CN114045305A - 多转座子系统 - Google Patents

多转座子系统 Download PDF

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CN114045305A
CN114045305A CN202111205699.1A CN202111205699A CN114045305A CN 114045305 A CN114045305 A CN 114045305A CN 202111205699 A CN202111205699 A CN 202111205699A CN 114045305 A CN114045305 A CN 114045305A
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薛博夫
杨银辉
刘杰
陈莉
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Abstract

本公开提供一种用于将一种或多种外源核苷酸序列整合到哺乳动物宿主细胞基因组中的方法，所述方法包括通过使用至少两种转座子系统将所述一种或多种外源核苷酸序列整合到所述哺乳动物宿主细胞基因组中。

Description

多转座子系统
技术领域
本公开涉及将外源核苷酸序列整合到宿主细胞基因组中的方法，具体地，涉及通过使用多转座子系统将外源核苷酸序列整合到哺乳动物宿主细胞中的方法。
背景技术
转座子(transposon)是指可改变其在基因组内的位置的DNA序列。转座子可产生或逆转突变并改变细胞基因组的大小。DNA转座子在表达的转座酶(transpotase)作用下，可以以简单的剪切-粘贴的方式从一个DNA位点易位到另一个位点。转座是一个精确的过程，其中将限定的DNA片段，通常是转座子两端的直接重复序列(direct repeat，简称DR)和与它们相连的反向重复序列(invert repeat，简称IR)以及中间的插入序列(insertsequence，简称IS)，从一个DNA分子中切出并移动到相同或不同DNA分子或基因组中的另一个位点。
目前已有利用转座子系统将目的基因插入宿主细胞基因组的方法被公开。然而，大多数转座子系统在插入靶基因时都具有插入拷贝数的上限。尤其是当涉及多个靶基因的插入时，已有的方法无法以较高的拷贝数插入多个靶基因，并且也无法有效地调节插入的多个靶基因拷贝数的比率。
发明概述
在一个方面，本公开提供一种用于将一种或多种外源核苷酸序列整合到哺乳动物宿主细胞基因组中的方法，所述方法包括通过使用至少两种转座子系统将所述一种或多种外源核苷酸序列整合到所述哺乳动物宿主细胞基因组中。
在一个实施方案中，在本公开的用于将一种或多种外源核苷酸序列整合到哺乳动物宿主细胞基因组中的方法中，所述至少两种转座子系统包括：Tol1转座子系统、Tol2转座子系统、Frog Prince转座子系统、Minos转座子系统、Hsmar1转座子系统、Helraiser转座子系统、ZB转座子系统、Intruder转座子系统、SPINON转座子系统、TcBuster转座子系统、Passport转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PiggyBac(PB)转座子系统、Sleeping Beauty(SB)转座子系统，以及上述转座子系统的各种变体或衍生物。
在另一个实施方案中，在本公开的用于将一种或多种外源核苷酸序列整合到哺乳动物宿主细胞基因组中的方法中，所述至少两种转座子系统包括：Tol1转座子系统、Tol2转座子系统、ZB转座子系统、Intruder转座子系统、TcBuster转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PB转座子系统和SB转座子系统，以及上述转座子系统的各种变体或衍生物。
在另一个实施方案中，通过同时或相继使用所述至少两种转座子系统将所述一种或多种外源核苷酸序列整合到所述哺乳动物宿主细胞基因组中。
在另一个方面，本公开提供通过如上所述的本公开的方法获得的包含整合在其基因组中的一种或多种外源核苷酸序列的哺乳动物细胞。
在另一个方面，本公开提供一种哺乳动物细胞，所述哺乳动物细胞包含整合在所述哺乳动物细胞的基因组中的至少两种转座子。
在一个实施方案中，在所述哺乳动物细胞的基因组中，所述至少两种转座子的序列彼此不重叠。
在一个实施方案中，在本公开的哺乳动物细胞中，所述至少两种转座子包括：Tol1转座子、Tol2转座子、Frog Prince转座子、Minos转座子、Hsmar1转座子、Helraiser转座子、ZB转座子、Intruder转座子、SPINON转座子、TcBuster转座子、Passport转座子、Yabusame-1转座子、Uribo2转座子、PiggyBac(PB)转座子、Sleeping Beauty(SB)转座子，以及上述转座子的各种变体或衍生物。
在另一个实施方案中，在本公开的哺乳动物细胞中，所述至少两种转座子包括：Tol1转座子、Tol2转座子、ZB转座子、Intruder转座子、TcBuster转座子、Yabusame-1转座子、Uribo2转座子、PB转座子和SB转座子，以及上述转座子的各种变体或衍生物。
在另一个方面，本公开提供一种用于构建慢病毒生产细胞系的方法，所述方法包括通过使用至少两种转座子系统将慢病毒的gag、pol和rev基因的序列、病毒包膜蛋白的编码序列、以及携带目的核酸片段的病毒基因组转录盒序列整合到宿主细胞基因组中。
在一个实施方案中，在本公开的用于构建慢病毒生产细胞系的方法中，所述至少两种转座子系统包括：Tol1转座子系统、Tol2转座子系统、Frog Prince转座子系统、Minos转座子系统、Hsmar1转座子系统、Helraiser转座子系统、ZB转座子系统、Intruder转座子系统、SPINON转座子系统、TcBuster转座子系统、Passport转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PiggyBac(PB)转座子系统、Sleeping Beauty(SB)转座子系统，以及上述转座子系统的各种变体或衍生物。
在另一个实施方案中，在本公开的用于构建慢病毒生产细胞系的方法中，所述至少两种转座子系统包括：Tol1转座子系统、Tol2转座子系统、ZB转座子系统、Intruder转座子系统、TcBuster转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PB转座子系统和SB转座子系统，以及上述转座子系统的各种变体或衍生物。
在另一个方面，本公开提供一种慢病毒生产细胞系，其特征在于，所述慢病毒生产细胞系包含整合在其基因组中的至少两种转座子。
在一个实施方案中，在本公开的慢病毒生产细胞系中，所述至少两种转座子包括：Tol1转座子、Tol2转座子、Frog Prince转座子、Minos转座子、Hsmar1转座子、Helraiser转座子、ZB转座子、Intruder转座子、SPINON转座子、TcBuster转座子、Passport转座子、Yabusame-1转座子、Uribo2转座子、PiggyBac(PB)转座子、Sleeping Beauty(SB)转座子，以及上述转座子的各种变体或衍生物。
在另一个实施方案中，在本公开的慢病毒生产细胞系中，所述至少两种转座子包括：Tol1转座子、Tol2转座子、ZB转座子、Intruder转座子、TcBuster转座子、Yabusame-1转座子、Uribo2转座子、PB转座子和SB转座子，以及上述转座子的各种变体或衍生物。
发明详述
当在本文中使用时，“通过同时或相继使用至少两种转座子系统将一种或多种外源核苷酸序列整合到宿主细胞基因组中”包括，例如，使用两种以上的本公开的转座子系统同时或相继向宿主细胞基因组中整合同一种外源核苷酸序列，并且也包括使用两种以上的本公开的转座子系统同时或相继向宿主细胞基因组中整合两种以上的外源核苷酸序列。
当在本文中使用时，“整合在所述细胞的基因组中、两侧具有所述至少两种转座子系统的识别序列的一种或多种外源核苷酸序列”是指，宿主细胞基因组中整合有一种或多种外源核苷酸序列，并且至少两种类型的本公开的转座子系统的识别序列同时存在于所述一种或多种外源核苷酸序列的不同拷贝的两侧。如可以理解的，例如，当使用两种以上的本公开的转座子系统同时或相继向宿主细胞基因组中整合同一种外源核苷酸序列时，整合在宿主细胞基因组中的该种外源核苷酸序列的不同拷贝的两侧将具有相应的不同类型的转座子系统的识别序列；当使用两种以上的本公开的转座子系统同时或相继向宿主细胞基因组中整合两种以上的外源核苷酸序列时，整合在宿主细胞基因组中的所述两种以上的外源核苷酸序列的不同拷贝的两侧也将具有相应的不同类型的转座子系统的识别序列。
当在本文中使用时，术语“转座子(transposon)”或“可转座元件(transposableelement)”是指可以通过反式作用的转座酶的作用从第一多核苷酸中切去并且被整合到同一多核苷酸的第二位置中或整合到第二多核苷酸中的多核苷酸。转座子包含第一转座子末端和第二转座子末端，所述第一转座子末端和第二转座子末端是被转座酶识别并转座的多核苷酸序列，所述第一转座子末端和第二转座子末端在本文中可以被称为转座子系统的识别序列。转座子通常还包含位于所述两个转座子末端之间的目的多核苷酸序列，使得在转座酶的作用下所述目的多核苷酸序列与所述两个转座子末端一起被转座。当在本文中使用时，术语“转座子末端”或“转座子系统的识别序列”是指足以被转座酶识别和转座的顺式作用核苷酸序列。一对转座子末端通常包含成对的完美或不完美的重复(repeats)以使得两个不同转座子末端中成对的元件中相应的重复彼此反向互补。这些被称为反向末端重复(ITR)或末端反向重复(TIR)。转座子末端可以包含也可以不包含临近ITR的用于促进或增强转座的额外序列。如本文中使用的，“转座子系统”包括如上所述的“转座子”或“可转座元件”以及可以反式作用方式识别并移动所述“转座子”或“可转座元件”的相应的转座酶。当在本文中使用时，“所述至少两种转座子的序列彼此不重叠”是指，例如，当使用两种转座子时，假设第一转座子两端的识别序列分别为L1和R1，第二转座子两端的识别序列分别为L2和R2，则哺乳动物细胞基因组中不存在例如以下排列：L1-L2-R2-R1、L1-L2-R1-R2、L1-R2-L2-R1、L1-R2-R1-L2、R1-L2-R2-L1、R1-L2-L1-R2、R1-R2-L2-L1、R1-R2-L1-L2、L2-L1-R1-R2、L2-L1-R2-R1、L2-R1-L1-R2、L2-R1-R2-L1、R2-L1-R1-L2、R2-L1-L2-R1、R2-R1-L1-L2、R2-R1-L2-L1。
在本公开中，可以使用的转座子系统包括：Tol1转座子系统、Tol2转座子系统、Frog Prince转座子系统、Minos转座子系统、Hsmar1转座子系统、Helraiser转座子系统、ZB转座子系统、Intruder转座子系统、SPINON转座子系统、TcBuster转座子系统、Passport转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PiggyBac(PB)转座子系统、SleepingBeauty(SB)转座子系统，以及上述转座子系统的各种变体或衍生物。
Tol1转座子系统
Tol1转座子系统的介绍可参见，例如，国际申请WO2008072540(其内容通过引用结合于此)。在本文中，术语“Tol1转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Tol1转座子系统。
Tol2转座子系统
Tol2转座子系统的介绍可参见，例如，Ni,J.等(2016):Active recombinant Tol2transposase for gene transfer and gene discovery applications.In Mob DNA 7,p.6(其内容通过引用结合于此)，以及Kawakami K,Shima A.(1999):Identification ofthe Tol2 transposase of the medaka fish Oryzias latipes that catalyzesexcision of a nonautonomous Tol2 element in zebrafish Danio rerio.InGene.1999Nov 15；240(1):239-44(其内容通过引用结合于此)。关于TIR序列的优化可参见，例如，Urasaki,A.等(2006):Functional dissection of the Tol2 transposableelement identified the minimal cis-sequence and a highly repetitive sequencein the subterminal region essential for transposition.In Genetics 174(2),pp.639–649(其内容通过引用结合于此)。最小TIR序列为T2AL200R150G(GenBankaccession number AB262452)。在本文中，术语“Tol2转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Tol2转座子系统。
Frog Prince(FP)转座子系统
Frog Prince(青蛙王子)转座子系统的介绍可参见，例如，国际申请WO2003100070(其内容通过引用结合于此)以及Miskey C.等The Frog Prince:a reconstructedtransposon from Rana pipiens with high transpositional activity in vertebratecells.Nucleic Acids Res.2003；31(23):6873-6881(其内容通过引用结合于此)。在本文中，术语“Frog Prince转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Frog Prince转座子系统。
Minos转座子系统
Minos转座子系统的介绍可参见，例如，Metaxakis,Athanasios等(2005):Minosas a genetic and genomic tool in Drosophila melanogaster.In Genetics171(2),pp.571–581(其内容通过引用结合于此)以及Franz,G.等(1991):Minos,a newtransposable element from Drosophila hydei,is a member of the Tc1-like familyof transposons.In Nucleic acids research 19(23),p.6646(其内容通过引用结合于此)。在本文中，术语“Minos转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Minos转座子系统。
Hsmar1转座子系统
Hsmar1转座子系统的介绍可参见，例如，国际申请WO2006108525(其内容通过引用结合于此)，以及Miskey,Csaba等(2007):The ancient mariner sails again:transposition of the human Hsmar1 element by a reconstructed transposase andactivities of the SETMAR protein on transposon ends.In Molecular and cellularbiology 27(12),pp.4589–4600(其内容通过引用结合于此)。在本文中，术语“Hsmar1转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Hsmar1转座子系统。
Helraiser转座子系统
Helraiser是一种利用生物信息学方法重建的活性Helitron转座子，Helraiser转座子系统的介绍可参见，例如，Grabundzija,Ivana等(2016):A Helitron transposonreconstructed from bats reveals a novel mechanism of genome shuffling ineukaryotes.In Nature communications 7,p.10716(其内容通过引用结合于此)，Grabundzija,Ivana等(2018):Helraiser intermediates provide insight into themechanism of eukaryotic replicative transposition.In Nature communications 9(1),p.1278(其内容通过引用结合于此)，以及专利申请US20190323037(其内容通过引用结合于此)。在本文中，术语“Helraiser转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Helraiser转座子系统。
ZB转座子系统
ZB转座子系统的介绍可参见，例如，Shen,Dan等(2021):A native,highly activeTc1/mariner transposon from zebrafish(ZB)offers an efficient geneticmanipulation tool for vertebrates.In Nucleic acids research 49(4),pp.2126–2140(其内容通过引用结合于此)，以及CN105018523B(其内容通过引用结合于此)。在本文中，术语“ZB转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的ZB转座子系统。
Intruder(IT)转座子系统
Intruder转座子系统的介绍可参见，例如，Gao,Bo等(2020):Intruder(DD38E),arecently evolved sibling family of DD34E/Tc1 transposons in animals.In MobileDNA 11(1),p.32(其内容通过引用结合于此)。在本文中，术语“Intruder转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Intruder转座子系统。
SPINON转座子系统
SPINON转座子系统的介绍可参见，例如，Gilbert,C.等(2012):RampantHorizontal Transfer of SPIN Transposons in Squamate Reptiles.In Molecularbiology and evolution 29(2),pp.503–515(其内容通过引用结合于此)，以及Li,Xianghong等(2013):A resurrected mammalian hAT transposable element and aclosely related insect element are highly active in human cell culture.InProceedings of the National Academy of Sciences of the United States ofAmerica110(6),E478-87(其内容通过引用结合于此)。在本文中，术语“SPINON转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的SPINON转座子系统。
TcBuster转座子系统
TcBuster转座子系统的介绍可参见，例如，Woodard,Lauren E.等(2012):Comparative analysis of the recently discovered hAT transposon TcBuster inhuman cells.In PloS one 7(11),e42666(其内容通过引用结合于此)，Li,Xianghong等(2013):A resurrected mammalian hAT transposable element and a closely relatedinsect element are highly active in human cell culture.In Proceedings of theNational Academy of Sciences of the United States of America 110(6),E478-87(其内容通过引用结合于此)，以及US20180216087(其内容通过引用结合于此)和CN108728477A(其内容通过引用结合于此)。TcBusterCO(原始TcBuster)转座酶的序列可参见上述Li,Xianghong等(2013)。具有增强活性的多种TcBuster转座酶变种的序列描述于US20180216087。US20180216087和CN108728477A分别描述了TcBuster转座子系统的多种5’TIR和3’TIR序列变体。上述不同的5’TIR和3’TIR可组合使用。在本文中，术语“TcBuster转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的TcBuster转座子系统。
Passport转座子系统
Passport转座子系统的介绍可参见，例如，Clark,Karl J.等(2009):Passport,anative Tc1 transposon from flatfish,is functionally active in vertebratecells.In Nucleic acids research 37(4),pp.1239–1247(其内容通过引用结合于此)，以及WO2010008564(其内容通过引用结合于此)。在本文中，术语“Passport转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Passport转座子系统。
Yabusame-1转座子系统和Uribo2转座子系统
两种新的转座子-转座酶系统被公开，一种来源于家蚕(Bombyx mori)(Yabusame-1转座子系统)而另一种来源于热带爪蟾(Xenopus tropicalis)(Uribo2转座子系统)，其各自包含充当转座子末端并且与识别并作用于其上的转座酶组合使用的序列。关于以上转座子-转座酶系统的介绍以及相应的转座酶和转座子两端TIR的序列信息可参见，例如，Hottentot QP等,Targeted Locus Amplification and Next-Generation Sequencing.InGenotyping:Methods and Protocols.White SJ,Cantsilieris S,eds:185–196.(NewYork,NY:Springer):2017.pp.185–196；Hikosaka,Akira等(2007):Evolution of theXenopus piggyBac transposon family TxpB:domesticated and untamed strategiesof transposon subfamilies.In Molecular biology and evolution 24(12),pp.2648–2656；GenBank登录号BAD11135.1；GenBank登录号BAF82022；WO2017062668；WO2019028273；US9428767B2；以及US10041077B2(以上所有文献的内容通过引用结合于此)。在本文中，术语“Yabusame-1转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Yabusame-1转座子系统。在本文中，术语“Uribo2转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的Uribo2转座子系统。
PiggyBac转座子系统
来源于粉纹夜蛾(Trichoplusia ni)的“PiggyBac(PB)转座子系统”由PB转座酶和转座子组成，其能够通过剪切-粘贴机制在载体和染色体之间进行有效转座。在转座过程中，PB转座酶识别位于转座子载体两端的转座子特异性反向末端反向重复序列(Invertedterminal repeart，简称ITR)，并且有效地移动来自原始位点的，在5’ITR和3’ITR之间的插入序列并有效地将其整合至染色体TTAA位点中。PiggyBac转座子系统的强大活性使得PB转座子载体中两个ITR之间的目的插入序列很容易地被移动到靶基因组中。PB转座子系统中的转座酶和转座子的野生型和不同变体(如ePiggyBac)在本领域中是已知的。关于PiggyBac转座子系统的信息可以参见，例如专利文献US9428767B2、US10041077B2、US6218185B1、US6551825B1、US7105343B1、US6962810B2、US8592211B2、WO2006122442、WO2010085699、WO2010099296、WO2010099301、WO2012074758、US8592211B2等，以及非专利文献Lacoste,A.等(2009)."An efficient and reversible transposable system forgene delivery and lineage-specific differentiation in human embryonic stemcells."Cell Stem Cell 5(3):332-342；Yusa,K.等(2011)."A hyperactive piggyBactransposase for mammalian applications."Proc Natl Acad Sci USA 108(4):1531-1536；Meir,Yaa-Jyuhn J.等(2011):Genome-wide target profiling of piggyBac andTol2 in HEK 293:pros and cons for gene discovery and gene therapy.In BMCbiotechnology 11,p.28；Troyanovsky,Boris等(2016):The Functionality of MinimalPiggyBac Transposons in Mammalian Cells.In Molecular therapy.Nucleic acids 5(10),e369；Wen,Wen等(2020):An efficient Screening System in Yeast to Select aHyperactive piggyBac Transposase for Mammalian Applications.In Internationaljournal of molecular sciences 21(9)(上述文献通过引用结合与此)以及GenBank登录号ABC67521。在本文中，术语“PiggyBac(PB)转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的PB转座子系统。
Sleeping Beauty转座子系统
Sleeping Beauty(睡美人，SB)转座子系统由SB转座酶和转座子组成，其能够将特定的DNA插入序列插入脊椎动物的基因组中。SB转座酶可将转座子插入受体DNA序列中的TA二核苷酸碱基对中。插入位点可位于同一个DNA分子(或染色体)的其他位置或者位于另一个DNA分子(或染色体)中。SB转座子由目的插入序列及位于其两端的用于被SB转座酶识别的IR/DR序列(本身含有短的直接重复(direct repeat，DR)的反向重复(inverted repeat，IR))组成。转座酶可在转座子内进行编码，或者转座酶可由另一个来源提供。SB转座子系统中的转座酶、IR/DR序列和转座子的野生型和不同变体在本领域中是已知的。关于SB转座酶及其各种变种(例如，SB1至SB10，SB11，SB17，SB100X，SB130X)的描述及序列信息可参见例如，Ivics,Zoltán等(1997):Molecular Reconstruction of Sleeping Beauty,a Tc1-like Transposon from Fish,and Its Transposition in Human Cells.In Cell 91(4),pp.501–510；Baus,James等(2005):Hyperactive transposase mutants of the SleepingBeauty transposon.In Molecular therapy:the journal of the American Society ofGene Therapy 12(6),pp.1148–1156；Mátés,Lajos等(2009):Molecular evolution of anovel hyperactive Sleeping Beauty transposase enables robust stable genetransfer in vertebrates.In Nature genetics 41(6),pp.753–761；Voigt,Franka等(2016):Sleeping Beauty transposase structure allows rational design ofhyperactive variants for genetic engineering.In Nature communications 7,p.11126；Kesselring,Lisa等(2020):A single amino acid switch converts theSleeping Beauty transposase into an efficient unidirectional excisionase withutility in stem cell reprogramming.In Nucleic acids research48(1),pp.316–331；Querques,Irma等(2019):A highly soluble Sleeping Beauty transposase improvescontrol of gene insertion.In Nature biotechnology37(12),pp.1502–1512；WO9840510A1；WO2003089618A2；WO2009003671A2；WO2017046259A1；WO2017158029A1(上述文献的内容通过引用结合与此)。关于SB转座子的TIR以及转座子载体(例如，pT1，pT2，pT3，pT4)的描述及相关序列信息可进一步参见例如，Yant,Stephen R.等(2004):Mutationalanalysis of the N-terminal DNA-binding domain of sleeping beauty transposase:critical residues for DNA binding and hyperactivity in mammalian cells.InMolecular and cellular biology 24(20),pp.9239–9247；Cui,Zongbin等(2002):Structure–Function Analysis of the Inverted Terminal Repeats of the SleepingBeauty Transposon.In Journal of molecular biology 318(5),pp.1221–1235；Izsvák,Zsuzsanna等(2002):Involvement of a bifunctional,paired-like DNA-bindingdomain and a transpositional enhancer in Sleeping Beauty transposition.In TheJournal of biological chemistry 277(37),pp.34581–34588；Wang,Yongming等(2017):Regulated complex assembly safeguards the fidelity of Sleeping Beautytransposition.In Nucleic acids research 45(1),pp.311–326；以及Zayed,Hatem等(2004):Development of hyperactive sleeping beauty transposon vectors bymutational analysis.In Molecular therapy:the journal of the American Societyof Gene Therapy 9(2),pp.292–304。在本文中，术语“Sleeping Beauty(睡美人，SB)转座子系统”可以包括含有相应转座酶及其不同变体以及相应转座子及其不同变体的SB转座子系统。
如本文中使用的，可以被整合在宿主细胞基因组中的“外源核苷酸序列”或“目的核苷酸序列”可以例如是，基因，如编码多肽或蛋白质的核酸序列；可转录为有功能的核糖核酸(RNA)的核苷酸序列，如小分子干扰核糖核酸(small interfering RNA，siRNA)、长链非编码核糖核酸(long non-coding RNA，LncRNA)，CRISPR基因编辑系统的导向RNA(guideRNA，gRNA)、转运核糖核酸(transfer RNA，tRNA)、核糖体核糖核酸(Ribosomal RNA，rRNA)或其他功能性核糖核酸的编码序列；调控基因表达的元件，例如，启动子、增强子、内含子、终止子、翻译起始信号、聚腺苷酸化信号、病毒衍生的复制元件、RNA加工和输出元件(RNAprocessing and export element)、转录后反应元件(post transcriptional responsiveelement)、基质附着元件(matrix attachment element)、绝缘子(insulator)、影响染色质结构的元件；其他有功能的核酸序列，如同源重组序列、能和蛋白结合的DNA或RNA序列、能与其他检测用核酸片段(如引物或探针)结合的核苷酸序列；任意一段来在自然界的核酸序列或人造核苷酸序列；也可以是以上一段或多段核苷酸序列的组合。
转座子和转座酶可以通过多种方式进入细胞完成转座功能，例如通过质粒瞬时转染，通过病毒载体转导，通过转染编码转座酶的RNA，通过转染转座酶蛋白的方式递送到细胞内。本公开以质粒瞬时转染方法为例，但其他转座子系统递送方法是本领域中已知的，递送方法的改变并不影响本发明的精神和原则，均应包含在权利要求的保护范围之内。
实施例
提供以下实施例用以对本发明的技术方案进行说明，以下实施例不应被认为是对本发明的范围和精神的限制。
实施例1:质粒构建
以下实施例中使用的分子克隆技术，如DNA片段的PCR扩增，DNA片段的限制酶消化，DNA片段的凝聚回收，通过T4 DNA连接酶的两个或以上DNA片段的连接，在感受态细胞中转化连接产物，质粒抽提及鉴定是本领域中已知的。下面的实施例中涉及以下试剂：PCR酶(Thermo，F-530S)；限制性酶(NEB)；T4 DNA连接酶(Invitrogen，15224041)；DNA片段凝聚回收试剂盒(Omega，D2500-02)；质粒小提试剂盒(TIANGEN，DP105-03)；感受态细胞(EPI400，Lucigen Inc.，C400CH10)；下表1中标注“GenScript合成”的核酸序列由GenScript公司合成并被用于构建本公开中的质粒。下表2中用于质粒构建、转座酶突变和qPCR检测的引物由通用生物系统(安徽)有限公司合成。质粒测序及鉴定由GUANGZHOU IGE BIOTECHNOLOGYLTD进行。下表3列举了本公开使用的质粒编号、名称、插入物的核酸序号、插入酶切位点和插入的质粒载体的编号。以下实施例中所涉及的各质粒中采用的功能元件的序列信息和证明本公开效用的实施例仅是作为实施本公开的示例，而不应当被视为限制本发明的保护范围，本领域技术人员可以预期可以通过用具有相似生物学功能的其他序列代替以下实施例中使用的质粒上的功能元件的序列来实现本公开的技术效果，上述序列包括但不限于骨架序列(如复制起点，抗性基因等)，限制性内切酶位点，转座子重复序列，诱导表达系统的响应元件序列，绝缘子序列，启动子序列，内含子序列，PolyA序列，不同密码子优化的基因序列，以上功能元件序列和基因序列的突变体，以及以上功能元件序列和基因序列的克隆位置，克隆序列和克隆方向。具体的质粒构建方法如下所述：
