
cttggtgtca tactgtgggc cttggaagtt ggatgcagct tgggatggac tcagcgaggt 6900
acagcttttg gccgtacctc ccggagagag ggccagaaac attcagaccc tgcctggaat 6960
attcaagaca aaggacgggg acatcggagc agttgctctg gactaccctg cagggacctc 7020
aggatctccg atcctagaca aatgtggaag agtgatagga ctctatggca atggggttgt 7080
gatcaagaat ggaagctatg ttagtgctat aacccaggga aagagggagg aggagactcc 7140
ggttgaatgt ttcgaaccct cgatgctgaa gaagaagcag ctaactgtct tggatctgca 7200
tccaggagcc ggaaaaacca ggagagttct tcctgaaata gtccgtgaag ccataaaaaa 7260
gagactccgg acagtgatct tggcaccaac tagggttgtc gctgctgaga tggaggaggc 7320
cttgagagga cttccggtgc gttacatgac aacagcagtc aacgtcaccc attctgggac 7380
agaaatcgtt gatttgatgt gccatgccac tttcacttca cgcttactac aacccatcag 7440
agtccctaat tacaatctct acatcatgga tgaagcccac ttcacagacc cctcaagtat 7500
agctgcaaga ggatacatat caacaagggt tgaaatgggc gaggcggctg ccatttttat 7560
gactgccaca ccaccaggaa cccgtgatgc gtttcctgac tctaactcac caatcatgga 7620
cacagaagtg gaagtcccag agagagcctg gagctcaggc tttgattggg tgacagacca 7680
ttctgggaaa acagtttggt tcgttccaag cgtgagaaac ggaaatgaaa tcgcagcctg 7740
tctgacaaag gctggaaagc gggtcataca gctcagcagg aagacttttg agacagaatt 7800
tcagaaaaca aaaaatcaag agtgggactt tgtcataaca actgacatct cagagatggg 7860
cgccaacttc aaggctgacc gggtcataga ctctaggaga tgcctaaaac cagtcatact 7920
tgatggtgag agagtcatct tggctgggcc catgcctgtc acgcatgcta gtgctgctca 7980
gaggagagga cgtataggca ggaaccctaa caaacctgga gatgagtaca tgtatggagg 8040
tgggtgtgca gagactgatg aaggccatgc acactggctt gaagcaagaa tgcttcttga 8100
caacatctac ctccaggatg gcctcatagc ctcgctctat cggcctgagg ccgataaggt 8160
agccgccatt gagggagagt ttaagctgag gacagagcaa aggaagacct tcgtggaact 8220
catgaagaga ggagaccttc ccgtctggct agcctatcag gttgcatctg ccggaataac 8280
ttacacagac agaagatggt gctttgatgg cacaaccaac aacaccataa tggaagacag 8340
tgtaccagca gaggtttgga caaagtatgg agagaagaga gtgctcaaac cgagatggat 8400
ggatgctagg gtctgttcag accatgcggc cctgaagtcg ttcaaagaat tcgccgctgg 8460
aaaaagagga gcggctttgg gagtaatgga ggccctggga acactgccag gacacatgac 8520
agagaggttt caggaagcca ttgacaacct cgccgtgctc atgcgagcag agactggaag 8580
caggccttat aaggcagcgg cagcccaact gccggagacc ctagagacca ttatgctctt 8640
aggtttgctg ggaacagttt cactggggat cttcttcgtc ttgatgcgga ataagggcat 8700
cgggaagatg ggctttggaa tggtaaccct tggggccagt gcatggctca tgtggctttc 8760
ggaaattgaa ccagccagaa ttgcatgtgt cctcattgtt gtgtttttat tactggtggt 8820
gctcataccc gagccagaga agcaaagatc tccccaagat aaccagatgg caattatcat 8880
catggtggca gtgggccttc taggtttgat aactgcaaac gaacttggat ggctggaaag 8940
aacaaaaaat gacatagctc atctaatggg aaggagagaa gaaggagcaa ccatgggatt 9000
ctcaatggac attgatctgc ggccagcctc cgcctgggct atctatgccg cattgacaac 9060
tctcatcacc ccagctgtcc aacatgcggt aaccacttca tacaacaact actccttaat 9120
ggcgatggcc acacaagctg gagtgctgtt tggcatgggc aaagggatgc cattttatgc 9180
atgggacctt ggagtcccgc tgctaatgat gggttgctat tcacaattaa cacccctgac 9240
tctgatagta gctatcattc tgcttgtggc gcactacatg tacttgatcc caggcctaca 9300
agcggcagca gcgcgtgctg cccagaaaag gacagcagct ggcatcatga agaatcccgt 9360
tgtggatgga atagtggtaa ctgacattga cacaatgaca atagaccccc aggtggagaa 9420
gaagatggga caagtgttac tcatagcagt agccatctcc agtgctgtgc tgctgcggac 9480
cgcctgggga tggggggagg ctggagctct gatcacagca gcgacctcca ccttgtggga 9540
aggctctcca aacaaatact ggaactcctc tacagccacc tcactgtgca acatcttcag 9600
aggaagctat ctggcaggag cttcccttat ctatacagtg acgagaaacg ctggcctggt 9660
taagagacgt ggaggtggga cgggagagac tctgggagag aagtggaaag ctcgtctgaa 9720
tcagatgtcg gccctggagt tctactctta taaaaagtca ggtatcactg aagtgtgtag 9780
agaggaggct cgccgtgccc tcaaggatgg agtggccaca ggaggacatg ccgtatcccg 9840
gggaagtgca aagctcagat ggttggtgga gagaggatat ctgcagccct atgggaaggt 9900
tgttgacctc ggatgtggca gagggggctg gagctattat gccgccacca tccgcaaagt 9960
gcaggaggtg agaggataca caaagggagg tcccggtcat gaagaaccca tgctggtgca 10020
aagctatggg tggaacatag ttcgtctcaa gagtggagtg gacgtcttcc acatggcggc 10080
tgagccgtgt gacactctgc tgtgtgacat aggtgagtca tcatctagtc ctgaagtgga 10140
agagacacga acactcagag tgctctctat ggtgggggac tggcttgaaa aaagaccagg 10200
ggccttctgt ataaaggtgc tgtgcccata caccagcact atgatggaaa ccatggagcg 10260
actgcaacgt aggcatgggg gaggattagt cagagtgcca ttgtctcgca actccacaca 10320
tgagatgtac tgggtctctg gggcaaagag caacatcata aaaagtgtgt ccaccacaag 10380
tcagctcctc ctgggacgca tggatggccc caggaggcca gtgaaatatg aggaggatgt 10440
gaacctcggc tcgggtacac gagctgtggc aagctgtgct gaggctccta acatgaaaat 10500
catcggcagg cgcattgaga gaatccgcaa tgaacatgca gaaacatggt ttcttgatga 10560
aaaccaccca tacaggacat gggcctacca tgggagctac gaagccccca cgcaaggatc 10620
agcgtcttcc ctcgtgaacg gggttgttag actcctgtca aagccttggg acgtggtgac 10680
tggagttaca ggaatagcca tgactgacac cacaccatac ggccaacaaa gagtcttcaa 10740
agaaaaagtg gacaccaggg tgccagatcc ccaagaaggc actcgccagg taatgaacat 10800
agtctcttcc tggctgtgga aggagctggg gaaacgcaag cggccacgcg tctgcaccaa 10860
agaagagttt atcaacaagg tgcgcagcaa tgcagcactg ggagcaatat ttgaagagga 10920
aaaagaatgg aagacggctg tggaagctgt gaatgatcca aggttttggg ccctagtgga 10980
tagggagaga gaacaccacc tgagaggaga gtgtcacagc tgtgtgtaca acatgatggg 11040
aaaaagagaa aagaagcaag gagagttcgg gaaagcaaaa ggtagccgcg ccatctggta 11100
catgtggttg ggagccagat tcttggagtt tgaagccctt ggattcttga acgaggacca 11160
ttggatggga agagaaaact caggaggtgg agtcgaaggg ttaggattgc aaagacttgg 11220
atacattcta gaagaaatga atcgggcacc aggaggaaag atgtacgcag atgacactgc 11280
tggctgggac acccgcatta gtaagtttga tctggagaat gaagctctga ttaccaacca 11340
aatggaggaa gggcacagaa ctctggcgtt ggccgtgatt aaatacacat accaaaacaa 11400
agtggtgaag gttctcagac cagctgaagg aggaaaaaca gttatggaca tcatttcaag 11460
acaagaccag agagggagtg gacaagttgt cacttatgct ctcaacacat tcaccaactt 11520
ggtggtgcag cttatccgga acatggaagc tgaggaagtg ttagagatgc aagacttatg 11580
gttgttgagg aagccagaga aagtgaccag atggttgcag agcaatggat gggatagact 11640
caaacgaatg gcggtcagtg gagatgactg cgttgtgaag ccaatcgatg ataggtttgc 11700
acatgccctc aggttcttga atgacatggg aaaagttagg aaagacacac aggagtggaa 11760
accctcgact ggatggagca attgggaaga agtcccgttc tgctcccacc acttcaacaa 11820
gctgtacctc aaggatggga gatccattgt ggtcccttgc cgccaccaag atgaactgat 11880
tggccgagct cgcgtctcac caggggcagg atggagcatc cgggagactg cctgtcttgc 11940
aaaatcatat gcgcagatgt ggcagctcct ttatttccac agaagagacc ttcgactgat 12000
ggctaatgcc atttgctcgg ctgtgccagt tgactgggta ccaactggga gaaccacctg 12060
gtcaatccat ggaaagggag aatggatgac cactgaggac atgctcatgg tgtggaatag 12120
agtgtggatt gaggagaacg accatatgga ggacaagact cctgtaacaa aatggacaga 12180
cattccctat ctaggaaaaa gggaggactt atggtgtgga tcccttatag ggcacagacc 12240
ccgcaccact tgggctgaaa acatcaaaga cacagtcaac atggtgcgca ggatcatagg 12300
tgatgaagaa aagtacatgg actatctatc cacccaagtc cgctacttgg gtgaggaagg 12360
gtccacaccc ggagtgttgt aagcaccaat tttagtgttg tcaggcctgc tagtcagcca 12420
cagtttgggg aaagctgtgc agcctgtaac ccccccagga gaagctggga aaccaagctc 12480
atagtcaggc cgagaacgcc atggcacgga agaagccatg ctgcctgtga gcccctcaga 12540
ggacactgag tcaaaaaacc ccacgcgctt ggaagcgcag gatgggaaaa gaaggtggcg 12600
accttcccca cccttcaatc tggggcctga actggagact agctgtgaat ctccagcaga 12660
gggactagtg gttagaggag accccccgga aaacgcaaaa cagcatattg acgctgggaa 12720
agaccagaga ctccatgagt ttccaccacg ctggccgcca ggcacagatc gccgaacagc 12780
ggcggccggt gtggggaaat ccatggtttc tggccggcat ggtcccagcc tcctcgctgg 12840
cgccggctgg gcaacatgct tcggcatggc gaatgggac 12879
<210> 2
<211> 10795
<212> DNA
<213> Artificial
<400> 2
agttgttgat ctgtgtgagt cagactgcga cagttcgagt ctgaagcgag agctaacaac 60
agtatcaaca ggtttaattt ggatttggaa acgagagttt ctggtcatga aaaacccaaa 120
gaagaaatcc ggaggattcc ggattgtcaa tatgctaaaa cgcggagtag cccgtgtaaa 180
ccccttggga ggtttgaaga ggttgccagc cggacttctg ctgggtcatg gacccatcag 240
aatggttttg gcgatactag cctttttgag atttacagca atcaagccat cactgggcct 300
tatcaacaga tggggttccg tggggaaaaa agaggctatg gaaataataa agaagttcaa 360
gaaagatctt gctgccatgt tgagaataat caatgctagg aaagagagga agagacgtgg 420
cgcagacacc agcatcggaa tcattggcct cctgctgact acagccatgg cagcagagat 480
cactagacgc gggagtgcat actacatgta cttggatagg agcgatgccg ggaaggccat 540
ttcgtttgct accacattgg gagtgaacaa gtgccacgta cagatcatgg acctcgggca 600
catgtgtgac gccaccatga gttatgagtg ccctatgctg gatgagggag tggaaccaga 660
tgatgtcgat tgctggtgca acacgacatc aacttgggtt gtgtacggaa cctgtcatca 720
caaaaaaggt gaggcacggc gatctagaag agccgtgacg ctcccttctc actctacaag 780
gaagttgcaa acgcggtcgc agacctggtt agaatcaaga gaatacacga agcacttgat 840
caaggttgaa aactggatat tcaggaaccc cgggtttgcg ctagtggccg ttgccattgc 900
ctggcttttg ggaagctcga cgagccaaaa agtcatatac ttggtcatga tactgctgat 960
tgccccggca tacagtatca ggtgcattgg agtcagcaat agagacttcg tggagggcat 1020
gtcaggtggg acctgggttg atgttgtctt ggaacatgga ggctgcgtta ccgtgatggc 1080
acaggacaag ccaacagtcg acatagagtt ggtcacgacg acggttagta acatggccga 1140
ggtaagatcc tattgctacg aggcatcgat atcggacatg gcttcggaca gtcgttgccc 1200
aacacaaggt gaagcctacc ttgacaagca atcagacact caatatgtct gcaaaagaac 1260
attagtggac agaggttggg gaaacggttg tggacttttt ggcaaaggga gcttggtgac 1320
atgtgccaag tttacgtgtt ctaagaagat gaccgggaag agcattcaac cggaaaatct 1380
ggagtatcgg ataatgctat cagtgcatgg ctcccagcat agcgggatga ttggatatga 1440
aactgacgaa aatagagcga aagtcgaggt tacgcctaat tcaccaagag cggaagcaac 1500
cttgggaggc tttggaagct taggacttga ctgtgaacca aggacaggcc ttgacttttc 1560
agatctgtat tacctgacca tgaacaataa gcattggttg gtgcacaaag agtggtttca 1620
tgacatccca ttgccttggc atgctggggc agacaccgga actccacact ggaacaacaa 1680
agaggcattg gtagaattca aggatgccca cgccaagagg caaaccgtcg tcgttctggg 1740
gagccaggaa ggagccgttc acacggctct cgctggagct ctagaggctg agatggatgg 1800
tgcaaaggga aggctgttct ctggccattt gaaatgccgc ctaaaaatgg acaagcttag 1860
attgaagggc gtgtcatatt ccttgtgcac tgcggcattc acattcacca aggtcccagc 1920
tgaaacactg catggaacag tcacagtgga ggtgcagtat gcagggacag atggaccctg 1980
caagatccca gtccagatgg cggtggacat gcagaccctg accccagttg gaaggctgat 2040
aaccgccaac cccgtgatta ctgaaagcac tgagaactca aagatgatgt tggagcttga 2100
cccaccattt ggggattctt acattgtcat aggagttggg gacaagaaaa tcacccacca 2160
ctggcatagg agtggtagca ccatcggaaa ggcatttgag gccactgtga gaggcgccaa 2220
gagaatggca gtcctggggg atacagcctg ggacttcgga tcagtcgggg gtgtgttcaa 2280
ctcactgggt aagggcattc accagatttt tggagcagcc ttcaaatcac tgtttggagg 2340
aatgtcctgg ttctcacaga tcctcatagg cacgctgcta gtgtggttag gtttgaacac 2400
aaagaatgga tctatctccc tcacatgctt ggccctgggg ggagtgatga tcttcctctc 2460
cacggctgtt tctgctgacg tggggtgctc agtggacttc tcaaaaaagg aaacgagatg 2520
tggcacgggg gtattcatct ataatgatgt tgaagcctgg agggaccggt acaagtacca 2580
tcctgactcc ccccgcagat tggcagcagc agtcaagcag gcctgggaag aggggatctg 2640
tgggatctca tccgtttcaa gaatggaaaa catcatgtgg aaatcagtag aaggggagct 2700
caatgctatc ctagaggaga atggagttca actgacagtt gttgtgggat ctgtaaaaaa 2760
ccccatgtgg agaggtccac aaagattgcc agtgcctgtg aatgagctgc cccatggctg 2820
gaaagcctgg gggaaatcgt attttgttag ggcggcaaag accaacaaca gttttgttgt 2880
cgacggtgac acactgaagg aatgtccgct tgagcacaga gcatggaata gttttcttgt 2940
ggaggatcac gggtttggag tcttccacac cagtgtctgg cttaaggtca gagaagatta 3000
ctcattagaa tgtgacccag ccgtcatagg aacagctgtt aagggaaggg aggccgcgca 3060
cagtgatctg ggctattgga ttgaaagtga aaagaatgac acatggaggc tgaagagggc 3120
ccacctgatt gagatgaaaa catgtgaatg gccaaagtct cacacattgt ggacagatgg 3180
agtagaagaa agtgatctta tcatacccaa gtctttagct ggtccactca gccaccacaa 3240
caccagagag ggttacagaa cccaagtgaa agggccatgg cacagtgaag agcttgaaat 3300
ccggtttgag gaatgtccag gcaccaaggt ttacgtggag gagacatgcg gaactagagg 3360
accatctctg agatcaacta ctgcaagtgg aagggtcatt gaggaatggt gctgtaggga 3420
atgcacaatg cccccactat cgtttcgagc aaaagacggc tgctggtatg gaatggagat 3480
aaggcccagg aaagaaccag agagcaactt agtgaggtca atggtgacag cggggtcaac 3540
cgatcatatg gaccacttct ctcttggagt gcttgtgatt ctactcatgg tgcaggaggg 3600
gttgaagaag agaatgacca caaagatcat catgagcaca tcaatggcag tgctggtagt 3660
catgatcttg ggaggatttt caatgagtga cctggccaag cttgtgatcc tgatgggtgc 3720
tactttcgca gaaatgaaca ctggaggaga tgtagctcac ttggcattgg tagcggcatt 3780
taaagtcaga ccagccttgc tggtctcctt cattttcaga gccaattgga caccccgtga 3840
gagcatgctg ctagccctgg cttcgtgtct tctgcaaact gcgatctctg ctcttgaagg 3900
tgacttgatg gtcctcatta atggatttgc tttggcctgg ttggcaattc gagcaatggc 3960
cgtgccacgc actgacaaca tcgctctacc aatcttggct gctctaacac cactagctcg 4020
aggcacactg ctcgtggcat ggagagcggg cctggctact tgtggaggga tcatgctcct 4080
ctccctgaaa gggaaaggta gtgtgaagaa gaacctgcca tttgtcatgg ccctgggatt 4140
gacagctgtg agggtagtag accctattaa tgtggtagga ctactgttac tcacaaggag 4200
tgggaagcgg agctggcccc ctagtgaagt tctcacagcc gttggcctga tatgtgcact 4260
ggccggaggg tttgccaagg cagacattga gatggctgga cccatggctg cagtaggctt 4320
gctaattgtc agctatgtgg tctcgggaaa gagtgtggac atgtacattg aaagagcagg 4380
tgacatcaca tgggaaaagg acgcggaagt cactggaaac agtcctcggc ttgacgtggc 4440
actggatgag agtggtgact tctccttggt agaggaagat ggtccaccca tgagagagat 4500
catactcaag gtggtcctga tggccatctg tggcatgaac ccaatagcta taccttttgc 4560
tgcaggagcg tggtatgtgt atgtgaagac tgggaaaagg agtggcgccc tctgggacgt 4620
gcctgctccc aaagaagtga agaaaggaga gaccacagat ggagtgtaca gagtgatgac 4680
tcgcagactg ctaggttcaa cacaggttgg agtgggagtc atgcaagagg gagtcttcca 4740
caccatgtgg cacgttacaa aaggagccgc actgaggagc ggtgagggaa gacttgatcc 4800
atactggggg gatgtcaagc aggacttggt gtcatactgt gggccttgga agttggatgc 4860
agcttgggat ggactcagcg aggtacagct tttggccgta cctcccggag agagggccag 4920
aaacattcag accctgcctg gaatattcaa gacaaaggac ggggacatcg gagcagttgc 4980
tctggactac cctgcaggga cctcaggatc tccgatccta gacaaatgtg gaagagtgat 5040
aggactctat ggcaatgggg ttgtgatcaa gaatggaagc tatgttagtg ctataaccca 5100
gggaaagagg gaggaggaga ctccggttga atgtttcgaa ccctcgatgc tgaagaagaa 5160
gcagctaact gtcttggatc tgcatccagg agccggaaaa accaggagag ttcttcctga 5220
aatagtccgt gaagccataa aaaagagact ccggacagtg atcttggcac caactagggt 5280
tgtcgctgct gagatggagg aggccttgag aggacttccg gtgcgttaca tgacaacagc 5340
agtcaacgtc acccattctg ggacagaaat cgttgatttg atgtgccatg ccactttcac 5400
ttcacgctta ctacaaccca tcagagtccc taattacaat ctctacatca tggatgaagc 5460
ccacttcaca gacccctcaa gtatagctgc aagaggatac atatcaacaa gggttgaaat 5520
gggcgaggcg gctgccattt ttatgactgc cacaccacca ggaacccgtg atgcgtttcc 5580
tgactctaac tcaccaatca tggacacaga agtggaagtc ccagagagag cctggagctc 5640
aggctttgat tgggtgacag accattctgg gaaaacagtt tggttcgttc caagcgtgag 5700
aaacggaaat gaaatcgcag cctgtctgac aaaggctgga aagcgggtca tacagctcag 5760
caggaagact tttgagacag aatttcagaa aacaaaaaat caagagtggg actttgtcat 5820
aacaactgac atctcagaga tgggcgccaa cttcaaggct gaccgggtca tagactctag 5880
gagatgccta aaaccagtca tacttgatgg tgagagagtc atcttggctg ggcccatgcc 5940
tgtcacgcat gctagtgctg ctcagaggag aggacgtata ggcaggaacc ctaacaaacc 6000
tggagatgag tacatgtatg gaggtgggtg tgcagagact gatgaaggcc atgcacactg 6060
gcttgaagca agaatgcttc ttgacaacat ctacctccag gatggcctca tagcctcgct 6120
ctatcggcct gaggccgata aggtagccgc cattgaggga gagtttaagc tgaggacaga 6180
gcaaaggaag accttcgtgg aactcatgaa gagaggagac cttcccgtct ggctagccta 6240
tcaggttgca tctgccggaa taacttacac agacagaaga tggtgctttg atggcacaac 6300
caacaacacc ataatggaag acagtgtacc agcagaggtt tggacaaagt atggagagaa 6360
gagagtgctc aaaccgagat ggatggatgc tagggtctgt tcagaccatg cggccctgaa 6420
gtcgttcaaa gaattcgccg ctggaaaaag aggagcggct ttgggagtaa tggaggccct 6480
gggaacactg ccaggacaca tgacagagag gtttcaggaa gccattgaca acctcgccgt 6540
gctcatgcga gcagagactg gaagcaggcc ttataaggca gcggcagccc aactgccgga 6600
gaccctagag accattatgc tcttaggttt gctgggaaca gtttcactgg ggatcttctt 6660
cgtcttgatg cggaataagg gcatcgggaa gatgggcttt ggaatggtaa cccttggggc 6720
cagtgcatgg ctcatgtggc tttcggaaat tgaaccagcc agaattgcat gtgtcctcat 6780
tgttgtgttt ttattactgg tggtgctcat acccgagcca gagaagcaaa gatctcccca 6840