1.转座酶质粒的构建：将合成的序列SEQ ID NO:1，SEQ ID NO:6，SEQ ID NO:11，SEQ ID NO:15，SEQ ID NO:19，SEQ ID NO:23，SEQ ID NO:28，SEQ ID NO:32，SEQ ID NO:36，SEQ ID NO:41，SEQ ID NO:49，SEQ ID NO:54，SEQ ID NO:55，SEQ ID NO:60，SEQ IDNO:61，SEQ ID NO:69，SEQ ID NO:72和SEQ ID NO:71分别用限制性酶ClaI和XhoI消化，并且连接至质粒06.01.1812(SEQ ID NO:90)的限制性位点ClaI和XhoI，从而分别构建质粒06.01.1494，06.01.1504，06.01.1527，06.01.1535，06.01.1538，06.01.1579，06.01.1573，06.01.1582，06.01.1596，06.01.1614，06.01.1679，06.01.1687，06.01.1740，06.01.1770，06.01.1790，06.01.1581，06.01.1892和06.01.1903。分别将合成的序列SEQ ID NO:70和SEQ ID NO:78用BamHI和XhoI消化，并且连接至质粒06.01.1812(SEQ ID NO:90)的限制性位点BamHI和XhoI，从而分别构建质粒06.01.1757和06.01.1807。
2.转座酶突变体质粒的构建
TcBuster转座酶突变体质粒的构建：通过利用融合PCR(fusion PCR)将使用质粒06.01.1614作为模板，S3F和TcBmKE573-R，TcBmKE573-F和S_IRES-R作为引物进行PCR扩增的两个DNA片段连接，构建TcBuster#2编码序列。通过利用融合PCR将使用质粒06.01.1614作为模板，S3F和TcBmA358-R，TcBmA358-F和S_IRES-R作为引物进行PCR扩增的两个DNA片段连接，构建TcBuster#3编码序列。通过利用融合PCR将使用质粒06.01.1614作为模板，S3F和TcBmI452-R，TcBmI452-F和S_IRES-R作为引物进行PCR扩增的两个DNA片段连接，构建TcBuster#4编码序列。通过利用融合PCR将使用质粒06.01.1614作为模板，S3F和TcBmN85-R，TcBmN85-F和S_IRES-R作为引物进行PCR扩增的两个DNA片段连接，构建TcBuster#5编码序列。将以上片段(TcBuster#2、TcBuster#3、TcBuster#4、TcBuster#5编码序列)分别用ClaI和XhoI酶消化，并且连接至质粒06.01.1812(SEQ ID NO:90)的限制性位点ClaI和XhoI，从而分别构建质粒06.01.1681，06.01.1696，06.01.1703和06.01.1705。
家蚕Yabusame-1转座酶突变体质粒的构建：通过利用融合PCR将使用质粒06.01.1687作为模板，S3F和C_YabF321D-R，C_YabF321D-F和C_YabSK-R，C_YabSK-F和S_IRES-R作为引物进行PCR扩增的三个DNA片段连接，构建Yabusame-1#3编码序列。使用质粒06.01.1687作为模板，C_optiHBm-F和S_IRES-R作为引物，对Yabusame-1#4编码序列进行PCR扩增。使用质粒06.01.1740作为模板，C_optiHBm#2-F和S_IRES-R作为引物，对Yabusame-1#5编码序列PCR扩增。将以上片段(Yabusame-1#3、Yabusame-1#4、Yabusame-1#5编码序列)分别用ClaI和XhoI酶消化，并且连接至质粒06.01.1812(SEQ ID NO:90)的限制性位点ClaI和XhoI，从而分别构建质粒06.01.1517，06.01.1778和06.01.1795。
热带爪蟾Uribo2转座酶突变体质粒的构建：通过利用融合PCR将使用质粒06.01.1770作为模板，S3F和C_XtUP148T-R，C_XtUP148T-F和C_XtUD359N-R，C_XtUD359N-F和C_XtUA462H-R，C_XtUA462H-F和C_XtUF576R-R作为引物进行PCR扩增的四个DNA片段连接，构建Uribo2#3编码序列。通过利用融合PCR将使用质粒06.01.1770作为模板，S3F和C_XtUS193K-R，C_XtUS193K-F和C_XtUD359N-R，C_XtUD359N-F和C_XtUA462H-R，C_XtUA462H-F和S_IRES-R作为引物进行PCR扩增的四个DNA片段连接，构建Uribo2#4编码序列。使用质粒06.01.1770作为模板，C_XtU#1-F和S_IRES-R作为引物，对Uribo2#5编码序列进行PCR扩增。使用质粒06.01.1790作为模板，C_XtU#2-F和S_IRES-R作为引物，对Uribo2#6编码序列进行PCR扩增。将以上片段(Uribo2#3、Uribo2#4、Uribo2#5、Uribo2#6编码序列)分别用ClaI和XhoI酶消化，并且连接至质粒06.01.1812(SEQ ID NO:90)的限制性位点ClaI和XhoI，从而分别构建质粒06.01.1850，06.01.1862，06.01.1872和06.01.1884。
SB转座酶突变体质粒的构建：通过利用融合PCR将使用质粒06.01.1807作为模板，S3F和C_SB100#2-R，C_SB100#2-F和S_IRES-R作为引物进行PCR扩增的两个DNA片段连接，构建SB100#2编码序列。将以上片段用ClaI和XhoI酶消化，并且连接至质粒06.01.1812(SEQID NO:90)的限制性位点ClaI和XhoI，从而构建质粒06.01.1941。
3.转座子质粒的构建：分别用NotI和AsiSI酶消化合成的序列SEQ ID NO:5，SEQID NO:10，SEQ ID NO:14，SEQ ID NO:18，SEQ ID NO:22，SEQ ID NO:31，SEQ ID NO:35，SEQID NO:40，SEQ ID NO:45，SEQ ID NO:48，SEQ ID NO:53，SEQ ID NO:59，SEQ ID NO:65，SEQID NO:68，SEQ ID NO:77，SEQ ID NO:76，SEQ ID NO:88和SEQ ID NO:89，并连接至质粒06.01.1955(SEQ ID NO:91)限制性位点NotI和AsiSI，从而分别构建质粒06.01.1939，06.01.1946，06.01.1952，06.01.1957，06.01.1958，06.01.1982，06.01.1985，06.01.2014，06.01.2016，06.01.2018，06.01.2029，06.01.2037，06.01.2052，06.01.2056，06.01.1917，06.01.2072，06.01.1367和06.01.2099。用BbsI和AsiSI消化合成的序列SEQ ID NO:27，并连接至质粒06.01.1955(SEQ ID NO:91)的限制性位点NotI和AsiSI，从而构建质粒06.01.1967。
4.具有puromycin(Puro)抗性基因和hPGK-luciferase-ires-EGFP序列的转座子质粒的构建：分别用SbfI/PacI和PacI/AscI消化合成的序列SEQ ID NO:93和SEQ ID NO:92，并分别连接至质粒06.01.1939，06.01.1946，06.01.1952，06.01.1957，06.01.1958，06.01.1967，06.01.1982，06.01.1985，06.01.2014，06.01.2016，06.01.2018，06.01.2029，06.01.2037，06.01.2052，06.01.2056，06.01.1917，06.01.2072，06.01.1367和06.01.2099的限制性位点SbfI和AscI，从而构建质粒06.01.2141，06.01.2143，06.01.2148，06.01.2170，06.01.2206，06.01.2218，06.01.2229，06.01.2250，06.01.2259，06.01.2263，06.01.2273，06.01.2277，06.01.2286，06.01.2289，06.01.2305，06.01.2331，06.01.2336，06.01.2343和06.01.2327。
5.具有hygromycin(Hygro)抗性基因和hPGK-luciferase-ires-EGFP序列的转座子质粒的构建：分别用SbfI/PacI和PacI/AscI消化合成的序列SEQ ID NO:94和SEQ ID NO:92，并分别连接至质粒06.01.1939，06.01.1946，06.01.1952，06.01.1957，06.01.1958，06.01.1967，06.01.1982，06.01.1985，06.01.2014，06.01.2016，06.01.2018，06.01.2029，06.01.2037，06.01.2052，06.01.2056，06.01.1917，06.01.2072，06.01.1367和06.01.2099的限制性位点SbfI和AscI，从而构建质粒06.01.3233，06.01.2347，06.01.3321，06.01.3331，06.01.3372，06.01.2358，06.01.3428，06.01.3455，06.01.3457，06.01.2360，06.01.2362，06.01.2879，06.01.2370，06.01.2379，06.01.2420，06.01.2429，06.01.3105，06.01.2433和06.01.2430。
6.具有blasticidin抗性基因和hPGK-luciferase-ires-EGFP序列的转座子质粒的构建：分别用SbfI/PacI和PacI/AscI消化合成的序列SEQ ID NO:95和SEQ ID NO:92，并连接至质粒06.01.1367的限制性位点SbfI和AscI，从而构建质粒06.01.3335。
用于慢病毒稳定生产细胞系的转座子质粒的构建：分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1939的限制性位点SbfI和AscI，从而构建质粒06.01.4301，06.01.4302，06.01.4303和06.01.4304。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ IDNO:98和SEQ ID NO:99，并连接至质粒06.01.1946的限制性位点SbfI和AscI，从而构建质粒06.01.4305，06.01.4306，06.01.4307和06.01.4308。分别用SbfI/AscI消化合成的序列SEQID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1952的限制性位点SbfI和AscI，从而构建质粒06.01.4309，06.01.4310，06.01.4311和06.01.4312。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1957的限制性位点SbfI和AscI，从而构建质粒06.01.4313，06.01.4314，06.01.4315和06.01.4316。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1958的限制性位点SbfI和AscI，从而构建质粒06.01.4317，06.01.4318，06.01.4319和06.01.4320。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1967的限制性位点SbfI和AscI，从而构建质粒06.01.4321，06.01.4322，06.01.4323和06.01.4324。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1982的限制性位点SbfI和AscI，从而构建质粒06.01.4325，06.01.4326，06.01.4327和06.01.4328。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1985的限制性位点SbfI和AscI，从而构建质粒06.01.4329，06.01.4330，06.01.4331和06.01.4332。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.2014的限制性位点SbfI和AscI，从而构建质粒06.01.4333，06.01.4334，06.01.4335和06.01.4336。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.2016的限制性位点SbfI和AscI，从而构建质粒06.01.4337，06.01.4338，06.01.4339和06.01.4340。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.2029的限制性位点SbfI和AscI，从而构建质粒06.01.4341，06.01.4342，06.01.4343和06.01.4344。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.2037的限制性位点SbfI和AscI，从而构建质粒06.01.4345，06.01.4346，06.01.4347和06.01.4348。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.2052的限制性位点SbfI和AscI，从而构建质粒06.01.4349，06.01.4350，06.01.4351和06.01.4352。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1917的限制性位点SbfI和AscI，从而构建质粒06.01.4353，06.01.4354，06.01.4355和06.01.4356。分别用SbfI/AscI消化合成的序列SEQ ID NO:96，SEQ ID NO:97，SEQ ID NO:98和SEQ ID NO:99，并连接至质粒06.01.1367的限制性位点SbfI和AscI，从而构建质粒06.01.4357，06.01.4358，06.01.4359和06.01.4360。用SbfI/AscI消化合成的序列SEQ ID NO:100，并连接至质粒06.01.1939，06.01.1946，06.01.1952，06.01.1957，06.01.1958，06.01.1967，06.01.1982，06.01.1985，06.01.2014，06.01.2016，06.01.2029，06.01.2037，06.01.2052，06.01.1917和06.01.1367的限制性位点SbfI和AscI，从而构建质粒06.01.4361，06.01.4362，06.01.4363，06.01.4364，06.01.4365，06.01.4366，06.01.4367，06.01.4368，06.01.4369，06.01.4370，06.01.4371，06.01.4372，06.01.4373，06.01.4374和06.01.4375。
表1：根据本公开的序列的概述
Figure BDA0003306737850000181
Figure BDA0003306737850000191
Figure BDA0003306737850000201
表2：用于质粒构建的引物
Figure BDA0003306737850000202
表3：质粒名称及构建信息
Figure BDA0003306737850000203
Figure BDA0003306737850000211
Figure BDA0003306737850000221
Figure BDA0003306737850000231
Figure BDA0003306737850000241
实施例2:使用多转座子系统测试基因插入效率及靶基因活性
对于大多数生物制品的生产，例如哺乳动物细胞表达的重组蛋白生产，单位体积培养物的表达水平与目的核苷酸片段在工程细胞基因组中的插入拷贝数成正相关。增加目的核苷酸片段的插入拷贝数是提高生产细胞系表达水平最有效的策略之一。然而，大多数转座子系统在插入一段或多段目的核苷酸片段时具有插入拷贝数的上限。本发明的发明人证明，使用本公开中公开的多转座子系统能够有效增加目的核苷酸片段(GOI)在细胞内插入拷贝数的上限，并显著提高目的蛋白的表达量。
hPGK-Luciferase-ires-EGFP-WPRE做为目的核苷酸片段被用于检测多转座子系统在插入目的基因中的有效性：hPGK-Luciferase-ires-EGFP-WPRE在被转染到哺乳动物细胞中后，将表达荧光素酶(luciferase)和EGFP蛋白。细胞中荧光素酶的活性和其蛋白表达量高度正相关，并且可以通过荧光素酶测定来测量。另外此目的核苷酸片段还含有WPRE序列，其被用作通过qPCR量化宿主细胞基因组中插入拷贝数的标签。将此目的核苷酸片段分别连接三种抗性基因PuroR(嘌呤霉素抗性基因)、HygroR(潮霉素抗性基因)和BSD(杀稻瘟菌素抗性基因)，以用于在转染后快速筛选在基因组中稳定插入目的核苷酸片段的阳性细胞群。将上述三种携带不同抗性基因的目的核苷酸片段PuroR(R)-hPGK-Luciferase-ires-EGFP-WPRE、HygroR(R)-hPGK-Luciferase-ires-EGFP-WPRE和BSD(R)-hPGK-Luciferase-ires-EGFP-WPRE分别克隆到含有转座酶识别序列末端反向重复(TIR)的不同转座子质粒中并用于后续测试多转座子系统在插入目的核苷酸片段的有效性。
首先用包含PuroR(R)-hPGK-Luciferase-ires-EGFP-WPRE目的核苷酸片段的第一转座子质粒和相应的转座酶表达质粒共转染293T细胞(ATCC，CRL3216)，并且筛选嘌呤霉素抗性群体。然后用包含HygroR(R)-hPGK-Luciferase-ires-EGFP-WPRE目的核苷酸片段的不同于第一转座子的第二转座子质粒和相应的转座酶表达质粒共转染上述嘌呤霉素抗性细胞，并且筛选嘌呤霉素和潮霉素双抗性细胞群。之后通过检测双抗性细胞群的荧光素酶活性对比荧光素酶表达量并且通过qPCR检测双抗性细胞群的平均WPRE拷贝数。第一和第二转座子质粒以及对应的转座酶质粒编号，测量的荧光素酶活性以及通过qPCR测得的WPRE拷贝数如表4所示。具体实验步骤简述于下。
通过转座子系统在293T细胞基因组中稳定插入目的核苷酸片段实验流程简述如下。在37℃和5％CO2条件下培养293T细胞(ATCC，CRL3216)，培养基为补充有10％FBS(ExCell，11H 116)的DMEM完全培养基(DMEM(Sigam，D6429)。以8E+05细胞/孔将293T细胞接种在6孔板(Corning，3516)中。在培养24小时后，根据如“MolecμLar Cloning:ALaboratory Manual(Fourth edition)Chapter15,Michael R.Green,Cold Spring HarborLaboratory Press,2012”中所述的磷酸钙转染方法制备转染试剂，并将200μL含0.12mol/L氯化钙，1xHEPES缓冲液和5.5μg总质粒的转染试剂添加到各孔中。利用磷酸钙以5:1的摩尔比共转染转座子质粒和转座酶质粒，转座子和转座酶的质粒编号如表4所示。在转染24小时后，将培养基换成含有2.5μg/ml嘌呤霉素(Aladdin P113126)的新鲜DMEM完全培养基。在抗生素压力下进行连续至少3代筛选直至细胞稳定生长。之后，根据相同的实验方法，将以上构建的细胞用第二转座子质粒及其相应的转座酶质粒共转染，并且在含有200μg/ml潮霉素(Shenggong A600230-0001)的DMEM完全培养基中至少培养三代。
通过荧光素酶检测试剂盒检测各细胞系的荧光素酶活性实验流程简述如下。以1E+04细胞/孔将各细胞系接种到96孔板(Corning 3916)中，每种细胞接种复孔。培养48小时后，使用
Figure BDA0003306737850000261
荧光素酶测定系统(Promega，E2610)试剂盒并根据使用说明(Promega，FB037)检测各孔的相对荧光素酶单位(RLU)，检测仪器为荧光微孔板读数计(Perkin Elmer VictorⅤ)。
通过qPCR测量各细胞系WPRE拷贝数的实验流程简述如下。收集以上各细胞系每种1.0E+06个细胞，并根据基因组DNA纯化试剂盒(TIANGEN，DP304-03)的使用说明提取基因组gDNA。使用试剂盒中的洗脱缓冲液将纯化后的gDNA调节至50ng/μl。将质粒06.01.2141用去离子水稀释至47.9ng/μl(对应5.0E+09拷贝数/μL)作为WPRE的标准品，并将此标准品进一步稀释至8.0E+06拷贝数/μL。再将此8E+06拷贝数/μL标准品以两倍连续梯度稀释至1.5625E+04拷贝数/μL，并将此9个连续稀释的样品用作WPRE序列的标准曲线样品。将1μL各细胞系的gDNA样品和qPCR标准曲线样品添加至Taqman probe qPCR试剂混合物中，并用水补足至20μL，其中所述qPCR试剂包含10μL NovoStart Probe qPCR SuperMix和0.4μL ROXI染料(Novoprotein Scientific Inc.,E091-01A)，以及0.4μL浓度为10uM的WPRE-taqman-F正向引物和WPRE-taqman-R反向引物和0.4μL浓度为10μM的WPRE-Probe Taqman探针(由General Biosystems(Anhui)Co.,Ltd.合成)，引物和探针的具体信息如以上表2所示，其中正向和反向引物以及WPRE的探针分别为SEQ ID NO:130，SEQ ID NO:131和SEQ ID NO:132。在ABI 7900实时PCR检测仪上以AQ程序和如下步骤进行PCR反应：95℃5分钟，95℃30秒-60℃30秒-72℃30秒40个循环，60℃30秒。基于标准曲线和样品的CT值计算各样品中WPRE片段的拷贝数浓度(拷贝数/μL)，然后按照每个细胞含有6pg基因组DNA计算每细胞含有WPRE片段的拷贝数(拷贝数/细胞)。
表4总结了通过不同转座子组合构建的双抗性细胞系的荧光素酶活性RLU和WPRE的插入拷贝数。仅通过单一转座子构建的细胞系的平均荧光素酶活性和WPRE插入拷贝数分别为2.67E+05RLU和3.12拷贝数(WPRE)/细胞。能获得的最佳细胞的荧光素酶活性和WPRE插入拷贝数分别为5.11E+05RLU和5.14拷贝数(WPRE)/细胞。使用本公开描述的双转座子方法构建细胞系的平均荧光素酶活性和WPRE插入拷贝数分别增加至4.45E+05RLU和5.83拷贝(WPRE)/细胞，提高了66.62％和87.10％。能获得的最佳细胞的荧光素酶活性和WPRE插入拷贝数分别为8.12E+05RLU和12.04拷贝数(WPRE)/细胞。而使用同种转座子系统通过两次瞬时转染及抗性筛选所构建的细胞系的荧光素酶活性和WPRE插入拷贝数都略差于同种转座子系统瞬转一次构建的细胞系，其荧光素酶活性和WPRE插入拷贝数分别为2.36E+05RLU和2.80拷贝数(WPRE)/细胞。使用双专座子系统构建的细胞系比使用其中任意一个单转座子系统构建的细胞系在荧光素酶活性和WPRE插入拷贝数上都有显著提高。另外，Tol1、Tol2、ZB转座子、Intruder转座子、TcBuster、Yabusame-1、Uribo2、Sleeping Beauty和piggyBac转座子系统有较高的活性。使用以上转座子系统组合构建的细胞系(共36条细胞)的平均荧光素酶活性和WPRE插入拷贝数分别为5.47E+05RLU和7.53拷贝数(WPRE)/细胞，比单独使用这9种转座子系统构建细胞系的平均荧光酶活性(3.19E+05RLU)和平均WPRE插入拷贝数(3.92拷贝/细胞)分别提高了71.36％和92.08％。
选择上述实验中第二转座子系统使用piggyBac转座子系统(06.01.1757和06.01.2429)的13种细胞系并使用Sleeping Beauty转座子系统(06.01.1807和06.01.3335)做为第三种转座子系统将BSD(R)-hPGK-Luciferase-ires-EGFP-WPRE目的核苷酸片段插入到上述细胞的基因组中(如表5所示)。细胞培养，质粒转染，抗生素选择，荧光素酶测定和WPRE拷贝数的qPCR量化的实验操作如上所述。使用3ug/mL杀稻瘟菌素S(SHANGHAI MAOKANG BIOTECHNOLOGY，Cat.No.#MS0007)筛选BSD阳性细胞。荧光酶素活性和WPRE基因组插入拷贝数的结果如表5所述。通过三转座子系统构建的细胞系的平均荧光素酶活性和WPRE插入拷贝数分别为7.22E+05RLU和9.46拷贝(WPRE)/细胞。最优细胞系的荧光素酶活性和WPRE插入拷贝数分别为9.52E+05和12.76拷贝(WPRE)/细胞，比通过SB和PB双转座子系统构建的细胞系的平均荧光素酶活性和WPRE插入拷贝数(6.04E+05和7.89拷贝(WPRE)/细胞)分别高57.72％和61.75％。
表4：使用双转座子系统的基因插入拷贝数和靶基因活性测试
Figure BDA0003306737850000281
Figure BDA0003306737850000291
Figure BDA0003306737850000301
Figure BDA0003306737850000311
表5：使用三转座子系统的基因插入拷贝数和靶基因活性测试
Figure BDA0003306737850000312
Figure BDA0003306737850000321
实施例3：使用多转座子系统构建慢病毒稳定生产细胞系
复杂细胞系的构建通常需要对宿主细胞进行多个修饰和筛选步骤，包括插入多个目的核苷酸片段，调节插入的多个目的核苷酸片段的插入比率，对之前修饰过的细胞进行后续修饰。本发明的发明人证明，本公开中所述的方法能够有效地以明显更高的拷贝数在宿主细胞基因组中插入多个目的核苷酸片段，并且能够有效地调节插入的多个目的核苷酸片段的插入比例。病毒载体稳定生产细胞系的构建通常需要分两步插入多段核苷酸片段：首先将编码病毒包装蛋白的核苷酸片段插入宿主细胞；然后将具有包装信号序列的且含有目的序列的核苷酸片段插入上一步中构建的包装细胞系从而构建生产细胞系。以下实施例以病毒载体稳定生产细胞系的构建为例进一步证明多转座子系统在宿主细胞系基因组中插入多目的核苷酸片段的有效性。本公开中所述的方法能够显著提高构建的慢病毒稳定生产细胞系的产毒产量。本领域技术人员可以理解，本公开中公开的方法同样可以适用于构建其他涉及插入多个目的核苷酸片段的复杂细胞系。
在本实施例中，首先通过第一转座子系统将用于慢病毒包装的rev(SEQ ID NO:97)，VSV-G(SEQ ID NO:98)，gag/pol(SEQ ID NO:96)的表达盒以及用于调控其表达的激活物rtTA和阻遏物CymR蛋白的编码序列(SEQ ID NO:99)稳定整合到293T细胞的基因组中以构建慢病毒(LV)包装细胞系。然后，通过不同于第一转座子系统的第二转座子系统将携带目的核酸片段的慢病毒基因组转录盒(SEQ ID NO:100，具有hPGK-luciferase-ires-EGFP序列，其仅是作为目的核酸片段的一个实例，本领域技术人员可以预期使用类似方法可以构建任何其他目的核酸序列)整合到以上构建的LV包装细胞系的基因组中从而构建慢病毒生产细胞系。SEQ ID NO:99上的潮霉素抗性基因用于LV包装细胞系的筛选，SEQ ID NO:100上的嘌呤霉素抗性基因用于LV生产细胞系的筛选。在抗生素筛选后，将获得的LV生产细胞系培养并用DOX(1μg/ml，盐酸多西环素，Sangon Biotech(Shanghai)，A600889)和Cumate(200μg/ml，Aladdin，I107765)诱导以用于慢病毒生产。将上述使用不同转座子系统组合构建的生产细胞系诱导后生产的慢病毒转导HT1080细胞，之后通过荧光素酶活性测量来自不同生产细胞系的转导滴度。本实施例描述了通过首先使用第一转座子系统整合rev，VSVG，gag，pol，然后通过第二转座子系统整合携带目的核酸片段的慢病毒基因组转录盒来构建LV生产细胞系的方法，本领域技术人员可以预期其他组合，即，可以通过第一转座子系统整合rev，VSVG，gag，pol和携带目的核酸片段的慢病毒基因组转录盒中的任意一个或多个，然后通过第二转座子系统整合剩余项。本领域技术人员还可以预期通过三种，四种，五种或甚至超过五种转座子系统来整合上述rev，VSVG，gag，pol及携带目的核酸片段的慢病毒基因组转录盒。
具体实验过程简述如下。以1.5E+06细胞/培养皿将293T细胞接种到60mm培养皿中并在37℃和5％CO2条件下用3ml DMEM完全培养基培养24小时。根据PEI法转染细胞：在转染期间将500μL转染试剂添加至各60mm培养皿，转染试剂包含5.6μg总质粒。在5.6μg质粒中，携带gag/pol，rev，VSVG和rtTA/CymR的转座子质粒分别为3.5μg，0.4μg，0.5μg和0.7μg；携带第一转座酶基因的质粒为0.5μg。以4:1的质量比将PEI MAX(Polysciences，24765-1)与质粒混合，并且在将所有混合物孵育15分钟后将混合物添加至细胞。24小时后，培养基替换为补充有200μg/ml潮霉素的DMEM完全培养基。在该条件下将细胞连续培养至少3代直至细胞系稳定。之后，通过第二转座子系统将含有GOI的慢病毒基因组转录盒整合到各包装细胞系中。再次根据PEI法转染细胞，在转染期间将500μL转染试剂添加至各60mm培养皿，转染试剂包含4.3μg总质粒，其中具有4.0μg转座子质粒和0.3μg转座酶质粒。以4:1的质量比将PEIMAX(Polysciences，24765-1)与质粒混合，并且在将所有混合物孵育15分钟后将混合物添加至细胞。24小时后，培养基替换为补充有2.5μg/ml嘌呤霉素的DMEM完全培养基。在该条件下将细胞连续培养至少3代直至细胞系稳定。表6概述了本实施例中所使用的质粒的组合。使用单个转座子系统的LV生产细胞系构建被用作对照。使用单个转座子质粒但没加转座酶质粒的细胞做为阴性对照。如前所述，以1.5E6细胞/培养皿将293T细胞接种到60mm培养皿中并在37℃和5％CO2在3ml DMEM完全培养基中培养24小时。根据PEI法转染细胞：在转染期间将500μL转染试剂添加至各60mm培养皿，转染试剂包含9.9μg质粒。在9.9μg质粒中，携带gag/pol，rev，VSVG，rtTA/CymR和包含GOI的病毒转录盒的转座子质粒分别为3.5μg，0.4μg，0.5μg，0.7μg和4.0μg；携带转座酶基因的质粒为0.8μg(阴性对照使用06.01.1812质粒代替携带转座酶基因的质粒)。以4:1的质量比将PEI MAX(Polysciences，24765-1)与质粒混合，并且在将所有混合物孵育15分钟后将混合物添加至细胞。24小时后，培养基替换为补充有2.5μg/ml嘌呤霉素的DMEM完全培养基。在该条件下将细胞连续培养至少3代直至细胞系稳定。
通过HT1080细胞转导后的荧光素酶测定检测稳定慢病毒生产细胞系的产毒能力。简言之，以8E+05细胞/孔将表6和表7中的各细胞系分别接种到6孔板(Corning 3516)中并在37℃和5％CO2条件下在DMEM完全培养基中培养。在培养24小时后，将培养基替换为含诱导剂1μg/ml DOX(盐酸多西环素，Sangon Biotech(Shanghai)，A600889)，200μg/ml Cumate(Aladdin，I107765)和5mmol/L丁酸钠(Sigma，303410)的DMEM完全培养基，以诱导产毒。48小时后，收集含慢病毒的培养基并以14000rpm离心10分钟以收集病毒上清。在收获病毒样品前24小时，以1E+04细胞/孔在96孔板(Corning 3916)中接种HT1080细胞并在DMEM完全培养基中培养24小时。在HT1080细胞中添加病毒样品前1小时，将HT1080细胞的培养基替换为含8μg/ml polybrene(Sigam，H9268)的DMEM完全培养基。之后，将50μL病毒样品添加至上述96孔板的各孔中。继续培养48小时后，使用
Figure BDA0003306737850000341
荧光素酶测定系统(Promega，E2610)试剂盒并根据使用说明(Promega，FB037)检测各孔的相对荧光素酶单位(RLU)，检测仪器为荧光微孔板读数计(Perkin Elmer VictorⅤ)。通过荧光素酶测定测量的不同慢病毒生产细胞系的病毒滴度结果概述在表6和表7中。
由表6和表7可见，通过双转座子系统构建的生产细胞系的病毒滴度(平均滴度为7.94+05TU(RLU)/mL)显著高于通过单个转座子系统构建的细胞系的病毒滴度(平均滴度为1.94E+04TU(RLU)/mL)。阴性对照细胞系产毒滴度平均值为6.25E+02接近荧光素酶检测背景值。此外，由下表6和7可见，使用Tol1、Tol2、ZB转座子、Intruder转座子、TcBuster、Yabusame-1、Uribo2、Sleeping Beauty和piggyBac转座子系统的组合构建的慢病毒生产细胞系的产毒能力显著高于其他组合，由以上转座子系统组合构建的生产细胞系的产毒滴度平均值为1.87E+06TU(RLU)/mL。
表6：使用双转座子系统构建慢病毒稳定生产细胞系
Figure BDA0003306737850000351
Figure BDA0003306737850000361
Figure BDA0003306737850000371
Figure BDA0003306737850000381
Figure BDA0003306737850000391
表7：使用单转座子系统构建慢病毒稳定生产细胞系
Figure BDA0003306737850000392
Figure BDA0003306737850000401
本公开的上述实施例仅是为了清楚说明本发明所作的举例，而并非是对本发明的实施方式的限定。对于所属领域的普通技术用户来说，在上述说明的基础上还可以做出其他不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明权利要求的保护范围之内。
序列表
<110> 深圳市深研生物科技有限公司
<120> 多转座子系统
<130> P20200004B
<160> 132
<170> PatentIn version 3.5
<210> 1
<211> 2578
<212> DNA
<213> 人工序列
<400> 1
tatcgatgcc accatggaaa agaagcggag caagccttct ggcgctcaat ttagaaagaa 60
aagaaaggaa gaggaagaaa agagagataa ggaaaagggc gccctgctga gatactttgg 120
cagctccacc accgcccagg acgagaccag caccagcctg ccagctatct ctagcgcaac 180
cgtgaccgtg tcccctccac aggatgagct gcctagcaca agctctgcca cccacgtggt 240
gcctcagctt ctgcctgagc agtctttcga tagcgaggcc gaagatgtgg tcccctctac 300
gtccacccag ctggaaacca gcgagatgcc tggcgacgag acacctctga cccctaccgc 360
cgaggaccag cctctgccta ctgatcctgc caagtggcct agccccctga ccgatagaat 420
cagaatggaa ctggttagaa gaggaccttc tagtatcccc cccgacttcg tgttccccag 480
aaacgacagc gatggcagat catgccacca tcactacttc cggaagaccc tggtgagcgg 540
cgagaagatc gccagaacct ggctgatgta cagcaaggtg aagaatagcc tgttttgctt 600
ctgttgtaag ctgttctcta acaagaatat caacctcacc acctctggaa cagcgaactg 660
gaagcacgcc agcacttacc tgaccgccca cgagaagagc cccgagcacc tgaactgcat 720
gaaagcctgg aaagaactgt ccggccggat tcggagcgga aaaaccatcg acaagcagga 780
gatggccctg ctggaagagg aacgggtgcg ctggcgggcc gtgctcacac ggctgatcgc 840
catcgtgcag tctctggctg tgcgcaacct ggccctgaga ggccacacag agacactgtt 900
caccagcagc aacggcaact tcctgaagga agtggagctg atggctagat tcgaccctat 960
catgaaggac cacctgaaca gagtgctgag aggcaccgcc tcccataatt cttatatcgg 1020
acaccacgta caaaacgagc tgatcgacct gctgagcagc aaaatcctgt ctgccatcgt 1080
tgacgacatc aagaaggcca agtactttag catcatcctg gattgcaccc tggacatcag 1140
ccacaccgag cagctgagcg tgatcatcag agtcgtgagc ctgatggaaa agccccagat 1200
aagagagcac ttcatgggct tcctggaggc cgaggaaagt acaggccagc acctggcctc 1260
tatgatcctg aacagactgg aagaactggg catcagcttc gaggactgtc ggggccagag 1320
ctatgacaac ggcgctaata tgaaaggcaa gaacaagggc gtccaggcca gactgctgga 1380
gaagaacccc cgggccctgt ttctgccctg tggcgctcat accctgaatc tggtggtgtg 1440
cgatgcagct aagagatccg tggacgccat gagctacttc ggcgtgctcc agaaactgta 1500
caccctgttc tctgcgagcg cccagcggtg ggccatcctg aagagccagg tgtctattac 1560
actgaagagc tggaccgaaa ccagatggga gtctaagatc aagagcatcg agcctatgcg 1620
gtaccaggga gccgccgtga gggaagctct catcgaggtg cgggacaaaa ccaaggaccc 1680
cgtgatcaaa gctgaggccc agagcctgtc tgaggaagtt ggaagctaca gattcaacat 1740
ctgcacagtg gtgtggcacg acatcctatc cacaatcaag cacgtgagta agctgatgca 1800
gtctcctaac atgcacgtgg atctggccgt gagcctgcta aaaaaaaccg agcagagcct 1860
tcagtcttac agagccaatg gattcgtgaa cgcccaaatg gccgccaagg aaatgtgcaa 1920
ggaaatgaac gtggaagcta tcctgaaaca gaagcggatt aggagcacaa agtgccagtt 1980
ctcgtacgag agccacgatg agcccttcag cgacgccctc aagaagctgg aagtggagtt 2040
cttcaacgtg gtggtggacg aggctctgtc cgccatcgct gagcgcttca gcacactgga 2100
agtggtccag aacagattcg gcgtgctgac caacttccct tccctgggcg atgaggagct 2160
tacagagcag tgcgaggccc tgggcaacat tctgcacttc gagaaaaatt gggacctgga 2220
cagcagagag ctggtgcagg agatcaagaa cctgccgaac ttaccgagca ccacaccttc 2280
cctgctggaa ctgatcagct tcatgtccga caaggacctg tcagaaattt accctaactt 2340
ttggaccgcc ctgagaatcg ccctgacact ccctgtgacc gtggcccagg ccgagagaag 2400
cttctccaag ctgaagctga tcaagtcata cctgagaagc accatgtctc aggagagact 2460
gacaaacctg gccgtggtgt ctatcaacca cagcgtgggc gaacaaatca gctacgatga 2520
tgtgatcgac gagttcgcca gcagaaaagc cagaaaagtg cggttttgat aactcgag 2578
<210> 2
<211> 851
<212> PRT
<213> 人工序列
<400> 2
Met Glu Lys Lys Arg Ser Lys Pro Ser Gly Ala Gln Phe Arg Lys Lys
1 5 10 15
Arg Lys Glu Glu Glu Glu Lys Arg Asp Lys Glu Lys Gly Ala Leu Leu
20 25 30
Arg Tyr Phe Gly Ser Ser Thr Thr Ala Gln Asp Glu Thr Ser Thr Ser
35 40 45
Leu Pro Ala Ile Ser Ser Ala Thr Val Thr Val Ser Pro Pro Gln Asp
50 55 60
Glu Leu Pro Ser Thr Ser Ser Ala Thr His Val Val Pro Gln Leu Leu
65 70 75 80
Pro Glu Gln Ser Phe Asp Ser Glu Ala Glu Asp Val Val Pro Ser Thr
85 90 95
Ser Thr Gln Leu Glu Thr Ser Glu Met Pro Gly Asp Glu Thr Pro Leu
100 105 110
Thr Pro Thr Ala Glu Asp Gln Pro Leu Pro Thr Asp Pro Ala Lys Trp
115 120 125
Pro Ser Pro Leu Thr Asp Arg Ile Arg Met Glu Leu Val Arg Arg Gly
130 135 140
Pro Ser Ser Ile Pro Pro Asp Phe Val Phe Pro Arg Asn Asp Ser Asp
145 150 155 160
Gly Arg Ser Cys His His His Tyr Phe Arg Lys Thr Leu Val Ser Gly
165 170 175
Glu Lys Ile Ala Arg Thr Trp Leu Met Tyr Ser Lys Val Lys Asn Ser
180 185 190
Leu Phe Cys Phe Cys Cys Lys Leu Phe Ser Asn Lys Asn Ile Asn Leu
195 200 205
Thr Thr Ser Gly Thr Ala Asn Trp Lys His Ala Ser Thr Tyr Leu Thr
210 215 220
Ala His Glu Lys Ser Pro Glu His Leu Asn Cys Met Lys Ala Trp Lys
225 230 235 240
Glu Leu Ser Gly Arg Ile Arg Ser Gly Lys Thr Ile Asp Lys Gln Glu
245 250 255
Met Ala Leu Leu Glu Glu Glu Arg Val Arg Trp Arg Ala Val Leu Thr
260 265 270
Arg Leu Ile Ala Ile Val Gln Ser Leu Ala Val Arg Asn Leu Ala Leu
275 280 285
Arg Gly His Thr Glu Thr Leu Phe Thr Ser Ser Asn Gly Asn Phe Leu
290 295 300
Lys Glu Val Glu Leu Met Ala Arg Phe Asp Pro Ile Met Lys Asp His
305 310 315 320
Leu Asn Arg Val Leu Arg Gly Thr Ala Ser His Asn Ser Tyr Ile Gly
325 330 335
His His Val Gln Asn Glu Leu Ile Asp Leu Leu Ser Ser Lys Ile Leu
340 345 350
Ser Ala Ile Val Asp Asp Ile Lys Lys Ala Lys Tyr Phe Ser Ile Ile
355 360 365
Leu Asp Cys Thr Leu Asp Ile Ser His Thr Glu Gln Leu Ser Val Ile
370 375 380
Ile Arg Val Val Ser Leu Met Glu Lys Pro Gln Ile Arg Glu His Phe
385 390 395 400
Met Gly Phe Leu Glu Ala Glu Glu Ser Thr Gly Gln His Leu Ala Ser
405 410 415
Met Ile Leu Asn Arg Leu Glu Glu Leu Gly Ile Ser Phe Glu Asp Cys
420 425 430
Arg Gly Gln Ser Tyr Asp Asn Gly Ala Asn Met Lys Gly Lys Asn Lys
435 440 445
Gly Val Gln Ala Arg Leu Leu Glu Lys Asn Pro Arg Ala Leu Phe Leu
450 455 460
Pro Cys Gly Ala His Thr Leu Asn Leu Val Val Cys Asp Ala Ala Lys
465 470 475 480
Arg Ser Val Asp Ala Met Ser Tyr Phe Gly Val Leu Gln Lys Leu Tyr
485 490 495
Thr Leu Phe Ser Ala Ser Ala Gln Arg Trp Ala Ile Leu Lys Ser Gln
500 505 510
Val Ser Ile Thr Leu Lys Ser Trp Thr Glu Thr Arg Trp Glu Ser Lys
515 520 525
Ile Lys Ser Ile Glu Pro Met Arg Tyr Gln Gly Ala Ala Val Arg Glu
530 535 540
Ala Leu Ile Glu Val Arg Asp Lys Thr Lys Asp Pro Val Ile Lys Ala
545 550 555 560
Glu Ala Gln Ser Leu Ser Glu Glu Val Gly Ser Tyr Arg Phe Asn Ile
565 570 575
Cys Thr Val Val Trp His Asp Ile Leu Ser Thr Ile Lys His Val Ser
580 585 590
Lys Leu Met Gln Ser Pro Asn Met His Val Asp Leu Ala Val Ser Leu
595 600 605
Leu Lys Lys Thr Glu Gln Ser Leu Gln Ser Tyr Arg Ala Asn Gly Phe
610 615 620
Val Asn Ala Gln Met Ala Ala Lys Glu Met Cys Lys Glu Met Asn Val
625 630 635 640
Glu Ala Ile Leu Lys Gln Lys Arg Ile Arg Ser Thr Lys Cys Gln Phe
645 650 655
Ser Tyr Glu Ser His Asp Glu Pro Phe Ser Asp Ala Leu Lys Lys Leu
660 665 670
Glu Val Glu Phe Phe Asn Val Val Val Asp Glu Ala Leu Ser Ala Ile
675 680 685
Ala Glu Arg Phe Ser Thr Leu Glu Val Val Gln Asn Arg Phe Gly Val
690 695 700
Leu Thr Asn Phe Pro Ser Leu Gly Asp Glu Glu Leu Thr Glu Gln Cys
705 710 715 720
Glu Ala Leu Gly Asn Ile Leu His Phe Glu Lys Asn Trp Asp Leu Asp
725 730 735
Ser Arg Glu Leu Val Gln Glu Ile Lys Asn Leu Pro Asn Leu Pro Ser
740 745 750
Thr Thr Pro Ser Leu Leu Glu Leu Ile Ser Phe Met Ser Asp Lys Asp
755 760 765
Leu Ser Glu Ile Tyr Pro Asn Phe Trp Thr Ala Leu Arg Ile Ala Leu
770 775 780
Thr Leu Pro Val Thr Val Ala Gln Ala Glu Arg Ser Phe Ser Lys Leu
785 790 795 800
Lys Leu Ile Lys Ser Tyr Leu Arg Ser Thr Met Ser Gln Glu Arg Leu
805 810 815
Thr Asn Leu Ala Val Val Ser Ile Asn His Ser Val Gly Glu Gln Ile
820 825 830
Ser Tyr Asp Asp Val Ile Asp Glu Phe Ala Ser Arg Lys Ala Arg Lys
835 840 845
Val Arg Phe
850
<210> 3
<211> 200
<212> DNA
<213> 人工序列
<400> 3
cagtagcggt tctaggcacg ggccgtccgg gcggtggcct ggggcggaaa actgaagggg 60
ggcggcaccg gcggctcagc cctttgtaat atattaatat gcaccactat tggtttactt 120
atgtcacagt ttgtaagttt gtaacagcct gaacctggcc gcgccgccgc cctcgccccg 180
cagctgcgct ctcctgtctt 200
<210> 4
<211> 505
<212> DNA
<213> 人工序列
<400> 4
atatttttag ccaatagaat ttccataaat ctgtaggtag ttttaaaaat gaatatttac 60
catttactgc aactctatgg ggacaaaaca taatgtaaca ggtcataact aaaaatgtgc 120
caatcaaagg attgaagacg gaaaacatga gttaattttt cttctctgaa gtagagttcg 180
atatagaaca tgacaattta aatttccaat tcataaatgt ttttaaaata tttattttat 240
attatttatt taacattgag tttgattcaa tattttctta gctaactgta tttttgccat 300
gcttatggtc ttttattttt tgtgttctga taacttttat aatgcttttc agaattttga 360
catcttttgt atccacttct taatttcaat gacaataaaa catttcagtt gacgaagaca 420
aacaaagttc tgttgtgact atgggggggg ggggcgcctg gggatggtct cgcccgggga 480
gtaattcagg gtagaaccgc cactg 505
<210> 5
<211> 764
<212> DNA
<213> 人工序列
<400> 5
gcggccgccc tttagccagt agcggttcta ggcacgggcc gtccgggcgg tggcctgggg 60
cggaaaactg aaggggggcg gcaccggcgg ctcagccctt tgtaatatat taatatgcac 120
cactattggt ttacttatgt cacagtttgt aagtttgtaa cagcctgaac ctggccgcgc 180
cgccgccctc gccccgcagc tgcgctctcc tgtcttcctg caggtacgat caagcggcgc 240
gccatatttt tagccaatag aatttccata aatctgtagg tagttttaaa aatgaatatt 300
taccatttac tgcaactcta tggggacaaa acataatgta acaggtcata actaaaaatg 360
tgccaatcaa aggattgaag acggaaaaca tgagttaatt tttcttctct gaagtagagt 420
tcgatataga acatgacaat ttaaatttcc aattcataaa tgtttttaaa atatttattt 480
tatattattt atttaacatt gagtttgatt caatattttc ttagctaact gtatttttgc 540
catgcttatg gtcttttatt ttttgtgttc tgataacttt tataatgctt ttcagaattt 600
tgacatcttt tgtatccact tcttaatttc aatgacaata aaacatttca gttgacgaag 660
acaaacaaag ttctgttgtg actatggggg gggggggcgc ctggggatgg tctcgcccgg 720
ggagtaattc agggtagaac cgccactgcc tttagcgcga tcgc 764
<210> 6
<211> 1972
<212> DNA
<213> 人工序列
<400> 6
tatcgatgcc accatggaag aggtgtgcga cagctctgct gccgcctctt caacagtgca 60
gaaccagcct caggaccagg agcacccctg gccttacctg cgggagttct tcagtctgag 120
cggagtgaac aaggacagct tcaagatgaa gtgcgtgctg tgcctgccac tgaacaagga 180
aattagcgcc ttcaagtctt ctccaagcaa cctgcggaag cacatcgaga gaatgcaccc 240
taactacctg aagaactaca gcaaattgac agctcagaag cggaagatcg gcacctccac 300
acacgccagc agcagcaagc agctgaaagt cgatagcgtg tttcctgtga agcacgtgtc 360
gcccgtgacc gtgaataagg ccattctgag atacatcatc cagggcctgc atccattcag 420
caccgtggac ctgccttcct tcaaagaact gatctctacc ctgcagcccg gcatcagcgt 480
gatcacccgg cctaccctga gatccaagat cgcggaggcc gctctgatca tgaagcaaaa 540
ggtgaccgcc gctatgagcg aagtggaatg gatcgccacc acaaccgact gctggacggc 600
cagaagaaag tccttcatcg gcgtgaccgc ccattggatt aaccctggct cactggagag 660
acacagcgcc gccctggcct gcaagcggct gatgggctct cataccttcg aagtcctggc 720
ctccgccatg aacgacatcc acagcgagta cgagatccgg gacaaagttg tgtgtaccac 780
caccgacagc ggcagcaatt tcatgaaagc ctttagagta ttcggcgtgg agaacaatga 840
catcgagaca gaggcccgga ggtgcgagag cgacgacaca gatagtgaag gatgtggcga 900
aggctccgac ggcgtggaat ttcaggatgc ctctagggtc ctggatcagg acgacggatt 960
tgagttccag ctgcccaagc accaaaaatg cgcctgtcac ctgctgaacc tggtgagctc 1020
tgtggatgcc cagaaggccc tgagcaacga gcactacaag aagctttata gaagcgtgtt 1080
cggaaagtgt caggctctgt ggaacaaaag cagcagaagc gccctggccg ctgaggccgt 1140
ggagagcgag agccggctgc agctgctgcg gcctaaccag acaagatgga atagcacctt 1200
catggccgtg gatagaatcc tccaaatctg caaggaggcc ggcgagggcg ccctgcgcaa 1260
catctgcacc tctctggagg tgcctatgtt caaccccgct gaaatgctgt tcctgaccga 1320
gtgggccaac accatgagac ccgtggccaa ggtgctggac atcctgcagg ctgagacaaa 1380
cacccagctg ggctggttgc tgcctagcgt gcaccagctg agcctgaaac tgcaaagact 1440
gcaccactct ctgagatact gcgaccccct ggtggacgcc ctgcagcagg gtatccagac 1500
cagattcaag cacatgtttg aagaccctga gatcatcgcc gctgccatcc tgctgcctaa 1560
gttccggaca agctggacaa atgatgaaac catcatcaag agaggcatgg actacatcag 1620
agttcacctg gaacctctgg atcacaagaa agagctggca aacagcagta gcgatgacga 1680
ggacttcttc gccagcctca agcctacaac ccacgaggcc agcaaagaac tggacggcta 1740
cctggcctgc gtgtccgaca ccagagagag cctgctgacc ttccccgcta tctgtagcct 1800
gagcatcaag acaaataccc ctctgcctgc cagcgccgcc tgcgagagac tgttctccac 1860
cgctggcctg cttttcagcc ctaagagagc cagactggat acaaacaact ttgagaacca 1920
gctcctgctg aaactcaatc tgcggttcta caacttcgaa tgataactcg ag 1972
<210> 7
<211> 649
<212> PRT
<213> 人工序列
<400> 7
Met Glu Glu Val Cys Asp Ser Ser Ala Ala Ala Ser Ser Thr Val Gln
1 5 10 15
Asn Gln Pro Gln Asp Gln Glu His Pro Trp Pro Tyr Leu Arg Glu Phe
20 25 30
Phe Ser Leu Ser Gly Val Asn Lys Asp Ser Phe Lys Met Lys Cys Val
35 40 45
Leu Cys Leu Pro Leu Asn Lys Glu Ile Ser Ala Phe Lys Ser Ser Pro
50 55 60
Ser Asn Leu Arg Lys His Ile Glu Arg Met His Pro Asn Tyr Leu Lys
65 70 75 80
Asn Tyr Ser Lys Leu Thr Ala Gln Lys Arg Lys Ile Gly Thr Ser Thr
85 90 95
His Ala Ser Ser Ser Lys Gln Leu Lys Val Asp Ser Val Phe Pro Val
100 105 110
Lys His Val Ser Pro Val Thr Val Asn Lys Ala Ile Leu Arg Tyr Ile
115 120 125
Ile Gln Gly Leu His Pro Phe Ser Thr Val Asp Leu Pro Ser Phe Lys
130 135 140
Glu Leu Ile Ser Thr Leu Gln Pro Gly Ile Ser Val Ile Thr Arg Pro
145 150 155 160
Thr Leu Arg Ser Lys Ile Ala Glu Ala Ala Leu Ile Met Lys Gln Lys
165 170 175
Val Thr Ala Ala Met Ser Glu Val Glu Trp Ile Ala Thr Thr Thr Asp
180 185 190
Cys Trp Thr Ala Arg Arg Lys Ser Phe Ile Gly Val Thr Ala His Trp
195 200 205
Ile Asn Pro Gly Ser Leu Glu Arg His Ser Ala Ala Leu Ala Cys Lys
210 215 220
Arg Leu Met Gly Ser His Thr Phe Glu Val Leu Ala Ser Ala Met Asn
225 230 235 240
Asp Ile His Ser Glu Tyr Glu Ile Arg Asp Lys Val Val Cys Thr Thr
245 250 255
Thr Asp Ser Gly Ser Asn Phe Met Lys Ala Phe Arg Val Phe Gly Val
260 265 270
Glu Asn Asn Asp Ile Glu Thr Glu Ala Arg Arg Cys Glu Ser Asp Asp
275 280 285
Thr Asp Ser Glu Gly Cys Gly Glu Gly Ser Asp Gly Val Glu Phe Gln
290 295 300
Asp Ala Ser Arg Val Leu Asp Gln Asp Asp Gly Phe Glu Phe Gln Leu
305 310 315 320
Pro Lys His Gln Lys Cys Ala Cys His Leu Leu Asn Leu Val Ser Ser
325 330 335
Val Asp Ala Gln Lys Ala Leu Ser Asn Glu His Tyr Lys Lys Leu Tyr
340 345 350
Arg Ser Val Phe Gly Lys Cys Gln Ala Leu Trp Asn Lys Ser Ser Arg
355 360 365
Ser Ala Leu Ala Ala Glu Ala Val Glu Ser Glu Ser Arg Leu Gln Leu
370 375 380
Leu Arg Pro Asn Gln Thr Arg Trp Asn Ser Thr Phe Met Ala Val Asp
385 390 395 400
Arg Ile Leu Gln Ile Cys Lys Glu Ala Gly Glu Gly Ala Leu Arg Asn
405 410 415
Ile Cys Thr Ser Leu Glu Val Pro Met Phe Asn Pro Ala Glu Met Leu
420 425 430
Phe Leu Thr Glu Trp Ala Asn Thr Met Arg Pro Val Ala Lys Val Leu
435 440 445
Asp Ile Leu Gln Ala Glu Thr Asn Thr Gln Leu Gly Trp Leu Leu Pro
450 455 460
Ser Val His Gln Leu Ser Leu Lys Leu Gln Arg Leu His His Ser Leu
465 470 475 480
Arg Tyr Cys Asp Pro Leu Val Asp Ala Leu Gln Gln Gly Ile Gln Thr
485 490 495
Arg Phe Lys His Met Phe Glu Asp Pro Glu Ile Ile Ala Ala Ala Ile
500 505 510
Leu Leu Pro Lys Phe Arg Thr Ser Trp Thr Asn Asp Glu Thr Ile Ile
515 520 525
Lys Arg Gly Met Asp Tyr Ile Arg Val His Leu Glu Pro Leu Asp His
530 535 540
Lys Lys Glu Leu Ala Asn Ser Ser Ser Asp Asp Glu Asp Phe Phe Ala
545 550 555 560
Ser Leu Lys Pro Thr Thr His Glu Ala Ser Lys Glu Leu Asp Gly Tyr
565 570 575
Leu Ala Cys Val Ser Asp Thr Arg Glu Ser Leu Leu Thr Phe Pro Ala
580 585 590
Ile Cys Ser Leu Ser Ile Lys Thr Asn Thr Pro Leu Pro Ala Ser Ala
595 600 605
Ala Cys Glu Arg Leu Phe Ser Thr Ala Gly Leu Leu Phe Ser Pro Lys
610 615 620
Arg Ala Arg Leu Asp Thr Asn Asn Phe Glu Asn Gln Leu Leu Leu Lys
625 630 635 640
Leu Asn Leu Arg Phe Tyr Asn Phe Glu
645
<210> 8
<211> 200
<212> DNA
<213> 人工序列
<400> 8
cagaggtgta aagtacttga gtaattttac ttgattactg tacttaagta ttatttttgg 60
ggatttttac tttacttgag tacaattaaa aatcaatact tttactttta cttaattaca 120
tttttttaga aaaaaaagta ctttttactc cttacaattt tatttacagt caaaaagtac 180
ttattttttg gagatcactt 200
<210> 9
<211> 150
<212> DNA
<213> 人工序列
<400> 9
aatactcaag tacaatttta atggagtact tttttacttt tactcaagta agattctagc 60
cagatacttt tacttttaat tgagtaaaat tttccctaag tacttgtact ttcacttgag 120
taaaattttt gagtactttt tacacctctg 150
<210> 10
<211> 459
<212> DNA
<213> 人工序列
<400> 10
gcggccgcgg taatcccaga ggtgtaaagt acttgagtaa ttttacttga ttactgtact 60
taagtattat ttttggggat ttttacttta cttgagtaca attaaaaatc aatactttta 120
cttttactta attacatttt tttagaaaaa aaagtacttt ttactcctta caattttatt 180
tacagtcaaa aagtacttat tttttggaga tcacttcctg caggtacgat caagcggcgc 240
gcccttaaac aagaatctct agttttcttt cttgctttta cttttacttc cttaatactc 300
aagtacaatt ttaatggagt acttttttac ttttactcaa gtaagattct agccagatac 360
ttttactttt aattgagtaa aattttccct aagtacttgt actttcactt gagtaaaatt 420
tttgagtact ttttacacct ctgggtaatc cgcgatcgc 459
<210> 11
<211> 1045
<212> DNA
<213> 人工序列
<400> 11
aatcgatgcc accatgcctc ggcccaagga aatccaagaa cagctgcgga agaaagtgat 60
tgagatttac cagtctggca agggctacaa ggctatcagc aaggccctgg gcatccagcg 120
gaccacagtg cgggccatca tccacaagtg gagacggcac ggcaccgtgg tgaacctgcc 180
tagaagcggc agacctccaa aaatcacccc tagagcccag agaagactga tccaggaggt 240
gaccaaagat cctaccacca caagcaagga gctgcaggcc agcctcgcct ctgtgaaggt 300
gtccgtgcac gccagcacca tcagaaagcg gcttggaaag aacggcctgc acggccgcgt 360
gcccagacgg aagcctctgc tgagcaagaa gaatatcaag gctagactga acttcagcac 420
cacccacctg gatgaccctc aggacttctg ggacaacatc ctgtggaccg acgagacaaa 480
ggtggaactg ttcggccggt gcgtgtctaa atacatctgg agacggagaa acaccgcctt 540
ccataagaag aatatcatcc ccacagtcaa gtacggcggc ggaagcgtga tggtgtgggg 600
ctgcttcgcc gccagcggcc ctggcagact ggccgtgatc aagggcacaa tgaacagcgc 660
cgtgtaccaa gagatcctga aggaaaacgt gaggccttct gtcagggtgc tgaagctgaa 720