agataaccag atggcaatta tcatcatggt ggcagtgggc cttctaggtt tgataactgc 6900
aaacgaactt ggatggctgg aaagaacaaa aaatgacata gctcatctaa tgggaaggag 6960
agaagaagga gcaaccatgg gattctcaat ggacattgat ctgcggccag cctccgcctg 7020
ggctatctat gccgcattga caactctcat caccccagct gtccaacatg cggtaaccac 7080
ttcatacaac aactactcct taatggcgat ggccacacaa gctggagtgc tgtttggcat 7140
gggcaaaggg atgccatttt atgcatggga ccttggagtc ccgctgctaa tgatgggttg 7200
ctattcacaa ttaacacccc tgactctgat agtagctatc attctgcttg tggcgcacta 7260
catgtacttg atcccaggcc tacaagcggc agcagcgcgt gctgcccaga aaaggacagc 7320
agctggcatc atgaagaatc ccgttgtgga tggaatagtg gtaactgaca ttgacacaat 7380
gacaatagac ccccaggtgg agaagaagat gggacaagtg ttactcatag cagtagccat 7440
ctccagtgct gtgctgctgc ggaccgcctg gggatggggg gaggctggag ctctgatcac 7500
agcagcgacc tccaccttgt gggaaggctc tccaaacaaa tactggaact cctctacagc 7560
cacctcactg tgcaacatct tcagaggaag ctatctggca ggagcttccc ttatctatac 7620
agtgacgaga aacgctggcc tggttaagag acgtggaggt gggacgggag agactctggg 7680
agagaagtgg aaagctcgtc tgaatcagat gtcggccctg gagttctact cttataaaaa 7740
gtcaggtatc actgaagtgt gtagagagga ggctcgccgt gccctcaagg atggagtggc 7800
cacaggagga catgccgtat cccggggaag tgcaaagctc agatggttgg tggagagagg 7860
atatctgcag ccctatggga aggttgttga cctcggatgt ggcagagggg gctggagcta 7920
ttatgccgcc accatccgca aagtgcagga ggtgagagga tacacaaagg gaggtcccgg 7980
tcatgaagaa cccatgctgg tgcaaagcta tgggtggaac atagttcgtc tcaagagtgg 8040
agtggacgtc ttccacatgg cggctgagcc gtgtgacact ctgctgtgtg acataggtga 8100
gtcatcatct agtcctgaag tggaagagac acgaacactc agagtgctct ctatggtggg 8160
ggactggctt gaaaaaagac caggggcctt ctgtataaag gtgctgtgcc catacaccag 8220
cactatgatg gaaaccatgg agcgactgca acgtaggcat gggggaggat tagtcagagt 8280
gccattgtct cgcaactcca cacatgagat gtactgggtc tctggggcaa agagcaacat 8340
cataaaaagt gtgtccacca caagtcagct cctcctggga cgcatggatg gccccaggag 8400
gccagtgaaa tatgaggagg atgtgaacct cggctcgggt acacgagctg tggcaagctg 8460
tgctgaggct cctaacatga aaatcatcgg caggcgcatt gagagaatcc gcaatgaaca 8520
tgcagaaaca tggtttcttg atgaaaacca cccatacagg acatgggcct accatgggag 8580
ctacgaagcc cccacgcaag gatcagcgtc ttccctcgtg aacggggttg ttagactcct 8640
gtcaaagcct tgggacgtgg tgactggagt tacaggaata gccatgactg acaccacacc 8700
atacggccaa caaagagtct tcaaagaaaa agtggacacc agggtgccag atccccaaga 8760
aggcactcgc caggtaatga acatagtctc ttcctggctg tggaaggagc tggggaaacg 8820
caagcggcca cgcgtctgca ccaaagaaga gtttatcaac aaggtgcgca gcaatgcagc 8880
actgggagca atatttgaag aggaaaaaga atggaagacg gctgtggaag ctgtgaatga 8940
tccaaggttt tgggccctag tggataggga gagagaacac cacctgagag gagagtgtca 9000
cagctgtgtg tacaacatga tgggaaaaag agaaaagaag caaggagagt tcgggaaagc 9060
aaaaggtagc cgcgccatct ggtacatgtg gttgggagcc agattcttgg agtttgaagc 9120
ccttggattc ttgaacgagg accattggat gggaagagaa aactcaggag gtggagtcga 9180
agggttagga ttgcaaagac ttggatacat tctagaagaa atgaatcggg caccaggagg 9240
aaagatgtac gcagatgaca ctgctggctg ggacacccgc attagtaagt ttgatctgga 9300
gaatgaagct ctgattacca accaaatgga ggaagggcac agaactctgg cgttggccgt 9360
gattaaatac acataccaaa acaaagtggt gaaggttctc agaccagctg aaggaggaaa 9420
aacagttatg gacatcattt caagacaaga ccagagaggg agtggacaag ttgtcactta 9480
tgctctcaac acattcacca acttggtggt gcagcttatc cggaacatgg aagctgagga 9540
agtgttagag atgcaagact tatggttgtt gaggaagcca gagaaagtga ccagatggtt 9600
gcagagcaat ggatgggata gactcaaacg aatggcggtc agtggagatg actgcgttgt 9660
gaagccaatc gatgataggt ttgcacatgc cctcaggttc ttgaatgaca tgggaaaagt 9720
taggaaagac acacaggagt ggaaaccctc gactggatgg agcaattggg aagaagtccc 9780
gttctgctcc caccacttca acaagctgta cctcaaggat gggagatcca ttgtggtccc 9840
ttgccgccac caagatgaac tgattggccg agctcgcgtc tcaccagggg caggatggag 9900
catccgggag actgcctgtc ttgcaaaatc atatgcgcag atgtggcagc tcctttattt 9960
ccacagaaga gaccttcgac tgatggctaa tgccatttgc tcggctgtgc cagttgactg 10020
ggtaccaact gggagaacca cctggtcaat ccatggaaag ggagaatgga tgaccactga 10080
ggacatgctc atggtgtgga atagagtgtg gattgaggag aacgaccata tggaggacaa 10140
gactcctgta acaaaatgga cagacattcc ctatctagga aaaagggagg acttatggtg 10200
tggatccctt atagggcaca gaccccgcac cacttgggct gaaaacatca aagacacagt 10260
caacatggtg cgcaggatca taggtgatga agaaaagtac atggactatc tatccaccca 10320
agtccgctac ttgggtgagg aagggtccac acccggagtg ttgtaagcac caattttagt 10380
gttgtcaggc ctgctagtca gccacagttt ggggaaagct gtgcagcctg taaccccccc 10440
aggagaagct gggaaaccaa gctcatagtc aggccgagaa cgccatggca cggaagaagc 10500
catgctgcct gtgagcccct cagaggacac tgagtcaaaa aaccccacgc gcttggaagc 10560
gcaggatggg aaaagaaggt ggcgaccttc cccacccttc aatctggggc ctgaactgga 10620
gactagctgt gaatctccag cagagggact agtggttaga ggagaccccc cggaaaacgc 10680
aaaacagcat attgacgctg ggaaagacca gagactccat gagtttccac cacgctggcc 10740
gccaggcaca gatcgccgaa cagcggcggc cggtgtgggg aaatccatgg tttct 10795
<210> 3
<211> 1987
<212> DNA
<213> Artificial
<400> 3
agcgctagcg gagtgtatac tggcttacta tgttggcact gatgagggtg tcagtgaagt 60
gcttcatgtg gcaggagaaa aaaggctgca ccggtgcgtc agcagaatat gtgatacagg 120
atatattccg cttcctcgct cactgactcg ctacgctcgg tcgttcgact gcggcgagcg 180
gaaatggctt acgaacgggg cggagatttc ctggaagatg ccaggaagat acttaacagg 240
gaagtgagag ggccgcggca aagccgtttt tccataggct ccgcccccct gacaagcatc 300
acgaaatctg acgctcaaat cagtggtggc gaaacccgac aggactataa agataccagg 360
cgtttcccct ggcggctccc tcgtgcgctc tcctgttcct gcctttcggt ttaccggtgt 420
cattccgctg ttatggccgc gtttgtctca ttccacgcct gacactcagt tccgggtagg 480
cagttcgctc caagctggac tgtatgcacg aaccccccgt tcagtccgac cgctgcgcct 540
tatccggtaa ctatcgtctt gagtccaacc cggaaagaca tgcaaaagca ccactggcag 600
cagccactgg taattgattt agaggagtta gtcttgaagt catgcgccgg ttaaggctaa 660
actgaaagga caagttttgg tgactgcgct cctccaagcc agttacctcg gttcaaagag 720
ttggtagctc agagaacctt cgaaaaaccg ccctgcaagg cggttttttc gttttcagag 780
caagagatta cgcgcagacc aaaacgatct caagaagatc atcttattaa ggggtctgac 840
gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc 900
ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag 960
taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt 1020
ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac gatacgggag 1080
ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc accggctcca 1140
gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg tcctgcaact 1200
ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag tagttcgcca 1260
gttaatagtt tgcgcaacgt tgttgccatt gctgcaggca tcgtggtgtc acgctcgtcg 1320
tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac atgatccccc 1380
atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag aagtaagttg 1440
gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac tgtcatgcca 1500
tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg agaatagtgt 1560
atgcggcgac cgagttgctc ttgcccggcg tcaacacggg ataataccgc gccacatagc 1620
agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc 1680
ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg atcttcagca 1740
tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa 1800
aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt tcaatattat 1860
tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg tatttagaaa 1920
aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga cgtgtcgacg 1980
cggccgc 1987
<210> 4
<211> 3419
<212> PRT
<213> Artificial
<400> 4
Met Lys Asn Pro Lys Lys Lys Ser Gly Gly Phe Arg Ile Val Asn Met
1 5 10 15
Leu Lys Arg Gly Val Ala Arg Val Asn Pro Leu Gly Gly Leu Lys Arg
20 25 30
Leu Pro Ala Gly Leu Leu Leu Gly His Gly Pro Ile Arg Met Val Leu
35 40 45
Ala Ile Leu Ala Phe Leu Arg Phe Thr Ala Ile Lys Pro Ser Leu Gly
50 55 60
Leu Ile Asn Arg Trp Gly Ser Val Gly Lys Lys Glu Ala Met Glu Ile
65 70 75 80
Ile Lys Lys Phe Lys Lys Asp Leu Ala Ala Met Leu Arg Ile Ile Asn
85 90 95
Ala Arg Lys Glu Arg Lys Arg Arg Gly Ala Asp Thr Ser Ile Gly Ile
100 105 110
Ile Gly Leu Leu Leu Thr Thr Ala Met Ala Ala Glu Ile Thr Arg Arg
115 120 125
Gly Ser Ala Tyr Tyr Met Tyr Leu Asp Arg Ser Asp Ala Gly Lys Ala
130 135 140
Ile Ser Phe Ala Thr Thr Leu Gly Val Asn Lys Cys His Val Gln Ile
145 150 155 160
Met Asp Leu Gly His Met Cys Asp Ala Thr Met Ser Tyr Glu Cys Pro
165 170 175
Met Leu Asp Glu Gly Val Glu Pro Asp Asp Val Asp Cys Trp Cys Asn
180 185 190
Thr Thr Ser Thr Trp Val Val Tyr Gly Thr Cys His His Lys Lys Gly
195 200 205
Glu Ala Arg Arg Ser Arg Arg Ala Val Thr Leu Pro Ser His Ser Thr
210 215 220
Arg Lys Leu Gln Thr Arg Ser Gln Thr Trp Leu Glu Ser Arg Glu Tyr
225 230 235 240
Thr Lys His Leu Ile Lys Val Glu Asn Trp Ile Phe Arg Asn Pro Gly
245 250 255
Phe Ala Leu Val Ala Val Ala Ile Ala Trp Leu Leu Gly Ser Ser Thr
260 265 270
Ser Gln Lys Val Ile Tyr Leu Val Met Ile Leu Leu Ile Ala Pro Ala
275 280 285
Tyr Ser Ile Arg Cys Ile Gly Val Ser Asn Arg Asp Phe Val Glu Gly
290 295 300
Met Ser Gly Gly Thr Trp Val Asp Val Val Leu Glu His Gly Gly Cys
305 310 315 320
Val Thr Val Met Ala Gln Asp Lys Pro Thr Val Asp Ile Glu Leu Val
325 330 335
Thr Thr Thr Val Ser Asn Met Ala Glu Val Arg Ser Tyr Cys Tyr Glu
340 345 350
Ala Ser Ile Ser Asp Met Ala Ser Asp Ser Arg Cys Pro Thr Gln Gly
355 360 365
Glu Ala Tyr Leu Asp Lys Gln Ser Asp Thr Gln Tyr Val Cys Lys Arg
370 375 380
Thr Leu Val Asp Arg Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys
385 390 395 400
Gly Ser Leu Val Thr Cys Ala Lys Phe Thr Cys Ser Lys Lys Met Thr
405 410 415
Gly Lys Ser Ile Gln Pro Glu Asn Leu Glu Tyr Arg Ile Met Leu Ser
420 425 430
Val His Gly Ser Gln His Ser Gly Met Ile Gly Tyr Glu Thr Asp Glu
435 440 445
Asn Arg Ala Lys Val Glu Val Thr Pro Asn Ser Pro Arg Ala Glu Ala
450 455 460
Thr Leu Gly Gly Phe Gly Ser Leu Gly Leu Asp Cys Glu Pro Arg Thr
465 470 475 480
Gly Leu Asp Phe Ser Asp Leu Tyr Tyr Leu Thr Met Asn Asn Lys His
485 490 495
Trp Leu Val His Lys Glu Trp Phe His Asp Ile Pro Leu Pro Trp His
500 505 510
Ala Gly Ala Asp Thr Gly Thr Pro His Trp Asn Asn Lys Glu Ala Leu
515 520 525
Val Glu Phe Lys Asp Ala His Ala Lys Arg Gln Thr Val Val Val Leu
530 535 540
Gly Ser Gln Glu Gly Ala Val His Thr Ala Leu Ala Gly Ala Leu Glu
545 550 555 560
Ala Glu Met Asp Gly Ala Lys Gly Arg Leu Phe Ser Gly His Leu Lys
565 570 575
Cys Arg Leu Lys Met Asp Lys Leu Arg Leu Lys Gly Val Ser Tyr Ser
580 585 590
Leu Cys Thr Ala Ala Phe Thr Phe Thr Lys Val Pro Ala Glu Thr Leu
595 600 605
His Gly Thr Val Thr Val Glu Val Gln Tyr Ala Gly Thr Asp Gly Pro
610 615 620
Cys Lys Ile Pro Val Gln Met Ala Val Asp Met Gln Thr Leu Thr Pro
625 630 635 640
Val Gly Arg Leu Ile Thr Ala Asn Pro Val Ile Thr Glu Ser Thr Glu
645 650 655
Asn Ser Lys Met Met Leu Glu Leu Asp Pro Pro Phe Gly Asp Ser Tyr
660 665 670
Ile Val Ile Gly Val Gly Asp Lys Lys Ile Thr His His Trp His Arg
675 680 685
Ser Gly Ser Thr Ile Gly Lys Ala Phe Glu Ala Thr Val Arg Gly Ala
690 695 700
Lys Arg Met Ala Val Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser Val
705 710 715 720
Gly Gly Val Phe Asn Ser Leu Gly Lys Gly Ile His Gln Ile Phe Gly
725 730 735
Ala Ala Phe Lys Ser Leu Phe Gly Gly Met Ser Trp Phe Ser Gln Ile
740 745 750
Leu Ile Gly Thr Leu Leu Val Trp Leu Gly Leu Asn Thr Lys Asn Gly
755 760 765
Ser Ile Ser Leu Thr Cys Leu Ala Leu Gly Gly Val Met Ile Phe Leu
770 775 780
Ser Thr Ala Val Ser Ala Asp Val Gly Cys Ser Val Asp Phe Ser Lys
785 790 795 800
Lys Glu Thr Arg Cys Gly Thr Gly Val Phe Ile Tyr Asn Asp Val Glu
805 810 815
Ala Trp Arg Asp Arg Tyr Lys Tyr His Pro Asp Ser Pro Arg Arg Leu
820 825 830
Ala Ala Ala Val Lys Gln Ala Trp Glu Glu Gly Ile Cys Gly Ile Ser
835 840 845
Ser Val Ser Arg Met Glu Asn Ile Met Trp Lys Ser Val Glu Gly Glu
850 855 860
Leu Asn Ala Ile Leu Glu Glu Asn Gly Val Gln Leu Thr Val Val Val
865 870 875 880
Gly Ser Val Lys Asn Pro Met Trp Arg Gly Pro Gln Arg Leu Pro Val
885 890 895
Pro Val Asn Glu Leu Pro His Gly Trp Lys Ala Trp Gly Lys Ser Tyr
900 905 910
Phe Val Arg Ala Ala Lys Thr Asn Asn Ser Phe Val Val Asp Gly Asp
915 920 925
Thr Leu Lys Glu Cys Pro Leu Glu His Arg Ala Trp Asn Ser Phe Leu
930 935 940
Val Glu Asp His Gly Phe Gly Val Phe His Thr Ser Val Trp Leu Lys
945 950 955 960
Val Arg Glu Asp Tyr Ser Leu Glu Cys Asp Pro Ala Val Ile Gly Thr
965 970 975
Ala Val Lys Gly Arg Glu Ala Ala His Ser Asp Leu Gly Tyr Trp Ile
980 985 990
Glu Ser Glu Lys Asn Asp Thr Trp Arg Leu Lys Arg Ala His Leu Ile
995 1000 1005
Glu Met Lys Thr Cys Glu Trp Pro Lys Ser His Thr Leu Trp Thr Asp
1010 1015 1020
Gly Val Glu Glu Ser Asp Leu Ile Ile Pro Lys Ser Leu Ala Gly Pro
1025 1030 1035 1040
Leu Ser His His Asn Thr Arg Glu Gly Tyr Arg Thr Gln Val Lys Gly
1045 1050 1055
Pro Trp His Ser Glu Glu Leu Glu Ile Arg Phe Glu Glu Cys Pro Gly
1060 1065 1070
Thr Lys Val Tyr Val Glu Glu Thr Cys Gly Thr Arg Gly Pro Ser Leu
1075 1080 1085
Arg Ser Thr Thr Ala Ser Gly Arg Val Ile Glu Glu Trp Cys Cys Arg
1090 1095 1100
Glu Cys Thr Met Pro Pro Leu Ser Phe Arg Ala Lys Asp Gly Cys Trp
1105 1110 1115 1120
Tyr Gly Met Glu Ile Arg Pro Arg Lys Glu Pro Glu Ser Asn Leu Val
1125 1130 1135
Arg Ser Met Val Thr Ala Gly Ser Thr Asp His Met Asp His Phe Ser
1140 1145 1150
Leu Gly Val Leu Val Ile Leu Leu Met Val Gln Glu Gly Leu Lys Lys
1155 1160 1165
Arg Met Thr Thr Lys Ile Ile Met Ser Thr Ser Met Ala Val Leu Val
1170 1175 1180
Val Met Ile Leu Gly Gly Phe Ser Met Ser Asp Leu Ala Lys Leu Val
1185 1190 1195 1200
Ile Leu Met Gly Ala Thr Phe Ala Glu Met Asn Thr Gly Gly Asp Val
1205 1210 1215
Ala His Leu Ala Leu Val Ala Ala Phe Lys Val Arg Pro Ala Leu Leu
1220 1225 1230
Val Ser Phe Ile Phe Arg Ala Asn Trp Thr Pro Arg Glu Ser Met Leu
1235 1240 1245
Leu Ala Leu Ala Ser Cys Leu Leu Gln Thr Ala Ile Ser Ala Leu Glu
1250 1255 1260
Gly Asp Leu Met Val Leu Ile Asn Gly Phe Ala Leu Ala Trp Leu Ala
1265 1270 1275 1280
Ile Arg Ala Met Ala Val Pro Arg Thr Asp Asn Ile Ala Leu Pro Ile
1285 1290 1295
Leu Ala Ala Leu Thr Pro Leu Ala Arg Gly Thr Leu Leu Val Ala Trp
1300 1305 1310
Arg Ala Gly Leu Ala Thr Cys Gly Gly Ile Met Leu Leu Ser Leu Lys
1315 1320 1325
Gly Lys Gly Ser Val Lys Lys Asn Leu Pro Phe Val Met Ala Leu Gly
1330 1335 1340
Leu Thr Ala Val Arg Val Val Asp Pro Ile Asn Val Val Gly Leu Leu
1345 1350 1355 1360
Leu Leu Thr Arg Ser Gly Lys Arg Ser Trp Pro Pro Ser Glu Val Leu
1365 1370 1375
Thr Ala Val Gly Leu Ile Cys Ala Leu Ala Gly Gly Phe Ala Lys Ala
1380 1385 1390
Asp Ile Glu Met Ala Gly Pro Met Ala Ala Val Gly Leu Leu Ile Val
1395 1400 1405
Ser Tyr Val Val Ser Gly Lys Ser Val Asp Met Tyr Ile Glu Arg Ala
1410 1415 1420
Gly Asp Ile Thr Trp Glu Lys Asp Ala Glu Val Thr Gly Asn Ser Pro
1425 1430 1435 1440
Arg Leu Asp Val Ala Leu Asp Glu Ser Gly Asp Phe Ser Leu Val Glu
1445 1450 1455
Glu Asp Gly Pro Pro Met Arg Glu Ile Ile Leu Lys Val Val Leu Met
1460 1465 1470
Ala Ile Cys Gly Met Asn Pro Ile Ala Ile Pro Phe Ala Ala Gly Ala
1475 1480 1485
Trp Tyr Val Tyr Val Lys Thr Gly Lys Arg Ser Gly Ala Leu Trp Asp
1490 1495 1500
Val Pro Ala Pro Lys Glu Val Lys Lys Gly Glu Thr Thr Asp Gly Val
1505 1510 1515 1520
Tyr Arg Val Met Thr Arg Arg Leu Leu Gly Ser Thr Gln Val Gly Val
1525 1530 1535
Gly Val Met Gln Glu Gly Val Phe His Thr Met Trp His Val Thr Lys
1540 1545 1550
Gly Ala Ala Leu Arg Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp Gly
1555 1560 1565
Asp Val Lys Gln Asp Leu Val Ser Tyr Cys Gly Pro Trp Lys Leu Asp
1570 1575 1580
Ala Ala Trp Asp Gly Leu Ser Glu Val Gln Leu Leu Ala Val Pro Pro
585 1590 1595 1600
Gly Glu Arg Ala Arg Asn Ile Gln Thr Leu Pro Gly Ile Phe Lys Thr
1605 1610 1615
Lys Asp Gly Asp Ile Gly Ala Val Ala Leu Asp Tyr Pro Ala Gly Thr
1620 1625 1630
Ser Gly Ser Pro Ile Leu Asp Lys Cys Gly Arg Val Ile Gly Leu Tyr
1635 1640 1645
Gly Asn Gly Val Val Ile Lys Asn Gly Ser Tyr Val Ser Ala Ile Thr
1650 1655 1660
Gln Gly Lys Arg Glu Glu Glu Thr Pro Val Glu Cys Phe Glu Pro Ser
665 1670 1675 1680