gagaacctgg gtgctgcagc aggataacga ccccaagcac accagcaagt caacaacaga 780
gtggctgaag aagaacaaga tgaagaccct ggaatggccc agccagagcc ctgatctgaa 840
ccctatcgag atgctgtggt acgacctgaa aaaggccgtg cacgccagaa aaccctccaa 900
tgtcaccgag ctgggccagt tttgtaaaga cgagtgggcc aagatcccac caggcagatg 960
caagtccctg atcgccagat atagaaaaag actggtggcc gttgtggctg ctaagggagg 1020
acctactagc tactgataac tcgag 1045
<210> 12
<211> 340
<212> PRT
<213> 人工序列
<400> 12
Met Pro Arg Pro Lys Glu Ile Gln Glu Gln Leu Arg Lys Lys Val Ile
1 5 10 15
Glu Ile Tyr Gln Ser Gly Lys Gly Tyr Lys Ala Ile Ser Lys Ala Leu
20 25 30
Gly Ile Gln Arg Thr Thr Val Arg Ala Ile Ile His Lys Trp Arg Arg
35 40 45
His Gly Thr Val Val Asn Leu Pro Arg Ser Gly Arg Pro Pro Lys Ile
50 55 60
Thr Pro Arg Ala Gln Arg Arg Leu Ile Gln Glu Val Thr Lys Asp Pro
65 70 75 80
Thr Thr Thr Ser Lys Glu Leu Gln Ala Ser Leu Ala Ser Val Lys Val
85 90 95
Ser Val His Ala Ser Thr Ile Arg Lys Arg Leu Gly Lys Asn Gly Leu
100 105 110
His Gly Arg Val Pro Arg Arg Lys Pro Leu Leu Ser Lys Lys Asn Ile
115 120 125
Lys Ala Arg Leu Asn Phe Ser Thr Thr His Leu Asp Asp Pro Gln Asp
130 135 140
Phe Trp Asp Asn Ile Leu Trp Thr Asp Glu Thr Lys Val Glu Leu Phe
145 150 155 160
Gly Arg Cys Val Ser Lys Tyr Ile Trp Arg Arg Arg Asn Thr Ala Phe
165 170 175
His Lys Lys Asn Ile Ile Pro Thr Val Lys Tyr Gly Gly Gly Ser Val
180 185 190
Met Val Trp Gly Cys Phe Ala Ala Ser Gly Pro Gly Arg Leu Ala Val
195 200 205
Ile Lys Gly Thr Met Asn Ser Ala Val Tyr Gln Glu Ile Leu Lys Glu
210 215 220
Asn Val Arg Pro Ser Val Arg Val Leu Lys Leu Lys Arg Thr Trp Val
225 230 235 240
Leu Gln Gln Asp Asn Asp Pro Lys His Thr Ser Lys Ser Thr Thr Glu
245 250 255
Trp Leu Lys Lys Asn Lys Met Lys Thr Leu Glu Trp Pro Ser Gln Ser
260 265 270
Pro Asp Leu Asn Pro Ile Glu Met Leu Trp Tyr Asp Leu Lys Lys Ala
275 280 285
Val His Ala Arg Lys Pro Ser Asn Val Thr Glu Leu Gly Gln Phe Cys
290 295 300
Lys Asp Glu Trp Ala Lys Ile Pro Pro Gly Arg Cys Lys Ser Leu Ile
305 310 315 320
Ala Arg Tyr Arg Lys Arg Leu Val Ala Val Val Ala Ala Lys Gly Gly
325 330 335
Pro Thr Ser Tyr
340
<210> 13
<211> 250
<212> DNA
<213> 人工序列
<400> 13
cagtggtgtg aaaaagtgtt tgcccccttc ctcatttcct gttcctttgc atgtttgtca 60
cacttaagtg tttcggaaca tcaaaccaat ttaaacaata gtcaaggaca acacaagtaa 120
acacaaaatg caatttgtaa atgaaggtgt ttattattaa aggtgaaaaa aaatccaaac 180
catcatggcc ctgtgtgaaa aagtgattgc cccccttgtt aaaacatact ataactgtgg 240
ttgtccacac 250
<210> 14
<211> 551
<212> DNA
<213> 人工序列
<400> 14
gcggccgcta tacagtggtg tgaaaaagtg tttgccccct tcctcatttc ctgttccttt 60
gcatgtttgt cacacttaag tgtttcggaa catcaaacca atttaaacaa tagtcaagga 120
caacacaagt aaacacaaaa tgcaatttgt aaatgaaggt gtttattatt aaaggtgaaa 180
aaaaatccaa accatcatgg ccctgtgtga aaaagtgatt gccccccttg ttaaaacata 240
ctataactgt ggttgtccac accctgcagg tacgatcaag cggcgcgccg tgtggacaac 300
cacagttata gtatgtttta acaagggggg caatcacttt ttcacacagg gccatgatgg 360
tttggatttt ttttcacctt taataataaa caccttcatt tacaaattgc attttgtgtt 420
tacttgtgtt gtccttgact attgtttaaa ttggtttgat gttccgaaac acttaagtgt 480
gacaaacatg caaaggaaca ggaaatgagg aagggggcaa acactttttc acaccactgt 540
atagcgatcg c 551
<210> 15
<211> 1048
<212> DNA
<213> 人工序列
<400> 15
tatcgatgcc accatggtgc gcggaaagcc tatcagcaag gaaatccggg tgctgatcag 60
agattacttt aagtccggca aaaccctgac cgagatcagc aagcagctga atctgcccaa 120
gagctctgtg cacggcgtga ttcaaatctt caagaagaac ggcaacattg aaaacaacat 180
cgccaacaga ggcagaacca gcgctatcac acctagagac aagcggcagc tcgccaagat 240
cgtgaaagcc gatagaagac agagcctgcg gaacctggcc tccaagtggt cccagaccat 300
cggaaagacc gttaagagag agtggacaag acagcagctg aaaagcatcg gctacggctt 360
ctacaaggcc aaggaaaagc ctctgctgac cctgagacaa aagaagaaac ggctgcagtg 420
ggccagagaa agaatgagct ggacccagcg gcagtgggac accatcatct tcagcgacga 480
ggccaaattc gacgtgtccg tgggcgacac aagaaagcgc gtgatcagaa agcggagcga 540
gacatatcac aaggactgcc tgaagaggac cacaaaattc cccgccagca ccatggtctg 600
gggctgcatg agcgccaaag gtctgggaaa gctgcatttc atcgagggca ccgtgaacgc 660
cgaaaagtac atcaacatcc tgcaggacag cctgctgcct tctatcccca agctgtctga 720
ttgcggcgag ttcaccttcc agcaagacgg cgcttcttct cacaccgcca agcggacaaa 780
gaattggctg caatacaacc agatggaagt gctggactgg cccagcaaca gccctgatct 840
gagcccaatc gagaacatct ggtggctgat gaaaaaccag ctcagaaacg agcctcagag 900
aaatattagc gacctgaaga tcaagctgca ggagatgtgg gatagcatct ctcaggagca 960
ctgtaaaaat ctgctgagca gcatgcctaa gcgggtgaag tgcgtgatgc aagctaaggg 1020
cgacgtgaca cagttctgat aactcgag 1048
<210> 16
<211> 341
<212> PRT
<213> 人工序列
<400> 16
Met Val Arg Gly Lys Pro Ile Ser Lys Glu Ile Arg Val Leu Ile Arg
1 5 10 15
Asp Tyr Phe Lys Ser Gly Lys Thr Leu Thr Glu Ile Ser Lys Gln Leu
20 25 30
Asn Leu Pro Lys Ser Ser Val His Gly Val Ile Gln Ile Phe Lys Lys
35 40 45
Asn Gly Asn Ile Glu Asn Asn Ile Ala Asn Arg Gly Arg Thr Ser Ala
50 55 60
Ile Thr Pro Arg Asp Lys Arg Gln Leu Ala Lys Ile Val Lys Ala Asp
65 70 75 80
Arg Arg Gln Ser Leu Arg Asn Leu Ala Ser Lys Trp Ser Gln Thr Ile
85 90 95
Gly Lys Thr Val Lys Arg Glu Trp Thr Arg Gln Gln Leu Lys Ser Ile
100 105 110
Gly Tyr Gly Phe Tyr Lys Ala Lys Glu Lys Pro Leu Leu Thr Leu Arg
115 120 125
Gln Lys Lys Lys Arg Leu Gln Trp Ala Arg Glu Arg Met Ser Trp Thr
130 135 140
Gln Arg Gln Trp Asp Thr Ile Ile Phe Ser Asp Glu Ala Lys Phe Asp
145 150 155 160
Val Ser Val Gly Asp Thr Arg Lys Arg Val Ile Arg Lys Arg Ser Glu
165 170 175
Thr Tyr His Lys Asp Cys Leu Lys Arg Thr Thr Lys Phe Pro Ala Ser
180 185 190
Thr Met Val Trp Gly Cys Met Ser Ala Lys Gly Leu Gly Lys Leu His
195 200 205
Phe Ile Glu Gly Thr Val Asn Ala Glu Lys Tyr Ile Asn Ile Leu Gln
210 215 220
Asp Ser Leu Leu Pro Ser Ile Pro Lys Leu Ser Asp Cys Gly Glu Phe
225 230 235 240
Thr Phe Gln Gln Asp Gly Ala Ser Ser His Thr Ala Lys Arg Thr Lys
245 250 255
Asn Trp Leu Gln Tyr Asn Gln Met Glu Val Leu Asp Trp Pro Ser Asn
260 265 270
Ser Pro Asp Leu Ser Pro Ile Glu Asn Ile Trp Trp Leu Met Lys Asn
275 280 285
Gln Leu Arg Asn Glu Pro Gln Arg Asn Ile Ser Asp Leu Lys Ile Lys
290 295 300
Leu Gln Glu Met Trp Asp Ser Ile Ser Gln Glu His Cys Lys Asn Leu
305 310 315 320
Leu Ser Ser Met Pro Lys Arg Val Lys Cys Val Met Gln Ala Lys Gly
325 330 335
Asp Val Thr Gln Phe
340
<210> 17
<211> 257
<212> DNA
<213> 人工序列
<400> 17
atacgagccc caaccactat taattcgaac agcatgtttt ttttgcagtg cgcaatgttt 60
aacacactat attatcaata ctactaaaga taacacatac caatgcattt cgtctcaaag 120
agaattttat tctcttcacg acgaaaaaaa aagttttgct ctatttccaa caacaacaaa 180
aatatgagta atttattcaa acggtttgct taagagataa gaaaaaagtg accactatta 240
attcgaacgc ggcgtaa 257
<210> 18
<211> 561
<212> DNA
<213> 人工序列
<400> 18
gcggccgcta atacgagccc caaccactat taattcgaac agcatgtttt ttttgcagtg 60
cgcaatgttt aacacactat attatcaata ctactaaaga taacacatac caatgcattt 120
cgtctcaaag agaattttat tctcttcacg acgaaaaaaa aagttttgct ctatttccaa 180
caacaacaaa aatatgagta atttattcaa acggtttgct taagagataa gaaaaaagtg 240
accactatta attcgaacgc ggcgtaacct gcaggtacga tcaagcggcg cgccttacgc 300
cgcgttcgaa ttaatagtgg tcactttttt cttatctctt aagcaaaccg tttgaataaa 360
ttactcatat ttttgttgtt gttggaaata gagcaaaact ttttttttcg tcgtgaagag 420
aataaaattc tctttgagac gaaatgcatt ggtatgtgtt atctttagta gtattgataa 480
tatagtgtgt taaacattgc gcactgcaaa aaaaacatgc tgttcgaatt aatagtggtt 540
ggggctcgta ttagcgatcg c 561
<210> 19
<211> 1054
<212> DNA
<213> 人工序列
<400> 19
aatcgatgcc accatggaaa tgatgctgga caagaagcag atccgggcca tcttcctgtt 60
cgagttcaag atgggcagaa aggccgccga aaccaccagg aacatcaaca acgcctttgg 120
ccctggaaca gccaatgagc ggaccgtgca gtggtggttc aaaaagttcc ggaagggcga 180
cgagagcctg gaagatgagg aacggagcgg cagacccagc gaagtggaca acgaccagct 240
gagagccatt atcgaggctg atcctctgac caccactaga gaggttgccg aggaactgaa 300
cgtggaccac tctacagtgg tccggcacct gaagcagatc ggcaaggtga agaaactgga 360
caagtgggtc ccccacgagc tgagcgagaa ccagaaaaac agaagattcg aggtgtccag 420
cagcctgctg ctgagaaaca acaatgagcc tttcctggat agaatcgtga cctgtgacga 480
aaagtggatc ctgtacgaca acagacgccg gagcgcccag tggctggata gagaagaagc 540
ccctaagcac tttccaaagc caaacctgca ccagaagaaa gtgatggtga cagtgtggtg 600
gtccgccgct ggcgtgatcc attattcttt tctgaatcct ggagaaacca tcaccagcga 660
gaagtactgc cagcagatcg acgagatgca cagaaagctc caaagactgc agcctgccct 720
ggtgaatcgg aagggcccca tcctgctgca cgacaacgcc agacctcatg tggctcaacc 780
tacactgcaa aaactgaatg agctgggcta cgaggtgctg cctcaccccc cctacagccc 840
tgacctgtct cctaccgatt accacttctt caagcacctc gataacttcc tgcagggcaa 900
gcggttccac aaccagcagg acgccgagaa cgcttttcag gagttcgtgg aaagcagaag 960
cacagatttc tacgccaccg gaatcaacaa gctgatctct agatggcaga aatgcgtgga 1020
ctgcaacggc agctacttcg actgataact cgag 1054
<210> 20
<211> 343
<212> PRT
<213> 人工序列
<400> 20
Met Glu Met Met Leu Asp Lys Lys Gln Ile Arg Ala Ile Phe Leu Phe
1 5 10 15
Glu Phe Lys Met Gly Arg Lys Ala Ala Glu Thr Thr Arg Asn Ile Asn
20 25 30
Asn Ala Phe Gly Pro Gly Thr Ala Asn Glu Arg Thr Val Gln Trp Trp
35 40 45
Phe Lys Lys Phe Arg Lys Gly Asp Glu Ser Leu Glu Asp Glu Glu Arg
50 55 60
Ser Gly Arg Pro Ser Glu Val Asp Asn Asp Gln Leu Arg Ala Ile Ile
65 70 75 80
Glu Ala Asp Pro Leu Thr Thr Thr Arg Glu Val Ala Glu Glu Leu Asn
85 90 95
Val Asp His Ser Thr Val Val Arg His Leu Lys Gln Ile Gly Lys Val
100 105 110
Lys Lys Leu Asp Lys Trp Val Pro His Glu Leu Ser Glu Asn Gln Lys
115 120 125
Asn Arg Arg Phe Glu Val Ser Ser Ser Leu Leu Leu Arg Asn Asn Asn
130 135 140
Glu Pro Phe Leu Asp Arg Ile Val Thr Cys Asp Glu Lys Trp Ile Leu
145 150 155 160
Tyr Asp Asn Arg Arg Arg Ser Ala Gln Trp Leu Asp Arg Glu Glu Ala
165 170 175
Pro Lys His Phe Pro Lys Pro Asn Leu His Gln Lys Lys Val Met Val
180 185 190
Thr Val Trp Trp Ser Ala Ala Gly Val Ile His Tyr Ser Phe Leu Asn
195 200 205
Pro Gly Glu Thr Ile Thr Ser Glu Lys Tyr Cys Gln Gln Ile Asp Glu
210 215 220
Met His Arg Lys Leu Gln Arg Leu Gln Pro Ala Leu Val Asn Arg Lys
225 230 235 240
Gly Pro Ile Leu Leu His Asp Asn Ala Arg Pro His Val Ala Gln Pro
245 250 255
Thr Leu Gln Lys Leu Asn Glu Leu Gly Tyr Glu Val Leu Pro His Pro
260 265 270
Pro Tyr Ser Pro Asp Leu Ser Pro Thr Asp Tyr His Phe Phe Lys His
275 280 285
Leu Asp Asn Phe Leu Gln Gly Lys Arg Phe His Asn Gln Gln Asp Ala
290 295 300
Glu Asn Ala Phe Gln Glu Phe Val Glu Ser Arg Ser Thr Asp Phe Tyr
305 310 315 320
Ala Thr Gly Ile Asn Lys Leu Ile Ser Arg Trp Gln Lys Cys Val Asp
325 330 335
Cys Asn Gly Ser Tyr Phe Asp
340
<210> 21
<211> 30
<212> DNA
<213> 人工序列
<400> 21
ttaggttggt gcaaaagtaa ttgcggtttt 30
<210> 22
<211> 302
<212> DNA
<213> 人工序列
<400> 22
gcggccgcta ttaggttggt gcaaaagtaa ttgcggtttt tgcattgttg gaatttgccg 60
tttgatattg gaatacattc ttaaataaat gtggttatgt tatacatcat tttaatgcgc 120
atttctcgct ttacgttttt ttgctaatga cttattactt gctgtttatt ttatgtttat 180
tttagactcc tgcaggtacg atcaagcggc gcgcctaaag atgtgtttga gcctagttat 240
aatgatttaa aattcacggt ccaaaaccgc aattactttt gcaccaacct aatagcgatc 300
gc 302
<210> 23
<211> 4514
<212> DNA
<213> 人工序列
<400> 23
aatcgatgcc accatgagca aggaacagct cctaatccag agaagctctg ccgccgaaag 60
atgcagaaga tacagacaaa agatgagcgc agagcaaaga gcctctgacc tggaaagaag 120
acggcggctg cagcaaaacg tgagcgagga acaactgctg gagaagcggc gaagcgaggc 180
cgagaagcag cggcggcacc ggcagaagat gagcaaagac cagagagcct tcgaggtgga 240
aaggagaagg tggcggagac aaaatatgtc tcgggaacag agcagcacaa gcacgaccaa 300
caccggcaga aactgcctgc tgagcaagaa cggcgtgcat gaggatgcta tcctggaaca 360
cagctgcggc ggcatgaccg tgcggtgcga gttttgcctg tctctgaatt tcagcgacga 420
gaagccaagc gatggaaagt tcaccagatg ctgcagcaaa ggcaaggtgt gccccaatga 480
catacacttc ccagactacc cggcctatct gaagcggctg atgaccaatg aggactcaga 540
ttctaagaat ttcatggaaa acatcagaag cattaactcc agcttcgctt ttgccagcat 600
gggcgccaat atcgccagcc cttctggcta cggcccttat tgcttcagaa tccacggcca 660
ggtctaccac agaacaggca ctttgcaccc tagcgatgga gtgtcccgga agtttgccca 720
gctgtacatc ctggatacag ccgaggctac aagcaagcgg ctggccatgc ccgagaacca 780
gggctgtagc gagcgcctga tgatcaacat caataacctg atgcacgaga tcaacgagct 840
gacaaagagc tacaagatgc tgcacgaggt cgagaaagag gctcagagcg aagccgctgc 900
caagggaatt gcccctactg aggtgacaat ggccatcaag tacgacagaa actctgaccc 960
tggccggtat aacagccctc gggtgaccga agtggctgtg atatttagga acgaggacgg 1020
cgaacccccc ttcgagagag acctgctgat ccactgcaag cccgacccta acaatcctaa 1080
tgccaccaag atgaagcaga tcagcatcct gttccctacc ctggacgcaa tsgacctacc 1140
ctatcttgtt cccccacggc gagaagggct ggggcaccga catcgcactg agactgagag 1200
acaactccgt gatcgacaac aacacgagac agaatgtgcg cacccgggtg acccagatgc 1260
agtactacgg cttccacctg tctgtgcggg atacattcaa tcctatcctc aacgcaggca 1320
agctgacaca gcagttcatc gtcgacagct acagcaagat ggaagccaac agaattaact 1380
tcatcaaagc caatcagtct aagctgagag tcgaaaaata tagcggcctg atggactacc 1440
tgaagagcag atccgaaaac gacaacgtgc ctatcggtaa gatgattatc ctgccctcta 1500
gtttcgaagg cagccctaga aacatgcagc agcggtacca ggatgccatg gccatcgtga 1560
ccaaatacgg caagcctgac ctgtttatca caatgacctg taaccctaag tgggccgata 1620
tcaccaacaa ccttcaaaga tggcagaaag tggaaaatcg tcctgatctg gtggccagag 1680
tgttcaacat caaacttaac gccctgctca atgatatctg caagttccac ctgtttggca 1740
aggtgatcgc caagatccac gtgatcgagt tccagaagag aggcctgcct cacgcccaca 1800
tcctgctcat cctggacagc gagagcaagc tgcggtctga ggacgatatt gacagaatag 1860
tgaaagccga gatccctgac gaggaccagt gccctagact gtttcagatc gtgaagagca 1920
acatggtgca cggcccctgt ggtatccaga atcctaactc cccttgcatg gaaaacggca 1980
aatgcagcaa gggatatccc aaggaatttc agaacgccac catcggcaac atagacggct 2040
accccaagta caagagaaga agcggtagca caatgagcat tggaaacaag gttgtcgaca 2100
acacctggat cgttccttac aacccttacc tgtgcctgaa gtacaactgc cacatcaacg 2160
tggaagtgtg tgccagtatc aagtctgtga agtacctgtt caagtacatc tacaaaggcc 2220
acgactgcgc gaacatccaa ataagcgaga aaaacatcat caaccacgat gaagtgcagg 2280
actttatcga cagtagatac gtgtccgccc ctgaggccgt gtggagactg ttcgccatgc 2340
ggatgcacga ccaatctcac gccatcaccc gtctggctat tcacctgccc aacgaccaga 2400
acttgtactt ccataccgat gatttcgccg aggtgctgga cagagccaaa aggcacaaca 2460
gcaccctgat ggcttggttc cttctgaaca gggaagatag tgacgcaaga aattactact 2520
actgggagat cccacagcac tacgtgttca acaacagcct gtggaccaag cgcagaaagg 2580
gcgggaacaa ggtcctgggc agactgttca ccgtctcttt ccgggaaccg gaacggtact 2640
acctgagact gctgctgctg cacgtgaagg gcgccatcag ctttgaagat ctgcggacag 2700
tcggcggcgt gacgtacgac accttccacg aggccgctaa acaccgtgga ctgctgctcg 2760
atgacaccat ctggaaggac accatcgacg acgccatcat tctgaatatg cccaagcagc 2820
tgcggcagct gttcgcctac atctgcgtat ttggctgccc ctcagccgcc gacaagctgt 2880
gggacgaaaa caagtcccat ttcatcgagg acttctgctg gaagctgcac agacgggaag 2940
gtgcctgcgt gaactgtgaa atgcacgccc tgaatgagat ccaggaggtg ttcacactgc 3000
atggaatgaa atgcagccac ttcaagctcc ctgactaccc cctgctgatg aacgccaaca 3060
catgcgacca gctgtacgag cagcagcagg ccgaggtgct gatcaacagc ctgaacgatg 3120
agcagctggc cgcgttccaa acaatcacga gcgccatcga ggaccagacc gtgcacccca 3180
aatgcttctt cctggacggc cctggtggca gcggcaagac atacctgtac aaagtgctga 3240
cccactacat ccggggcaga ggaggcaccg tgctgcccac agccagcacc ggcatcgccg 3300
ctaatctcct gctgggcgga cggaccttcc actctcagta caagctacca attcctctga 3360
atgagacatc tataagcaga ctggacatca aaagcgaggt ggccaagacc atcaagaagg 3420
cccagctgct gatcattgat gagtgcacca tggctagctc ccacgccatc aacgccatcg 3480
accggttgtt aagagagatc atgaacctta acgtggcctt cggaggcaag gttctgctgc 3540
ttggaggcga ctttcggcag tgtctgagca tcgtgcctca cgccatgaga agcgccatcg 3600
tccagacctc cctgaagtat tgtaatgtgt ggggctgttt caggaagctg agcctaaaga 3660
ccaacatgag aagcgaggac tccgcctact ccgaatggct ggtgaagctg ggcgacggca 3720
agctggacag cagcttccat ctgggcatgg acatcatcga gatcccccat gaaatgatct 3780
gcaacggctc gatcatcgaa gctacgttcg gaaattccat ctccatcgac aacatcaaaa 3840
acatcagcaa acgcgctatc ctgtgtccta aaaacgagca cgtgcagaag ctgaacgagg 3900
aaatcctgga cattctggac ggagattttc acacatacct gtcagatgat tccatcgaca 3960
gcaccgacga cgccgagaag gaaaatttcc ctatcgagtt cctgaacagc atcaccccta 4020
gcggcatgcc ttgtcacaag ctgaaactga aggtgggggc tatcatcatg ctcctgagaa 4080
acctgaacag caagtgggga ctgtgcaacg gcaccagatt catcatcaag agactgcggc 4140
ctaacatcat cgaggctgaa gtattgaccg gctctgctga gggcgaggtg gtgctgatcc 4200
ctagaattga cctgagtcct agcgacacag gcctgccatt caagctgatc agacggcaat 4260
ttcccgtgat gcctgctttc gccatgacaa tcaacaagtc tcagggccag acactggatc 4320
gggtgggcat cttcctgcct gagcctgtgt tcgcccacgg ccagctgtat gtggccttca 4380
gccgggtgag aagagcctgt gacgtgaagg tgaaggtggt taatacctcc agccagggca 4440
aactggtgaa gcacagcgaa agcgtgttca cgctgaacgt ggtgtaccgc gagatcctag 4500
aatgataact cgag 4514
<210> 24
<211> 1496
<212> PRT
<213> 人工序列
<400> 24
Met Ser Lys Glu Gln Leu Leu Ile Gln Arg Ser Ser Ala Ala Glu Arg
1 5 10 15
Cys Arg Arg Tyr Arg Gln Lys Met Ser Ala Glu Gln Arg Ala Ser Asp
20 25 30
Leu Glu Arg Arg Arg Arg Leu Gln Gln Asn Val Ser Glu Glu Gln Leu
35 40 45
Leu Glu Lys Arg Arg Ser Glu Ala Glu Lys Gln Arg Arg His Arg Gln
50 55 60
Lys Met Ser Lys Asp Gln Arg Ala Phe Glu Val Glu Arg Arg Arg Trp
65 70 75 80
Arg Arg Gln Asn Met Ser Arg Glu Gln Ser Ser Thr Ser Thr Thr Asn
85 90 95
Thr Gly Arg Asn Cys Leu Leu Ser Lys Asn Gly Val His Glu Asp Ala
100 105 110
Ile Leu Glu His Ser Cys Gly Gly Met Thr Val Arg Cys Glu Phe Cys
115 120 125
Leu Ser Leu Asn Phe Ser Asp Glu Lys Pro Ser Asp Gly Lys Phe Thr
130 135 140
Arg Cys Cys Ser Lys Gly Lys Val Cys Pro Asn Asp Ile His Phe Pro
145 150 155 160
Asp Tyr Pro Ala Tyr Leu Lys Arg Leu Met Thr Asn Glu Asp Ser Asp
165 170 175
Ser Lys Asn Phe Met Glu Asn Ile Arg Ser Ile Asn Ser Ser Phe Ala
180 185 190
Phe Ala Ser Met Gly Ala Asn Ile Ala Ser Pro Ser Gly Tyr Gly Pro
195 200 205
Tyr Cys Phe Arg Ile His Gly Gln Val Tyr His Arg Thr Gly Thr Leu
210 215 220
His Pro Ser Asp Gly Val Ser Arg Lys Phe Ala Gln Leu Tyr Ile Leu
225 230 235 240
Asp Thr Ala Glu Ala Thr Ser Lys Arg Leu Ala Met Pro Glu Asn Gln
245 250 255
Gly Cys Ser Glu Arg Leu Met Ile Asn Ile Asn Asn Leu Met His Glu
260 265 270
Ile Asn Glu Leu Thr Lys Ser Tyr Lys Met Leu His Glu Val Glu Lys
275 280 285
Glu Ala Gln Ser Glu Ala Ala Ala Lys Gly Ile Ala Pro Thr Glu Val
290 295 300
Thr Met Ala Ile Lys Tyr Asp Arg Asn Ser Asp Pro Gly Arg Tyr Asn
305 310 315 320
Ser Pro Arg Val Thr Glu Val Ala Val Ile Phe Arg Asn Glu Asp Gly
325 330 335
Glu Pro Pro Phe Glu Arg Asp Leu Leu Ile His Cys Lys Pro Asp Pro
340 345 350
Asn Asn Pro Asn Ala Thr Lys Met Lys Gln Ile Ser Ile Leu Phe Pro
355 360 365
Thr Leu Asp Ala Met Thr Tyr Pro Ile Leu Phe Pro His Gly Glu Lys
370 375 380
Gly Trp Gly Thr Asp Ile Ala Leu Arg Leu Arg Asp Asn Ser Val Ile
385 390 395 400
Asp Asn Asn Thr Arg Gln Asn Val Arg Thr Arg Val Thr Gln Met Gln
405 410 415
Tyr Tyr Gly Phe His Leu Ser Val Arg Asp Thr Phe Asn Pro Ile Leu
420 425 430
Asn Ala Gly Lys Leu Thr Gln Gln Phe Ile Val Asp Ser Tyr Ser Lys
435 440 445
Met Glu Ala Asn Arg Ile Asn Phe Ile Lys Ala Asn Gln Ser Lys Leu
450 455 460
Arg Val Glu Lys Tyr Ser Gly Leu Met Asp Tyr Leu Lys Ser Arg Ser
465 470 475 480
Glu Asn Asp Asn Val Pro Ile Gly Lys Met Ile Ile Leu Pro Ser Ser
485 490 495
Phe Glu Gly Ser Pro Arg Asn Met Gln Gln Arg Tyr Gln Asp Ala Met
500 505 510
Ala Ile Val Thr Lys Tyr Gly Lys Pro Asp Leu Phe Ile Thr Met Thr
515 520 525
Cys Asn Pro Lys Trp Ala Asp Ile Thr Asn Asn Leu Gln Arg Trp Gln
530 535 540
Lys Val Glu Asn Arg Pro Asp Leu Val Ala Arg Val Phe Asn Ile Lys
545 550 555 560
Leu Asn Ala Leu Leu Asn Asp Ile Cys Lys Phe His Leu Phe Gly Lys
565 570 575
Val Ile Ala Lys Ile His Val Ile Glu Phe Gln Lys Arg Gly Leu Pro
580 585 590
His Ala His Ile Leu Leu Ile Leu Asp Ser Glu Ser Lys Leu Arg Ser
595 600 605
Glu Asp Asp Ile Asp Arg Ile Val Lys Ala Glu Ile Pro Asp Glu Asp
610 615 620
Gln Cys Pro Arg Leu Phe Gln Ile Val Lys Ser Asn Met Val His Gly
625 630 635 640
Pro Cys Gly Ile Gln Asn Pro Asn Ser Pro Cys Met Glu Asn Gly Lys
645 650 655
Cys Ser Lys Gly Tyr Pro Lys Glu Phe Gln Asn Ala Thr Ile Gly Asn
660 665 670
Ile Asp Gly Tyr Pro Lys Tyr Lys Arg Arg Ser Gly Ser Thr Met Ser
675 680 685
Ile Gly Asn Lys Val Val Asp Asn Thr Trp Ile Val Pro Tyr Asn Pro
690 695 700
Tyr Leu Cys Leu Lys Tyr Asn Cys His Ile Asn Val Glu Val Cys Ala
705 710 715 720
Ser Ile Lys Ser Val Lys Tyr Leu Phe Lys Tyr Ile Tyr Lys Gly His
725 730 735
Asp Cys Ala Asn Ile Gln Ile Ser Glu Lys Asn Ile Ile Asn His Asp
740 745 750
Glu Val Gln Asp Phe Ile Asp Ser Arg Tyr Val Ser Ala Pro Glu Ala
755 760 765
Val Trp Arg Leu Phe Ala Met Arg Met His Asp Gln Ser His Ala Ile
770 775 780
Thr Arg Leu Ala Ile His Leu Pro Asn Asp Gln Asn Leu Tyr Phe His
785 790 795 800
Thr Asp Asp Phe Ala Glu Val Leu Asp Arg Ala Lys Arg His Asn Ser
805 810 815
Thr Leu Met Ala Trp Phe Leu Leu Asn Arg Glu Asp Ser Asp Ala Arg
820 825 830
Asn Tyr Tyr Tyr Trp Glu Ile Pro Gln His Tyr Val Phe Asn Asn Ser
835 840 845
Leu Trp Thr Lys Arg Arg Lys Gly Gly Asn Lys Val Leu Gly Arg Leu
850 855 860
Phe Thr Val Ser Phe Arg Glu Pro Glu Arg Tyr Tyr Leu Arg Leu Leu
865 870 875 880
Leu Leu His Val Lys Gly Ala Ile Ser Phe Glu Asp Leu Arg Thr Val
885 890 895
Gly Gly Val Thr Tyr Asp Thr Phe His Glu Ala Ala Lys His Arg Gly
900 905 910
Leu Leu Leu Asp Asp Thr Ile Trp Lys Asp Thr Ile Asp Asp Ala Ile
915 920 925
Ile Leu Asn Met Pro Lys Gln Leu Arg Gln Leu Phe Ala Tyr Ile Cys
930 935 940
Val Phe Gly Cys Pro Ser Ala Ala Asp Lys Leu Trp Asp Glu Asn Lys
945 950 955 960
Ser His Phe Ile Glu Asp Phe Cys Trp Lys Leu His Arg Arg Glu Gly
965 970 975
Ala Cys Val Asn Cys Glu Met His Ala Leu Asn Glu Ile Gln Glu Val
980 985 990
Phe Thr Leu His Gly Met Lys Cys Ser His Phe Lys Leu Pro Asp Tyr
995 1000 1005
Pro Leu Leu Met Asn Ala Asn Thr Cys Asp Gln Leu Tyr Glu Gln
1010 1015 1020
Gln Gln Ala Glu Val Leu Ile Asn Ser Leu Asn Asp Glu Gln Leu
1025 1030 1035
Ala Ala Phe Gln Thr Ile Thr Ser Ala Ile Glu Asp Gln Thr Val
1040 1045 1050
His Pro Lys Cys Phe Phe Leu Asp Gly Pro Gly Gly Ser Gly Lys
1055 1060 1065
Thr Tyr Leu Tyr Lys Val Leu Thr His Tyr Ile Arg Gly Arg Gly
1070 1075 1080
Gly Thr Val Leu Pro Thr Ala Ser Thr Gly Ile Ala Ala Asn Leu
1085 1090 1095
Leu Leu Gly Gly Arg Thr Phe His Ser Gln Tyr Lys Leu Pro Ile
1100 1105 1110
Pro Leu Asn Glu Thr Ser Ile Ser Arg Leu Asp Ile Lys Ser Glu
1115 1120 1125
Val Ala Lys Thr Ile Lys Lys Ala Gln Leu Leu Ile Ile Asp Glu
1130 1135 1140
Cys Thr Met Ala Ser Ser His Ala Ile Asn Ala Ile Asp Arg Leu
1145 1150 1155
Leu Arg Glu Ile Met Asn Leu Asn Val Ala Phe Gly Gly Lys Val
1160 1165 1170
Leu Leu Leu Gly Gly Asp Phe Arg Gln Cys Leu Ser Ile Val Pro
1175 1180 1185
His Ala Met Arg Ser Ala Ile Val Gln Thr Ser Leu Lys Tyr Cys
1190 1195 1200
Asn Val Trp Gly Cys Phe Arg Lys Leu Ser Leu Lys Thr Asn Met
1205 1210 1215
Arg Ser Glu Asp Ser Ala Tyr Ser Glu Trp Leu Val Lys Leu Gly
1220 1225 1230
Asp Gly Lys Leu Asp Ser Ser Phe His Leu Gly Met Asp Ile Ile
1235 1240 1245
Glu Ile Pro His Glu Met Ile Cys Asn Gly Ser Ile Ile Glu Ala
1250 1255 1260
Thr Phe Gly Asn Ser Ile Ser Ile Asp Asn Ile Lys Asn Ile Ser
1265 1270 1275
Lys Arg Ala Ile Leu Cys Pro Lys Asn Glu His Val Gln Lys Leu
1280 1285 1290
Asn Glu Glu Ile Leu Asp Ile Leu Asp Gly Asp Phe His Thr Tyr
1295 1300 1305
Leu Ser Asp Asp Ser Ile Asp Ser Thr Asp Asp Ala Glu Lys Glu
1310 1315 1320
Asn Phe Pro Ile Glu Phe Leu Asn Ser Ile Thr Pro Ser Gly Met
1325 1330 1335
Pro Cys His Lys Leu Lys Leu Lys Val Gly Ala Ile Ile Met Leu
1340 1345 1350
Leu Arg Asn Leu Asn Ser Lys Trp Gly Leu Cys Asn Gly Thr Arg
1355 1360 1365
Phe Ile Ile Lys Arg Leu Arg Pro Asn Ile Ile Glu Ala Glu Val
1370 1375 1380
Leu Thr Gly Ser Ala Glu Gly Glu Val Val Leu Ile Pro Arg Ile
1385 1390 1395
Asp Leu Ser Pro Ser Asp Thr Gly Leu Pro Phe Lys Leu Ile Arg
1400 1405 1410
Arg Gln Phe Pro Val Met Pro Ala Phe Ala Met Thr Ile Asn Lys
1415 1420 1425
Ser Gln Gly Gln Thr Leu Asp Arg Val Gly Ile Phe Leu Pro Glu
1430 1435 1440
Pro Val Phe Ala His Gly Gln Leu Tyr Val Ala Phe Ser Arg Val
1445 1450 1455
Arg Arg Ala Cys Asp Val Lys Val Lys Val Val Asn Thr Ser Ser
1460 1465 1470
Gln Gly Lys Leu Val Lys His Ser Glu Ser Val Phe Thr Leu Asn
1475 1480 1485
Val Val Tyr Arg Glu Ile Leu Glu
1490 1495
<210> 25
<211> 150
<212> DNA
<213> 人工序列
<400> 25
tcctatataa taaaagagaa acatgcaaat tgaccatccc tccgctacgc tcaagccacg 60
cccaccagcc aatcagaagt gactatgcaa attaacccaa caaagatggc agttaaattt 120
gcatacgcag gtgtcaagcg ccccaggagg 150
<210> 26
<211> 150
<212> DNA
<213> 人工序列
<400> 26
aaatttatgt attattttca tatacatttt actcatttcc tttcatctct cacacttcta 60
ttatagagaa agggcaaata gcaatattaa aatatttcct ctaattaatt ccctttcaat 120
gtgcacgaat ttcgtgcacc gggccactag 150
<210> 27
<211> 875
<212> DNA
<213> 人工序列
<400> 27
aggccttgtc ttccatatcc tatataataa aagagaaaca tgcaaattga ccatccctcc 60
gctacgctca agccacgccc accagccaat cagaagtgac tatgcaaatt aacccaacaa 120
agatggcagt taaatttgca tacgcaggtg tcaagcgccc caggaggcaa cggcggccgc 180
gggctcccag gaccttcgct ggccccggga ggcgaggccg gccgcgccta gccacacccg 240
cgggctcccg ggaccttcgc cagcagagag cagagcggga gagcgggcgg agagcgggag 300
gtttggagga cttggcagag caggaggccg ctggacatag agcagagcga gagagagggt 360
ggcttggagg gcgtggctcc ctctgtcacc ccagcttcct catcacagct gtggaaactg 420
acagcaggga ggaggaagtc ccacccccac agaatcagcc agaatcagcc gttggtcaga 480
cagctctcag cggcctgaca gccaggactc tcattcacct gcatctcaga ccgtgacagt 540
agagaggtgg gactcctgca ggtacgatca agcggcgcgc ctttaatcac tttatcagtc 600
attgtttgca tcaatgttgt ttttatatca tgtttttgtt gtttttatat catgtctttg 660
ttgttgttat atcatgttgt tattgtttat ttattaataa atttatgtat tattttcata 720
tacattttac tcatttcctt tcatctctca cacttctatt atagagaaag ggcaaatagc 780
aatattaaaa tatttcctct aattaattcc ctttcaatgt gcacgaattt cgtgcaccgg 840
gccactagta tttaaataaa aagcaaagcg atcgc 875
<210> 28
<211> 1048
<212> DNA
<213> 人工序列
<400> 28
aatcgatgcc accatgatgg gcaagaacaa agagctgagc caagacctgc ggagcctgat 60
cgtggaaaag catttcgacg gcaacggtta tcggagaatc agcagaatgc tgaatgtgcc 120
cgtctccacc gtgggcgcta tcatccggaa gtggaagaag cacaaattca ccatcaacag 180
acctagatct ggcgccccta gaaagatccc tgtgcggggc gtgcagcgga tcatcagacg 240
ggtgctgcaa gagcctagaa caaccagagc tgaactgcag gaagatctgg cctctgccgg 300
cacaatcgtg tccaagaaga caatttctaa tgccctgaac caccacggca tccacgcccg 360
gagccctcgg aaaacccctc tgctgaacaa gaaacacgtg gaagccagac tgaaattcgc 420
caaacagcac ctggagaagc ctgtggacta ctgggagaca attgtgtgga gcgacgagag 480
caagatcgag ttgtttggaa gccacagcac ccaccacgtc tggagaagga acggcaccgc 540
ccaccatcct aagaacacaa tccccaccgt taagttcgga ggcggcagca tcatggtgtg 600
gggctgtttt agcgctagag gaaccggcag gctgcacatc atcgagggaa gaatgaacgg 660
cgagatgtac agagatatcc tggataagaa cctgctgcct tccacaagaa aactgaagat 720
gaagcgcggc tggaccttcc agcaggataa cgaccccaag cacaaggcca aggaaaccat 780
gaaatggttc cagagaaaga aaatcaagct gctggagtgg cctagccaga gcccagacct 840
gaacccaatc gagaacctgt ggcgggaact gaagatcaag gtgcacaaga gaggcccccg 900
gaatctgcag gacctgaaga ccgtgtgcgt ggaggaatgg gccagaatca cccccgagca 960
gtgcagaaga ctggtgtctc catacaagcg gagactggaa gccgtgatca ccaacaaggg 1020
cttcagcaca aagtactgat aactcgag 1048
<210> 29
<211> 341
<212> PRT
<213> 人工序列
<400> 29
Met Met Gly Lys Asn Lys Glu Leu Ser Gln Asp Leu Arg Ser Leu Ile
1 5 10 15
Val Glu Lys His Phe Asp Gly Asn Gly Tyr Arg Arg Ile Ser Arg Met
20 25 30
Leu Asn Val Pro Val Ser Thr Val Gly Ala Ile Ile Arg Lys Trp Lys
35 40 45
Lys His Lys Phe Thr Ile Asn Arg Pro Arg Ser Gly Ala Pro Arg Lys
50 55 60
Ile Pro Val Arg Gly Val Gln Arg Ile Ile Arg Arg Val Leu Gln Glu
65 70 75 80
Pro Arg Thr Thr Arg Ala Glu Leu Gln Glu Asp Leu Ala Ser Ala Gly
85 90 95
Thr Ile Val Ser Lys Lys Thr Ile Ser Asn Ala Leu Asn His His Gly
100 105 110
Ile His Ala Arg Ser Pro Arg Lys Thr Pro Leu Leu Asn Lys Lys His
115 120 125
Val Glu Ala Arg Leu Lys Phe Ala Lys Gln His Leu Glu Lys Pro Val
130 135 140
Asp Tyr Trp Glu Thr Ile Val Trp Ser Asp Glu Ser Lys Ile Glu Leu
145 150 155 160
Phe Gly Ser His Ser Thr His His Val Trp Arg Arg Asn Gly Thr Ala
165 170 175
His His Pro Lys Asn Thr Ile Pro Thr Val Lys Phe Gly Gly Gly Ser
180 185 190
Ile Met Val Trp Gly Cys Phe Ser Ala Arg Gly Thr Gly Arg Leu His
195 200 205
Ile Ile Glu Gly Arg Met Asn Gly Glu Met Tyr Arg Asp Ile Leu Asp
210 215 220
Lys Asn Leu Leu Pro Ser Thr Arg Lys Leu Lys Met Lys Arg Gly Trp
225 230 235 240
Thr Phe Gln Gln Asp Asn Asp Pro Lys His Lys Ala Lys Glu Thr Met
245 250 255
Lys Trp Phe Gln Arg Lys Lys Ile Lys Leu Leu Glu Trp Pro Ser Gln
260 265 270
Ser Pro Asp Leu Asn Pro Ile Glu Asn Leu Trp Arg Glu Leu Lys Ile
275 280 285
Lys Val His Lys Arg Gly Pro Arg Asn Leu Gln Asp Leu Lys Thr Val
290 295 300
Cys Val Glu Glu Trp Ala Arg Ile Thr Pro Glu Gln Cys Arg Arg Leu
305 310 315 320
Val Ser Pro Tyr Lys Arg Arg Leu Glu Ala Val Ile Thr Asn Lys Gly
325 330 335
Phe Ser Thr Lys Tyr
340
<210> 30
<211> 201
<212> DNA
<213> 人工序列
<400> 30
cagcggggaa aataagtatt tgacacatca gcatttttat cagtaagggg atttctaagt 60
gggctactga cacaaaattc ctaccagatg tagccatcaa gccaaatatt gaattcatac 120
aaagaaatca gaacatttaa gtatacaagt tgagtcataa taaataaagt gaaatgacac 180
agggaataag tattgaacac a 201
<210> 31
<211> 455
<212> DNA
<213> 人工序列
<400> 31
gcggccgcat atacagcggg gaaaataagt atttgacaca tcagcatttt tatcagtaag 60
gggatttcta agtgggctac tgacacaaaa ttcctaccag atgtagccat caagccaaat 120
attgaattca tacaaagaaa tcagaacatt taagtataca agttgagtca taataaataa 180
agtgaaatga cacagggaat aagtattgaa cacacctgca ggtacgatca agcggcgcgc 240
ctgtgttcaa tacttattcc ctgtgtcatt tcactttatt tattatgact caacttgtat 300
acttaaatgt tctgatttct ttgtatgaat tcaatatttg gcttgatggc tacatctggt 360
aggaattttg tgtcagtagc ccacttagaa atccccttac tgataaaaat gctgatgtgt 420
caaatactta ttttccccgc tgtatatgcg atcgc 455
<210> 32
<211> 1048
<212> DNA
<213> 人工序列
<400> 32
aatcgatgcc accatggcca gactgagcac cgccacaaga cacaaggtgg tgatcctgca 60
ccagcaagga ctttcccagg ccgaaatcag ccggcagacc ggcgtgtcca gatgcgccgt 120
gcaggccctg ctgaagaaac ataaggaaac cggcaatgtg gaagatagac ggcggagcgg 180
cagacctaga aagctgacag ctgccgacga gcgccacatc atgctgacca gcctgcggaa 240
ccggaagatg agctccagcg ccatcagcag cgagctggct gagaacagcg gtacactggt 300
gcaccctagc acagtgcgca gatctctggt cagatctgga ctgcacggca gactggccgc 360
taagaagcct tacctgagaa ggggcaacaa ggccaaaaga ctgaattacg ccagaaagca 420
caggaactgg ggcgccgaaa agtggcagca ggttctgtgg accgacgagt ctaagttcga 480
gattttcgga tgcagcagaa gacagttcgt gcggcggcgg gccggcgaga gatacaccaa 540
cgagtgcctg caggccaccg tgaagcatgg cggaggatct ctgcaggtgt ggggctgtat 600
cagcgctaat ggcgtgggcg acctcgtgcg gatcaacggc ctgctgaacg ccgagaagta 660
cagacagatc ctgatccacc acgccatccc ctctggcaga cacctgatcg gccctaagtt 720
catcctgcaa cacgacaacg accccaagca caccgctaaa gtgattaaga actacctgca 780
gagaaaagag gaacagggcg tgctggaagt gatggtgtgg cccccccaga gccctgatct 840
gaacatcatc gagagcgtgt gggattacat gaagcgggaa aaacagctga gactgcctaa 900
aagcaccgag gaactgtggc tggtcctgca ggacgtgtgg gccaacctgc cagctgagtt 960
tctgcaaaag ctgtgcgcca gcgtgcctcg gagaatcgac gccgtgctga aggccaaggg 1020
cggccacaca aagtattgat aactcgag 1048
<210> 33
<211> 341
<212> PRT
<213> 人工序列
<400> 33
Met Ala Arg Leu Ser Thr Ala Thr Arg His Lys Val Val Ile Leu His
1 5 10 15
Gln Gln Gly Leu Ser Gln Ala Glu Ile Ser Arg Gln Thr Gly Val Ser
20 25 30
Arg Cys Ala Val Gln Ala Leu Leu Lys Lys His Lys Glu Thr Gly Asn
35 40 45
Val Glu Asp Arg Arg Arg Ser Gly Arg Pro Arg Lys Leu Thr Ala Ala
50 55 60
Asp Glu Arg His Ile Met Leu Thr Ser Leu Arg Asn Arg Lys Met Ser
65 70 75 80
Ser Ser Ala Ile Ser Ser Glu Leu Ala Glu Asn Ser Gly Thr Leu Val
85 90 95
His Pro Ser Thr Val Arg Arg Ser Leu Val Arg Ser Gly Leu His Gly
100 105 110
Arg Leu Ala Ala Lys Lys Pro Tyr Leu Arg Arg Gly Asn Lys Ala Lys
115 120 125
Arg Leu Asn Tyr Ala Arg Lys His Arg Asn Trp Gly Ala Glu Lys Trp
130 135 140
Gln Gln Val Leu Trp Thr Asp Glu Ser Lys Phe Glu Ile Phe Gly Cys
145 150 155 160
Ser Arg Arg Gln Phe Val Arg Arg Arg Ala Gly Glu Arg Tyr Thr Asn
165 170 175
Glu Cys Leu Gln Ala Thr Val Lys His Gly Gly Gly Ser Leu Gln Val
180 185 190
Trp Gly Cys Ile Ser Ala Asn Gly Val Gly Asp Leu Val Arg Ile Asn
195 200 205
Gly Leu Leu Asn Ala Glu Lys Tyr Arg Gln Ile Leu Ile His His Ala
210 215 220
Ile Pro Ser Gly Arg His Leu Ile Gly Pro Lys Phe Ile Leu Gln His
225 230 235 240
Asp Asn Asp Pro Lys His Thr Ala Lys Val Ile Lys Asn Tyr Leu Gln
245 250 255
Arg Lys Glu Glu Gln Gly Val Leu Glu Val Met Val Trp Pro Pro Gln
260 265 270
Ser Pro Asp Leu Asn Ile Ile Glu Ser Val Trp Asp Tyr Met Lys Arg
275 280 285
Glu Lys Gln Leu Arg Leu Pro Lys Ser Thr Glu Glu Leu Trp Leu Val
290 295 300
Leu Gln Asp Val Trp Ala Asn Leu Pro Ala Glu Phe Leu Gln Lys Leu
305 310 315 320
Cys Ala Ser Val Pro Arg Arg Ile Asp Ala Val Leu Lys Ala Lys Gly
325 330 335
Gly His Thr Lys Tyr
340
<210> 34
<211> 210
<212> DNA
<213> 人工序列
<400> 34
cagtactgtg caaaagtttt aggcaggtgt gaaaaaatgc tgtaaagtaa gaatgctttc 60
aaaaatagac atgttaatag tttatattta tcaattaaca aaatgcaaag tgagtgaaca 120
gaagaaaaat ctacatcaaa tcaatatttg gtgtgaccac cctttgcctt caaaacagca 180
tcaattcttc taggtacact tgcacacagt 210
<210> 35
<211> 467
<212> DNA
<213> 人工序列
<400> 35