Met Leu Lys Lys Lys Gln Leu Thr Val Leu Asp Leu His Pro Gly Ala
1685 1690 1695
Gly Lys Thr Arg Arg Val Leu Pro Glu Ile Val Arg Glu Ala Ile Lys
1700 1705 1710
Lys Arg Leu Arg Thr Val Ile Leu Ala Pro Thr Arg Val Val Ala Ala
1715 1720 1725
Glu Met Glu Glu Ala Leu Arg Gly Leu Pro Val Arg Tyr Met Thr Thr
1730 1735 1740
Ala Val Asn Val Thr His Ser Gly Thr Glu Ile Val Asp Leu Met Cys
745 1750 1755 1760
His Ala Thr Phe Thr Ser Arg Leu Leu Gln Pro Ile Arg Val Pro Asn
1765 1770 1775
Tyr Asn Leu Tyr Ile Met Asp Glu Ala His Phe Thr Asp Pro Ser Ser
1780 1785 1790
Ile Ala Ala Arg Gly Tyr Ile Ser Thr Arg Val Glu Met Gly Glu Ala
1795 1800 1805
Ala Ala Ile Phe Met Thr Ala Thr Pro Pro Gly Thr Arg Asp Ala Phe
1810 1815 1820
Pro Asp Ser Asn Ser Pro Ile Met Asp Thr Glu Val Glu Val Pro Glu
1825 1830 1835 1840
Arg Ala Trp Ser Ser Gly Phe Asp Trp Val Thr Asp His Ser Gly Lys
1845 1850 1855
Thr Val Trp Phe Val Pro Ser Val Arg Asn Gly Asn Glu Ile Ala Ala
1860 1865 1870
Cys Leu Thr Lys Ala Gly Lys Arg Val Ile Gln Leu Ser Arg Lys Thr
1875 1880 1885
Phe Glu Thr Glu Phe Gln Lys Thr Lys Asn Gln Glu Trp Asp Phe Val
1890 1895 1900
Ile Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys Ala Asp Arg
1905 1910 1915 1920
Val Ile Asp Ser Arg Arg Cys Leu Lys Pro Val Ile Leu Asp Gly Glu
1925 1930 1935
Arg Val Ile Leu Ala Gly Pro Met Pro Val Thr His Ala Ser Ala Ala
1940 1945 1950
Gln Arg Arg Gly Arg Ile Gly Arg Asn Pro Asn Lys Pro Gly Asp Glu
1955 1960 1965
Tyr Met Tyr Gly Gly Gly Cys Ala Glu Thr Asp Glu Gly His Ala His
1970 1975 1980
Trp Leu Glu Ala Arg Met Leu Leu Asp Asn Ile Tyr Leu Gln Asp Gly
1985 1990 1995 2000
Leu Ile Ala Ser Leu Tyr Arg Pro Glu Ala Asp Lys Val Ala Ala Ile
2005 2010 2015
Glu Gly Glu Phe Lys Leu Arg Thr Glu Gln Arg Lys Thr Phe Val Glu
2020 2025 2030
Leu Met Lys Arg Gly Asp Leu Pro Val Trp Leu Ala Tyr Gln Val Ala
2035 2040 2045
Ser Ala Gly Ile Thr Tyr Thr Asp Arg Arg Trp Cys Phe Asp Gly Thr
2050 2055 2060
Thr Asn Asn Thr Ile Met Glu Asp Ser Val Pro Ala Glu Val Trp Thr
2065 2070 2075 2080
Lys Tyr Gly Glu Lys Arg Val Leu Lys Pro Arg Trp Met Asp Ala Arg
2085 2090 2095
Val Cys Ser Asp His Ala Ala Leu Lys Ser Phe Lys Glu Phe Ala Ala
2100 2105 2110
Gly Lys Arg Gly Ala Ala Leu Gly Val Met Glu Ala Leu Gly Thr Leu
2115 2120 2125
Pro Gly His Met Thr Glu Arg Phe Gln Glu Ala Ile Asp Asn Leu Ala
2130 2135 2140
Val Leu Met Arg Ala Glu Thr Gly Ser Arg Pro Tyr Lys Ala Ala Ala
2145 2150 2155 2160
Ala Gln Leu Pro Glu Thr Leu Glu Thr Ile Met Leu Leu Gly Leu Leu
2165 2170 2175
Gly Thr Val Ser Leu Gly Ile Phe Phe Val Leu Met Arg Asn Lys Gly
2180 2185 2190
Ile Gly Lys Met Gly Phe Gly Met Val Thr Leu Gly Ala Ser Ala Trp
2195 2200 2205
Leu Met Trp Leu Ser Glu Ile Glu Pro Ala Arg Ile Ala Cys Val Leu
2210 2215 2220
Ile Val Val Phe Leu Leu Leu Val Val Leu Ile Pro Glu Pro Glu Lys
2225 2230 2235 2240
Gln Arg Ser Pro Gln Asp Asn Gln Met Ala Ile Ile Ile Met Val Ala
2245 2250 2255
Val Gly Leu Leu Gly Leu Ile Thr Ala Asn Glu Leu Gly Trp Leu Glu
2260 2265 2270
Arg Thr Lys Asn Asp Ile Ala His Leu Met Gly Arg Arg Glu Glu Gly
2275 2280 2285
Ala Thr Met Gly Phe Ser Met Asp Ile Asp Leu Arg Pro Ala Ser Ala
2290 2295 2300
Trp Ala Ile Tyr Ala Ala Leu Thr Thr Leu Ile Thr Pro Ala Val Gln
2305 2310 2315 2320
His Ala Val Thr Thr Ser Tyr Asn Asn Tyr Ser Leu Met Ala Met Ala
2325 2330 2335
Thr Gln Ala Gly Val Leu Phe Gly Met Gly Lys Gly Met Pro Phe Tyr
2340 2345 2350
Ala Trp Asp Leu Gly Val Pro Leu Leu Met Met Gly Cys Tyr Ser Gln
2355 2360 2365
Leu Thr Pro Leu Thr Leu Ile Val Ala Ile Ile Leu Leu Val Ala His
2370 2375 2380
Tyr Met Tyr Leu Ile Pro Gly Leu Gln Ala Ala Ala Ala Arg Ala Ala
2385 2390 2395 2400
Gln Lys Arg Thr Ala Ala Gly Ile Met Lys Asn Pro Val Val Asp Gly
2405 2410 2415
Ile Val Val Thr Asp Ile Asp Thr Met Thr Ile Asp Pro Gln Val Glu
2420 2425 2430
Lys Lys Met Gly Gln Val Leu Leu Ile Ala Val Ala Ile Ser Ser Ala
2435 2440 2445
Val Leu Leu Arg Thr Ala Trp Gly Trp Gly Glu Ala Gly Ala Leu Ile
2450 2455 2460
Thr Ala Ala Thr Ser Thr Leu Trp Glu Gly Ser Pro Asn Lys Tyr Trp
2465 2470 2475 2480
Asn Ser Ser Thr Ala Thr Ser Leu Cys Asn Ile Phe Arg Gly Ser Tyr
2485 2490 2495
Leu Ala Gly Ala Ser Leu Ile Tyr Thr Val Thr Arg Asn Ala Gly Leu
2500 2505 2510
Val Lys Arg Arg Gly Gly Gly Thr Gly Glu Thr Leu Gly Glu Lys Trp
2515 2520 2525
Lys Ala Arg Leu Asn Gln Met Ser Ala Leu Glu Phe Tyr Ser Tyr Lys
2530 2535 2540
Lys Ser Gly Ile Thr Glu Val Cys Arg Glu Glu Ala Arg Arg Ala Leu
2545 2550 2555 2560
Lys Asp Gly Val Ala Thr Gly Gly His Ala Val Ser Arg Gly Ser Ala
2565 2570 2575
Lys Leu Arg Trp Leu Val Glu Arg Gly Tyr Leu Gln Pro Tyr Gly Lys
2580 2585 2590
Val Val Asp Leu Gly Cys Gly Arg Gly Gly Trp Ser Tyr Tyr Ala Ala
2595 2600 2605
Thr Ile Arg Lys Val Gln Glu Val Arg Gly Tyr Thr Lys Gly Gly Pro
2610 2615 2620
Gly His Glu Glu Pro Met Leu Val Gln Ser Tyr Gly Trp Asn Ile Val
2625 2630 2635 2640
Arg Leu Lys Ser Gly Val Asp Val Phe His Met Ala Ala Glu Pro Cys
2645 2650 2655
Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Ser Ser Pro Glu Val
2660 2665 2670
Glu Glu Thr Arg Thr Leu Arg Val Leu Ser Met Val Gly Asp Trp Leu
2675 2680 2685
Glu Lys Arg Pro Gly Ala Phe Cys Ile Lys Val Leu Cys Pro Tyr Thr
2690 2695 2700
Ser Thr Met Met Glu Thr Met Glu Arg Leu Gln Arg Arg His Gly Gly
2705 2710 2715 2720
Gly Leu Val Arg Val Pro Leu Ser Arg Asn Ser Thr His Glu Met Tyr
2725 2730 2735
Trp Val Ser Gly Ala Lys Ser Asn Ile Ile Lys Ser Val Ser Thr Thr
2740 2745 2750
Ser Gln Leu Leu Leu Gly Arg Met Asp Gly Pro Arg Arg Pro Val Lys
2755 2760 2765
Tyr Glu Glu Asp Val Asn Leu Gly Ser Gly Thr Arg Ala Val Ala Ser
2770 2775 2780
Cys Ala Glu Ala Pro Asn Met Lys Ile Ile Gly Arg Arg Ile Glu Arg
2785 2790 2795 2800
Ile Arg Asn Glu His Ala Glu Thr Trp Phe Leu Asp Glu Asn His Pro
2805 2810 2815
Tyr Arg Thr Trp Ala Tyr His Gly Ser Tyr Glu Ala Pro Thr Gln Gly
2820 2825 2830
Ser Ala Ser Ser Leu Val Asn Gly Val Val Arg Leu Leu Ser Lys Pro
2835 2840 2845
Trp Asp Val Val Thr Gly Val Thr Gly Ile Ala Met Thr Asp Thr Thr
2850 2855 2860
Pro Tyr Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Arg Val
2865 2870 2875 2880
Pro Asp Pro Gln Glu Gly Thr Arg Gln Val Met Asn Ile Val Ser Ser
2885 2890 2895
Trp Leu Trp Lys Glu Leu Gly Lys Arg Lys Arg Pro Arg Val Cys Thr
2900 2905 2910
Lys Glu Glu Phe Ile Asn Lys Val Arg Ser Asn Ala Ala Leu Gly Ala
2915 2920 2925
Ile Phe Glu Glu Glu Lys Glu Trp Lys Thr Ala Val Glu Ala Val Asn
2930 2935 2940
Asp Pro Arg Phe Trp Ala Leu Val Asp Arg Glu Arg Glu His His Leu
2945 2950 2955 2960
Arg Gly Glu Cys His Ser Cys Val Tyr Asn Met Met Gly Lys Arg Glu
2965 2970 2975
Lys Lys Gln Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg Ala Ile Trp
2980 2985 2990
Tyr Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu Ala Leu Gly Phe
2995 3000 3005
Leu Asn Glu Asp His Trp Met Gly Arg Glu Asn Ser Gly Gly Gly Val
3010 3015 3020
Glu Gly Leu Gly Leu Gln Arg Leu Gly Tyr Ile Leu Glu Glu Met Asn
3025 3030 3035 3040
Arg Ala Pro Gly Gly Lys Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp
3045 3050 3055
Thr Arg Ile Ser Lys Phe Asp Leu Glu Asn Glu Ala Leu Ile Thr Asn
3060 3065 3070
Gln Met Glu Glu Gly His Arg Thr Leu Ala Leu Ala Val Ile Lys Tyr
3075 3080 3085
Thr Tyr Gln Asn Lys Val Val Lys Val Leu Arg Pro Ala Glu Gly Gly
3090 3095 3100
Lys Thr Val Met Asp Ile Ile Ser Arg Gln Asp Gln Arg Gly Ser Gly
3105 3110 3115 3120
Gln Val Val Thr Tyr Ala Leu Asn Thr Phe Thr Asn Leu Val Val Gln
3125 3130 3135
Leu Ile Arg Asn Met Glu Ala Glu Glu Val Leu Glu Met Gln Asp Leu
3140 3145 3150
Trp Leu Leu Arg Lys Pro Glu Lys Val Thr Arg Trp Leu Gln Ser Asn
3155 3160 3165
Gly Trp Asp Arg Leu Lys Arg Met Ala Val Ser Gly Asp Asp Cys Val
3170 3175 3180
Val Lys Pro Ile Asp Asp Arg Phe Ala His Ala Leu Arg Phe Leu Asn
3185 3190 3195 3200
Asp Met Gly Lys Val Arg Lys Asp Thr Gln Glu Trp Lys Pro Ser Thr
3205 3210 3215
Gly Trp Ser Asn Trp Glu Glu Val Pro Phe Cys Ser His His Phe Asn
3220 3225 3230
Lys Leu Tyr Leu Lys Asp Gly Arg Ser Ile Val Val Pro Cys Arg His
3235 3240 3245
Gln Asp Glu Leu Ile Gly Arg Ala Arg Val Ser Pro Gly Ala Gly Trp
3250 3255 3260
Ser Ile Arg Glu Thr Ala Cys Leu Ala Lys Ser Tyr Ala Gln Met Trp
3265 3270 3275 3280
Gln Leu Leu Tyr Phe His Arg Arg Asp Leu Arg Leu Met Ala Asn Ala
3285 3290 3295
Ile Cys Ser Ala Val Pro Val Asp Trp Val Pro Thr Gly Arg Thr Thr
3300 3305 3310
Trp Ser Ile His Gly Lys Gly Glu Trp Met Thr Thr Glu Asp Met Leu
3315 3320 3325
Met Val Trp Asn Arg Val Trp Ile Glu Glu Asn Asp His Met Glu Asp
3330 3335 3340
Lys Thr Pro Val Thr Lys Trp Thr Asp Ile Pro Tyr Leu Gly Lys Arg
3345 3350 3355 3360
Glu Asp Leu Trp Cys Gly Ser Leu Ile Gly His Arg Pro Arg Thr Thr
3365 3370 3375
Trp Ala Glu Asn Ile Lys Asp Thr Val Asn Met Val Arg Arg Ile Ile
3380 3385 3390
Gly Asp Glu Glu Lys Tyr Met Asp Tyr Leu Ser Thr Gln Val Arg Tyr
3395 3400 3405
Leu Gly Glu Glu Gly Ser Thr Pro Gly Val Leu
3410 3415
<210> 5
<211> 13764
<212> DNA
<213> Artificial
<400> 5
agcgctagcg gagtgtatac tggcttacta tgttggcact gatgagggtg tcagtgaagt 60
gcttcatgtg gcaggagaaa aaaggctgca ccggtgcgtc agcagaatat gtgatacagg 120
atatattccg cttcctcgct cactgactcg ctacgctcgg tcgttcgact gcggcgagcg 180
gaaatggctt acgaacgggg cggagatttc ctggaagatg ccaggaagat acttaacagg 240
gaagtgagag ggccgcggca aagccgtttt tccataggct ccgcccccct gacaagcatc 300
acgaaatctg acgctcaaat cagtggtggc gaaacccgac aggactataa agataccagg 360
cgtttcccct ggcggctccc tcgtgcgctc tcctgttcct gcctttcggt ttaccggtgt 420
cattccgctg ttatggccgc gtttgtctca ttccacgcct gacactcagt tccgggtagg 480
cagttcgctc caagctggac tgtatgcacg aaccccccgt tcagtccgac cgctgcgcct 540
tatccggtaa ctatcgtctt gagtccaacc cggaaagaca tgcaaaagca ccactggcag 600
cagccactgg taattgattt agaggagtta gtcttgaagt catgcgccgg ttaaggctaa 660
actgaaagga caagttttgg tgactgcgct cctccaagcc agttacctcg gttcaaagag 720
ttggtagctc agagaacctt cgaaaaaccg ccctgcaagg cggttttttc gttttcagag 780
caagagatta cgcgcagacc aaaacgatct caagaagatc atcttattaa ggggtctgac 840
gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc 900
ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag 960
taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt 1020
ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac gatacgggag 1080
ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc accggctcca 1140
gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg tcctgcaact 1200
ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag tagttcgcca 1260
gttaatagtt tgcgcaacgt tgttgccatt gctgcaggca tcgtggtgtc acgctcgtcg 1320
tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac atgatccccc 1380
atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag aagtaagttg 1440
gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac tgtcatgcca 1500
tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg agaatagtgt 1560
atgcggcgac cgagttgctc ttgcccggcg tcaacacggg ataataccgc gccacatagc 1620
agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc 1680
ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg atcttcagca 1740
tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa 1800
aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt tcaatattat 1860
tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg tatttagaaa 1920
aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga cgtgtcgacg 1980
cggccgcgct agcgatgatt taggtgacac tatagaagtt gttgatctgt gtgagtcaga 2040
ctgcgacagt tcgagtctga agcgagagct aacaacagta tcaacaggtt taatttggat 2100
ttggaaacga gagtttctgg tcatgaaaaa cccaaagaag aaatccggag gattccggat 2160
tgtcaatatg ctaaaacgcg gagtagcccg tgtaaacggt accgagctca tggccaagcc 2220
caccgagaac aacgaagact tcaacatcgt ggccgtggcc agcaacttcg cgaccacgga 2280
tctcgatgct gaccgcggga agttgcccgg caagaagctg ccgctggagg tgctcaaaga 2340
gatggaagcc aatgcccgga aagctggctg caccaggggc tgtctgatct gcctgtccca 2400
catcaagtgc acgcccaaga tgaagaagtt catcccagga cgctgccaca cctacgaagg 2460
cgacaaagag tccgcacagg gcggcatagg cgaggcgatc gtcgacattc ctgagattcc 2520
tgggttcaag gacttggagc ccatggagca gttcatcgca caggtcgatc tgtgtgtgga 2580
ctgcacaact ggctgcctca aagggcttgc caacgtgcag tgttctgacc tgctcaagaa 2640
gtggctgccg caacgctgtg cgacctttgc cagcaagatc cagggccagg tggacaagat 2700
caagggggcc ggtggtgaca ccggtaactt tgaccttctc aagttggccg gcgacgtcga 2760
gtccaaccca gggcccctgc agcaaatttt cgtgaagacc ctgacgggca agaccatcac 2820
tcttgaggtc gagcccagtg acaccatcga gaatgtcaag gccaagatcc aagacaagga 2880
aggcatccca cctgaccagc agaggctgat attcgcgggc aaacagctgg aggatggccg 2940
caccctgtcc gactacaaca tccagaaaga gtccaccttg cacctggtgc tgcgtctccg 3000
cggtggaatg aagaacccaa agaaaaaatc aggaggattt cggatagtca acatgctaaa 3060
acgcggcgta gcccgtgtta accccttggg aggtttgaag aggttgccag ccggacttct 3120
gctgggtcat ggacccatca gaatggtttt ggcgatacta gcctttttga gatttacagc 3180
aatcaagcca tcactgggcc ttatcaacag atggggttcc gtggggaaaa aagaggctat 3240
ggaaataata aagaagttca agaaagatct tgctgccatg ttgagaataa tcaatgctag 3300
gaaagagagg aagagacgtg gcgcagacac cagcatcgga atcattggcc tcctgctgac 3360
tacagccatg gcagcagaga tcactagacg cgggagtgca tactacatgt acttggatag 3420
gagcgatgcc gggaaggcca tttcgtttgc taccacattg ggagtgaaca agtgccacgt 3480
acagatcatg gacctcgggc acatgtgtga cgccaccatg agttatgagt gccctatgct 3540
ggatgaggga gtggaaccag atgatgtcga ttgctggtgc aacacgacat caacttgggt 3600
tgtgtacgga acctgtcatc acaaaaaagg tgaggcacgg cgatctagaa gagccgtgac 3660
gctcccttct cactctacaa ggaagttgca aacgcggtcg cagacctggt tagaatcaag 3720
agaatacacg aagcacttga tcaaggttga aaactggata ttcaggaacc ccgggtttgc 3780
gctagtggcc gttgccattg cctggctttt gggaagctcg acgagccaaa aagtcatata 3840
cttggtcatg atactgctga ttgccccggc atacagtatc aggtgcattg gagtcagcaa 3900
tagagacttc gtggagggca tgtcaggtgg gacctgggtt gatgttgtct tggaacatgg 3960
aggctgcgtt accgtgatgg cacaggacaa gccaacagtc gacatagagt tggtcacgac 4020
gacggttagt aacatggccg aggtaagatc ctattgctac gaggcatcga tatcggacat 4080
ggcttcggac agtcgttgcc caacacaagg tgaagcctac cttgacaagc aatcagacac 4140
tcaatatgtc tgcaaaagaa cattagtgga cagaggttgg ggaaacggtt gtggactttt 4200
tggcaaaggg agcttggtga catgtgccaa gtttacgtgt tctaagaaga tgaccgggaa 4260
gagcattcaa ccggaaaatc tggagtatcg gataatgcta tcagtgcatg gctcccagca 4320
tagcgggatg attggatatg aaactgacga aaatagagcg aaagtcgagg ttacgcctaa 4380
ttcaccaaga gcggaagcaa ccttgggagg ctttggaagc ttaggacttg actgtgaacc 4440
aaggacaggc cttgactttt cagatctgta ttacctgacc atgaacaata agcattggtt 4500
ggtgcacaaa gagtggtttc atgacatccc attgccttgg catgctgggg cagacaccgg 4560
aactccacac tggaacaaca aagaggcatt ggtagaattc aaggatgccc acgccaagag 4620
gcaaaccgtc gtcgttctgg ggagccagga aggagccgtt cacacggctc tcgctggagc 4680
tctagaggct gagatggatg gtgcaaaggg aaggctgttc tctggccatt tgaaatgccg 4740
cctaaaaatg gacaagctta gattgaaggg cgtgtcatat tccttgtgca ctgcggcatt 4800
cacattcacc aaggtcccag ctgaaacact gcatggaaca gtcacagtgg aggtgcagta 4860
tgcagggaca gatggaccct gcaagatccc agtccagatg gcggtggaca tgcagaccct 4920
gaccccagtt ggaaggctga taaccgccaa ccccgtgatt actgaaagca ctgagaactc 4980
aaagatgatg ttggagcttg acccaccatt tggggattct tacattgtca taggagttgg 5040
ggacaagaaa atcacccacc actggcatag gagtggtagc accatcggaa aggcatttga 5100
ggccactgtg agaggcgcca agagaatggc agtcctgggg gatacagcct gggacttcgg 5160
atcagtcggg ggtgtgttca actcactggg taagggcatt caccagattt ttggagcagc 5220
cttcaaatca ctgtttggag gaatgtcctg gttctcacag atcctcatag gcacgctgct 5280
agtgtggtta ggtttgaaca caaagaatgg atctatctcc ctcacatgct tggccctggg 5340
gggagtgatg atcttcctct ccacggctgt ttctgctgac gtggggtgct cagtggactt 5400
ctcaaaaaag gaaacgagat gtggcacggg ggtattcatc tataatgatg ttgaagcctg 5460
gagggaccgg tacaagtacc atcctgactc cccccgcaga ttggcagcag cagtcaagca 5520
ggcctgggaa gaggggatct gtgggatctc atccgtttca agaatggaaa acatcatgtg 5580