gcggccgcta cagtactgtg caaaagtttt aggcaggtgt gaaaaaatgc tgtaaagtaa 60
gaatgctttc aaaaatagac atgttaatag tttatattta tcaattaaca aaatgcaaag 120
tgagtgaaca gaagaaaaat ctacatcaaa tcaatatttg gtgtgaccac cctttgcctt 180
caaaacagca tcaattcttc taggtacact tgcacacagt cctgcaggta cgatcaagcg 240
gcgcgccact gtgtgcaagt gtacctagaa gaattgatgc tgttttgaag gcaaagggtg 300
gtcacaccaa atattgattt gatgtagatt tttcttctgt tcactcactt tgcattttgt 360
taattgataa atataaacta ttaacatgtc tatttttgaa agcattctta ctttacagca 420
ttttttcaca cctgcctaaa acttttgcac agtactgtag cgatcgc 467
<210> 36
<211> 1831
<212> DNA
<213> 人工序列
<400> 36
aatcgatgcc accatgacca tggacagagt cgagaagaac gtgaagaagc ggaagtacag 60
cgaggatttc cttcagtacg gctttaccag catcatcaca gctggcatcg agaagcctca 120
atgtgtgatc tgctgcgagg tgctgtctgc tgaaagcatg aagcctaaca agctgaagcg 180
gcacttcgac agcaagcacc ccagcttcgc cggaaaggac accaactact ttagatccaa 240
ggccgatggc ctgaaaaagg ccagactgga tacaggcggc aagtaccaca aacagaacgt 300
ggccgccatc gaagcctctt acctggtggc cctgagaatc gcccgagcta tgaagcccca 360
cacaatcgcc gaggacctgc tgctgcctgc tgccaaggac atcgtgaggg tgatgatcgg 420
agatgaattc gtgaccaagc tgagcgcaat ctctctgtcc aacgacaccg tgcggagaag 480
aattgacgac atgagcgccg acatcctgga ccaggtgatc caggaaatca agtctgcccc 540
actgcccatc ttcagcatcc agctggacga atctaccgac gtggccaact gcagccagct 600
gctggtgtac gtgcggtaca tcaatgacgg cgacttcaag gacgagttcc tgttctgcaa 660
gcccctggaa atgacaacca ccgccagaga cgttttcgac acagtgggca gctttctgaa 720
ggaacacaag atcagctggg aaaaggtctg tggcgtgtgc accgatggag cccccgccat 780
gctgggctgc agatcaggct tccaaagact ggtactgaat gagagcccta aggtgatcgg 840
cacccactgc atgatccaca gacagatcct ggccaccaaa acactcccac aggagctgca 900
agaggtgatg aagagcgtga tttcctccgt gaacttcgtg aaggccagca ccctgaacag 960
cagactgttt agccagctgt gcaacgagct cgacgcccct aacaacgccc tgctctttca 1020
caccgaggtg cgctggctgt ccagaggcaa ggtgctgaaa cgggtgttcg agctcagaga 1080
tgaactgaag accttcttca accagaaagc cagacctcag ttcgaggccc tgttcagcga 1140
caagagcgag ctgcagaaaa tcgcctacct ggtggacatc ttcgccattc tgaatgagct 1200
gaacctgtcc ctgcagggcc ctaatgccac atgtctggat ctgagcgaga agatcagatc 1260
ttttcagatg aaactgcagc tgtggcagaa gaagctggat gagaacaaga tctacatgct 1320
gcctacactg agcgcttttt tcgaggaaca tgacatcgag cctgacaagc ggatcaccat 1380
gatcatcagc gtgaaagagc acctgcacat gctggctgat gagatcagca gctacttccc 1440
aaatctgcca gatacacctt tcgccctggc cagatctcct ttcactgtga aggtggaaga 1500
tgtgcccgag accgctcagg aggaattcat cgagctgatc aacagcgacg ccgctaggac 1560
cgacttcagc accatgcctg tgaccaagtt ctggatcaag tgcctgcagt cttatcctgt 1620
gctgagcgaa accgtgctgc ggctgctgct gcccttcccc accacctacc tgtgtgaaac 1680
aggattttct tctctgctcg ttatcaagtc gaaatataga agccggctgg tggtcgaaga 1740
tgaccttcgg tgcgcgctgg ccaaaacagc ccctagaatc tccgatctgg tccggaagaa 1800
acagagccag cctagccact gataactcga g 1831
<210> 37
<211> 602
<212> PRT
<213> 人工序列
<400> 37
Met Thr Met Asp Arg Val Glu Lys Asn Val Lys Lys Arg Lys Tyr Ser
1 5 10 15
Glu Asp Phe Leu Gln Tyr Gly Phe Thr Ser Ile Ile Thr Ala Gly Ile
20 25 30
Glu Lys Pro Gln Cys Val Ile Cys Cys Glu Val Leu Ser Ala Glu Ser
35 40 45
Met Lys Pro Asn Lys Leu Lys Arg His Phe Asp Ser Lys His Pro Ser
50 55 60
Phe Ala Gly Lys Asp Thr Asn Tyr Phe Arg Ser Lys Ala Asp Gly Leu
65 70 75 80
Lys Lys Ala Arg Leu Asp Thr Gly Gly Lys Tyr His Lys Gln Asn Val
85 90 95
Ala Ala Ile Glu Ala Ser Tyr Leu Val Ala Leu Arg Ile Ala Arg Ala
100 105 110
Met Lys Pro His Thr Ile Ala Glu Asp Leu Leu Leu Pro Ala Ala Lys
115 120 125
Asp Ile Val Arg Val Met Ile Gly Asp Glu Phe Val Thr Lys Leu Ser
130 135 140
Ala Ile Ser Leu Ser Asn Asp Thr Val Arg Arg Arg Ile Asp Asp Met
145 150 155 160
Ser Ala Asp Ile Leu Asp Gln Val Ile Gln Glu Ile Lys Ser Ala Pro
165 170 175
Leu Pro Ile Phe Ser Ile Gln Leu Asp Glu Ser Thr Asp Val Ala Asn
180 185 190
Cys Ser Gln Leu Leu Val Tyr Val Arg Tyr Ile Asn Asp Gly Asp Phe
195 200 205
Lys Asp Glu Phe Leu Phe Cys Lys Pro Leu Glu Met Thr Thr Thr Ala
210 215 220
Arg Asp Val Phe Asp Thr Val Gly Ser Phe Leu Lys Glu His Lys Ile
225 230 235 240
Ser Trp Glu Lys Val Cys Gly Val Cys Thr Asp Gly Ala Pro Ala Met
245 250 255
Leu Gly Cys Arg Ser Gly Phe Gln Arg Leu Val Leu Asn Glu Ser Pro
260 265 270
Lys Val Ile Gly Thr His Cys Met Ile His Arg Gln Ile Leu Ala Thr
275 280 285
Lys Thr Leu Pro Gln Glu Leu Gln Glu Val Met Lys Ser Val Ile Ser
290 295 300
Ser Val Asn Phe Val Lys Ala Ser Thr Leu Asn Ser Arg Leu Phe Ser
305 310 315 320
Gln Leu Cys Asn Glu Leu Asp Ala Pro Asn Asn Ala Leu Leu Phe His
325 330 335
Thr Glu Val Arg Trp Leu Ser Arg Gly Lys Val Leu Lys Arg Val Phe
340 345 350
Glu Leu Arg Asp Glu Leu Lys Thr Phe Phe Asn Gln Lys Ala Arg Pro
355 360 365
Gln Phe Glu Ala Leu Phe Ser Asp Lys Ser Glu Leu Gln Lys Ile Ala
370 375 380
Tyr Leu Val Asp Ile Phe Ala Ile Leu Asn Glu Leu Asn Leu Ser Leu
385 390 395 400
Gln Gly Pro Asn Ala Thr Cys Leu Asp Leu Ser Glu Lys Ile Arg Ser
405 410 415
Phe Gln Met Lys Leu Gln Leu Trp Gln Lys Lys Leu Asp Glu Asn Lys
420 425 430
Ile Tyr Met Leu Pro Thr Leu Ser Ala Phe Phe Glu Glu His Asp Ile
435 440 445
Glu Pro Asp Lys Arg Ile Thr Met Ile Ile Ser Val Lys Glu His Leu
450 455 460
His Met Leu Ala Asp Glu Ile Ser Ser Tyr Phe Pro Asn Leu Pro Asp
465 470 475 480
Thr Pro Phe Ala Leu Ala Arg Ser Pro Phe Thr Val Lys Val Glu Asp
485 490 495
Val Pro Glu Thr Ala Gln Glu Glu Phe Ile Glu Leu Ile Asn Ser Asp
500 505 510
Ala Ala Arg Thr Asp Phe Ser Thr Met Pro Val Thr Lys Phe Trp Ile
515 520 525
Lys Cys Leu Gln Ser Tyr Pro Val Leu Ser Glu Thr Val Leu Arg Leu
530 535 540
Leu Leu Pro Phe Pro Thr Thr Tyr Leu Cys Glu Thr Gly Phe Ser Ser
545 550 555 560
Leu Leu Val Ile Lys Ser Lys Tyr Arg Ser Arg Leu Val Val Glu Asp
565 570 575
Asp Leu Arg Cys Ala Leu Ala Lys Thr Ala Pro Arg Ile Ser Asp Leu
580 585 590
Val Arg Lys Lys Gln Ser Gln Pro Ser His
595 600
<210> 38
<211> 250
<212> DNA
<213> 人工序列
<400> 38
cagcggttct caacctgtgg gtcgcgaccc ctttgggggt caaacgaccc tttcacaggg 60
gtcgcctaag accatcggaa aacacatatt tccgatggtc ttaggaaccg agacaccgct 120
cctctatccg tctccaggcg ggtccgccca catgcagata cgcccacata bgagtacccg 180
gcgtgatgac atcatcgcgc caaccccatc acatacaccc cgtacaaata caggtgtatg 240
tgacagggtt 250
<210> 39
<211> 250
<212> DNA
<213> 人工序列
<400> 39
gtaattagaa ataaatattt cacaatatat aattacatat tgtttttgtg attaatcact 60
atgctttaat tatgttcaat ttgtaacaat gaaaatacat cctgcatatc agatatttac 120
attacgattc ataacagtag caaaattaca gttatgaagt agcaacgaaa ataattttat 180
ggttgggggt caccacaaca tgaggaactg tattaaaggg tcgcggcatt aggaaggttg 240
agaaccactg 250
<210> 40
<211> 808
<212> DNA
<213> 人工序列
<400> 40
gcggccgcct ttaacacagc ggttctcaac ctgtgggtcg cgaccccttt gggggtcaaa 60
cgaccctttc acaggggtcg cctaagacca tcggaaaaca catatttccg atggtcttag 120
gaaccgagac accgctcctc tatccgtctc caggcgggtc cgcccacatg cagatacgcc 180
cacatacgag tacccggcgt gatgacatca tcgcgccaac cccatcacat acaccccgta 240
caaatacagg tgtatgtgac agggttggcg ccataatgta cttatgcgga ccagtcacac 300
atgtgtagag agcagctact gtgtagaaag cagctactgt gttgaaagca gctactctgt 360
taaaagcagc tactgtgttg aaagcagcag tattggaggt aaaacctgca ggtacgatca 420
agcggcgcgc ccgttggctt tttacgcata ctgttgcaaa atgtagcaat gtagtttact 480
gttgttatat taagactgtt acccatgcta caccatgctt caagacaaaa tttcatttat 540
ttgtaattag aaataaatat ttcacaatat ataattacat attgtttttg tgattaatca 600
ctatgcttta attatgttca atttgtaaca atgaaaatac atcctgcata tcagatattt 660
acattacgat tcataacagt agcaaaatta cagttatgaa gtagcaacga aaataatttt 720
atggttgggg gtcaccacaa catgaggaac tgtattaaag ggtcgcggca ttaggaaggt 780
tgagaaccac tgctttaaca gcgatcgc 808
<210> 41
<211> 1933
<212> DNA
<213> 人工序列
<400> 41
aatcgatgcc accatgatgc tgaattggct gaagtctgga aagctggaaa gccagagcca 60
ggagcagagc agctgctacc tggaaaattc taactgcctg ccccccacac tggacagcac 120
cgacatcatc ggcgaagaga acaaggccgg tacaaccagc cggaagaaaa gaaagtacga 180
cgaggactac ctgaacttcg gattcacctg gaccggcgac aaggacgagc ctaacggcct 240
gtgtgtgatc tgcgaacagg tggtgaacaa cagctccctg aatcctgcca aactgaaacg 300
gcacctggat acgaaacacc ctaccctgaa gggcaagtca gagtacttca agagaaagtg 360
caacgagctg aaccagaaaa agcacacctt tgagagatac gtcagagatg acaacaagaa 420
tctgttaaaa gcctcttatc tggtgtccct gagaatcgct aagcagggcg aagcgtacac 480
catcgccgag aaactgatca agccttgcac caaggacctg accacctgcg tgttcggcga 540
gaagttcgca agcaaggtgg acctggtgcc cctgagcgcc accaccatca gccgaagaat 600
cgaggacatg agctacttct gtgaggccgt gctggtcaac aggctgaaga atgccaagtg 660
tggctttacc cttcagatgg acgagtccac cgacgtggcc ggcctggcta tcctgctggt 720
gtttgtgcgg tacatccacg agagctcttt cgaagaggat atgctgttct gcaaggccct 780
gcctacacag accacaggcg aggaaatctt caacctgctg aacgcttact ttgagaagca 840
cagcatccct tggaacctgt gttaccacat ctgtaccgat ggagccaagg ctatggtggg 900
cgtgatcaag ggagttatcg ctagaatcaa gaagctggtg ccagatatca aagctagcca 960
ctgctgcctg cacagacacg ccctggccgt caagcggatc cccaatgccc tgcatgaggt 1020
gctgaacgat gccgtgaaga tgatcaactt catcaagtct agacctctga acgccagagt 1080
gttcgccctg ctgtgcgacg atctgggctc cctgcataag aacctgctgc tgcacacaga 1140
aacccggtgg ctcagccggg gcaaggtgct gacaagattc tgggagctga gagacgagat 1200
ccgcatcttt ttcaacgagc gggagttcgc cggcaagctg aacgacacca gctggctgca 1260
gaacctagcc tacatcgccg atatcttcag ctatctgaat gaagtgaacc tgagcctgca 1320
aggccctaat tccaccattt tcaaggtgaa cagcagaatc aatagcatca aaagcaagct 1380
gaagctctgg gaggaatgca tcacaaagaa caacaccaag tgcttcgcca acctgaacga 1440
tttcttagaa acctccaaca cagccctgga ccccaatctc aaaagcaata tcctggagca 1500
cctgaacggc ctgaaaaaca ccttcctgga atactttcca cctacatgca acaacatcag 1560
ctgggtggaa aaccccttca acgagtgcgg caacgtggac acactgccta tcaaggaacg 1620
ggagcagcta atcgacatca gaaccgacac cacactgaag tcttcttttg ttcctgacgg 1680
catcggacct ttctggatca agctgatgga tgaattcccc gagatttcta agagagccgt 1740
gaaggaactg atgccttttg tgaccactta cctgtgcgag aagagcttca gcgtgtacgt 1800
ggccacaaag accaaataca gaaaccggct ggacgccgag gacgacatga gactgcaact 1860
gaccacaatc cacccagata ttgataacct gtgtaacaac aaacaggccc agaagtctca 1920
ctgataactc gag 1933
<210> 42
<211> 636
<212> PRT
<213> 人工序列
<400> 42
Met Met Leu Asn Trp Leu Lys Ser Gly Lys Leu Glu Ser Gln Ser Gln
1 5 10 15
Glu Gln Ser Ser Cys Tyr Leu Glu Asn Ser Asn Cys Leu Pro Pro Thr
20 25 30
Leu Asp Ser Thr Asp Ile Ile Gly Glu Glu Asn Lys Ala Gly Thr Thr
35 40 45
Ser Arg Lys Lys Arg Lys Tyr Asp Glu Asp Tyr Leu Asn Phe Gly Phe
50 55 60
Thr Trp Thr Gly Asp Lys Asp Glu Pro Asn Gly Leu Cys Val Ile Cys
65 70 75 80
Glu Gln Val Val Asn Asn Ser Ser Leu Asn Pro Ala Lys Leu Lys Arg
85 90 95
His Leu Asp Thr Lys His Pro Thr Leu Lys Gly Lys Ser Glu Tyr Phe
100 105 110
Lys Arg Lys Cys Asn Glu Leu Asn Gln Lys Lys His Thr Phe Glu Arg
115 120 125
Tyr Val Arg Asp Asp Asn Lys Asn Leu Leu Lys Ala Ser Tyr Leu Val
130 135 140
Ser Leu Arg Ile Ala Lys Gln Gly Glu Ala Tyr Thr Ile Ala Glu Lys
145 150 155 160
Leu Ile Lys Pro Cys Thr Lys Asp Leu Thr Thr Cys Val Phe Gly Glu
165 170 175
Lys Phe Ala Ser Lys Val Asp Leu Val Pro Leu Ser Asp Thr Thr Ile
180 185 190
Ser Arg Arg Ile Glu Asp Met Ser Tyr Phe Cys Glu Ala Val Leu Val
195 200 205
Asn Arg Leu Lys Asn Ala Lys Cys Gly Phe Thr Leu Gln Met Asp Glu
210 215 220
Ser Thr Asp Val Ala Gly Leu Ala Ile Leu Leu Val Phe Val Arg Tyr
225 230 235 240
Ile His Glu Ser Ser Phe Glu Glu Asp Met Leu Phe Cys Lys Ala Leu
245 250 255
Pro Thr Gln Thr Thr Gly Glu Glu Ile Phe Asn Leu Leu Asn Ala Tyr
260 265 270
Phe Glu Lys His Ser Ile Pro Trp Asn Leu Cys Tyr His Ile Cys Thr
275 280 285
Asp Gly Ala Lys Ala Met Val Gly Val Ile Lys Gly Val Ile Ala Arg
290 295 300
Ile Lys Lys Leu Val Pro Asp Ile Lys Ala Ser His Cys Cys Leu His
305 310 315 320
Arg His Ala Leu Ala Val Lys Arg Ile Pro Asn Ala Leu His Glu Val
325 330 335
Leu Asn Asp Ala Val Lys Met Ile Asn Phe Ile Lys Ser Arg Pro Leu
340 345 350
Asn Ala Arg Val Phe Ala Leu Leu Cys Asp Asp Leu Gly Ser Leu His
355 360 365
Lys Asn Leu Leu Leu His Thr Glu Val Arg Trp Leu Ser Arg Gly Lys
370 375 380
Val Leu Thr Arg Phe Trp Glu Leu Arg Asp Glu Ile Arg Ile Phe Phe
385 390 395 400
Asn Glu Arg Glu Phe Ala Gly Lys Leu Asn Asp Thr Ser Trp Leu Gln
405 410 415
Asn Leu Ala Tyr Ile Ala Asp Ile Phe Ser Tyr Leu Asn Glu Val Asn
420 425 430
Leu Ser Leu Gln Gly Pro Asn Ser Thr Ile Phe Lys Val Asn Ser Arg
435 440 445
Ile Asn Ser Ile Lys Ser Lys Leu Lys Leu Trp Glu Glu Cys Ile Thr
450 455 460
Lys Asn Asn Thr Glu Cys Phe Ala Asn Leu Asn Asp Phe Leu Glu Thr
465 470 475 480
Ser Asn Thr Ala Leu Asp Pro Asn Leu Lys Ser Asn Ile Leu Glu His
485 490 495
Leu Asn Gly Leu Lys Asn Thr Phe Leu Glu Tyr Phe Pro Pro Thr Cys
500 505 510
Asn Asn Ile Ser Trp Val Glu Asn Pro Phe Asn Glu Cys Gly Asn Val
515 520 525
Asp Thr Leu Pro Ile Lys Glu Arg Glu Gln Leu Ile Asp Ile Arg Thr
530 535 540
Asp Thr Thr Leu Lys Ser Ser Phe Val Pro Asp Gly Ile Gly Pro Phe
545 550 555 560
Trp Ile Lys Leu Met Asp Glu Phe Pro Glu Ile Ser Lys Arg Ala Val
565 570 575
Lys Glu Leu Met Pro Phe Val Thr Thr Tyr Leu Cys Glu Lys Ser Phe
580 585 590
Ser Val Tyr Val Ala Thr Lys Thr Lys Tyr Arg Asn Arg Leu Asp Ala
595 600 605
Glu Asp Asp Met Arg Leu Gln Leu Thr Thr Ile His Pro Asp Ile Asp
610 615 620
Asn Leu Cys Asn Asn Lys Gln Ala Gln Lys Ser His
625 630 635
<210> 43
<211> 328
<212> DNA
<213> 人工序列
<400> 43
cagtgttctt caacctgtgt tccgcggaac cctagggttc cacccaaagg ctttcggggt 60
tccgcgagtc attgcttcaa ttcgagagac gtcggccgcg ccgctcttca gaatgcacat 120
gcgtcaatcg gagtttcatg ttgaaacatg ttatccattc gcatagttga cttacactgc 180
acttaacctt aattttcaaa aatatgtaac tgtacttgtg gtcgtagttt tgttgttgtt 240
tttggtttag acaagcaaag gtaagttaac ttacagtttt aaaataaatt gtattttgtt 300
tgatcctaac ctagaatcgt tcagaaat 328
<210> 44
<211> 458
<212> DNA
<213> 人工序列
<400> 44
tatatctatg atctcgcagt ctccggcgag caccggaggc agggcattgc caccgcgctc 60
atcaatctcc tcaagcatga ggccaacgcg cttggtgctt atgtgatcta cgtgcaagca 120
gattacggtg acgatcccgc agtggctctc tatacaaagt tgggcatacg ggaagaagtg 180
atgcactttg atatcgaccc aagtaccgcc acctaacaat tcgttcaagc cgagatcggc 240
ttcccggccg cggagttgtt cggtaaattg tcacaacgcc gcgaatatag tctttaccat 300
gcccttggct agaccaaagc acgggctcac cttgttcgta acaagtcaac gcagctgtcc 360
ctaaaatctc atctgggtgt attactaaat gaagggttcc ataaaaaaaa atatctcgac 420
aaagggttcc gccggatggc aaaggttgaa gaacactg 458
<210> 45
<211> 845
<212> DNA
<213> 人工序列
<400> 45
gcggccgctc ctagatcagt gttcttcaac ctgtgttccg cggaacccta gggttccacc 60
caaaggcttt cggggttccg cgagtcattg cttcaattcg agagacgtcg gccgcgccgc 120
tcttcagaat gcacatgcgt caatcggagt ttcatgttga aacatgttat ccattcgcat 180
agttgactta cactgcactt aaccttaatt ttcaaaaata tgtaactgta cttgtggtcg 240
tagttttgtt gttgtttttg gtttagacaa gcaaaggtaa gttaacttac agttttaaaa 300
taaattgtat tttgtttgat cctaacctag aatcgttcag aaatcctgca ggtacgatca 360
agcggcgcgc ctatatctat gatctcgcag tctccggcga gcaccggagg cagggcattg 420
ccaccgcgct catcaatctc ctcaagcatg aggccaacgc gcttggtgct tatgtgatct 480
acgtgcaagc agattacggt gacgatcccg cagtggctct ctatacaaag ttgggcatac 540
gggaagaagt gatgcacttt gatatcgacc caagtaccgc cacctaacaa ttcgttcaag 600
ccgagatcgg cttcccggcc gcggagttgt tcggtaaatt gtcacaacgc cgcgaatata 660
gtctttacca tgcccttggc tagaccaaag cacgggctca ccttgttcgt aacaagtcaa 720
cgcagctgtc cctaaaatct catctgggtg tattactaaa tgaagggttc cataaaaaaa 780
aatatctcga caaagggttc cgccggatgg caaaggttga agaacactgt cctagatgcg 840
atcgc 845
<210> 46
<211> 328
<212> DNA
<213> 人工序列
<400> 46
cagtgttctt caacctgtgt tccgcggaac cctagggttc cacccaaagg ctttcggggt 60
tccgcgagtc attgcttcaa ttcgagagac gtcggccgcg ccgctcttca gaatgcacat 120
gcgtcaatcg gagtttcatg ttgaaacatg ttatccattc gcatagttga cttacactgc 180
acttaacctt aattttcaaa aatatgtaac tgtacttgtg gtcgtagttt tgttgttgtt 240
ttaggtttag acaagcaaag gtaagttaac ttacagtttt aaaataaatt gtattttgtt 300
tgatcctaac ctagaatcgt tcagaaat 328
<210> 47
<211> 250
<212> DNA
<213> 人工序列
<400> 47
tttttatttt ttattttata tattatttta tttggaatat ttatcttttt gtttaaagtt 60
tgtttaaata aatgcaaatt taaatcttat ttagagtttt tattaccaaa gcacgggctc 120
accttgttcg taacaagtca acgcagctgt ccctaaaatc tcatctgggt gtattactaa 180
atgaagggtt ccataaaaaa aaatatctcg acaaagggtt ccgccggatg gcaaaggttg 240
aagaacactg 250
<210> 48
<211> 637
<212> DNA
<213> 人工序列
<400> 48
gcggccgctc ctagatcagt gttcttcaac ctgtgttccg cggaacccta gggttccacc 60
caaaggcttt cggggttccg cgagtcattg cttcaattcg agagacgtcg gccgcgccgc 120
tcttcagaat gcacatgcgt caatcggagt ttcatgttga aacatgttat ccattcgcat 180
agttgactta cactgcactt aaccttaatt ttcaaaaata tgtaactgta cttgtggtcg 240
tagttttgtt gttgttttag gtttagacaa gcaaaggtaa gttaacttac agttttaaaa 300
taaattgtat tttgtttgat cctaacctag aatcgttcag aaatcctgca ggtacgatca 360
agcggcgcgc ctttttattt tttattttat atattatttt atttggaata tttatctttt 420
tgtttaaagt ttgtttaaat aaatgcaaat ttaaatctta tttagagttt ttattaccaa 480
agcacgggct caccttgttc gtaacaagtc aacgcagctg tccctaaaat ctcatctggg 540
tgtattacta aatgaagggt tccataaaaa aaaatatctc gacaaagggt tccgccggat 600
ggcaaaggtt gaagaacact gtcctagatg cgatcgc 637
<210> 49
<211> 1042
<212> DNA
<213> 人工序列
<400> 49
aatcgatgcc accatgaaga caaaggaact gacaaagcaa gtgagagata aggtggtgga 60
aaagtatgag gccggcctgg gctacaagaa gatcagcaga gccctgaata tcagcctgtc 120
tacaattaag tctatcatcc ggaagtggaa agagtacggc accacagcca acctgcctag 180
aggcggacgg ccaccaaagc tcaagagcag aacccggaga aaactcatca gagaggccac 240
aagacggcct atggtcaccc tggaagagct gcagagaagc acagccgagg tgggcgagtc 300
tgtgcaccgg accaccatct cccgcctgct gcataagtcc ggcctgtacg gcagagtggc 360
ccggcggaag cctctgctga aaggcatcca caagaagagc agactggaat tcgccagaag 420
ccacgtgggc gacaccgcta acatgtggaa gaaagtgctg tggagcgacg agacaaagat 480
cgagctgttt ggcctgaacg ctaagcggta cgtgtggcgg aaacctaaca ccgcccacca 540
ccccgagcac accatcccca ccgtgaaaca cggaggagga agcattatgc tgtggggctg 600
cttcagcagc gccggaaccg gcaagctggt tagaatcgag ggcaaaatgg acggcgccaa 660
gtaccgggaa atcctggaag agaacctgat gcagtccgcc aaagacctga gactgggcag 720
aaggtttatc ttccagcagg acaacgaccc caagcacact gctagagcca ccaaggaatg 780
gttcggactg aagaacgtga acgtgctgaa gtggcctagc cagagccctg atctgaatcc 840
tatcgagaat ctgtggcagg atctgaagat cgctgtccac agaagatctc ctagcaacct 900
gaccgagctg cacctgttct gccaggagga atggaccaac ctcagcatct ctaggtgtgc 960
caagctggtg gaaacctacc ccaagagact ggccgccgtg atcgccgcta agggcggcag 1020
caccaaatac tgataactcg ag 1042
<210> 50
<211> 339
<212> PRT
<213> 人工序列
<400> 50
Met Lys Thr Lys Glu Leu Thr Lys Gln Val Arg Asp Lys Val Val Glu
1 5 10 15
Lys Tyr Glu Ala Gly Leu Gly Tyr Lys Lys Ile Ser Arg Ala Leu Asn
20 25 30
Ile Ser Leu Ser Thr Ile Lys Ser Ile Ile Arg Lys Trp Lys Glu Tyr
35 40 45
Gly Thr Thr Ala Asn Leu Pro Arg Gly Gly Arg Pro Pro Lys Leu Lys
50 55 60
Ser Arg Thr Arg Arg Lys Leu Ile Arg Glu Ala Thr Arg Arg Pro Met
65 70 75 80
Val Thr Leu Glu Glu Leu Gln Arg Ser Thr Ala Glu Val Gly Glu Ser
85 90 95
Val His Arg Thr Thr Ile Ser Arg Leu Leu His Lys Ser Gly Leu Tyr
100 105 110
Gly Arg Val Ala Arg Arg Lys Pro Leu Leu Lys Gly Ile His Lys Lys
115 120 125
Ser Arg Leu Glu Phe Ala Arg Ser His Val Gly Asp Thr Ala Asn Met
130 135 140
Trp Lys Lys Val Leu Trp Ser Asp Glu Thr Lys Ile Glu Leu Phe Gly
145 150 155 160
Leu Asn Ala Lys Arg Tyr Val Trp Arg Lys Pro Asn Thr Ala His His
165 170 175
Pro Glu His Thr Ile Pro Thr Val Lys His Gly Gly Gly Ser Ile Met
180 185 190
Leu Trp Gly Cys Phe Ser Ser Ala Gly Thr Gly Lys Leu Val Arg Ile
195 200 205
Glu Gly Lys Met Asp Gly Ala Lys Tyr Arg Glu Ile Leu Glu Glu Asn
210 215 220
Leu Met Gln Ser Ala Lys Asp Leu Arg Leu Gly Arg Arg Phe Ile Phe
225 230 235 240
Gln Gln Asp Asn Asp Pro Lys His Thr Ala Arg Ala Thr Lys Glu Trp
245 250 255
Phe Gly Leu Lys Asn Val Asn Val Leu Lys Trp Pro Ser Gln Ser Pro
260 265 270
Asp Leu Asn Pro Ile Glu Asn Leu Trp Gln Asp Leu Lys Ile Ala Val
275 280 285
His Arg Arg Ser Pro Ser Asn Leu Thr Glu Leu His Leu Phe Cys Gln
290 295 300
Glu Glu Trp Thr Asn Leu Ser Ile Ser Arg Cys Ala Lys Leu Val Glu
305 310 315 320
Thr Tyr Pro Lys Arg Leu Ala Ala Val Ile Ala Ala Lys Gly Gly Ser
325 330 335
Thr Lys Tyr
<210> 51
<211> 385
<212> DNA
<213> 人工序列
<400> 51
tacagtgcct tgcataagta ttcaccccct ttggactttt ctacattttg tcatgctata 60
accacagatt aaaatttatt tcatcgtgag tttatgtaat ggaccaacac aaaatagtgc 120
atcatttgga agtgggggga aatattacat ggatttcaca attatttaca aataaaaatc 180
tgaaaagtgt tgagtgcata tgtattcacc ccctttactg tgaaacccct aacaaagatc 240
tggtgcgacc aattgcattc acaagtcaca tttgcaagtc acataattag taaatagggt 300
ccacctgtct gcaatttaat ctcagtataa atacacctgt tctgtgacgg actcagagtt 360
tgttggagat cattactgaa caaac 385
<210> 52
<211> 237
<212> DNA
<213> 人工序列
<400> 52
ggttctacca agtattgaca caggggggtg aatacttatg cacccaacag atgtcaactt 60
ttttgttctc attattgttt gtgtcacaat aaaatttatt ttgcacctcc aaagtactat 120
gcatgttttg ttgatcaaac gggaaaaagt ttatttaagt ctatttgaat tccagttagt 180
aacagtacat aatgggaaaa agtccaaggg gggtgaatac ttatgcaagg cactgta 237
<210> 53
<211> 669
<212> DNA
<213> 人工序列
<400> 53
gcggccgcta tacagtgcct tgcataagta ttcaccccct ttggactttt ctacattttg 60
tcatgctata accacagatt aaaatttatt tcatcgtgag tttatgtaat ggaccaacac 120
aaaatagtgc atcatttgga agtgggggga aatattacat ggatttcaca attatttaca 180
aataaaaatc tgaaaagtgt tgagtgcata tgtattcacc ccctttactg tgaaacccct 240
aacaaagatc tggtgcgacc aattgcattc acaagtcaca tttgcaagtc acataattag 300
taaatagggt ccacctgtct gcaatttaat ctcagtataa atacacctgt tctgtgacgg 360
actcagagtt tgttggagat cattactgaa caaaccctgc aggtacgatc aagcggcgcg 420
ccggttctac caagtattga cacagggggg tgaatactta tgcacccaac agatgtcaac 480
ttttttgttc tcattattgt ttgtgtcaca ataaaattta ttttgcacct ccaaagtact 540
atgcatgttt tgttgatcaa acgggaaaaa gtttatttaa gtctatttga attccagtta 600
gtaacagtac ataatgggaa aaagtccaag gggggtgaat acttatgcaa ggcactgtat 660
agcgatcgc 669
<210> 54
<211> 1903
<212> DNA
<213> 人工序列
<400> 54
aatcgatgcc accatggccc ctaagaaaaa gagaaaggtg ggcatccacg gcgtgcccgc 60
tgccgacatc gagagacagg aagagagaat tagagccatg ctggaagagg agctgtcaga 120
ttacagcgat gaatccagca gcgaagatga aacagatcac tgtagcgagc acgaggtgaa 180
ttacgacacc gaggaagaga gaatcgactc cgtcgacgtg ccatctaatt ctagacaaga 240
agaggccaat gccatcatcg ccaacgaatc cgacagcgac cctgatgatg atctgcctct 300
gagcctcgtg cggcagagag cctccgcctc tagacaggtg tccggcccct tctatacaag 360
caaggacggc accaagtggt acaagaattg ccagcgccca aatgtgcggc tgagatctga 420
gaacatcgtg acagaacagg cccaggtgaa gaatatagcc agagatgcca gcaccgaata 480
cgagtgctgg aacatcttcg tgaccagcga tatgctgcag gaaatcctga cccacaccaa 540
ctccagcatc agacaccggc agaccaagac cgccgctgag aacagcagcg ccgagacaag 600
cttctacatg caggagacca ccctgtgtga actgaaggcc ctgatcgctc tgctgtacct 660
ggccgggctg atcaagagca acagacagtc tctcaaggac ctgtggcgga cagacggcac 720
cggcgtggac atctttcgga caacaatgtc cctgcagaga ttccagtttc tgcagaacaa 780
catcaggttc gacgacaaga gcacgagaga cgagagaaag caaaccgaca acatggctgc 840
cttccgcagc atcttcgacc agttcgtgca gtgctgccag aatgcctact ctcctagcga 900
gttcctaaca atcgacgaga tgctgctgag cttccggggc agatgcctgt ttcgggtgta 960
catccctaac aaacctgcta agtacggcat caagatcctg gccctggtgg acgccaagaa 1020
tttctacgtg gtcaacctgg aagtctacgc tggcaagcag cccagcggac cttacgccgt 1080
gagcaacaga cctttcgagg ttgtggaaag gctgattcag cccgtggcca gaagccaccg 1140
gaacgtgacc ttcgataact ggttcaccgg ctacgagctg atgctgcatc tgctcaacga 1200
gtatagactg acctctgtcg gaaccgtgag aaagaacaag agacagatcc ccgagagctt 1260
tatccgcacc gacagacagc ctaacagcag cgttttcggc ttccaaaagg acatcaccct 1320
ggtgtcctac gcccctaaga agaacaaagt ggtggtggtg atgagcacaa tgcaccacga 1380
caacagcatc gacgagtcta ccggagagaa gcagaaacct gagatgatca ccttttacaa 1440
cagcacaaag gccggcgtgg acgtggtcga tgagctgtgc gctaactaca acgtgagtag 1500
aaattctaag cggtggccca tgaccctctt ctatggcgtg ctgaacatgg ccgctatcaa 1560
cgcctgcatc atctaccgga caaacaaaaa cgtgaccatc aaaagaacag agttcatcag 1620
aagcctgggc ctgtctatga tctacgagca cctgcacagc cggaacaaga agaagaacat 1680
ccccacctac ctgcggcaac ggattgaaaa acagctgggc gagccttccc caagacacgt 1740
gaacgtgcct ggaagatacg tgaggtgtca ggactgcccc tacaagaaag accggaagac 1800
aaaaagatct tgtaacgcct gtgctaaacc tatctgcatg gaacatgcca agttcctgtg 1860
cgaaaactgc gccgaactgg acagcagcct gtgataactc gag 1903
<210> 55
<211> 1903
<212> DNA
<213> 人工序列
<400> 55
aatcgatgcc accatggctc ctaaaaagaa aagaaaagtg ggcatccacg gcgtgcctgc 60
cgctgatatc gagcggcagg aggaacggat tagagccatg ctggaagaag aactgagcga 120
ctacagcgac gagtctagtt ctgaagatga gacagaccac tgcagcgaac acgaggtgaa 180
ctacgacacc gaggaagaga gaatcgacag cgtcgatgtg ccatctaaca gcagacagga 240
ggaggccaac gccatcatcg ccaatgaaag cgacagcgac cccgacgacg acctgcctct 300
gagcctggtc cggcaacggg ccagcgcttc tcgccagatg agcggcccgc actacacatc 360
taaggatggc accaagtggt acaagaactg tcagaggcct aatgtgcggc tcagaagcga 420
gaacatcgtg accgagcagg cccaggtgaa gaacatcgcc agagacgcct ccacagagta 480
cgagtgctgg aacatcttcg tgaccagcga tatgctgcaa gaaatcctga cccacaccaa 540
ctctagcatc agatggagac agacaaagac cgccgctgaa aactcctccg cctctaccag 600
cttttacatg caggagacaa ccctgtgtga actgaaggcc ctgataggac tgctgtacat 660
cgcaggcctg attaagtcca acagacagag cctgaaagac ctgtggcgga ccgacggcac 720
cggcgtggac attttcagaa ccacaatgag cctgcagaga ttccagtttc tgcagaacaa 780
catccggttc gacgataaga gcacacggga tgagagaaag cagaccgaca acatggccgc 840
cttcagatct atcttcgacc agttcgtgca gagctgccag aatgcctaca gtcctagcga 900
attcctgacc atcgacgaga tgctgctgag cttccgggga agatgcctgt tcagagtgta 960
catcccaaac aagcctgcca agtacggcat caagatcctt gctctggtgg atgccaagaa 1020
cttctacgtg aaaaatctgg aagtctacgc cggcaagcag cccagcggcc cttatgctgt 1080
gtctaataga cctttcgagg ttgtggaaag actgatccag cccgtggcca gaagccacag 1140
aaatgtgact tttgataact ggttcaccgg ctacgaactg atgctgcatc tcctaaacga 1200
gtacagactg accagcgtgg gcacagtgcg caagaataag agacagatcc ccgagtcatt 1260
catcagaaca gataggcagc ctaactctag cgttttcggc ttccaaaagg acatcaccct 1320
ggtcagctac gcccctaaga agaacaaggt ggtggtggtg atgagcacca tgcaccacga 1380
caacagcatc gacgagagca caggcgagaa gcagaaacct gagatgatca ccttttataa 1440
cagcaccaag gccggagtgg acgtggtgga cgagctgtgc gccaactata acgtgtccag 1500
aaacagcaag agatggccta tgaccctgtt ttacggagtg ctgaacatgg ccgccatcaa 1560
cgcctgtatc atctaccgga caaacaaaaa cgttacaatc aagcggaccg agttcatcag 1620
atccctgggc ctgagcatga tctacgagca tctgcacagc agaaacaaga agaaaaatat 1680
ccctacctac ctgcggcaac ggatcgagaa gcagctgggc gaaccttccc ccagacacgt 1740
gaacgtgcct ggtagatacg tgcggtgcca ggactgcccc tacaagaagg atagaaaaac 1800
caagcggtca tgcaacgcct gcgccaagcc catctgtatg gaacacgcca aattcctgtg 1860
cgagaattgc gctgagctgg actcccacct gtgataactc gag 1903
<210> 56
<211> 610
<212> PRT
<213> 人工序列
<400> 56
Met Asp Ile Glu Arg Gln Glu Glu Arg Ile Arg Ala Met Leu Glu Glu
1 5 10 15
Glu Leu Ser Asp Tyr Ser Asp Glu Ser Ser Ser Glu Asp Glu Thr Asp
20 25 30
His Cys Ser Glu His Glu Val Asn Tyr Asp Thr Glu Glu Glu Arg Ile
35 40 45
Asp Ser Val Asp Val Pro Ser Asn Ser Arg Gln Glu Glu Ala Asn Ala
50 55 60
Ile Ile Ala Asn Glu Ser Asp Ser Asp Pro Asp Asp Asp Leu Pro Leu
65 70 75 80
Ser Leu Val Arg Gln Arg Ala Ser Ala Ser Arg Gln Val Ser Gly Pro
85 90 95
Phe Tyr Thr Ser Lys Asp Gly Thr Lys Trp Tyr Lys Asn Cys Gln Arg
100 105 110
Pro Asn Val Arg Leu Arg Ser Glu Asn Ile Val Thr Glu Gln Ala Gln
115 120 125
Val Lys Asn Ile Ala Arg Asp Ala Ser Thr Glu Tyr Glu Cys Trp Asn
130 135 140
Ile Phe Val Thr Ser Asp Met Leu Gln Glu Ile Leu Thr His Thr Asn
145 150 155 160
Ser Ser Ile Arg His Arg Gln Thr Lys Thr Ala Ala Glu Asn Ser Ser
165 170 175
Ala Glu Thr Ser Phe Tyr Met Gln Glu Thr Thr Leu Cys Glu Leu Lys
180 185 190
Ala Leu Ile Ala Leu Leu Tyr Leu Ala Gly Leu Ile Lys Ser Asn Arg
195 200 205
Gln Ser Leu Lys Asp Leu Trp Arg Thr Asp Gly Thr Gly Val Asp Ile
210 215 220
Phe Arg Thr Thr Met Ser Leu Gln Arg Phe Gln Phe Leu Gln Asn Asn
225 230 235 240
Ile Arg Phe Asp Asp Lys Ser Thr Arg Asp Glu Arg Lys Gln Thr Asp
245 250 255
Asn Met Ala Ala Phe Arg Ser Ile Phe Asp Gln Phe Val Gln Cys Cys
260 265 270
Gln Asn Ala Tyr Ser Pro Ser Glu Phe Leu Thr Ile Asp Glu Met Leu
275 280 285
Leu Ser Phe Arg Gly Arg Cys Leu Phe Arg Val Tyr Ile Pro Asn Lys
290 295 300
Pro Ala Lys Tyr Gly Ile Lys Ile Leu Ala Leu Val Asp Ala Lys Asn
305 310 315 320
Phe Tyr Val Val Asn Leu Glu Val Tyr Ala Gly Lys Gln Pro Ser Gly
325 330 335
Pro Tyr Ala Val Ser Asn Arg Pro Phe Glu Val Val Glu Arg Leu Ile
340 345 350
Gln Pro Val Ala Arg Ser His Arg Asn Val Thr Phe Asp Asn Trp Phe
355 360 365
Thr Gly Tyr Glu Leu Met Leu His Leu Leu Asn Glu Tyr Arg Leu Thr
370 375 380
Ser Val Gly Thr Val Arg Lys Asn Lys Arg Gln Ile Pro Glu Ser Phe
385 390 395 400
Ile Arg Thr Asp Arg Gln Pro Asn Ser Ser Val Phe Gly Phe Gln Lys
405 410 415
Asp Ile Thr Leu Val Ser Tyr Ala Pro Lys Lys Asn Lys Val Val Val
420 425 430
Val Met Ser Thr Met His His Asp Asn Ser Ile Asp Glu Ser Thr Gly
435 440 445
Glu Lys Gln Lys Pro Glu Met Ile Thr Phe Tyr Asn Ser Thr Lys Ala
450 455 460
Gly Val Asp Val Val Asp Glu Leu Cys Ala Asn Tyr Asn Val Ser Arg
465 470 475 480
Asn Ser Lys Arg Trp Pro Met Thr Leu Phe Tyr Gly Val Leu Asn Met
485 490 495
Ala Ala Ile Asn Ala Cys Ile Ile Tyr Arg Thr Asn Lys Asn Val Thr
500 505 510
Ile Lys Arg Thr Glu Phe Ile Arg Ser Leu Gly Leu Ser Met Ile Tyr
515 520 525
Glu His Leu His Ser Arg Asn Lys Lys Lys Asn Ile Pro Thr Tyr Leu
530 535 540
Arg Gln Arg Ile Glu Lys Gln Leu Gly Glu Pro Ser Pro Arg His Val
545 550 555 560
Asn Val Pro Gly Arg Tyr Val Arg Cys Gln Asp Cys Pro Tyr Lys Lys
565 570 575
Asp Arg Lys Thr Lys Arg Ser Cys Asn Ala Cys Ala Lys Pro Ile Cys
580 585 590
Met Glu His Ala Lys Phe Leu Cys Glu Asn Cys Ala Glu Leu Asp Ser
595 600 605
Ser Leu
610
<210> 57
<211> 221
<212> DNA
<213> 人工序列
<400> 57
cccggcgagc atgaggcagg gtatctcata ccctggtaaa attttaaagt tgtgtatttt 60
ataaaatttt cgtctgacaa cactagcgcg ctcagtagct ggaggcagga gcgtgcggga 120
ggggatagtg gcgtgatcgc agtgtggcac gggacaccgg cgagatattc gtgtgcaaac 180
ctgtttcggg tatgttatac cctgcctcat tgttgacgta t 221
<210> 58
<211> 208
<212> DNA
<213> 人工序列
<400> 58
tttaagaaaa agattaataa ataataataa tttcataatt aaaaacttct ttcattgaat 60
gccattaaat aaaccattat tttacaaaat aagatcaaca taattgagta aataataata 120
agaacaatat tatagtacaa caaaatatgg gtatgtcata ccctgccaca ttcttgatgt 180
aacttttttt cacctcatgc tcgccggg 208
<210> 59
<211> 794
<212> DNA
<213> 人工序列
<400> 59
gcggccgctt aattatcccg gcgagcatga ggcagggtat ctcataccct ggtaaaattt 60
taaagttgtg tattttataa aattttcgtc tgacaacact agcgcgctca gtagctggag 120
gcaggagcgt gcgggagggg atagtggcgt gatcgcagtg tggcacggga caccggcgag 180
atattcgtgt gcaaacctgt ttcgggtatg ttataccctg cctcattgtt gacgtatttt 240
ttttatgtaa tttttccgat tattaatttc aactgtttta ttggtatttt tatgttatcc 300
attgttcttt ttttatgatt tactgtatcg gttgtctttc gttcctttag ttgagttttt 360
ttttattatt ttcagttttt gatcaaacct gcaggtacga tcaagcggcg cgcctcatat 420
ttttagttta aaaaaataat tatatgtttt ataatgaaaa gaatctcatt atctttcagt 480
attaggttga tttatattcc aaagaataat atttttgtta aattgttgat ttttgtaaac 540
ctctaaatgt ttgttgctaa aattactgtg tttaagaaaa agattaataa ataataataa 600
tttcataatt aaaaacttct ttcattgaat gccattaaat aaaccattat tttacaaaat 660
aagatcaaca taattgagta aataataata agaacaatat tatagtacaa caaaatatgg 720
gtatgtcata ccctgccaca ttcttgatgt aacttttttt cacctcatgc tcgccgggtt 780
atttaagcga tcgc 794
<210> 60
<211> 1840
<212> DNA
<213> 人工序列
<400> 60
aatcgatgcc accatggccc ctaagaaaaa gcggaaggtg ggcatccacg gcgtgcccgc 60
cgctgccaag agattctaca gcgccgaaga ggctgccgcc cactgcatgg cctcttccag 120
cgaagaattc agcggcagcg acagcgagta cgtgccacca gccagcgaga gcgacagcag 180
caccgaggaa agctggtgca gcagctctac tgtgtctgcc ctggaagaac ctatggaagt 240
ggacgaggac gtggacgacc tggaagatca ggaggctgga gatcgggccg acgccgccgc 300
tggcggcgag cctgcctggg gccctccttg caacttcccc ccagagatcc ctccattcac 360
caccgtgccc ggagttaagg ttgataccag caactttgag cctattaact tcttccagct 420
cttcatgacc gaggccatcc tgcaggacat ggtgctgtac acaaacgtgt acgccgagca 480
gtacctgacc cagaatcctc tgcctagata cgccagagca catgcctggc accctacaga 540
catcgccgag atgaagcgct tcgtgggcct gacactggcc atgggcctga tcaaggccaa 600
cagcctggaa agctactggg acaccacaac agtcctgtcc atccccgtgt tctctgctac 660
aatgagcaga aacagatacc agctgctgct gagatttctg cactttaaca acaatgccac 720
agccgtgcct cccgaccaac ctggccacga ccggctgcat aagctgagac ctctgattga 780
ttctctgagc gagagattcg ccgccgtcta cacaccctgc cagaacatct gcatcgacga 840
gtccctgctg ctgttcaagg gaagactgca atttagacag tacatcccca gcaagcgggc 900
ccgatacggc atcaagttct acaagctgtg cgagagctcc agcggctaca cgagctactt 960
cctgatctac gagggcaagg acagcaagct ggacccccca ggctgccctc ctgatctgac 1020
cgtgtcgggc aagatcgtgt gggagctgat cagccccctg ttgggccagg gcttccacct 1080
gtacgtggac aacttctatt ctagcatccc cctgtttacc gccctgtact gcctggatac 1140
acctgcttgt ggcacaatca acagaaatcg gaagggcctg cctagagccc tgctggacaa 1200
gaaactgaac agaggagaaa cctacgccct gcggaaaaac gagctgctcg ccatcaagtt 1260
tttcgataag aagaatgtgt tcatgctgac cagcatccac gatgagtcag tgatccggga 1320
acagagagtg ggcagacctc ctaaaaacaa gcctctgtgt tccaaggaat acagcaaata 1380
catgggaggc gtggacagaa ccgaccagct ccaacactac tacaacgcca ccaggaagac 1440
cagagcctgg tacaaaaaag tgggaatcta cctgatccag atggctttgc ggaactctta 1500