gaaatcagta gaaggggagc tcaatgctat cctagaggag aatggagttc aactgacagt 5640
tgttgtggga tctgtaaaaa accccatgtg gagaggtcca caaagattgc cagtgcctgt 5700
gaatgagctg ccccatggct ggaaagcctg ggggaaatcg tattttgtta gggcggcaaa 5760
gaccaacaac agttttgttg tcgacggtga cacactgaag gaatgtccgc ttgagcacag 5820
agcatggaat agttttcttg tggaggatca cgggtttgga gtcttccaca ccagtgtctg 5880
gcttaaggtc agagaagatt actcattaga atgtgaccca gccgtcatag gaacagctgt 5940
taagggaagg gaggccgcgc acagtgatct gggctattgg attgaaagtg aaaagaatga 6000
cacatggagg ctgaagaggg cccacctgat tgagatgaaa acatgtgaat ggccaaagtc 6060
tcacacattg tggacagatg gagtagaaga aagtgatctt atcataccca agtctttagc 6120
tggtccactc agccaccaca acaccagaga gggttacaga acccaagtga aagggccatg 6180
gcacagtgaa gagcttgaaa tccggtttga ggaatgtcca ggcaccaagg tttacgtgga 6240
ggagacatgc ggaactagag gaccatctct gagatcaact actgcaagtg gaagggtcat 6300
tgaggaatgg tgctgtaggg aatgcacaat gcccccacta tcgtttcgag caaaagacgg 6360
ctgctggtat ggaatggaga taaggcccag gaaagaacca gagagcaact tagtgaggtc 6420
aatggtgaca gcggggtcaa ccgatcatat ggaccacttc tctcttggag tgcttgtgat 6480
tctactcatg gtgcaggagg ggttgaagaa gagaatgacc acaaagatca tcatgagcac 6540
atcaatggca gtgctggtag tcatgatctt gggaggattt tcaatgagtg acctggccaa 6600
gcttgtgatc ctgatgggtg ctactttcgc agaaatgaac actggaggag atgtagctca 6660
cttggcattg gtagcggcat ttaaagtcag accagccttg ctggtctcct tcattttcag 6720
agccaattgg acaccccgtg agagcatgct gctagccctg gcttcgtgtc ttctgcaaac 6780
tgcgatctct gctcttgaag gtgacttgat ggtcctcatt aatggatttg ctttggcctg 6840
gttggcaatt cgagcaatgg ccgtgccacg cactgacaac atcgctctac caatcttggc 6900
tgctctaaca ccactagctc gaggcacact gctcgtggca tggagagcgg gcctggctac 6960
ttgtggaggg atcatgctcc tctccctgaa agggaaaggt agtgtgaaga agaacctgcc 7020
atttgtcatg gccctgggat tgacagctgt gagggtagta gaccctatta atgtggtagg 7080
actactgtta ctcacaagga gtgggaagcg gagctggccc cctagtgaag ttctcacagc 7140
cgttggcctg atatgtgcac tggccggagg gtttgccaag gcagacattg agatggctgg 7200
acccatggct gcagtaggct tgctaattgt cagctatgtg gtctcgggaa agagtgtgga 7260
catgtacatt gaaagagcag gtgacatcac atgggaaaag gacgcggaag tcactggaaa 7320
cagtcctcgg cttgacgtgg cactggatga gagtggtgac ttctccttgg tagaggaaga 7380
tggtccaccc atgagagaga tcatactcaa ggtggtcctg atggccatct gtggcatgaa 7440
cccaatagct ataccttttg ctgcaggagc gtggtatgtg tatgtgaaga ctgggaaaag 7500
gagtggcgcc ctctgggacg tgcctgctcc caaagaagtg aagaaaggag agaccacaga 7560
tggagtgtac agagtgatga ctcgcagact gctaggttca acacaggttg gagtgggagt 7620
catgcaagag ggagtcttcc acaccatgtg gcacgttaca aaaggagccg cactgaggag 7680
cggtgaggga agacttgatc catactgggg ggatgtcaag caggacttgg tgtcatactg 7740
tgggccttgg aagttggatg cagcttggga tggactcagc gaggtacagc ttttggccgt 7800
acctcccgga gagagggcca gaaacattca gaccctgcct ggaatattca agacaaagga 7860
cggggacatc ggagcagttg ctctggacta ccctgcaggg acctcaggat ctccgatcct 7920
agacaaatgt ggaagagtga taggactcta tggcaatggg gttgtgatca agaatggaag 7980
ctatgttagt gctataaccc agggaaagag ggaggaggag actccggttg aatgtttcga 8040
accctcgatg ctgaagaaga agcagctaac tgtcttggat ctgcatccag gagccggaaa 8100
aaccaggaga gttcttcctg aaatagtccg tgaagccata aaaaagagac tccggacagt 8160
gatcttggca ccaactaggg ttgtcgctgc tgagatggag gaggccttga gaggacttcc 8220
ggtgcgttac atgacaacag cagtcaacgt cacccattct gggacagaaa tcgttgattt 8280
gatgtgccat gccactttca cttcacgctt actacaaccc atcagagtcc ctaattacaa 8340
tctctacatc atggatgaag cccacttcac agacccctca agtatagctg caagaggata 8400
catatcaaca agggttgaaa tgggcgaggc ggctgccatt tttatgactg ccacaccacc 8460
aggaacccgt gatgcgtttc ctgactctaa ctcaccaatc atggacacag aagtggaagt 8520
cccagagaga gcctggagct caggctttga ttgggtgaca gaccattctg ggaaaacagt 8580
ttggttcgtt ccaagcgtga gaaacggaaa tgaaatcgca gcctgtctga caaaggctgg 8640
aaagcgggtc atacagctca gcaggaagac ttttgagaca gaatttcaga aaacaaaaaa 8700
tcaagagtgg gactttgtca taacaactga catctcagag atgggcgcca acttcaaggc 8760
tgaccgggtc atagactcta ggagatgcct aaaaccagtc atacttgatg gtgagagagt 8820
catcttggct gggcccatgc ctgtcacgca tgctagtgct gctcagagga gaggacgtat 8880
aggcaggaac cctaacaaac ctggagatga gtacatgtat ggaggtgggt gtgcagagac 8940
tgatgaaggc catgcacact ggcttgaagc aagaatgctt cttgacaaca tctacctcca 9000
ggatggcctc atagcctcgc tctatcggcc tgaggccgat aaggtagccg ccattgaggg 9060
agagtttaag ctgaggacag agcaaaggaa gaccttcgtg gaactcatga agagaggaga 9120
ccttcccgtc tggctagcct atcaggttgc atctgccgga ataacttaca cagacagaag 9180
atggtgcttt gatggcacaa ccaacaacac cataatggaa gacagtgtac cagcagaggt 9240
ttggacaaag tatggagaga agagagtgct caaaccgaga tggatggatg ctagggtctg 9300
ttcagaccat gcggccctga agtcgttcaa agaattcgcc gctggaaaaa gaggagcggc 9360
tttgggagta atggaggccc tgggaacact gccaggacac atgacagaga ggtttcagga 9420
agccattgac aacctcgccg tgctcatgcg agcagagact ggaagcaggc cttataaggc 9480
agcggcagcc caactgccgg agaccctaga gaccattatg ctcttaggtt tgctgggaac 9540
agtttcactg gggatcttct tcgtcttgat gcggaataag ggcatcggga agatgggctt 9600
tggaatggta acccttgggg ccagtgcatg gctcatgtgg ctttcggaaa ttgaaccagc 9660
cagaattgca tgtgtcctca ttgttgtgtt tttattactg gtggtgctca tacccgagcc 9720
agagaagcaa agatctcccc aagataacca gatggcaatt atcatcatgg tggcagtggg 9780
ccttctaggt ttgataactg caaacgaact tggatggctg gaaagaacaa aaaatgacat 9840
agctcatcta atgggaagga gagaagaagg agcaaccatg ggattctcaa tggacattga 9900
tctgcggcca gcctccgcct gggctatcta tgccgcattg acaactctca tcaccccagc 9960
tgtccaacat gcggtaacca cttcatacaa caactactcc ttaatggcga tggccacaca 10020
agctggagtg ctgtttggca tgggcaaagg gatgccattt tatgcatggg accttggagt 10080
cccgctgcta atgatgggtt gctattcaca attaacaccc ctgactctga tagtagctat 10140
cattctgctt gtggcgcact acatgtactt gatcccaggc ctacaagcgg cagcagcgcg 10200
tgctgcccag aaaaggacag cagctggcat catgaagaat cccgttgtgg atggaatagt 10260
ggtaactgac attgacacaa tgacaataga cccccaggtg gagaagaaga tgggacaagt 10320
gttactcata gcagtagcca tctccagtgc tgtgctgctg cggaccgcct ggggatgggg 10380
ggaggctgga gctctgatca cagcagcgac ctccaccttg tgggaaggct ctccaaacaa 10440
atactggaac tcctctacag ccacctcact gtgcaacatc ttcagaggaa gctatctggc 10500
aggagcttcc cttatctata cagtgacgag aaacgctggc ctggttaaga gacgtggagg 10560
tgggacggga gagactctgg gagagaagtg gaaagctcgt ctgaatcaga tgtcggccct 10620
ggagttctac tcttataaaa agtcaggtat cactgaagtg tgtagagagg aggctcgccg 10680
tgccctcaag gatggagtgg ccacaggagg acatgccgta tcccggggaa gtgcaaagct 10740
cagatggttg gtggagagag gatatctgca gccctatggg aaggttgttg acctcggatg 10800
tggcagaggg ggctggagct attatgccgc caccatccgc aaagtgcagg aggtgagagg 10860
atacacaaag ggaggtcccg gtcatgaaga acccatgctg gtgcaaagct atgggtggaa 10920
catagttcgt ctcaagagtg gagtggacgt cttccacatg gcggctgagc cgtgtgacac 10980
tctgctgtgt gacataggtg agtcatcatc tagtcctgaa gtggaagaga cacgaacact 11040
cagagtgctc tctatggtgg gggactggct tgaaaaaaga ccaggggcct tctgtataaa 11100
ggtgctgtgc ccatacacca gcactatgat ggaaaccatg gagcgactgc aacgtaggca 11160
tgggggagga ttagtcagag tgccattgtc tcgcaactcc acacatgaga tgtactgggt 11220
ctctggggca aagagcaaca tcataaaaag tgtgtccacc acaagtcagc tcctcctggg 11280
acgcatggat ggccccagga ggccagtgaa atatgaggag gatgtgaacc tcggctcggg 11340
tacacgagct gtggcaagct gtgctgaggc tcctaacatg aaaatcatcg gcaggcgcat 11400
tgagagaatc cgcaatgaac atgcagaaac atggtttctt gatgaaaacc acccatacag 11460
gacatgggcc taccatggga gctacgaagc ccccacgcaa ggatcagcgt cttccctcgt 11520
gaacggggtt gttagactcc tgtcaaagcc ttgggacgtg gtgactggag ttacaggaat 11580
agccatgact gacaccacac catacggcca acaaagagtc ttcaaagaaa aagtggacac 11640
cagggtgcca gatccccaag aaggcactcg ccaggtaatg aacatagtct cttcctggct 11700
gtggaaggag ctggggaaac gcaagcggcc acgcgtctgc accaaagaag agtttatcaa 11760
caaggtgcgc agcaatgcag cactgggagc aatatttgaa gaggaaaaag aatggaagac 11820
ggctgtggaa gctgtgaatg atccaaggtt ttgggcccta gtggataggg agagagaaca 11880
ccacctgaga ggagagtgtc acagctgtgt gtacaacatg atgggaaaaa gagaaaagaa 11940
gcaaggagag ttcgggaaag caaaaggtag ccgcgccatc tggtacatgt ggttgggagc 12000
cagattcttg gagtttgaag cccttggatt cttgaacgag gaccattgga tgggaagaga 12060
aaactcagga ggtggagtcg aagggttagg attgcaaaga cttggataca ttctagaaga 12120
aatgaatcgg gcaccaggag gaaagatgta cgcagatgac actgctggct gggacacccg 12180
cattagtaag tttgatctgg agaatgaagc tctgattacc aaccaaatgg aggaagggca 12240
cagaactctg gcgttggccg tgattaaata cacataccaa aacaaagtgg tgaaggttct 12300
cagaccagct gaaggaggaa aaacagttat ggacatcatt tcaagacaag accagagagg 12360
gagtggacaa gttgtcactt atgctctcaa cacattcacc aacttggtgg tgcagcttat 12420
ccggaacatg gaagctgagg aagtgttaga gatgcaagac ttatggttgt tgaggaagcc 12480
agagaaagtg accagatggt tgcagagcaa tggatgggat agactcaaac gaatggcggt 12540
cagtggagat gactgcgttg tgaagccaat cgatgatagg tttgcacatg ccctcaggtt 12600
cttgaatgac atgggaaaag ttaggaaaga cacacaggag tggaaaccct cgactggatg 12660
gagcaattgg gaagaagtcc cgttctgctc ccaccacttc aacaagctgt acctcaagga 12720
tgggagatcc attgtggtcc cttgccgcca ccaagatgaa ctgattggcc gagctcgcgt 12780
ctcaccaggg gcaggatgga gcatccggga gactgcctgt cttgcaaaat catatgcgca 12840
gatgtggcag ctcctttatt tccacagaag agaccttcga ctgatggcta atgccatttg 12900
ctcggctgtg ccagttgact gggtaccaac tgggagaacc acctggtcaa tccatggaaa 12960
gggagaatgg atgaccactg aggacatgct catggtgtgg aatagagtgt ggattgagga 13020
gaacgaccat atggaggaca agactcctgt aacaaaatgg acagacattc cctatctagg 13080
aaaaagggag gacttatggt gtggatccct tatagggcac agaccccgca ccacttgggc 13140
tgaaaacatc aaagacacag tcaacatggt gcgcaggatc ataggtgatg aagaaaagta 13200
catggactat ctatccaccc aagtccgcta cttgggtgag gaagggtcca cacccggagt 13260
gttgtaagca ccaattttag tgttgtcagg cctgctagtc agccacagtt tggggaaagc 13320
tgtgcagcct gtaacccccc caggagaagc tgggaaacca agctcatagt caggccgaga 13380
acgccatggc acggaagaag ccatgctgcc tgtgagcccc tcagaggaca ctgagtcaaa 13440
aaaccccacg cgcttggaag cgcaggatgg gaaaagaagg tggcgacctt ccccaccctt 13500
caatctgggg cctgaactgg agactagctg tgaatctcca gcagagggac tagtggttag 13560
aggagacccc ccggaaaacg caaaacagca tattgacgct gggaaagacc agagactcca 13620
tgagtttcca ccacgctggc cgccaggcac agatcgccga acagcggcgg ccggtgtggg 13680
gaaatccatg gtttctggcc ggcatggtcc cagcctcctc gctggcgccg gctgggcaac 13740
atgcttcggc atggcgaatg ggac 13764
<210> 6
<211> 13971
<212> DNA
<213> Artificial
<400> 6
agcgctagcg gagtgtatac tggcttacta tgttggcact gatgagggtg tcagtgaagt 60
gcttcatgtg gcaggagaaa aaaggctgca ccggtgcgtc agcagaatat gtgatacagg 120
atatattccg cttcctcgct cactgactcg ctacgctcgg tcgttcgact gcggcgagcg 180
gaaatggctt acgaacgggg cggagatttc ctggaagatg ccaggaagat acttaacagg 240
gaagtgagag ggccgcggca aagccgtttt tccataggct ccgcccccct gacaagcatc 300
acgaaatctg acgctcaaat cagtggtggc gaaacccgac aggactataa agataccagg 360
cgtttcccct ggcggctccc tcgtgcgctc tcctgttcct gcctttcggt ttaccggtgt 420
cattccgctg ttatggccgc gtttgtctca ttccacgcct gacactcagt tccgggtagg 480
cagttcgctc caagctggac tgtatgcacg aaccccccgt tcagtccgac cgctgcgcct 540
tatccggtaa ctatcgtctt gagtccaacc cggaaagaca tgcaaaagca ccactggcag 600
cagccactgg taattgattt agaggagtta gtcttgaagt catgcgccgg ttaaggctaa 660
actgaaagga caagttttgg tgactgcgct cctccaagcc agttacctcg gttcaaagag 720
ttggtagctc agagaacctt cgaaaaaccg ccctgcaagg cggttttttc gttttcagag 780
caagagatta cgcgcagacc aaaacgatct caagaagatc atcttattaa ggggtctgac 840
gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc 900
ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag 960
taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt 1020
ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac gatacgggag 1080
ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc accggctcca 1140
gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg tcctgcaact 1200
ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag tagttcgcca 1260
gttaatagtt tgcgcaacgt tgttgccatt gctgcaggca tcgtggtgtc acgctcgtcg 1320
tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac atgatccccc 1380
atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag aagtaagttg 1440
gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac tgtcatgcca 1500
tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg agaatagtgt 1560
atgcggcgac cgagttgctc ttgcccggcg tcaacacggg ataataccgc gccacatagc 1620
agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc 1680
ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg atcttcagca 1740
tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa 1800
aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt tcaatattat 1860
tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg tatttagaaa 1920
aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga cgtgtcgacg 1980
cggccgcgct agcgatgatt taggtgacac tatagaagtt gttgatctgt gtgagtcaga 2040
ctgcgacagt tcgagtctga agcgagagct aacaacagta tcaacaggtt taatttggat 2100
ttggaaacga gagtttctgg tcatgaaaaa cccaaagaag aaatccggag gattccggat 2160
tgtcaatatg ctaaaacgcg gagtagcccg tgtaaacggt accgagctca tggtgagcaa 2220
gggcgaggag ctgttcaccg gggtggtgcc catcctggtc gagctggacg gcgacgtaaa 2280
cggccacaag ttcagcgtgt ccggcgaggg cgagggcgat gccacctacg gcaagctgac 2340
cctgaagctg atctgcacca ccggcaagct gcccgtgccc tggcccaccc tggtgaccac 2400
cctgggctac ggcctgcagt gcttcgcccg ctaccccgac cacatgaagc agcacgactt 2460
cttcaagtcc gccatgcccg aaggctacgt ccaggagcgc accatcttct tcaaggacga 2520
cggcaactac aagacccgcg ccgaggtgaa gttcgagggc gacaccctgg tgaaccgcat 2580
cgagctgaag ggcatcgact tcaaggagga cggcaacatc ctggggcaca agctggagta 2640
caactacaac agccacaacg tctatatcac cgccgacaag cagaagaacg gcatcaaggc 2700
caacttcaag atccgccaca acatcgagga cggcggcgtg cagctcgccg accactacca 2760
gcagaacacc cccatcggcg acggccccgt gctgctgccc gacaaccact acctgagcta 2820
ccagtccgcc ctgagcaaag accccaacga gaagcgcgat cacatggtcc tgctggagtt 2880
cgtgaccgcc gccgggatca ctctcggcat ggacgagctg tacaagaccg gtaactttga 2940
ccttctcaag ttggccggcg acgtcgagtc caacccaggg cccctgcagc aaattttcgt 3000
gaagaccctg acgggcaaga ccatcactct tgaggtcgag cccagtgaca ccatcgagaa 3060
tgtcaaggcc aagatccaag acaaggaagg catcccacct gaccagcaga ggctgatatt 3120
cgcgggcaaa cagctggagg atggccgcac cctgtccgac tacaacatcc agaaagagtc 3180
caccttgcac ctggtgctgc gtctccgcgg tggaatgaag aacccaaaga aaaaatcagg 3240
aggatttcgg atagtcaaca tgctaaaacg cggcgtagcc cgtgttaacc ccttgggagg 3300
tttgaagagg ttgccagccg gacttctgct gggtcatgga cccatcagaa tggttttggc 3360
gatactagcc tttttgagat ttacagcaat caagccatca ctgggcctta tcaacagatg 3420
gggttccgtg gggaaaaaag aggctatgga aataataaag aagttcaaga aagatcttgc 3480
tgccatgttg agaataatca atgctaggaa agagaggaag agacgtggcg cagacaccag 3540
catcggaatc attggcctcc tgctgactac agccatggca gcagagatca ctagacgcgg 3600
gagtgcatac tacatgtact tggataggag cgatgccggg aaggccattt cgtttgctac 3660
cacattggga gtgaacaagt gccacgtaca gatcatggac ctcgggcaca tgtgtgacgc 3720
caccatgagt tatgagtgcc ctatgctgga tgagggagtg gaaccagatg atgtcgattg 3780
ctggtgcaac acgacatcaa cttgggttgt gtacggaacc tgtcatcaca aaaaaggtga 3840
ggcacggcga tctagaagag ccgtgacgct cccttctcac tctacaagga agttgcaaac 3900
gcggtcgcag acctggttag aatcaagaga atacacgaag cacttgatca aggttgaaaa 3960
ctggatattc aggaaccccg ggtttgcgct agtggccgtt gccattgcct ggcttttggg 4020
aagctcgacg agccaaaaag tcatatactt ggtcatgata ctgctgattg ccccggcata 4080
cagtatcagg tgcattggag tcagcaatag agacttcgtg gagggcatgt caggtgggac 4140
ctgggttgat gttgtcttgg aacatggagg ctgcgttacc gtgatggcac aggacaagcc 4200
aacagtcgac atagagttgg tcacgacgac ggttagtaac atggccgagg taagatccta 4260
ttgctacgag gcatcgatat cggacatggc ttcggacagt cgttgcccaa cacaaggtga 4320
agcctacctt gacaagcaat cagacactca atatgtctgc aaaagaacat tagtggacag 4380
aggttgggga aacggttgtg gactttttgg caaagggagc ttggtgacat gtgccaagtt 4440
tacgtgttct aagaagatga ccgggaagag cattcaaccg gaaaatctgg agtatcggat 4500
aatgctatca gtgcatggct cccagcatag cgggatgatt ggatatgaaa ctgacgaaaa 4560
tagagcgaaa gtcgaggtta cgcctaattc accaagagcg gaagcaacct tgggaggctt 4620
tggaagctta ggacttgact gtgaaccaag gacaggcctt gacttttcag atctgtatta 4680
cctgaccatg aacaataagc attggttggt gcacaaagag tggtttcatg acatcccatt 4740
gccttggcat gctggggcag acaccggaac tccacactgg aacaacaaag aggcattggt 4800
agaattcaag gatgcccacg ccaagaggca aaccgtcgtc gttctgggga gccaggaagg 4860
agccgttcac acggctctcg ctggagctct agaggctgag atggatggtg caaagggaag 4920
gctgttctct ggccatttga aatgccgcct aaaaatggac aagcttagat tgaagggcgt 4980
gtcatattcc ttgtgcactg cggcattcac attcaccaag gtcccagctg aaacactgca 5040
tggaacagtc acagtggagg tgcagtatgc agggacagat ggaccctgca agatcccagt 5100
ccagatggcg gtggacatgc agaccctgac cccagttgga aggctgataa ccgccaaccc 5160
cgtgattact gaaagcactg agaactcaaa gatgatgttg gagcttgacc caccatttgg 5220
ggattcttac attgtcatag gagttgggga caagaaaatc acccaccact ggcataggag 5280
tggtagcacc atcggaaagg catttgaggc cactgtgaga ggcgccaaga gaatggcagt 5340
cctgggggat acagcctggg acttcggatc agtcgggggt gtgttcaact cactgggtaa 5400
gggcattcac cagatttttg gagcagcctt caaatcactg tttggaggaa tgtcctggtt 5460
ctcacagatc ctcataggca cgctgctagt gtggttaggt ttgaacacaa agaatggatc 5520
tatctccctc acatgcttgg ccctgggggg agtgatgatc ttcctctcca cggctgtttc 5580
tgctgacgtg gggtgctcag tggacttctc aaaaaaggaa acgagatgtg gcacgggggt 5640
attcatctat aatgatgttg aagcctggag ggaccggtac aagtaccatc ctgactcccc 5700
ccgcagattg gcagcagcag tcaagcaggc ctgggaagag gggatctgtg ggatctcatc 5760
cgtttcaaga atggaaaaca tcatgtggaa atcagtagaa ggggagctca atgctatcct 5820
agaggagaat ggagttcaac tgacagttgt tgtgggatct gtaaaaaacc ccatgtggag 5880
aggtccacaa agattgccag tgcctgtgaa tgagctgccc catggctgga aagcctgggg 5940
gaaatcgtat tttgttaggg cggcaaagac caacaacagt tttgttgtcg acggtgacac 6000
actgaaggaa tgtccgcttg agcacagagc atggaatagt tttcttgtgg aggatcacgg 6060
gtttggagtc ttccacacca gtgtctggct taaggtcaga gaagattact cattagaatg 6120
tgacccagcc gtcataggaa cagctgttaa gggaagggag gccgcgcaca gtgatctggg 6180
ctattggatt gaaagtgaaa agaatgacac atggaggctg aagagggccc acctgattga 6240
gatgaaaaca tgtgaatggc caaagtctca cacattgtgg acagatggag tagaagaaag 6300
tgatcttatc atacccaagt ctttagctgg tccactcagc caccacaaca ccagagaggg 6360
ttacagaacc caagtgaaag ggccatggca cagtgaagag cttgaaatcc ggtttgagga 6420
atgtccaggc accaaggttt acgtggagga gacatgcgga actagaggac catctctgag 6480
atcaactact gcaagtggaa gggtcattga ggaatggtgc tgtagggaat gcacaatgcc 6540
cccactatcg tttcgagcaa aagacggctg ctggtatgga atggagataa ggcccaggaa 6600
agaaccagag agcaacttag tgaggtcaat ggtgacagcg gggtcaaccg atcatatgga 6660
ccacttctct cttggagtgc ttgtgattct actcatggtg caggaggggt tgaagaagag 6720
aatgaccaca aagatcatca tgagcacatc aatggcagtg ctggtagtca tgatcttggg 6780
aggattttca atgagtgacc tggccaagct tgtgatcctg atgggtgcta ctttcgcaga 6840
aatgaacact ggaggagatg tagctcactt ggcattggta gcggcattta aagtcagacc 6900
agccttgctg gtctccttca ttttcagagc caattggaca ccccgtgaga gcatgctgct 6960
agccctggct tcgtgtcttc tgcaaactgc gatctctgct cttgaaggtg acttgatggt 7020
cctcattaat ggatttgctt tggcctggtt ggcaattcga gcaatggccg tgccacgcac 7080
tgacaacatc gctctaccaa tcttggctgc tctaacacca ctagctcgag gcacactgct 7140
cgtggcatgg agagcgggcc tggctacttg tggagggatc atgctcctct ccctgaaagg 7200
gaaaggtagt gtgaagaaga acctgccatt tgtcatggcc ctgggattga cagctgtgag 7260
ggtagtagac cctattaatg tggtaggact actgttactc acaaggagtg ggaagcggag 7320
ctggccccct agtgaagttc tcacagccgt tggcctgata tgtgcactgg ccggagggtt 7380
tgccaaggca gacattgaga tggctggacc catggctgca gtaggcttgc taattgtcag 7440
ctatgtggtc tcgggaaaga gtgtggacat gtacattgaa agagcaggtg acatcacatg 7500
ggaaaaggac gcggaagtca ctggaaacag tcctcggctt gacgtggcac tggatgagag 7560
tggtgacttc tccttggtag aggaagatgg tccacccatg agagagatca tactcaaggt 7620
ggtcctgatg gccatctgtg gcatgaaccc aatagctata ccttttgctg caggagcgtg 7680
gtatgtgtat gtgaagactg ggaaaaggag tggcgccctc tgggacgtgc ctgctcccaa 7740
agaagtgaag aaaggagaga ccacagatgg agtgtacaga gtgatgactc gcagactgct 7800
aggttcaaca caggttggag tgggagtcat gcaagaggga gtcttccaca ccatgtggca 7860
cgttacaaaa ggagccgcac tgaggagcgg tgagggaaga cttgatccat actgggggga 7920
tgtcaagcag gacttggtgt catactgtgg gccttggaag ttggatgcag cttgggatgg 7980
actcagcgag gtacagcttt tggccgtacc tcccggagag agggccagaa acattcagac 8040
cctgcctgga atattcaaga caaaggacgg ggacatcgga gcagttgctc tggactaccc 8100
tgcagggacc tcaggatctc cgatcctaga caaatgtgga agagtgatag gactctatgg 8160
caatggggtt gtgatcaaga atggaagcta tgttagtgct ataacccagg gaaagaggga 8220
ggaggagact ccggttgaat gtttcgaacc ctcgatgctg aagaagaagc agctaactgt 8280
cttggatctg catccaggag ccggaaaaac caggagagtt cttcctgaaa tagtccgtga 8340
agccataaaa aagagactcc ggacagtgat cttggcacca actagggttg tcgctgctga 8400
gatggaggag gccttgagag gacttccggt gcgttacatg acaacagcag tcaacgtcac 8460
ccattctggg acagaaatcg ttgatttgat gtgccatgcc actttcactt cacgcttact 8520
acaacccatc agagtcccta attacaatct ctacatcatg gatgaagccc acttcacaga 8580
cccctcaagt atagctgcaa gaggatacat atcaacaagg gttgaaatgg gcgaggcggc 8640
tgccattttt atgactgcca caccaccagg aacccgtgat gcgtttcctg actctaactc 8700
accaatcatg gacacagaag tggaagtccc agagagagcc tggagctcag gctttgattg 8760
ggtgacagac cattctggga aaacagtttg gttcgttcca agcgtgagaa acggaaatga 8820
aatcgcagcc tgtctgacaa aggctggaaa gcgggtcata cagctcagca ggaagacttt 8880
tgagacagaa tttcagaaaa caaaaaatca agagtgggac tttgtcataa caactgacat 8940
ctcagagatg ggcgccaact tcaaggctga ccgggtcata gactctagga gatgcctaaa 9000
accagtcata cttgatggtg agagagtcat cttggctggg cccatgcctg tcacgcatgc 9060
tagtgctgct cagaggagag gacgtatagg caggaaccct aacaaacctg gagatgagta 9120
catgtatgga ggtgggtgtg cagagactga tgaaggccat gcacactggc ttgaagcaag 9180
aatgcttctt gacaacatct acctccagga tggcctcata gcctcgctct atcggcctga 9240
ggccgataag gtagccgcca ttgagggaga gtttaagctg aggacagagc aaaggaagac 9300
cttcgtggaa ctcatgaaga gaggagacct tcccgtctgg ctagcctatc aggttgcatc 9360
tgccggaata acttacacag acagaagatg gtgctttgat ggcacaacca acaacaccat 9420
aatggaagac agtgtaccag cagaggtttg gacaaagtat ggagagaaga gagtgctcaa 9480
accgagatgg atggatgcta gggtctgttc agaccatgcg gccctgaagt cgttcaaaga 9540
attcgccgct ggaaaaagag gagcggcttt gggagtaatg gaggccctgg gaacactgcc 9600
aggacacatg acagagaggt ttcaggaagc cattgacaac ctcgccgtgc tcatgcgagc 9660
agagactgga agcaggcctt ataaggcagc ggcagcccaa ctgccggaga ccctagagac 9720
cattatgctc ttaggtttgc tgggaacagt ttcactgggg atcttcttcg tcttgatgcg 9780
gaataagggc atcgggaaga tgggctttgg aatggtaacc cttggggcca gtgcatggct 9840
catgtggctt tcggaaattg aaccagccag aattgcatgt gtcctcattg ttgtgttttt 9900
attactggtg gtgctcatac ccgagccaga gaagcaaaga tctccccaag ataaccagat 9960
ggcaattatc atcatggtgg cagtgggcct tctaggtttg ataactgcaa acgaacttgg 10020
atggctggaa agaacaaaaa atgacatagc tcatctaatg ggaaggagag aagaaggagc 10080
aaccatggga ttctcaatgg acattgatct gcggccagcc tccgcctggg ctatctatgc 10140
cgcattgaca actctcatca ccccagctgt ccaacatgcg gtaaccactt catacaacaa 10200
ctactcctta atggcgatgg ccacacaagc tggagtgctg tttggcatgg gcaaagggat 10260
gccattttat gcatgggacc ttggagtccc gctgctaatg atgggttgct attcacaatt 10320
aacacccctg actctgatag tagctatcat tctgcttgtg gcgcactaca tgtacttgat 10380
cccaggccta caagcggcag cagcgcgtgc tgcccagaaa aggacagcag ctggcatcat 10440
gaagaatccc gttgtggatg gaatagtggt aactgacatt gacacaatga caatagaccc 10500
ccaggtggag aagaagatgg gacaagtgtt actcatagca gtagccatct ccagtgctgt 10560
gctgctgcgg accgcctggg gatgggggga ggctggagct ctgatcacag cagcgacctc 10620
caccttgtgg gaaggctctc caaacaaata ctggaactcc tctacagcca cctcactgtg 10680
caacatcttc agaggaagct atctggcagg agcttccctt atctatacag tgacgagaaa 10740
cgctggcctg gttaagagac gtggaggtgg gacgggagag actctgggag agaagtggaa 10800
agctcgtctg aatcagatgt cggccctgga gttctactct tataaaaagt caggtatcac 10860
tgaagtgtgt agagaggagg ctcgccgtgc cctcaaggat ggagtggcca caggaggaca 10920
tgccgtatcc cggggaagtg caaagctcag atggttggtg gagagaggat atctgcagcc 10980
ctatgggaag gttgttgacc tcggatgtgg cagagggggc tggagctatt atgccgccac 11040
catccgcaaa gtgcaggagg tgagaggata cacaaaggga ggtcccggtc atgaagaacc 11100
catgctggtg caaagctatg ggtggaacat agttcgtctc aagagtggag tggacgtctt 11160
ccacatggcg gctgagccgt gtgacactct gctgtgtgac ataggtgagt catcatctag 11220
tcctgaagtg gaagagacac gaacactcag agtgctctct atggtggggg actggcttga 11280
aaaaagacca ggggccttct gtataaaggt gctgtgccca tacaccagca ctatgatgga 11340
aaccatggag cgactgcaac gtaggcatgg gggaggatta gtcagagtgc cattgtctcg 11400
caactccaca catgagatgt actgggtctc tggggcaaag agcaacatca taaaaagtgt 11460
gtccaccaca agtcagctcc tcctgggacg catggatggc cccaggaggc cagtgaaata 11520
tgaggaggat gtgaacctcg gctcgggtac acgagctgtg gcaagctgtg ctgaggctcc 11580
taacatgaaa atcatcggca ggcgcattga gagaatccgc aatgaacatg cagaaacatg 11640
gtttcttgat gaaaaccacc catacaggac atgggcctac catgggagct acgaagcccc 11700
cacgcaagga tcagcgtctt ccctcgtgaa cggggttgtt agactcctgt caaagccttg 11760
ggacgtggtg actggagtta caggaatagc catgactgac accacaccat acggccaaca 11820
aagagtcttc aaagaaaaag tggacaccag ggtgccagat ccccaagaag gcactcgcca 11880
ggtaatgaac atagtctctt cctggctgtg gaaggagctg gggaaacgca agcggccacg 11940
cgtctgcacc aaagaagagt ttatcaacaa ggtgcgcagc aatgcagcac tgggagcaat 12000
atttgaagag gaaaaagaat ggaagacggc tgtggaagct gtgaatgatc caaggttttg 12060
ggccctagtg gatagggaga gagaacacca cctgagagga gagtgtcaca gctgtgtgta 12120
caacatgatg ggaaaaagag aaaagaagca aggagagttc gggaaagcaa aaggtagccg 12180
cgccatctgg tacatgtggt tgggagccag attcttggag tttgaagccc ttggattctt 12240
gaacgaggac cattggatgg gaagagaaaa ctcaggaggt ggagtcgaag ggttaggatt 12300
gcaaagactt ggatacattc tagaagaaat gaatcgggca ccaggaggaa agatgtacgc 12360
agatgacact gctggctggg acacccgcat tagtaagttt gatctggaga atgaagctct 12420
gattaccaac caaatggagg aagggcacag aactctggcg ttggccgtga ttaaatacac 12480
ataccaaaac aaagtggtga aggttctcag accagctgaa ggaggaaaaa cagttatgga 12540
catcatttca agacaagacc agagagggag tggacaagtt gtcacttatg ctctcaacac 12600
attcaccaac ttggtggtgc agcttatccg gaacatggaa gctgaggaag tgttagagat 12660
gcaagactta tggttgttga ggaagccaga gaaagtgacc agatggttgc agagcaatgg 12720
atgggataga ctcaaacgaa tggcggtcag tggagatgac tgcgttgtga agccaatcga 12780
tgataggttt gcacatgccc tcaggttctt gaatgacatg ggaaaagtta ggaaagacac 12840
acaggagtgg aaaccctcga ctggatggag caattgggaa gaagtcccgt tctgctccca 12900
ccacttcaac aagctgtacc tcaaggatgg gagatccatt gtggtccctt gccgccacca 12960
agatgaactg attggccgag ctcgcgtctc accaggggca ggatggagca tccgggagac 13020
tgcctgtctt gcaaaatcat atgcgcagat gtggcagctc ctttatttcc acagaagaga 13080
ccttcgactg atggctaatg ccatttgctc ggctgtgcca gttgactggg taccaactgg 13140
gagaaccacc tggtcaatcc atggaaaggg agaatggatg accactgagg acatgctcat 13200
ggtgtggaat agagtgtgga ttgaggagaa cgaccatatg gaggacaaga ctcctgtaac 13260
aaaatggaca gacattccct atctaggaaa aagggaggac ttatggtgtg gatcccttat 13320
agggcacaga ccccgcacca cttgggctga aaacatcaaa gacacagtca acatggtgcg 13380
caggatcata ggtgatgaag aaaagtacat ggactatcta tccacccaag tccgctactt 13440
gggtgaggaa gggtccacac ccggagtgtt gtaagcacca attttagtgt tgtcaggcct 13500
gctagtcagc cacagtttgg ggaaagctgt gcagcctgta acccccccag gagaagctgg 13560
gaaaccaagc tcatagtcag gccgagaacg ccatggcacg gaagaagcca tgctgcctgt 13620
gagcccctca gaggacactg agtcaaaaaa ccccacgcgc ttggaagcgc aggatgggaa 13680
aagaaggtgg cgaccttccc cacccttcaa tctggggcct gaactggaga ctagctgtga 13740
atctccagca gagggactag tggttagagg agaccccccg gaaaacgcaa aacagcatat 13800
tgacgctggg aaagaccaga gactccatga gtttccacca cgctggccgc caggcacaga 13860
tcgccgaaca gcggcggccg gtgtggggaa atccatggtt tctggccggc atggtcccag 13920
cctcctcgct ggcgccggct gggcaacatg cttcggcatg gcgaatggga c 13971
<210> 7
<211> 12850
<212> DNA
<213> Artificial
<400> 7
agcgctagcg gagtgtatac tggcttacta tgttggcact gatgagggtg tcagtgaagt 60
gcttcatgtg gcaggagaaa aaaggctgca ccggtgcgtc agcagaatat gtgatacagg 120
atatattccg cttcctcgct cactgactcg ctacgctcgg tcgttcgact gcggcgagcg 180
gaaatggctt acgaacgggg cggagatttc ctggaagatg ccaggaagat acttaacagg 240
gaagtgagag ggccgcggca aagccgtttt tccataggct ccgcccccct gacaagcatc 300
acgaaatctg acgctcaaat cagtggtggc gaaacccgac aggactataa agataccagg 360
cgtttcccct ggcggctccc tcgtgcgctc tcctgttcct gcctttcggt ttaccggtgt 420
cattccgctg ttatggccgc gtttgtctca ttccacgcct gacactcagt tccgggtagg 480
cagttcgctc caagctggac tgtatgcacg aaccccccgt tcagtccgac cgctgcgcct 540
tatccggtaa ctatcgtctt gagtccaacc cggaaagaca tgcaaaagca ccactggcag 600
cagccactgg taattgattt agaggagtta gtcttgaagt catgcgccgg ttaaggctaa 660
actgaaagga caagttttgg tgactgcgct cctccaagcc agttacctcg gttcaaagag 720
ttggtagctc agagaacctt cgaaaaaccg ccctgcaagg cggttttttc gttttcagag 780
caagagatta cgcgcagacc aaaacgatct caagaagatc atcttattaa ggggtctgac 840
gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc 900
ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag 960
taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt 1020
ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac gatacgggag 1080
ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc accggctcca 1140
gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg tcctgcaact 1200
ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag tagttcgcca 1260
gttaatagtt tgcgcaacgt tgttgccatt gctgcaggca tcgtggtgtc acgctcgtcg 1320
tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac atgatccccc 1380
atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag aagtaagttg 1440
gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac tgtcatgcca 1500
tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg agaatagtgt 1560
atgcggcgac cgagttgctc ttgcccggcg tcaacacggg ataataccgc gccacatagc 1620
agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc 1680
ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg atcttcagca 1740
tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa 1800
aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt tcaatattat 1860
tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg tatttagaaa 1920
aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga cgtgtcgacg 1980
cggccgcgct agcgatgatt taggtgacac tatagaagtt gttgatctgt gtgagtcaga 2040
ctgcgacagt tcgagtctga agcgagagct aacaacagta tcaacaggtt taatttggat 2100
ttggaaacga gagtttctgg tcatgaaaaa cccaaagaag aaatccggag gattccggat 2160
tgtcaatatg ctaaaacgcg gagtagcccg tgtaaacccc ttgggaggtt tgaagaggtt 2220
gccagccgga cttctgctgg gtcatggacc catcagaatg gttttggcga tactagcctt 2280
tttgagattt acagcaatca agccatcact gggccttatc aacagatggg gttccgtggg 2340
gaaaaaagag gctatggaaa taataaagaa gttcaagaaa gatcttgctg ccatgttgag 2400
aataatcaat gctaggaaag agaggaagag acgtggcgca gacaccagca tcggaatcat 2460
tggcctcctg ctgactacag ccatggcagc agagatcact agacgcggga gtgcatacta 2520
catgtacttg gataggagcg atgccgggaa ggccatttcg tttgctacca cattgggagt 2580
gaacaagtgc cacgtacaga tcatggacct cgggcacatg tgtgacgcca ccatgagtta 2640
tgagtgccct atgctggatg agggagtgga accagatgat gtcgattgct ggtgcaacac 2700
gacatcaact tgggttgtgt acggaacctg tcatcacaaa aaaggtgagg cacggcgatc 2760
tagaagagcc gtgacgctcc cttctcactc tacaaggaag ttgcaaacgc ggtcgcagac 2820
ctggttagaa tcaagagaat acacgaagca cttgatcaag gttgaaaact ggatattcag 2880
gaaccccggg tttgcgctag tggccgttgc cattgcctgg cttttgggaa gctcgacgag 2940
ccaaaaagtc atatacttgg tcatgatact gctgattgcc ccggcataca gtatcaggtg 3000
cattggagtc agcaatagag acttcgtgga gggcatgtca ggtgggacct gggttgatgt 3060
tgtcttggaa catggaggct gcgttaccgt gatggcacag gacaagccaa cagtcgacat 3120
agagttggtc acgacgacgg ttagtaacat ggccgaggta agatcctatt gctacgaggc 3180
atcgatatcg gacatggctt cggacagtcg ttgcccaaca caaggtgaag cctaccttga 3240
caagcaatca gacactcaat atgtctgcaa aagaacatta gtggacagag gttggggaaa 3300
cggttgtgga ctttttggca aagggagctt ggtgacatgt gccaagttta cgtgttctaa 3360
gaagatgacc gggaagagca ttcaaccgga aaatctggag tatcggataa tgctatcagt 3420
gcatggctcc cagcatagcg ggatgattgg atatgaaact gacgaaaata gagcgaaagt 3480
cgaggttacg cctaattcac caagagcgga agcaaccttg ggaggctttg gaagcttagg 3540
acttgactgt gaaccaagga caggccttga cttttcagat ctgtattacc tgaccatgaa 3600
caataagcat tggttggtgc acaaagagtg gtttcatgac atcccattgc cttggcatgc 3660
tggggcagac accggaactc cacactggaa caacaaagag gcattggtag aattcaagga 3720
tgcccacgcc aagaggcaaa ccgtcgtcgt tctggggagc caggaaggag ccgttcacac 3780
ggctctcgct ggagctctag aggctgagat ggatggtgca aagggaaggc tgttctctgg 3840
ccatttgaaa tgccgcctaa aaatggacaa gcttagattg aagggcgtgt catattcctt 3900
gtgcactgcg gcattcacat tcaccaaggt cccagctgaa acactgcatg gaacagtcac 3960
agtggaggtg cagtatgcag ggacagatgg accctgcaag atcccagtcc agatggcggt 4020
ggacatgcag accctgaccc cagttggaag gctgataacc gccaaccccg tgattactga 4080
aagcactgag aactcaaaga tgatgttgga gcttgaccca ccatttgggg attcttacat 4140
tgtcatagga gttggggaca agaaaatcac ccaccactgg cataggagtg gtagcaccat 4200
cggaaaggca tttgaggcca ctgtgagagg cgccaagaga atggcagtcc tgggggatac 4260
agcctgggac ttcggatcag tcgggggtgt gttcaactca ctgggtaagg gcattcacca 4320
gatttttgga gcagccttca aatcactgtt tggaggaatg tcctggttct cacagatcct 4380
cataggcacg ctgctagtgt ggttaggttt gaacacaaag aatggatcta tctccctcac 4440
atgcttggcc ctggggggag tgatgatctt cctctccacg gctgtttctg ctgacgtggg 4500
gtgctcagtg gacttctcaa aaaaggaaac gagatgtggc acgggggtat tcatctataa 4560
tgatgttgaa gcctggaggg accggtacaa gtaccatcct gactcccccc gcagattggc 4620
agcagcagtc aagcaggcct gggaagaggg gatctgtggg atctcatccg tttcaagaat 4680
ggaaaacatc atgtggaaat cagtagaagg ggagctcaat gctatcctag aggagaatgg 4740
agttcaactg acagttgttg tgggatctgt aaaaaacccc atgtggagag gtccacaaag 4800
attgccagtg cctgtgaatg agctgcccca tggctggaaa gcctggggga aatcgtattt 4860
tgttagggcg gcaaagacca acaacagttt tgttgtcgac ggtgacacac tgaaggaatg 4920
tccgcttgag cacagagcat ggaatagttt tcttgtggag gatcacgggt ttggagtctt 4980
ccacaccagt gtctggctta aggtcagaga agattactca ttagaatgtg acccagccgt 5040
cataggaaca gctgttaagg gaagggaggc cgcgcacagt gatctgggct attggattga 5100
aagtgaaaag aatgacacat ggaggctgaa gagggcccac ctgattgaga tgaaaacatg 5160
tgaatggcca aagtctcaca cattgtggac agatggagta gaagaaagtg atcttatcat 5220
acccaagtct ttagctggtc cactcagcca ccacaacacc agagagggtt acagaaccca 5280
agtgaaaggg ccatggcaca gtgaagagct tgaaatccgg tttgaggaat gtccaggcac 5340
caaggtttac gtggaggaga catgcggaac tagaggacca tctctgagat caactactgc 5400
aagtggaagg gtcattgagg aatggtgctg tagggaatgc acaatgcccc cactatcgtt 5460
tcgagcaaaa gacggctgct ggtatggaat ggagataagg cccaggaaag aaccagagag 5520
caacttagtg aggtcaatgg tgacagcggg gtcaaccgat catatggacc acttctctct 5580
tggagtgctt gtgattctac tcatggtgca ggaggggttg aagaagagaa tgaccacaaa 5640
gatcatcatg agcacatcaa tggcagtgct ggtagtcatg atcttgggag gattttcaat 5700
gagtgacctg gccaagcttg tgatcctgat gggtgctact ttcgcagaaa tgaacactgg 5760
aggagatgta gctcacttgg cattggtagc ggcatttaaa gtcagaccag ccttgctggt 5820
ctccttcatt ttcagagcca attggacacc ccgtgagagc atgctgctag ccctggcttc 5880
gtgtcttctg caaactgcga tctctgctct tgaaggtgac ttgatggtcc tcattaatgg 5940
atttgctttg gcctggttgg caattcgagc aatggccgtg ccacgcactg acaacatcgc 6000
tctaccaatc ttggctgctc taacaccact agctcgaggc acactgctcg tggcatggag 6060
agcgggcctg gctacttgtg gagggatcat gctcctctcc ctgaaaggga aaggtagtgt 6120
gaagaagaac ctgccatttg tcatggccct gggattgaca gctgtgaggg tagtagaccc 6180
tattaatgtg gtaggactac tgttactcac aaggagtggg aagcggagct ggccccctag 6240
tgaagttctc acagccgttg gcctgatatg tgcactggcc ggagggtttg ccaaggcaga 6300
cattgagatg gctggaccca tggctgcagt aggcttgcta attgtcagct atgtggtctc 6360
gggaaagagt gtggacatgt acattgaaag agcaggtgac atcacatggg aaaaggacgc 6420
ggaagtcact ggaaacagtc ctcggcttga cgtggcactg gatgagagtg gtgacttctc 6480
cttggtagag gaagatggtc cacccatgag agagatcata ctcaaggtgg tcctgatggc 6540
catctgtggc atgaacccaa tagctatacc ttttgctgca ggagcgtggt atgtgtatgt 6600
gaagactggg aaaaggagtg gcgccctctg ggacgtgcct gctcccaaag aagtgaagaa 6660
aggagagacc acagatggag tgtacagagt gatgactcgc agactgctag gttcaacaca 6720
ggttggagtg ggagtcatgc aagagggagt cttccacacc atgtggcacg ttacaaaagg 6780
agccgcactg aggagcggtg agggaagact tgatccatac tggggggatg tcaagcagga 6840
cttggtgtca tactgtgggc cttggaagtt ggatgcagct tgggatggac tcagcgaggt 6900
acagcttttg gccgtacctc ccggagagag ggccagaaac attcagaccc tgcctggaat 6960
attcaagaca aaggacgggg acatcggagc agttgctctg gactaccctg cagggacctc 7020
aggatctccg atcctagaca aatgtggaag agtgatagga ctctatggca atggggttgt 7080
gatcaagaat ggaagctatg ttagtgctat aacccaggga aagagggagg aggagactcc 7140
ggttgaatgt ttcgaaccct cgatgctgaa gaagaagcag ctaactgtct tggatctgca 7200
tccaggagcc ggaaaaacca ggagagttct tcctgaaata gtccgtgaag ccataaaaaa 7260
gagactccgg acagtgatct tggcaccaac tagggttgtc gctgctgaga tggaggaggc 7320
cttgagagga cttccggtgc gttacatgac aacagcagtc aacgtcaccc attctgggac 7380
agaaatcgtt gatttgatgt gccatgccac tttcacttca cgcttactac aacccatcag 7440
agtccctaat tacaatctct acatcatgga tgaagcccac ttcacagacc cctcaagtat 7500
agctgcaaga ggatacatat caacaagggt tgaaatgggc gaggcggctg ccatttttat 7560
gactgccaca ccaccaggaa cccgtgatgc gtttcctgac tctaactcac caatcatgga 7620
cacagaagtg gaagtcccag agagagcctg gagctcaggc tttgattggg tgacagacca 7680
ttctgggaaa acagtttggt tcgttccaag cgtgagaaac ggaaatgaaa tcgcagcctg 7740
tctgacaaag gctggaaagc gggtcataca gctcagcagg aagacttttg agacagaatt 7800
tcagaaaaca aaaaatcaag agtgggactt tgtcataaca actgacatct cagagatggg 7860
cgccaacttc aaggctgacc gggtcataga ctctaggaga tgcctaaaac cagtcatact 7920
tgatggtgag agagtcatct tggctgggcc catgcctgtc acgcatgcta gtgctgctca 7980
gaggagagga cgtataggca ggaaccctaa caaacctgga gatgagtaca tgtatggagg 8040
tgggtgtgca gagactgatg aaggccatgc acactggctt gaagcaagaa tgcttcttga 8100
caacatctac ctccaggatg gcctcatagc ctcgctctat cggcctgagg ccgataaggt 8160
agccgccatt gagggagagt ttaagctgag gacagagcaa aggaagacct tcgtggaact 8220
catgaagaga ggagaccttc ccgtctggct agcctatcag gttgcatctg ccggaataac 8280
ttacacagac agaagatggt gctttgatgg cacaaccaac aacaccataa tggaagacag 8340
tgtaccagca gaggtttgga caaagtatgg agagaagaga gtgctcaaac cgagatggat 8400
ggatgctagg gtctgttcag accatgcggc cctgaagtcg ttcaaagaat tcgccgctgg 8460
aaaaagagga gcggctttgg gagtaatgga ggccctggga acactgccag gacacatgac 8520
agagaggttt caggaagcca ttgacaacct cgccgtgctc atgcgagcag agactggaag 8580
caggccttat aaggcagcgg cagcccaact gccggagacc ctagagacca ttatgctctt 8640
aggtttgctg ggaacagttt cactggggat cttcttcgtc ttgatgcgga ataagggcat 8700
cgggaagatg ggctttggaa tggtaaccct tggggccagt gcatggctca tgtggctttc 8760
ggaaattgaa ccagccagaa ttgcatgtgt cctcattgtt gtgtttttat tactggtggt 8820
gctcataccc gagccagaga agcaaagatc tccccaagat aaccagatgg caattatcat 8880
catggtggca gtgggccttc taggtttgat aactgcaaac gaacttggat ggctggaaag 8940
aacaaaaaat gacatagctc atctaatggg aaggagagaa gaaggagcaa ccatgggatt 9000
ctcaatggac attgatctgc ggccagcctc cgcctgggct atctatgccg cattgacaac 9060
tctcatcacc ccagctgtcc aacatgcggt aaccacttca tacaacaact actccttaat 9120
ggcgatggcc acacaagctg gagtgctgtt tggcatgggc aaagggatgc cattttatgc 9180
atgggacctt ggagtcccgc tgctaatgat gggttgctat tcacaattaa cacccctgac 9240
tctgatagta gctatcattc tgcttgtggc gcactacatg tacttgatcc caggcctaca 9300
agcggcagca gcgcgtgctg cccagaaaag gacagcagct ggcatcatga agaatcccgt 9360
tgtggatgga atagtggtaa ctgacattga cacaatgaca atagaccccc aggtggagaa 9420
gaagatggga caagtgttac tcatagcagt agccatctcc agtgctgtgc tgctgcggac 9480
cgcctgggga tggggggagg ctggagctct gatcacagca gcgacctcca ccttgtggga 9540
aggctctcca aacaaatact ggaactcctc tacagccacc tcactgtgca acatcttcag 9600
aggaagctat ctggcaggag cttcccttat ctatacagtg acgagaaacg ctggcctggt 9660
taagagacgt ggaggtggga cgggagagac tctgggagag aagtggaaag ctcgtctgaa 9720
tcagatgtcg gccctggagt tctactctta taaaaagtca ggtatcactg aagtgtgtag 9780
agaggaggct cgccgtgccc tcaaggatgg agtggccaca ggaggacatg ccgtatcccg 9840
gggaagtgca aagctcagat ggttggtgga gagaggatat ctgcagccct atgggaaggt 9900
tgttgacctc ggatgtggca gagggggctg gagctattat gccgccacca tccgcaaagt 9960
gcaggaggtg agaggataca caaagggagg tcccggtcat gaagaaccca tgctggtgca 10020
aagctatggg tggaacatag ttcgtctcaa gagtggagtg gacgtcttcc acatggcggc 10080
tgagccgtgt gacactctgc tgtgtgacat aggtgagtca tcatctagtc ctgaagtgga 10140
agagacacga acactcagag tgctctctat ggtgggggac tggcttgaaa aaagaccagg 10200
ggccttctgt ataaaggtgc tgtgcccata caccagcact atgatggaaa ccatggagcg 10260
actgcaacgt aggcatgggg gaggattagt cagagtgcca ttgtctcgca actccacaca 10320
tgagatgtac tgggtctctg gggcaaagag caacatcata aaaagtgtgt ccaccacaag 10380
tcagctcctc ctgggacgca tggatggccc caggaggcca gtgaaatatg aggaggatgt 10440
gaacctcggc tcgggtacac gagctgtggc aagctgtgct gaggctccta acatgaaaat 10500
catcggcagg cgcattgaga gaatccgcaa tgaacatgca gaaacatggt ttcttgatga 10560
aaaccaccca tacaggacat gggcctacca tgggagctac gaagccccca cgcaaggatc 10620
agcgtcttcc ctcgtgaacg gggttgttag actcctgtca aagccttggg acgtggtgac 10680
tggagttaca ggaatagcca tgactgacac cacaccatac ggccaacaaa gagtcttcaa 10740
agaaaaagtg gacaccaggg tgccagatcc ccaagaaggc actcgccagg taatgaacat 10800
agtctcttcc tggctgtgga aggagctggg gaaacgcaag cggccacgcg tctgcaccaa 10860
agaagagttt atcaacaagg tgcgcagcaa tgcagcactg ggagcaatat ttgaagagga 10920
aaaagaatgg aagacggctg tggaagctgt gaatgatcca aggttttggg ccctagtgga 10980
tagggagaga gaacaccacc tgagaggaga gtgtcacagc tgtgtgtaca acatgatggg 11040
aaaaagagaa aagaagcaag gagagttcgg gaaagcaaaa ggtagccgcg ccatctggta 11100
catgtggttg ggagccagat tcttggagtt tgaagccctt ggattcttga acgaggacca 11160
ttggatggga agagaaaact caggaggtgg agtcgaaggg ttaggattgc aaagacttgg 11220
atacattcta gaagaaatga atcgggcacc aggaggaaag atgtacgcag atgacactgc 11280
tggctgggac acccgcatta gtaagtttga tctggagaat gaagctctga ttaccaacca 11340
aatggaggaa gggcacagaa ctctggcgtt ggccgtgatt aaatacacat accaaaacaa 11400
agtggtgaag gttctcagac cagctgaagg aggaaaaaca gttatggaca tcatttcaag 11460
acaagaccag agagggagtg gacaagttgt cacttatgct ctcaacacat tcaccaactt 11520
ggtggtgcag cttatccgga acatggaagc tgaggaagtg ttagagatgc aagacttatg 11580
gttgttgagg aagccagaga aagtgaccag atggttgcag agcaatggat gggatagact 11640
caaacgaatg gcggtcagtg gagatgactg cgttgtgaag ccaatcgatg ataggtttgc 11700
acatgccctc aggttcttga atgacatggg aaaagttagg aaagacacac aggagtggaa 11760
accctcgact ggatggagca attgggaaga agtcccgttc tgctcccacc acttcaacaa 11820
gctgtacctc aaggatggga gatccattgt ggtcccttgc cgccaccaag atgaactgat 11880
tggccgagct cgcgtctcac caggggcagg atggagcatc cgggagactg cctgtcttgc 11940
aaaatcatat gcgcagatgt ggcagctcct ttatttccac agaagagacc ttcgactgat 12000
ggctaatgcc atttgctcgg ctgtgccagt tgactgggta ccaactggga gaaccacctg 12060
gtcaatccat ggaaagggag aatggatgac cactgaggac atgctcatgg tgtggaatag 12120
agtgtggatt gaggagaacg accatatgga ggacaagact cctgtaacaa aatggacaga 12180
cattccctat ctaggaaaaa gggaggactt atggtgtgga tcccttatag ggcacagacc 12240
ccgcaccact tgggctgaaa acatcaaaga cacagtcaac atggtgcgca ggatcatagg 12300
tgatgaagaa aagtacatgg actatctatc cacccaagtc cgctacttgg gtgaggaagg 12360
gtccacaccc ggagtgttgt aagcaccaat tttagtgttg tcaggcctgc tagtcagcca 12420
cagtttgggg aaagctgtgc agcctgtaac ccccccagga gaagctggga aaccaagctc 12480
atagtcaggc cgagaacgcc atggcacgga agaagccatg ctgcctgtga gcccctcaga 12540
ggacactgag tcaaaaaacc ccacgcgctt ggaagcgcag gatgggaaaa gaaggtggcg 12600
accttcccca cccttcaatc tggggcctga agggactagt ggttagagga gaccccccgg 12660
aaaacgcaaa acagcatatt gacgctggga aagaccagag actccatgag tttccaccac 12720
gctggccgcc aggcacagat cgccgaacag cggcggccgg tgtggggaaa tccatggttt 12780
ctggccggca tggtcccagc ctcctcgctg gcgccggctg ggcaacatgc ttcggcatgg 12840
cgaatgggac 12850
<210> 8
<211> 13735
<212> DNA
<213> Artificial
<400> 8
agcgctagcg gagtgtatac tggcttacta tgttggcact gatgagggtg tcagtgaagt 60
gcttcatgtg gcaggagaaa aaaggctgca ccggtgcgtc agcagaatat gtgatacagg 120
atatattccg cttcctcgct cactgactcg ctacgctcgg tcgttcgact gcggcgagcg 180
gaaatggctt acgaacgggg cggagatttc ctggaagatg ccaggaagat acttaacagg 240
gaagtgagag ggccgcggca aagccgtttt tccataggct ccgcccccct gacaagcatc 300
acgaaatctg acgctcaaat cagtggtggc gaaacccgac aggactataa agataccagg 360
cgtttcccct ggcggctccc tcgtgcgctc tcctgttcct gcctttcggt ttaccggtgt 420
cattccgctg ttatggccgc gtttgtctca ttccacgcct gacactcagt tccgggtagg 480
cagttcgctc caagctggac tgtatgcacg aaccccccgt tcagtccgac cgctgcgcct 540
tatccggtaa ctatcgtctt gagtccaacc cggaaagaca tgcaaaagca ccactggcag 600
cagccactgg taattgattt agaggagtta gtcttgaagt catgcgccgg ttaaggctaa 660
actgaaagga caagttttgg tgactgcgct cctccaagcc agttacctcg gttcaaagag 720
ttggtagctc agagaacctt cgaaaaaccg ccctgcaagg cggttttttc gttttcagag 780
caagagatta cgcgcagacc aaaacgatct caagaagatc atcttattaa ggggtctgac 840
gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc 900
ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag 960
taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt 1020
ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac gatacgggag 1080
ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc accggctcca 1140
gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg tcctgcaact 1200
ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag tagttcgcca 1260
gttaatagtt tgcgcaacgt tgttgccatt gctgcaggca tcgtggtgtc acgctcgtcg 1320
tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac atgatccccc 1380
atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag aagtaagttg 1440
gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac tgtcatgcca 1500
tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg agaatagtgt 1560
atgcggcgac cgagttgctc ttgcccggcg tcaacacggg ataataccgc gccacatagc 1620
agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc 1680
ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg atcttcagca 1740
tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa 1800
aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt tcaatattat 1860
tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg tatttagaaa 1920
aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga cgtgtcgacg 1980
cggccgcgct agcgatgatt taggtgacac tatagaagtt gttgatctgt gtgagtcaga 2040
ctgcgacagt tcgagtctga agcgagagct aacaacagta tcaacaggtt taatttggat 2100
ttggaaacga gagtttctgg tcatgaaaaa cccaaagaag aaatccggag gattccggat 2160
tgtcaatatg ctaaaacgcg gagtagcccg tgtaaacggt accgagctca tggccaagcc 2220
caccgagaac aacgaagact tcaacatcgt ggccgtggcc agcaacttcg cgaccacgga 2280
tctcgatgct gaccgcggga agttgcccgg caagaagctg ccgctggagg tgctcaaaga 2340
gatggaagcc aatgcccgga aagctggctg caccaggggc tgtctgatct gcctgtccca 2400
catcaagtgc acgcccaaga tgaagaagtt catcccagga cgctgccaca cctacgaagg 2460
cgacaaagag tccgcacagg gcggcatagg cgaggcgatc gtcgacattc ctgagattcc 2520
tgggttcaag gacttggagc ccatggagca gttcatcgca caggtcgatc tgtgtgtgga 2580
ctgcacaact ggctgcctca aagggcttgc caacgtgcag tgttctgacc tgctcaagaa 2640
gtggctgccg caacgctgtg cgacctttgc cagcaagatc cagggccagg tggacaagat 2700
caagggggcc ggtggtgaca ccggtaactt tgaccttctc aagttggccg gcgacgtcga 2760
gtccaaccca gggcccctgc agcaaatttt cgtgaagacc ctgacgggca agaccatcac 2820
tcttgaggtc gagcccagtg acaccatcga gaatgtcaag gccaagatcc aagacaagga 2880
aggcatccca cctgaccagc agaggctgat attcgcgggc aaacagctgg aggatggccg 2940
caccctgtcc gactacaaca tccagaaaga gtccaccttg cacctggtgc tgcgtctccg 3000
cggtggaatg aagaacccaa agaaaaaatc aggaggattt cggatagtca acatgctaaa 3060
acgcggcgta gcccgtgtta accccttggg aggtttgaag aggttgccag ccggacttct 3120
gctgggtcat ggacccatca gaatggtttt ggcgatacta gcctttttga gatttacagc 3180
aatcaagcca tcactgggcc ttatcaacag atggggttcc gtggggaaaa aagaggctat 3240
ggaaataata aagaagttca agaaagatct tgctgccatg ttgagaataa tcaatgctag 3300
gaaagagagg aagagacgtg gcgcagacac cagcatcgga atcattggcc tcctgctgac 3360
tacagccatg gcagcagaga tcactagacg cgggagtgca tactacatgt acttggatag 3420
gagcgatgcc gggaaggcca tttcgtttgc taccacattg ggagtgaaca agtgccacgt 3480
acagatcatg gacctcgggc acatgtgtga cgccaccatg agttatgagt gccctatgct 3540
ggatgaggga gtggaaccag atgatgtcga ttgctggtgc aacacgacat caacttgggt 3600
tgtgtacgga acctgtcatc acaaaaaagg tgaggcacgg cgatctagaa gagccgtgac 3660
gctcccttct cactctacaa ggaagttgca aacgcggtcg cagacctggt tagaatcaag 3720
agaatacacg aagcacttga tcaaggttga aaactggata ttcaggaacc ccgggtttgc 3780
gctagtggcc gttgccattg cctggctttt gggaagctcg acgagccaaa aagtcatata 3840
cttggtcatg atactgctga ttgccccggc atacagtatc aggtgcattg gagtcagcaa 3900
tagagacttc gtggagggca tgtcaggtgg gacctgggtt gatgttgtct tggaacatgg 3960
aggctgcgtt accgtgatgg cacaggacaa gccaacagtc gacatagagt tggtcacgac 4020
gacggttagt aacatggccg aggtaagatc ctattgctac gaggcatcga tatcggacat 4080
ggcttcggac agtcgttgcc caacacaagg tgaagcctac cttgacaagc aatcagacac 4140
tcaatatgtc tgcaaaagaa cattagtgga cagaggttgg ggaaacggtt gtggactttt 4200
tggcaaaggg agcttggtga catgtgccaa gtttacgtgt tctaagaaga tgaccgggaa 4260
gagcattcaa ccggaaaatc tggagtatcg gataatgcta tcagtgcatg gctcccagca 4320
tagcgggatg attggatatg aaactgacga aaatagagcg aaagtcgagg ttacgcctaa 4380
ttcaccaaga gcggaagcaa ccttgggagg ctttggaagc ttaggacttg actgtgaacc 4440
aaggacaggc cttgactttt cagatctgta ttacctgacc atgaacaata agcattggtt 4500
ggtgcacaaa gagtggtttc atgacatccc attgccttgg catgctgggg cagacaccgg 4560
aactccacac tggaacaaca aagaggcatt ggtagaattc aaggatgccc acgccaagag 4620
gcaaaccgtc gtcgttctgg ggagccagga aggagccgtt cacacggctc tcgctggagc 4680
tctagaggct gagatggatg gtgcaaaggg aaggctgttc tctggccatt tgaaatgccg 4740
cctaaaaatg gacaagctta gattgaaggg cgtgtcatat tccttgtgca ctgcggcatt 4800
cacattcacc aaggtcccag ctgaaacact gcatggaaca gtcacagtgg aggtgcagta 4860
tgcagggaca gatggaccct gcaagatccc agtccagatg gcggtggaca tgcagaccct 4920
gaccccagtt ggaaggctga taaccgccaa ccccgtgatt actgaaagca ctgagaactc 4980
aaagatgatg ttggagcttg acccaccatt tggggattct tacattgtca taggagttgg 5040
ggacaagaaa atcacccacc actggcatag gagtggtagc accatcggaa aggcatttga 5100
ggccactgtg agaggcgcca agagaatggc agtcctgggg gatacagcct gggacttcgg 5160
atcagtcggg ggtgtgttca actcactggg taagggcatt caccagattt ttggagcagc 5220
cttcaaatca ctgtttggag gaatgtcctg gttctcacag atcctcatag gcacgctgct 5280
agtgtggtta ggtttgaaca caaagaatgg atctatctcc ctcacatgct tggccctggg 5340
gggagtgatg atcttcctct ccacggctgt ttctgctgac gtggggtgct cagtggactt 5400
ctcaaaaaag gaaacgagat gtggcacggg ggtattcatc tataatgatg ttgaagcctg 5460
gagggaccgg tacaagtacc atcctgactc cccccgcaga ttggcagcag cagtcaagca 5520
ggcctgggaa gaggggatct gtgggatctc atccgtttca agaatggaaa acatcatgtg 5580
gaaatcagta gaaggggagc tcaatgctat cctagaggag aatggagttc aactgacagt 5640
tgttgtggga tctgtaaaaa accccatgtg gagaggtcca caaagattgc cagtgcctgt 5700
gaatgagctg ccccatggct ggaaagcctg ggggaaatcg tattttgtta gggcggcaaa 5760
gaccaacaac agttttgttg tcgacggtga cacactgaag gaatgtccgc ttgagcacag 5820
agcatggaat agttttcttg tggaggatca cgggtttgga gtcttccaca ccagtgtctg 5880
gcttaaggtc agagaagatt actcattaga atgtgaccca gccgtcatag gaacagctgt 5940
taagggaagg gaggccgcgc acagtgatct gggctattgg attgaaagtg aaaagaatga 6000
cacatggagg ctgaagaggg cccacctgat tgagatgaaa acatgtgaat ggccaaagtc 6060
tcacacattg tggacagatg gagtagaaga aagtgatctt atcataccca agtctttagc 6120
tggtccactc agccaccaca acaccagaga gggttacaga acccaagtga aagggccatg 6180
gcacagtgaa gagcttgaaa tccggtttga ggaatgtcca ggcaccaagg tttacgtgga 6240
ggagacatgc ggaactagag gaccatctct gagatcaact actgcaagtg gaagggtcat 6300
tgaggaatgg tgctgtaggg aatgcacaat gcccccacta tcgtttcgag caaaagacgg 6360
ctgctggtat ggaatggaga taaggcccag gaaagaacca gagagcaact tagtgaggtc 6420
aatggtgaca gcggggtcaa ccgatcatat ggaccacttc tctcttggag tgcttgtgat 6480
tctactcatg gtgcaggagg ggttgaagaa gagaatgacc acaaagatca tcatgagcac 6540
atcaatggca gtgctggtag tcatgatctt gggaggattt tcaatgagtg acctggccaa 6600
gcttgtgatc ctgatgggtg ctactttcgc agaaatgaac actggaggag atgtagctca 6660
cttggcattg gtagcggcat ttaaagtcag accagccttg ctggtctcct tcattttcag 6720
agccaattgg acaccccgtg agagcatgct gctagccctg gcttcgtgtc ttctgcaaac 6780
tgcgatctct gctcttgaag gtgacttgat ggtcctcatt aatggatttg ctttggcctg 6840
gttggcaatt cgagcaatgg ccgtgccacg cactgacaac atcgctctac caatcttggc 6900
tgctctaaca ccactagctc gaggcacact gctcgtggca tggagagcgg gcctggctac 6960
ttgtggaggg atcatgctcc tctccctgaa agggaaaggt agtgtgaaga agaacctgcc 7020
atttgtcatg gccctgggat tgacagctgt gagggtagta gaccctatta atgtggtagg 7080
actactgtta ctcacaagga gtgggaagcg gagctggccc cctagtgaag ttctcacagc 7140
cgttggcctg atatgtgcac tggccggagg gtttgccaag gcagacattg agatggctgg 7200
acccatggct gcagtaggct tgctaattgt cagctatgtg gtctcgggaa agagtgtgga 7260
catgtacatt gaaagagcag gtgacatcac atgggaaaag gacgcggaag tcactggaaa 7320
cagtcctcgg cttgacgtgg cactggatga gagtggtgac ttctccttgg tagaggaaga 7380
tggtccaccc atgagagaga tcatactcaa ggtggtcctg atggccatct gtggcatgaa 7440
cccaatagct ataccttttg ctgcaggagc gtggtatgtg tatgtgaaga ctgggaaaag 7500
gagtggcgcc ctctgggacg tgcctgctcc caaagaagtg aagaaaggag agaccacaga 7560
tggagtgtac agagtgatga ctcgcagact gctaggttca acacaggttg gagtgggagt 7620
catgcaagag ggagtcttcc acaccatgtg gcacgttaca aaaggagccg cactgaggag 7680
cggtgaggga agacttgatc catactgggg ggatgtcaag caggacttgg tgtcatactg 7740
tgggccttgg aagttggatg cagcttggga tggactcagc gaggtacagc ttttggccgt 7800
acctcccgga gagagggcca gaaacattca gaccctgcct ggaatattca agacaaagga 7860
cggggacatc ggagcagttg ctctggacta ccctgcaggg acctcaggat ctccgatcct 7920
agacaaatgt ggaagagtga taggactcta tggcaatggg gttgtgatca agaatggaag 7980
ctatgttagt gctataaccc agggaaagag ggaggaggag actccggttg aatgtttcga 8040
accctcgatg ctgaagaaga agcagctaac tgtcttggat ctgcatccag gagccggaaa 8100
aaccaggaga gttcttcctg aaatagtccg tgaagccata aaaaagagac tccggacagt 8160
gatcttggca ccaactaggg ttgtcgctgc tgagatggag gaggccttga gaggacttcc 8220
ggtgcgttac atgacaacag cagtcaacgt cacccattct gggacagaaa tcgttgattt 8280
gatgtgccat gccactttca cttcacgctt actacaaccc atcagagtcc ctaattacaa 8340
tctctacatc atggatgaag cccacttcac agacccctca agtatagctg caagaggata 8400
catatcaaca agggttgaaa tgggcgaggc ggctgccatt tttatgactg ccacaccacc 8460
aggaacccgt gatgcgtttc ctgactctaa ctcaccaatc atggacacag aagtggaagt 8520
cccagagaga gcctggagct caggctttga ttgggtgaca gaccattctg ggaaaacagt 8580
ttggttcgtt ccaagcgtga gaaacggaaa tgaaatcgca gcctgtctga caaaggctgg 8640
aaagcgggtc atacagctca gcaggaagac ttttgagaca gaatttcaga aaacaaaaaa 8700
tcaagagtgg gactttgtca taacaactga catctcagag atgggcgcca acttcaaggc 8760
tgaccgggtc atagactcta ggagatgcct aaaaccagtc atacttgatg gtgagagagt 8820
catcttggct gggcccatgc ctgtcacgca tgctagtgct gctcagagga gaggacgtat 8880
aggcaggaac cctaacaaac ctggagatga gtacatgtat ggaggtgggt gtgcagagac 8940
tgatgaaggc catgcacact ggcttgaagc aagaatgctt cttgacaaca tctacctcca 9000
ggatggcctc atagcctcgc tctatcggcc tgaggccgat aaggtagccg ccattgaggg 9060
agagtttaag ctgaggacag agcaaaggaa gaccttcgtg gaactcatga agagaggaga 9120
ccttcccgtc tggctagcct atcaggttgc atctgccgga ataacttaca cagacagaag 9180
atggtgcttt gatggcacaa ccaacaacac cataatggaa gacagtgtac cagcagaggt 9240
ttggacaaag tatggagaga agagagtgct caaaccgaga tggatggatg ctagggtctg 9300
ttcagaccat gcggccctga agtcgttcaa agaattcgcc gctggaaaaa gaggagcggc 9360
tttgggagta atggaggccc tgggaacact gccaggacac atgacagaga ggtttcagga 9420
agccattgac aacctcgccg tgctcatgcg agcagagact ggaagcaggc cttataaggc 9480
agcggcagcc caactgccgg agaccctaga gaccattatg ctcttaggtt tgctgggaac 9540
agtttcactg gggatcttct tcgtcttgat gcggaataag ggcatcggga agatgggctt 9600
tggaatggta acccttgggg ccagtgcatg gctcatgtgg ctttcggaaa ttgaaccagc 9660
cagaattgca tgtgtcctca ttgttgtgtt tttattactg gtggtgctca tacccgagcc 9720
agagaagcaa agatctcccc aagataacca gatggcaatt atcatcatgg tggcagtggg 9780
ccttctaggt ttgataactg caaacgaact tggatggctg gaaagaacaa aaaatgacat 9840
agctcatcta atgggaagga gagaagaagg agcaaccatg ggattctcaa tggacattga 9900
tctgcggcca gcctccgcct gggctatcta tgccgcattg acaactctca tcaccccagc 9960
tgtccaacat gcggtaacca cttcatacaa caactactcc ttaatggcga tggccacaca 10020
agctggagtg ctgtttggca tgggcaaagg gatgccattt tatgcatggg accttggagt 10080
cccgctgcta atgatgggtt gctattcaca attaacaccc ctgactctga tagtagctat 10140
cattctgctt gtggcgcact acatgtactt gatcccaggc ctacaagcgg cagcagcgcg 10200
tgctgcccag aaaaggacag cagctggcat catgaagaat cccgttgtgg atggaatagt 10260
ggtaactgac attgacacaa tgacaataga cccccaggtg gagaagaaga tgggacaagt 10320
gttactcata gcagtagcca tctccagtgc tgtgctgctg cggaccgcct ggggatgggg 10380
ggaggctgga gctctgatca cagcagcgac ctccaccttg tgggaaggct ctccaaacaa 10440
atactggaac tcctctacag ccacctcact gtgcaacatc ttcagaggaa gctatctggc 10500
aggagcttcc cttatctata cagtgacgag aaacgctggc ctggttaaga gacgtggagg 10560
tgggacggga gagactctgg gagagaagtg gaaagctcgt ctgaatcaga tgtcggccct 10620
ggagttctac tcttataaaa agtcaggtat cactgaagtg tgtagagagg aggctcgccg 10680
tgccctcaag gatggagtgg ccacaggagg acatgccgta tcccggggaa gtgcaaagct 10740
cagatggttg gtggagagag gatatctgca gccctatggg aaggttgttg acctcggatg 10800
tggcagaggg ggctggagct attatgccgc caccatccgc aaagtgcagg aggtgagagg 10860
atacacaaag ggaggtcccg gtcatgaaga acccatgctg gtgcaaagct atgggtggaa 10920
catagttcgt ctcaagagtg gagtggacgt cttccacatg gcggctgagc cgtgtgacac 10980
tctgctgtgt gacataggtg agtcatcatc tagtcctgaa gtggaagaga cacgaacact 11040
cagagtgctc tctatggtgg gggactggct tgaaaaaaga ccaggggcct tctgtataaa 11100
ggtgctgtgc ccatacacca gcactatgat ggaaaccatg gagcgactgc aacgtaggca 11160
tgggggagga ttagtcagag tgccattgtc tcgcaactcc acacatgaga tgtactgggt 11220
ctctggggca aagagcaaca tcataaaaag tgtgtccacc acaagtcagc tcctcctggg 11280
acgcatggat ggccccagga ggccagtgaa atatgaggag gatgtgaacc tcggctcggg 11340
tacacgagct gtggcaagct gtgctgaggc tcctaacatg aaaatcatcg gcaggcgcat 11400
tgagagaatc cgcaatgaac atgcagaaac atggtttctt gatgaaaacc acccatacag 11460
gacatgggcc taccatggga gctacgaagc ccccacgcaa ggatcagcgt cttccctcgt 11520
gaacggggtt gttagactcc tgtcaaagcc ttgggacgtg gtgactggag ttacaggaat 11580
agccatgact gacaccacac catacggcca acaaagagtc ttcaaagaaa aagtggacac 11640
cagggtgcca gatccccaag aaggcactcg ccaggtaatg aacatagtct cttcctggct 11700
gtggaaggag ctggggaaac gcaagcggcc acgcgtctgc accaaagaag agtttatcaa 11760
caaggtgcgc agcaatgcag cactgggagc aatatttgaa gaggaaaaag aatggaagac 11820
ggctgtggaa gctgtgaatg atccaaggtt ttgggcccta gtggataggg agagagaaca 11880
ccacctgaga ggagagtgtc acagctgtgt gtacaacatg atgggaaaaa gagaaaagaa 11940
gcaaggagag ttcgggaaag caaaaggtag ccgcgccatc tggtacatgt ggttgggagc 12000
cagattcttg gagtttgaag cccttggatt cttgaacgag gaccattgga tgggaagaga 12060
aaactcagga ggtggagtcg aagggttagg attgcaaaga cttggataca ttctagaaga 12120
aatgaatcgg gcaccaggag gaaagatgta cgcagatgac actgctggct gggacacccg 12180
cattagtaag tttgatctgg agaatgaagc tctgattacc aaccaaatgg aggaagggca 12240
cagaactctg gcgttggccg tgattaaata cacataccaa aacaaagtgg tgaaggttct 12300
cagaccagct gaaggaggaa aaacagttat ggacatcatt tcaagacaag accagagagg 12360
gagtggacaa gttgtcactt atgctctcaa cacattcacc aacttggtgg tgcagcttat 12420
ccggaacatg gaagctgagg aagtgttaga gatgcaagac ttatggttgt tgaggaagcc 12480
agagaaagtg accagatggt tgcagagcaa tggatgggat agactcaaac gaatggcggt 12540
cagtggagat gactgcgttg tgaagccaat cgatgatagg tttgcacatg ccctcaggtt 12600
cttgaatgac atgggaaaag ttaggaaaga cacacaggag tggaaaccct cgactggatg 12660
gagcaattgg gaagaagtcc cgttctgctc ccaccacttc aacaagctgt acctcaagga 12720
tgggagatcc attgtggtcc cttgccgcca ccaagatgaa ctgattggcc gagctcgcgt 12780
ctcaccaggg gcaggatgga gcatccggga gactgcctgt cttgcaaaat catatgcgca 12840
gatgtggcag ctcctttatt tccacagaag agaccttcga ctgatggcta atgccatttg 12900
ctcggctgtg ccagttgact gggtaccaac tgggagaacc acctggtcaa tccatggaaa 12960
gggagaatgg atgaccactg aggacatgct catggtgtgg aatagagtgt ggattgagga 13020
gaacgaccat atggaggaca agactcctgt aacaaaatgg acagacattc cctatctagg 13080
aaaaagggag gacttatggt gtggatccct tatagggcac agaccccgca ccacttgggc 13140
tgaaaacatc aaagacacag tcaacatggt gcgcaggatc ataggtgatg aagaaaagta 13200
catggactat ctatccaccc aagtccgcta cttgggtgag gaagggtcca cacccggagt 13260
gttgtaagca ccaattttag tgttgtcagg cctgctagtc agccacagtt tggggaaagc 13320
tgtgcagcct gtaacccccc caggagaagc tgggaaacca agctcatagt caggccgaga 13380
acgccatggc acggaagaag ccatgctgcc tgtgagcccc tcagaggaca ctgagtcaaa 13440
aaaccccacg cgcttggaag cgcaggatgg gaaaagaagg tggcgacctt ccccaccctt 13500
caatctgggg cctgaaggga ctagtggtta gaggagaccc cccggaaaac gcaaaacagc 13560
atattgacgc tgggaaagac cagagactcc atgagtttcc accacgctgg ccgccaggca 13620
cagatcgccg aacagcggcg gccggtgtgg ggaaatccat ggtttctggc cggcatggtc 13680
ccagcctcct cgctggcgcc ggctgggcaa catgcttcgg catggcgaat gggac 13735
<210> 9
<211> 13942
<212> DNA
<213> Artificial
<400> 9
agcgctagcg gagtgtatac tggcttacta tgttggcact gatgagggtg tcagtgaagt 60
gcttcatgtg gcaggagaaa aaaggctgca ccggtgcgtc agcagaatat gtgatacagg 120
atatattccg cttcctcgct cactgactcg ctacgctcgg tcgttcgact gcggcgagcg 180
gaaatggctt acgaacgggg cggagatttc ctggaagatg ccaggaagat acttaacagg 240
gaagtgagag ggccgcggca aagccgtttt tccataggct ccgcccccct gacaagcatc 300
acgaaatctg acgctcaaat cagtggtggc gaaacccgac aggactataa agataccagg 360
cgtttcccct ggcggctccc tcgtgcgctc tcctgttcct gcctttcggt ttaccggtgt 420
cattccgctg ttatggccgc gtttgtctca ttccacgcct gacactcagt tccgggtagg 480
cagttcgctc caagctggac tgtatgcacg aaccccccgt tcagtccgac cgctgcgcct 540
tatccggtaa ctatcgtctt gagtccaacc cggaaagaca tgcaaaagca ccactggcag 600
cagccactgg taattgattt agaggagtta gtcttgaagt catgcgccgg ttaaggctaa 660
actgaaagga caagttttgg tgactgcgct cctccaagcc agttacctcg gttcaaagag 720
ttggtagctc agagaacctt cgaaaaaccg ccctgcaagg cggttttttc gttttcagag 780
caagagatta cgcgcagacc aaaacgatct caagaagatc atcttattaa ggggtctgac 840
gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc 900
ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag 960
taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt 1020
ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac gatacgggag 1080
ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc accggctcca 1140
gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg tcctgcaact 1200
ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag tagttcgcca 1260
gttaatagtt tgcgcaacgt tgttgccatt gctgcaggca tcgtggtgtc acgctcgtcg 1320
tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac atgatccccc 1380
atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag aagtaagttg 1440
gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac tgtcatgcca 1500
tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg agaatagtgt 1560
atgcggcgac cgagttgctc ttgcccggcg tcaacacggg ataataccgc gccacatagc 1620
agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc 1680
ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg atcttcagca 1740
tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa 1800
aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt tcaatattat 1860
tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg tatttagaaa 1920
aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga cgtgtcgacg 1980
cggccgcgct agcgatgatt taggtgacac tatagaagtt gttgatctgt gtgagtcaga 2040
ctgcgacagt tcgagtctga agcgagagct aacaacagta tcaacaggtt taatttggat 2100
ttggaaacga gagtttctgg tcatgaaaaa cccaaagaag aaatccggag gattccggat 2160
tgtcaatatg ctaaaacgcg gagtagcccg tgtaaacggt accgagctca tggtgagcaa 2220
gggcgaggag ctgttcaccg gggtggtgcc catcctggtc gagctggacg gcgacgtaaa 2280
cggccacaag ttcagcgtgt ccggcgaggg cgagggcgat gccacctacg gcaagctgac 2340
cctgaagctg atctgcacca ccggcaagct gcccgtgccc tggcccaccc tggtgaccac 2400
cctgggctac ggcctgcagt gcttcgcccg ctaccccgac cacatgaagc agcacgactt 2460
cttcaagtcc gccatgcccg aaggctacgt ccaggagcgc accatcttct tcaaggacga 2520
cggcaactac aagacccgcg ccgaggtgaa gttcgagggc gacaccctgg tgaaccgcat 2580
cgagctgaag ggcatcgact tcaaggagga cggcaacatc ctggggcaca agctggagta 2640
caactacaac agccacaacg tctatatcac cgccgacaag cagaagaacg gcatcaaggc 2700
caacttcaag atccgccaca acatcgagga cggcggcgtg cagctcgccg accactacca 2760
gcagaacacc cccatcggcg acggccccgt gctgctgccc gacaaccact acctgagcta 2820
ccagtccgcc ctgagcaaag accccaacga gaagcgcgat cacatggtcc tgctggagtt 2880
cgtgaccgcc gccgggatca ctctcggcat ggacgagctg tacaagaccg gtaactttga 2940
ccttctcaag ttggccggcg acgtcgagtc caacccaggg cccctgcagc aaattttcgt 3000
gaagaccctg acgggcaaga ccatcactct tgaggtcgag cccagtgaca ccatcgagaa 3060
tgtcaaggcc aagatccaag acaaggaagg catcccacct gaccagcaga ggctgatatt 3120
cgcgggcaaa cagctggagg atggccgcac cctgtccgac tacaacatcc agaaagagtc 3180
caccttgcac ctggtgctgc gtctccgcgg tggaatgaag aacccaaaga aaaaatcagg 3240
aggatttcgg atagtcaaca tgctaaaacg cggcgtagcc cgtgttaacc ccttgggagg 3300
tttgaagagg ttgccagccg gacttctgct gggtcatgga cccatcagaa tggttttggc 3360
gatactagcc tttttgagat ttacagcaat caagccatca ctgggcctta tcaacagatg 3420
gggttccgtg gggaaaaaag aggctatgga aataataaag aagttcaaga aagatcttgc 3480
tgccatgttg agaataatca atgctaggaa agagaggaag agacgtggcg cagacaccag 3540
catcggaatc attggcctcc tgctgactac agccatggca gcagagatca ctagacgcgg 3600
gagtgcatac tacatgtact tggataggag cgatgccggg aaggccattt cgtttgctac 3660
cacattggga gtgaacaagt gccacgtaca gatcatggac ctcgggcaca tgtgtgacgc 3720
caccatgagt tatgagtgcc ctatgctgga tgagggagtg gaaccagatg atgtcgattg 3780
ctggtgcaac acgacatcaa cttgggttgt gtacggaacc tgtcatcaca aaaaaggtga 3840
ggcacggcga tctagaagag ccgtgacgct cccttctcac tctacaagga agttgcaaac 3900
gcggtcgcag acctggttag aatcaagaga atacacgaag cacttgatca aggttgaaaa 3960
ctggatattc aggaaccccg ggtttgcgct agtggccgtt gccattgcct ggcttttggg 4020
aagctcgacg agccaaaaag tcatatactt ggtcatgata ctgctgattg ccccggcata 4080
cagtatcagg tgcattggag tcagcaatag agacttcgtg gagggcatgt caggtgggac 4140
ctgggttgat gttgtcttgg aacatggagg ctgcgttacc gtgatggcac aggacaagcc 4200
aacagtcgac atagagttgg tcacgacgac ggttagtaac atggccgagg taagatccta 4260
ttgctacgag gcatcgatat cggacatggc ttcggacagt cgttgcccaa cacaaggtga 4320
agcctacctt gacaagcaat cagacactca atatgtctgc aaaagaacat tagtggacag 4380
aggttgggga aacggttgtg gactttttgg caaagggagc ttggtgacat gtgccaagtt 4440
tacgtgttct aagaagatga ccgggaagag cattcaaccg gaaaatctgg agtatcggat 4500
aatgctatca gtgcatggct cccagcatag cgggatgatt ggatatgaaa ctgacgaaaa 4560
tagagcgaaa gtcgaggtta cgcctaattc accaagagcg gaagcaacct tgggaggctt 4620
tggaagctta ggacttgact gtgaaccaag gacaggcctt gacttttcag atctgtatta 4680
cctgaccatg aacaataagc attggttggt gcacaaagag tggtttcatg acatcccatt 4740
gccttggcat gctggggcag acaccggaac tccacactgg aacaacaaag aggcattggt 4800
agaattcaag gatgcccacg ccaagaggca aaccgtcgtc gttctgggga gccaggaagg 4860
agccgttcac acggctctcg ctggagctct agaggctgag atggatggtg caaagggaag 4920
gctgttctct ggccatttga aatgccgcct aaaaatggac aagcttagat tgaagggcgt 4980
gtcatattcc ttgtgcactg cggcattcac attcaccaag gtcccagctg aaacactgca 5040
tggaacagtc acagtggagg tgcagtatgc agggacagat ggaccctgca agatcccagt 5100
ccagatggcg gtggacatgc agaccctgac cccagttgga aggctgataa ccgccaaccc 5160
cgtgattact gaaagcactg agaactcaaa gatgatgttg gagcttgacc caccatttgg 5220
ggattcttac attgtcatag gagttgggga caagaaaatc acccaccact ggcataggag 5280
tggtagcacc atcggaaagg catttgaggc cactgtgaga ggcgccaaga gaatggcagt 5340
cctgggggat acagcctggg acttcggatc agtcgggggt gtgttcaact cactgggtaa 5400
gggcattcac cagatttttg gagcagcctt caaatcactg tttggaggaa tgtcctggtt 5460
ctcacagatc ctcataggca cgctgctagt gtggttaggt ttgaacacaa agaatggatc 5520
tatctccctc acatgcttgg ccctgggggg agtgatgatc ttcctctcca cggctgtttc 5580
tgctgacgtg gggtgctcag tggacttctc aaaaaaggaa acgagatgtg gcacgggggt 5640
attcatctat aatgatgttg aagcctggag ggaccggtac aagtaccatc ctgactcccc 5700
ccgcagattg gcagcagcag tcaagcaggc ctgggaagag gggatctgtg ggatctcatc 5760
cgtttcaaga atggaaaaca tcatgtggaa atcagtagaa ggggagctca atgctatcct 5820
agaggagaat ggagttcaac tgacagttgt tgtgggatct gtaaaaaacc ccatgtggag 5880
aggtccacaa agattgccag tgcctgtgaa tgagctgccc catggctgga aagcctgggg 5940
gaaatcgtat tttgttaggg cggcaaagac caacaacagt tttgttgtcg acggtgacac 6000
actgaaggaa tgtccgcttg agcacagagc atggaatagt tttcttgtgg aggatcacgg 6060
gtttggagtc ttccacacca gtgtctggct taaggtcaga gaagattact cattagaatg 6120
tgacccagcc gtcataggaa cagctgttaa gggaagggag gccgcgcaca gtgatctggg 6180
ctattggatt gaaagtgaaa agaatgacac atggaggctg aagagggccc acctgattga 6240
gatgaaaaca tgtgaatggc caaagtctca cacattgtgg acagatggag tagaagaaag 6300
tgatcttatc atacccaagt ctttagctgg tccactcagc caccacaaca ccagagaggg 6360
ttacagaacc caagtgaaag ggccatggca cagtgaagag cttgaaatcc ggtttgagga 6420
atgtccaggc accaaggttt acgtggagga gacatgcgga actagaggac catctctgag 6480
atcaactact gcaagtggaa gggtcattga ggaatggtgc tgtagggaat gcacaatgcc 6540
cccactatcg tttcgagcaa aagacggctg ctggtatgga atggagataa ggcccaggaa 6600
agaaccagag agcaacttag tgaggtcaat ggtgacagcg gggtcaaccg atcatatgga 6660
ccacttctct cttggagtgc ttgtgattct actcatggtg caggaggggt tgaagaagag 6720
aatgaccaca aagatcatca tgagcacatc aatggcagtg ctggtagtca tgatcttggg 6780
aggattttca atgagtgacc tggccaagct tgtgatcctg atgggtgcta ctttcgcaga 6840
aatgaacact ggaggagatg tagctcactt ggcattggta gcggcattta aagtcagacc 6900
agccttgctg gtctccttca ttttcagagc caattggaca ccccgtgaga gcatgctgct 6960
agccctggct tcgtgtcttc tgcaaactgc gatctctgct cttgaaggtg acttgatggt 7020
cctcattaat ggatttgctt tggcctggtt ggcaattcga gcaatggccg tgccacgcac 7080
tgacaacatc gctctaccaa tcttggctgc tctaacacca ctagctcgag gcacactgct 7140
cgtggcatgg agagcgggcc tggctacttg tggagggatc atgctcctct ccctgaaagg 7200
gaaaggtagt gtgaagaaga acctgccatt tgtcatggcc ctgggattga cagctgtgag 7260
ggtagtagac cctattaatg tggtaggact actgttactc acaaggagtg ggaagcggag 7320
ctggccccct agtgaagttc tcacagccgt tggcctgata tgtgcactgg ccggagggtt 7380
tgccaaggca gacattgaga tggctggacc catggctgca gtaggcttgc taattgtcag 7440
ctatgtggtc tcgggaaaga gtgtggacat gtacattgaa agagcaggtg acatcacatg 7500
ggaaaaggac gcggaagtca ctggaaacag tcctcggctt gacgtggcac tggatgagag 7560
tggtgacttc tccttggtag aggaagatgg tccacccatg agagagatca tactcaaggt 7620
ggtcctgatg gccatctgtg gcatgaaccc aatagctata ccttttgctg caggagcgtg 7680
gtatgtgtat gtgaagactg ggaaaaggag tggcgccctc tgggacgtgc ctgctcccaa 7740
agaagtgaag aaaggagaga ccacagatgg agtgtacaga gtgatgactc gcagactgct 7800
aggttcaaca caggttggag tgggagtcat gcaagaggga gtcttccaca ccatgtggca 7860
cgttacaaaa ggagccgcac tgaggagcgg tgagggaaga cttgatccat actgggggga 7920
tgtcaagcag gacttggtgt catactgtgg gccttggaag ttggatgcag cttgggatgg 7980
actcagcgag gtacagcttt tggccgtacc tcccggagag agggccagaa acattcagac 8040
cctgcctgga atattcaaga caaaggacgg ggacatcgga gcagttgctc tggactaccc 8100
tgcagggacc tcaggatctc cgatcctaga caaatgtgga agagtgatag gactctatgg 8160
caatggggtt gtgatcaaga atggaagcta tgttagtgct ataacccagg gaaagaggga 8220
ggaggagact ccggttgaat gtttcgaacc ctcgatgctg aagaagaagc agctaactgt 8280
cttggatctg catccaggag ccggaaaaac caggagagtt cttcctgaaa tagtccgtga 8340
agccataaaa aagagactcc ggacagtgat cttggcacca actagggttg tcgctgctga 8400
gatggaggag gccttgagag gacttccggt gcgttacatg acaacagcag tcaacgtcac 8460
ccattctggg acagaaatcg ttgatttgat gtgccatgcc actttcactt cacgcttact 8520
acaacccatc agagtcccta attacaatct ctacatcatg gatgaagccc acttcacaga 8580
cccctcaagt atagctgcaa gaggatacat atcaacaagg gttgaaatgg gcgaggcggc 8640
tgccattttt atgactgcca caccaccagg aacccgtgat gcgtttcctg actctaactc 8700
accaatcatg gacacagaag tggaagtccc agagagagcc tggagctcag gctttgattg 8760
ggtgacagac cattctggga aaacagtttg gttcgttcca agcgtgagaa acggaaatga 8820
aatcgcagcc tgtctgacaa aggctggaaa gcgggtcata cagctcagca ggaagacttt 8880
tgagacagaa tttcagaaaa caaaaaatca agagtgggac tttgtcataa caactgacat 8940
ctcagagatg ggcgccaact tcaaggctga ccgggtcata gactctagga gatgcctaaa 9000
accagtcata cttgatggtg agagagtcat cttggctggg cccatgcctg tcacgcatgc 9060
tagtgctgct cagaggagag gacgtatagg caggaaccct aacaaacctg gagatgagta 9120
catgtatgga ggtgggtgtg cagagactga tgaaggccat gcacactggc ttgaagcaag 9180
aatgcttctt gacaacatct acctccagga tggcctcata gcctcgctct atcggcctga 9240
ggccgataag gtagccgcca ttgagggaga gtttaagctg aggacagagc aaaggaagac 9300
cttcgtggaa ctcatgaaga gaggagacct tcccgtctgg ctagcctatc aggttgcatc 9360
tgccggaata acttacacag acagaagatg gtgctttgat ggcacaacca acaacaccat 9420
aatggaagac agtgtaccag cagaggtttg gacaaagtat ggagagaaga gagtgctcaa 9480
accgagatgg atggatgcta gggtctgttc agaccatgcg gccctgaagt cgttcaaaga 9540
attcgccgct ggaaaaagag gagcggcttt gggagtaatg gaggccctgg gaacactgcc 9600
aggacacatg acagagaggt ttcaggaagc cattgacaac ctcgccgtgc tcatgcgagc 9660
agagactgga agcaggcctt ataaggcagc ggcagcccaa ctgccggaga ccctagagac 9720
cattatgctc ttaggtttgc tgggaacagt ttcactgggg atcttcttcg tcttgatgcg 9780
gaataagggc atcgggaaga tgggctttgg aatggtaacc cttggggcca gtgcatggct 9840
catgtggctt tcggaaattg aaccagccag aattgcatgt gtcctcattg ttgtgttttt 9900
attactggtg gtgctcatac ccgagccaga gaagcaaaga tctccccaag ataaccagat 9960
ggcaattatc atcatggtgg cagtgggcct tctaggtttg ataactgcaa acgaacttgg 10020
atggctggaa agaacaaaaa atgacatagc tcatctaatg ggaaggagag aagaaggagc 10080
aaccatggga ttctcaatgg acattgatct gcggccagcc tccgcctggg ctatctatgc 10140
cgcattgaca actctcatca ccccagctgt ccaacatgcg gtaaccactt catacaacaa 10200
ctactcctta atggcgatgg ccacacaagc tggagtgctg tttggcatgg gcaaagggat 10260
gccattttat gcatgggacc ttggagtccc gctgctaatg atgggttgct attcacaatt 10320
aacacccctg actctgatag tagctatcat tctgcttgtg gcgcactaca tgtacttgat 10380
cccaggccta caagcggcag cagcgcgtgc tgcccagaaa aggacagcag ctggcatcat 10440
gaagaatccc gttgtggatg gaatagtggt aactgacatt gacacaatga caatagaccc 10500
ccaggtggag aagaagatgg gacaagtgtt actcatagca gtagccatct ccagtgctgt 10560
gctgctgcgg accgcctggg gatgggggga ggctggagct ctgatcacag cagcgacctc 10620
caccttgtgg gaaggctctc caaacaaata ctggaactcc tctacagcca cctcactgtg 10680
caacatcttc agaggaagct atctggcagg agcttccctt atctatacag tgacgagaaa 10740
cgctggcctg gttaagagac gtggaggtgg gacgggagag actctgggag agaagtggaa 10800
agctcgtctg aatcagatgt cggccctgga gttctactct tataaaaagt caggtatcac 10860
tgaagtgtgt agagaggagg ctcgccgtgc cctcaaggat ggagtggcca caggaggaca 10920
tgccgtatcc cggggaagtg caaagctcag atggttggtg gagagaggat atctgcagcc 10980
ctatgggaag gttgttgacc tcggatgtgg cagagggggc tggagctatt atgccgccac 11040
catccgcaaa gtgcaggagg tgagaggata cacaaaggga ggtcccggtc atgaagaacc 11100
catgctggtg caaagctatg ggtggaacat agttcgtctc aagagtggag tggacgtctt 11160
ccacatggcg gctgagccgt gtgacactct gctgtgtgac ataggtgagt catcatctag 11220
tcctgaagtg gaagagacac gaacactcag agtgctctct atggtggggg actggcttga 11280
aaaaagacca ggggccttct gtataaaggt gctgtgccca tacaccagca ctatgatgga 11340
aaccatggag cgactgcaac gtaggcatgg gggaggatta gtcagagtgc cattgtctcg 11400
caactccaca catgagatgt actgggtctc tggggcaaag agcaacatca taaaaagtgt 11460
gtccaccaca agtcagctcc tcctgggacg catggatggc cccaggaggc cagtgaaata 11520
tgaggaggat gtgaacctcg gctcgggtac acgagctgtg gcaagctgtg ctgaggctcc 11580
taacatgaaa atcatcggca ggcgcattga gagaatccgc aatgaacatg cagaaacatg 11640
gtttcttgat gaaaaccacc catacaggac atgggcctac catgggagct acgaagcccc 11700
cacgcaagga tcagcgtctt ccctcgtgaa cggggttgtt agactcctgt caaagccttg 11760
ggacgtggtg actggagtta caggaatagc catgactgac accacaccat acggccaaca 11820
aagagtcttc aaagaaaaag tggacaccag ggtgccagat ccccaagaag gcactcgcca 11880
ggtaatgaac atagtctctt cctggctgtg gaaggagctg gggaaacgca agcggccacg 11940
cgtctgcacc aaagaagagt ttatcaacaa ggtgcgcagc aatgcagcac tgggagcaat 12000
atttgaagag gaaaaagaat ggaagacggc tgtggaagct gtgaatgatc caaggttttg 12060
ggccctagtg gatagggaga gagaacacca cctgagagga gagtgtcaca gctgtgtgta 12120
caacatgatg ggaaaaagag aaaagaagca aggagagttc gggaaagcaa aaggtagccg 12180
cgccatctgg tacatgtggt tgggagccag attcttggag tttgaagccc ttggattctt 12240
gaacgaggac cattggatgg gaagagaaaa ctcaggaggt ggagtcgaag ggttaggatt 12300
gcaaagactt ggatacattc tagaagaaat gaatcgggca ccaggaggaa agatgtacgc 12360
agatgacact gctggctggg acacccgcat tagtaagttt gatctggaga atgaagctct 12420
gattaccaac caaatggagg aagggcacag aactctggcg ttggccgtga ttaaatacac 12480
ataccaaaac aaagtggtga aggttctcag accagctgaa ggaggaaaaa cagttatgga 12540
catcatttca agacaagacc agagagggag tggacaagtt gtcacttatg ctctcaacac 12600
attcaccaac ttggtggtgc agcttatccg gaacatggaa gctgaggaag tgttagagat 12660
gcaagactta tggttgttga ggaagccaga gaaagtgacc agatggttgc agagcaatgg 12720
atgggataga ctcaaacgaa tggcggtcag tggagatgac tgcgttgtga agccaatcga 12780
tgataggttt gcacatgccc tcaggttctt gaatgacatg ggaaaagtta ggaaagacac 12840
acaggagtgg aaaccctcga ctggatggag caattgggaa gaagtcccgt tctgctccca 12900
ccacttcaac aagctgtacc tcaaggatgg gagatccatt gtggtccctt gccgccacca 12960
agatgaactg attggccgag ctcgcgtctc accaggggca ggatggagca tccgggagac 13020
tgcctgtctt gcaaaatcat atgcgcagat gtggcagctc ctttatttcc acagaagaga 13080
ccttcgactg atggctaatg ccatttgctc ggctgtgcca gttgactggg taccaactgg 13140
gagaaccacc tggtcaatcc atggaaaggg agaatggatg accactgagg acatgctcat 13200
ggtgtggaat agagtgtgga ttgaggagaa cgaccatatg gaggacaaga ctcctgtaac 13260
aaaatggaca gacattccct atctaggaaa aagggaggac ttatggtgtg gatcccttat 13320
agggcacaga ccccgcacca cttgggctga aaacatcaaa gacacagtca acatggtgcg 13380
caggatcata ggtgatgaag aaaagtacat ggactatcta tccacccaag tccgctactt 13440
gggtgaggaa gggtccacac ccggagtgtt gtaagcacca attttagtgt tgtcaggcct 13500
gctagtcagc cacagtttgg ggaaagctgt gcagcctgta acccccccag gagaagctgg 13560
gaaaccaagc tcatagtcag gccgagaacg ccatggcacg gaagaagcca tgctgcctgt 13620
gagcccctca gaggacactg agtcaaaaaa ccccacgcgc ttggaagcgc aggatgggaa 13680
aagaaggtgg cgaccttccc cacccttcaa tctggggcct gaagggacta gtggttagag 13740
gagacccccc ggaaaacgca aaacagcata ttgacgctgg gaaagaccag agactccatg 13800
agtttccacc acgctggccg ccaggcacag atcgccgaac agcggcggcc ggtgtgggga 13860
aatccatggt ttctggccgg catggtccca gcctcctcgc tggcgccggc tgggcaacat 13920
gcttcggcat ggcgaatggg ac 13942
<210> 10
<211> 19
<212> DNA
<213> Artificial
<400> 10
atttaggtga cactataga 19
<210> 11
<211> 68
<212> DNA
<213> Artificial
<400> 11
ggccggcatg gtcccagcct cctcgctggc gccggctggg caacatgctt cggcatggcg 60
aatgggac 68
<210> 12
<211> 75
<212> DNA
<213> Artificial
<400> 12
atgaagaacc caaagaaaaa atcaggagga tttcggatag tcaacatgct aaaacgcggc 60
gtagcccgtg ttaac 75
<210> 13
<211> 29
<212> DNA
<213> Artificial
<400> 13
ctggagacta gctgtgaatc tccagcaga 29

Claims (28)

1.一种cDNA，其特征在于，该cDNA包括寨卡病毒MR766毒株的核酸序列和一个低拷贝质粒骨架；寨卡病毒MR766毒株的核酸序列包括寨卡病毒MR766毒株5′到3′正向极性序列，病毒5′及3′非编码区及一个编码病毒蛋白的开放阅读框，所述的3′非编码区不包括SEQ IDNO 13所示的序列；寨卡病毒MR766毒株的核酸序列中，5′非编码区、编码病毒蛋白的开放阅读框、3′非编码区依次排列。
2.如权利要求1所述的cDNA，其特征在于，在权利要求1所述的cDNA的3′非编码区加入SEQ ID NO 13所示的序列。
3.如权利要求1所述的cDNA，其特征在于，在权利要求1所述的cDNA中插入报道基因荧光素酶Gluc编码序列，并在报道基因荧光素酶Gluc编码序列中删除SEQ ID NO 13所示的序列。
4.如权利要求1所述的cDNA，其特征在于，在权利要求1所述的DNA中插入荧光蛋白Venus编码序列，并在荧光蛋白Venus编码序列中删除SEQ ID NO 13所示的序列。
5.如权利要求1所述的cDNA，其特征在于，在权利要求1所述的cDNA中插入报道基因荧光素酶Gluc编码序列。
6.如权利要求1所述的cDNA，其特征在于，在权利要求1所述的cDNA中插入荧光蛋白Venus编码序列。
7.根据权利要求1-6中任意一种cDNA的序列构建的寨卡病毒RNA复制子及缺失结构蛋白的亚基因组复制子。
8.根据权利要求1-6中任意一种cDNA制备的重组病毒。
9.如权利要求1-6中任意一种cDNA，其特征在于，所述的寨卡病毒MR766毒株的核酸序列如SEQ ID NO 2所示。
10.如权利要求1-6中任意一种cDNA，其特征在于，所述的低拷贝质粒骨架的序列如SEQID NO 3所示。
11.如权利要求1-6中任意一种cDNA，其特征在于，所编码的开放阅读框病毒蛋白序列如SEQ ID NO 4所示。
12.如权利要求3或者5所述的cDNA，其特征在于，所述的报道基因荧光素酶Gluc编码序列如SEQ ID NO 5所示。
13.如权利要求4或6中所述的DNA，其特征在于，所述的荧光蛋白Venus编码序列如SEQID NO 6所示。
14.如权利要求1所述的cDNA，其特征在于，所述的序列如SEQ ID NO 1所示。
15.如权利要求1所述的cDNA，其特征在于，所述的序列如SEQ ID NO 9所示。
16.一种质粒，其特征在于，该质粒能通过体外转录产生含有权利要求1-6中任意一种cDNA相对应的RNA。
17.如权利要求16所述的质粒，其特征在于，所述的质粒包括：
a)利用其他分离株的部分序列替换权利要求1-6中任意一种cDNA的寨卡病毒全长感染克隆的部分序列得到的重组病毒克隆；
或者b)利用基因突变对权利要求1-6中任意一种cDNA的寨卡病毒中的序列进行突变得到的突变病毒克隆；
或者c)由权利要求1-6中任意一种cDNA的克隆产生的病毒经过适应性突变产生的减毒，复制非感染病毒及非复制性病毒等衍生克隆。
18.一种根据权利要求17所述质粒制备的疫苗。
19.一种根据权利要求17所述质粒制备的病毒载体。
20.一种根据权利要求17所述质粒制备的病毒颗粒。
21.一种检测权利要求8所述病毒的检测方法。
22.利用权利要求8所述病毒制备抗寨卡病毒抗体的方法。
23.利用权利要求8所述病毒免疫动物及分离抗寨卡病毒抗体的方法。
24.利用权利要求8所述病毒筛选人抗体库的方法。
25.利用权利要求8所述病毒进行的抗寨卡病毒药物的筛选。
26.利用权利要求8所述病毒用于检测寨卡病毒的试剂盒。
27.权利要求8所述病毒的应用，其特征在于，利用权利要求8所产生的病毒构建细胞系或者动物感染模型，用于药物筛选。
28.权利要求8所述病毒的应用，其特征在于，利用权利要求8所产生的病毒感染体外培养的组织模型，用于药物筛选的方法。
CN201810132277.8A 2018-02-09 2018-02-09 寨卡病毒mr766毒株的感染性克隆及其应用 Pending CN110129340A (zh)

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