tatcgtgtac aaggccgctg tgcctggccc caagctttct tactacaagt accaactgca 1560
gatcctgccc gccctgctgt tcggcggagt cgaggaacag accgtgcctg agatgcctcc 1620
atctgataat gtggccagac tgataggaaa gcacttcatc gacacactgc ctcctacccc 1680
tggcaaacag cggcctcaga agggctgtaa agtgtgcaga aagcggggca ttcgcagaga 1740
tacccggtat tattgtccta agtgccccag aaaccccggc ctgtgcttca agccctgttt 1800
cgagatctac cacacccagc tgcactactg ataactcgag 1840
<210> 61
<211> 1840
<212> DNA
<213> 人工序列
<400> 61
aatcgatgcc accatggccc ctaagaagaa gagaaaggtg ggcatccacg gcgtgcccgc 60
cgctgccaag cggttctaca gcgccgaaga agccgccgcc cattgtatgg ccagctctag 120
cgaagagttc agcggctctg atagcgagta cgtgcctcct gcttctgaga gcgacagctc 180
caccgaggaa agctggtgca gctccagcac cgtgtccgcc ctggaggagc ctatggaagt 240
ggacgaggac gtggacgacc tggaagatca ggaggctgga gatcgggctg atgccgctgc 300
cggaggagaa cctgcctggg gccccccttg taatttccct ccggagatcc ctccattcac 360
aaccgtgcca ggcgttaagg tggataccag caactttgaa cctatcaact tttttcagct 420
gttcatgacc gaggccatcc tgcaggacat ggtgctgtac acaaacgtgt acgccgagca 480
gtacctgacc cagaaccccc tgaccagagg cgccagagcc cacgcctggc accccaccga 540
catctgcgag atgaaacggt ttgtgggcct gaccctggcg atgggcctga tcaaggccaa 600
cagcctggag agctactggg acaccaccac agtgctgagc atccctgtgt tcggcgctac 660
aatgtcaaga aaccggtacc agctgctgct gagattcctg catttcaaca acaacgccac 720
cgccgtacct ccagatcagc ctggccacga tagactgcac aagctgagac ctctgattga 780
tagcctgtct gaaagattcg ccaatgtgta taccccctgc cagaacatct gcatcgacga 840
gtctctgctg ctgtttaagg gcagactgca gttcagacag tacatcccca gcaagcgggc 900
tagatacggc atcaaattct acaagctgtg tgaaagcagc agcggctaca ccagctactt 960
cctgatctac gagggcaagg acagcaagct ggacccccct ggatgtcctc ctgacctgac 1020
cgtttctggc aaaatcgtgt gggagctgat cagccctctg ctgggccagg gcttccacct 1080
gtatgtggac aatttctatt ctagcatccc cctgtttaca gccctctatt gtctgaacac 1140
cccagcatgc ggcaccatca acagaaatcg gaagggactc ccaagagcac tgctggataa 1200
gaaactgaac cggggcgaga catacgccct gagaaagaac gagctgctgg ccatcaagtt 1260
cttcgacaaa aaaaacgtgt tcatgctgac atccattcac gacgaatccg tgatccggga 1320
acagagagtg ggcagacccc ctaagaacaa gcccctgtgc agcaaggaat acagtaaata 1380
catgggcggc gtggaccgga ccgaccaact tcaacactac tacaacgcca caagaaaaac 1440
cagacactgg tacaagaagg tcggaatcta cctgatccag atggccctta ggaatagcta 1500
catcgtctac aaagccgccg tgcctggccc taagctgagc tactacaagt accagctcca 1560
gatcctgcct gccctgctgt tcggcggagt ggaagagcaa acagtgcccg agatgcctga 1620
ctccgataac gtggccagac tgatcggcaa gcacttcatc gacaccctgc ctcctacacc 1680
cgggaagcag cggccccaga agggctgcaa ggtgtgcaga aagagaggca tcaggcggga 1740
cacccggtac tactgcccca agtgccctag aaatcctggc ctgtgcgaga agccttgctt 1800
cgagatctat cacacacagc tgcactactg ataactcgag 1840
<210> 62
<211> 589
<212> PRT
<213> 人工序列
<400> 62
Met Ala Lys Arg Phe Tyr Ser Ala Glu Glu Ala Ala Ala His Cys Met
1 5 10 15
Ala Ser Ser Ser Glu Glu Phe Ser Gly Ser Asp Ser Glu Tyr Val Pro
20 25 30
Pro Ala Ser Glu Ser Asp Ser Ser Thr Glu Glu Ser Trp Cys Ser Ser
35 40 45
Ser Thr Val Ser Ala Leu Glu Glu Pro Met Glu Val Asp Glu Asp Val
50 55 60
Asp Asp Leu Glu Asp Gln Glu Ala Gly Asp Arg Ala Asp Ala Ala Ala
65 70 75 80
Gly Gly Glu Pro Ala Trp Gly Pro Pro Cys Asn Phe Pro Pro Glu Ile
85 90 95
Pro Pro Phe Thr Thr Val Pro Gly Val Lys Val Asp Thr Ser Asn Phe
100 105 110
Glu Pro Ile Asn Phe Phe Gln Leu Phe Met Thr Glu Ala Ile Leu Gln
115 120 125
Asp Met Val Leu Tyr Thr Asn Val Tyr Ala Glu Gln Tyr Leu Thr Gln
130 135 140
Asn Pro Leu Pro Arg Tyr Ala Arg Ala His Ala Trp His Pro Thr Asp
145 150 155 160
Ile Ala Glu Met Lys Arg Phe Val Gly Leu Thr Leu Ala Met Gly Leu
165 170 175
Ile Lys Ala Asn Ser Leu Glu Ser Tyr Trp Asp Thr Thr Thr Val Leu
180 185 190
Ser Ile Pro Val Phe Ser Ala Thr Met Ser Arg Asn Arg Tyr Gln Leu
195 200 205
Leu Leu Arg Phe Leu His Phe Asn Asn Asn Ala Thr Ala Val Pro Pro
210 215 220
Asp Gln Pro Gly His Asp Arg Leu His Lys Leu Arg Pro Leu Ile Asp
225 230 235 240
Ser Leu Ser Glu Arg Phe Ala Ala Val Tyr Thr Pro Cys Gln Asn Ile
245 250 255
Cys Ile Asp Glu Ser Leu Leu Leu Phe Lys Gly Arg Leu Gln Phe Arg
260 265 270
Gln Tyr Ile Pro Ser Lys Arg Ala Arg Tyr Gly Ile Lys Phe Tyr Lys
275 280 285
Leu Cys Glu Ser Ser Ser Gly Tyr Thr Ser Tyr Phe Leu Ile Tyr Glu
290 295 300
Gly Lys Asp Ser Lys Leu Asp Pro Pro Gly Cys Pro Pro Asp Leu Thr
305 310 315 320
Val Ser Gly Lys Ile Val Trp Glu Leu Ile Ser Pro Leu Leu Gly Gln
325 330 335
Gly Phe His Leu Tyr Val Asp Asn Phe Tyr Ser Ser Ile Pro Leu Phe
340 345 350
Thr Ala Leu Tyr Cys Leu Asp Thr Pro Ala Cys Gly Thr Ile Asn Arg
355 360 365
Asn Arg Lys Gly Leu Pro Arg Ala Leu Leu Asp Lys Lys Leu Asn Arg
370 375 380
Gly Glu Thr Tyr Ala Leu Arg Lys Asn Glu Leu Leu Ala Ile Lys Phe
385 390 395 400
Phe Asp Lys Lys Asn Val Phe Met Leu Thr Ser Ile His Asp Glu Ser
405 410 415
Val Ile Arg Glu Gln Arg Val Gly Arg Pro Pro Lys Asn Lys Pro Leu
420 425 430
Cys Ser Lys Glu Tyr Ser Lys Tyr Met Gly Gly Val Asp Arg Thr Asp
435 440 445
Gln Leu Gln His Tyr Tyr Asn Ala Thr Arg Lys Thr Arg Ala Trp Tyr
450 455 460
Lys Lys Val Gly Ile Tyr Leu Ile Gln Met Ala Leu Arg Asn Ser Tyr
465 470 475 480
Ile Val Tyr Lys Ala Ala Val Pro Gly Pro Lys Leu Ser Tyr Tyr Lys
485 490 495
Tyr Gln Leu Gln Ile Leu Pro Ala Leu Leu Phe Gly Gly Val Glu Glu
500 505 510
Gln Thr Val Pro Glu Met Pro Pro Ser Asp Asn Val Ala Arg Leu Ile
515 520 525
Gly Lys His Phe Ile Asp Thr Leu Pro Pro Thr Pro Gly Lys Gln Arg
530 535 540
Pro Gln Lys Gly Cys Lys Val Cys Arg Lys Arg Gly Ile Arg Arg Asp
545 550 555 560
Thr Arg Tyr Tyr Cys Pro Lys Cys Pro Arg Asn Pro Gly Leu Cys Phe
565 570 575
Lys Pro Cys Phe Glu Ile Tyr His Thr Gln Leu His Tyr
580 585
<210> 63
<211> 181
<212> DNA
<213> 人工序列
<400> 63
ccctttgcct gccaatcacg catgggatac gtcgtggcag taaaagggct taaatgccaa 60
cgacgcgtcc catacgttgt tggcatttta agtcttctct ctgcagcggc agcatgtgcc 120
gccgctgcag agagtttcta gcgatgacag cccctctggg caacgagccg ggggggctgt 180
c 181
<210> 64
<211> 234
<212> DNA
<213> 人工序列
<400> 64
tttgcatttt tagacattta gaagcctata tcttgttaca gaattggaat tacacaaaaa 60
ttctaccata ttttgaaagc ttaggttgtt ctgaaaaaaa caatatattg ttttcctggg 120
taaactaaaa gtcccctcga ggaaaggccc ctaaagtgaa acagtgcaaa acgttcaaaa 180
actgtctggc aatacaagtt ccactttggg acaaatcggc tggcagtgaa aggg 234
<210> 65
<211> 466
<212> DNA
<213> 人工序列
<400> 65
gcggccgctt aaccctttgc ctgccaatca cgcatgggat acgtcgtggc agtaaaaggg 60
cttaaatgcc aacgacgcgt cccatacgtt gttggcattt taagtcttct ctctgcagcg 120
gcagcatgtg ccgccgctgc agagagtttc tagcgatgac agcccctctg ggcaacgagc 180
cgggggggct gtccctgcag gtacgatcaa gcggcgcgcc tttgcatttt tagacattta 240
gaagcctata tcttgttaca gaattggaat tacacaaaaa ttctaccata ttttgaaagc 300
ttaggttgtt ctgaaaaaaa caatatattg ttttcctggg taaactaaaa gtcccctcga 360
ggaaaggccc ctaaagtgaa acagtgcaaa acgttcaaaa actgtctggc aatacaagtt 420
ccactttggg acaaatcggc tggcagtgaa agggttaagc gatcgc 466
<210> 66
<211> 96
<212> DNA
<213> 人工序列
<400> 66
cctttttact gccaatgacg catgggatac gtcgtggcag taaaagggct taaatgccaa 60
cgacgcgtcc catacgttgt tggcatttta attctt 96
<210> 67
<211> 148
<212> DNA
<213> 人工序列
<400> 67
ttgttctgaa aaaaacaata tattgttttc ctgggtaaac taaaagtccc ctcgaggaaa 60
ggcccctaaa gtgaaacagt gcaaaacgtt caaaaactgt ctggcaatac aagttccact 120
ttgaccaaaa cggctggcag taaaaggg 148
<210> 68
<211> 465
<212> DNA
<213> 人工序列
<400> 68
gcggccgctt aaccttttta ctgccaatga cgcatgggat acgtcgtggc agtaaaaggg 60
cttaaatgcc aacgacgcgt cccatacgtt gttggcattt taattcttct ctctgcagcg 120
gcagcatgtg ccgccgctgc agagagtttc tagcgatgac agcccctctg ggcaacgagc 180
cgggggggct gtccctgcag gtacgatcaa gcggcgcgcc tttgcatttt tagacattta 240
gaagcctata tcttgttaca gaattggaat tacacaaaaa ttctaccata ttttgaaagc 300
ttaggttgtt ctgaaaaaaa caatatattg ttttcctggg taaactaaaa gtcccctcga 360
ggaaaggccc ctaaagtgaa acagtgcaaa acgttcaaaa actgtctggc aatacaagtt 420
ccactttgac caaaacggct ggcagtaaaa gggttaagcg atcgc 465
<210> 69
<211> 1803
<212> DNA
<213> 人工序列
<400> 69
atcgatgcca ccatgggcag ctccctggac gatgagcaca tcctgtccgc cctgctgcag 60
tctgacgatg agctggtggg cgaggacagc gattccgaga tcagcgacca cgtgtccgag 120
gacgatgtgc agtccgacac agaggaggcc ttcatcgacg aggtgcacga ggtgcagccc 180
acctctagcg gctccgagat cctggatgag cagaacgtga tcgagcagcc tggctcctct 240
ctggcctcta ataagatcct gaccctgcca cagaggacaa tccgcggcaa gaacaagcac 300
tgctggtcta ccagcaagtc cacacggaga agccgggtgt ccgccctgaa ccacgtgcgg 360
tctcagagag gcccaaccag gatgtgccgc aatatctacg accccctgct gtgctttaag 420
ctgttcttta cagatgagat catcagcgag atcgtgaagt ggaccaacgc cgagatctcc 480
ctgaagaggc gcgagtctat gaccggcgcc acattcaggg acaccaatga ggatgagatc 540
tacgccttct ttggcatcct ggtcatgaca gccgtgcgga aggacaacca catgtccacc 600
gacgatctgt ttgatagatc tctgagcatg gtgtacgtga gcgtgatgag cagggaccgc 660
ttcgattttc tgatccggtg cctgagaatg gacgataaga gcatccggcc tacactgaga 720
gagaatgacg tgttcacccc agtgaggaag atctgggatc tgtttatcca ccagtgtatc 780
cagaactaca caccaggagc acacctgacc atcgacgagc agctgctggg cttccggggc 840
agatgccctt ttcgcatgta catcccaaat aagcccagca agtatggcat caagatcctg 900
atgatgtgcg attccggcac caagtacatg atcaacggca tgccatatct gggcaggggc 960
acccagacaa atggcgtgcc cctgggcgag tactatgtga aggagctgag caagcctgtg 1020
cacggctcct gccgcaacat cacatgtgac aattggttca ccagcatccc cctggccaag 1080
aacctgctgc aggagcctta taagctgacc atcgtgggca cagtgaggtc caacaagcgc 1140
gagatccccg aggtgctgaa gaattccagg tctcgccctg tgggcacatc tatgttctgc 1200
tttgatggcc cactgaccct ggtgagctac aagcccaagc ctgccaagat ggtgtatctg 1260
ctgagctcct gtgacgagga tgcctctatc aacgagagca ccggcaagcc ccagatggtc 1320
atgtactata atcagacaaa gggcggcgtg gacaccctgg atcagatgtg cagcgtgatg 1380
acctgttccc ggaagacaaa tagatggcct atggccctgc tgtacggcat gatcaacatc 1440
gcctgcatca attctttcat catctatagc cacaacgtgt ctagcaaggg cgagaaggtg 1500
cagtccagga agaagttcat gcgcaatctg tacatgtctc tgacatcctc ttttatgcgg 1560
aagagactgg aggcccccac cctgaagagg tatctgcgcg acaacatctc caatatcctg 1620
cctaacgagg tgccaggcac ctccgacgat tctacagagg agccagtgac caagaagcgg 1680
acctactgca catattgtcc ctctaagatc cggagaaagg ccaacgccag ctgcaagaag 1740
tgtaagaaag tgatctgtag agagcacaat atcgacatgt gccagagctg tttttgactc 1800
gag 1803
<210> 70
<211> 1806
<212> DNA
<213> 人工序列
<400> 70
ggatccgcca ccatgggcag ctccctggac gatgagcaca tcctgtccgc cctgctgcag 60
tctgacgatg agctggtggg cgaggacagc gattccgagg tgagcgacca cgtgtccgag 120
gacgatgtgc agagcgacac agaggaggcc ttcatcgatg aggtgcacga ggtgcagcca 180
acctctagcg gcagcgagat cctggatgag cagaacgtga tcgagcagcc tggctcctct 240
ctggcctcca ataagatcct gaccctgcca cagaggacaa tccgcggcaa gaacaagcac 300
tgctggtcta ccagcaagcc tacacggaga tcccgggtgt ctgccctgaa ccacgtgcgg 360
tcccagagag gcccaaccag gatgtgccgc aatatctacg accccctgct gtgctttaag 420
ctgttcttta cagatgagat catcagcgag atcgtgaagt ggaccaacgc cgagatctcc 480
ctgaagaggc gcgagagcat gacctccgcc acattcaggg acaccaatga ggatgagatc 540
tacgccttct ttggcatcct ggtcatgaca gccgtgcgga aggacaacca catgagcacc 600
gacgatctgt ttgatagatc cctgtctatg gtgtacgtga gcgtgatgag cagggaccgc 660
ttcgattttc tgatccggtg cctgagaatg gacgataagt ccatccggcc tacactgaga 720
gagaatgacg tgttcacccc agtgaggaag atctgggatc tgtttatcca ccagtgtatc 780
cagaactaca caccaggagc acacctgacc atcgacgagc agctgctggg cttccggggc 840
agatgccctt ttcgcgtgta catcccaaat aagccctcta agtatggcat caagatcctg 900
atgatgtgcg atagcggcac caagtacatg atcaacggca tgccatatct gggcaggggc 960
acccagacaa atggcgtgcc cctgggcgag tactatgtga aggagctgtc caagcctgtg 1020
cacggctctt gccgcaacat cacatgtgac aattggttca cctctatccc cctggccaag 1080
aacctgctgc aggagcctta taagctgacc atcgtgggca cagtgaggag caacaagcgc 1140
gagatccccg aggtgctgaa gaatagcagg tcccgccctg tgggcacatc catgttctgc 1200
tttgatggcc cactgaccct ggtgtcttac aagcccaagc ctgccaagat ggtgtatctg 1260
ctgagctcct gtgacgagga tgcctctatc aacgagagca ccggcaagcc ccagatggtc 1320
atgtactata atcagacaaa gggcggcgtg gacaccctgg atcagatgtg cagcgtgatg 1380
acctgttccc ggaagacaaa tagatggcct atggccctgc tgtacggcat gatcaacatc 1440
gcctgcatca attctttcat catctatagc cacaacgtgt ctagcaaggg cgagaaggtg 1500
cagagcagga agaagttcat gcgcaatctg tacatgggcc tgacatcctc ttttatgcgg 1560
aagagactgg aggcccccac cctgaagagg tatctgcgcg acaacatctc caatatcctg 1620
cctaaggagg tgccaggcac ctccgacgat tctacagagg agccagtgac caagaagcgg 1680
acctactgca catattgtcc ctccaagatc cggagaaagg cctctgccag ctgcaagaag 1740
tgtaagaaag tgatctgtag agagcacaac atcgacatgt gccagtcttg tttttgataa 1800
ctcgag 1806
<210> 71
<211> 1807
<212> DNA
<213> 人工序列
<400> 71
aatcgatgcc accatgggat ctagcctgga cgatgaacac atcctctctg ccctgctcca 60
gagcgacgac gagctggtcg gcgaggatag cgacagcgag gtgtccgacc acgtgtcaga 120
agatgatgtg cagagcgaca ccgaggaagc tttcatcgac gaggtccacg aggtgcaacc 180
caccagcagc ggaagcgaga tcctggacga gcagaacgtg atcgagcagc ctggctctag 240
cctggccagc aaccggatcc tgacactgcc tcagcggaca atcagaggca aaaacaagca 300
ctgctggtcc accagcaaga gcacccggag gagcagagtg tctgctctga acatcgtgcg 360
ctctcagaga ggccccacca gaatgtgcag aaacatctac gaccccctgt tgtgcttcaa 420
gctgtttttc accgacgaga ttatctctga aatcgtcaag tggacaaacg ctgaaatcag 480
cctgaagagg cgggaaagca tgacctccgc caccttcaga gatacaaatg aggacgagat 540
ctacgccttc ttcggcatcc tggtgatgac cgccgtgcgg aaagacaacc acatgagcac 600
cgatgacctg tttgacagaa gcctgagcat ggtctacgtg tccgtgatgt cgagagacag 660
attcgacttt ctgatccggt gcctgcggat ggacgataag tctatcagac ctaccctgag 720
agaaaacgac gtgttcaccc ctgtgagaaa gatctgggac ctgttcatcc accagtgtat 780
ccagaactac acccctggcg cccacctgac cattgacgag cagctgctgg gattcagagg 840
cagatgccct tttcgggtgt acatccccaa caagcccagc aagtacggca tcaagatcct 900
gatgatgtgt gacagcggta caaagtacat gattaacggc atgccttatc tgggcagagg 960
aacccagacc aacggcgtgc cacttggcga gtactacgtg aaggaactgt ccaaaccagt 1020
tcatggcagt tgtagaaaca tcacctgtga taactggttc acatctatcc ccctggctaa 1080
gaacctgctg caggagcctt acaagctgac aatcgtgggc acagtgcgct ctaacaagag 1140
ggaaatccct gaggtgctga aaaacagcag atcccggcct gtgggcacaa gcatgttctg 1200
cttcgacggc cctctgaccc tggtgagcta caagcctaag ccagccaaga tggtgtatct 1260
gctgagcagc tgcgacgagg atgccagcat caacgagagc acaggcaagc ctcaaatggt 1320
gatgtactac aaccagacaa agggaggcgt ggacaccctc gatcagatgt gttctgtgat 1380
gacctgcagc cggaagacca atagatggcc tatggccctg ctgtacggca tgatcaacat 1440
cgcctgcatc aatagcttca tcatctacag ccacaacgtg tcatccaaag gcgaaaaggt 1500
gcaaagcaga aagaagttca tgagaaacct gtacatgtcc ctgaccagca gcttcatgag 1560
aaagcggctg gaagccccta cactgaagcg gtatctgcgg gataatatct ctaatatctt 1620
acccaaagag gtgcccggaa caagcgatga tagcactgag gaacccgtca tgaagaaaag 1680
aacctactgc acctactgtc ctagcaagat cagaagaaaa gccaacgcct cttgcaagaa 1740
gtgcaaaaaa gtgatctgca gagagcacaa tatcgacatg tgccagagct gcttttgata 1800
actcgag 1807
<210> 72
<211> 1807
<212> DNA
<213> 人工序列
<400> 72
aatcgatgcc accatgggca gcagcttgga cgacgagcac atcctgtctg ctctgctcca 60
gagcgacgac gagctggtgg gcgaagattc agacagcgag gtgtcagacc acgtgtccga 120
ggacgatgtg cagagcgata ccgaggaagc ctttattgac gaagtgcatg aggtgcaacc 180
tacatccagc ggatctgaaa tcctggacga gcagaacgtg atcgagcagc ccggctctag 240
cctggccagc aacagaaacc tgaccctgcc ccagagaaca atcagaggca agaacaagca 300
ctgctggtcc acctctaaac ctacccggcg gagccgggcc agcgccctga acatcgtgcg 360
atctcagcgg ggacctacca gaatgtgcag aaacatttac gacccactgc tttgttttaa 420
gctgttcttc accgacgaaa tcatcagcga gatcgtgaaa tggaccaacg ccgagatcag 480
ccttaagaga agggaaagca tgacaagcgc tacattcaga gacaccaacg aggatgagat 540
ctacgccttc ttcggcatcc tggtgatgac cgccgtgcgg aaggacaacc acatgagcac 600
agatgacctg ttcgatagaa gcctgtctat ggtctacgtg agcgtgatga gcagagatag 660
attcgacttc ctgatccggt gcctgcggat ggacgataag agcatcagac ctaccctgag 720
agaaaacgac gtgttcaccc cagtgcgcaa aatctgggac ctgtttatcc accagtgcat 780
ccagaattac acccctggtg ctcacctgac catcgacgag caactgctgg gctttagagg 840
aagatgcccc ttcagagtgt acatccctaa caaaccctct aagtacggca tcaagatcct 900
gatgatgtgc gatagcggca ccaagtacat gatcaacggc atgccttatc tgggcagagg 960
cacccagacc aatggcgtgc ccctgggaga atactacgtg aaggaactga gcaagcctgt 1020
gcacggcagc tgtagaaata tcacctgcga caactggttc acaagcatcc ccctggccaa 1080
gaacctgctg caggagccct acaagctgac catcgttggc acagtgcggt ctaacaagag 1140
agaaattcct gaggtgctga agaacagccg gagccgcccc gtgggcacca gcatgttctg 1200
cttcgacggc cctctgacac tggttagcta caagccaaag cctgctaaga tggtgtacct 1260
gctgagcagc tgcgacgagg acgcctccat caacgagtcc acaggcaagc cgcaaatggt 1320
gatgtactac aaccagacaa agggcggagt ggacaccctg gatcagatgt gtagcgtcat 1380
gacctgtagc agaaagacca accggtggcc catggccctg ctgtacggaa tgatcaacat 1440
cgcctgcatc aactcattca tcatctatag ccacaacgtg tccagcaagg gcgagaaggt 1500
gcagagccgg aagaagttca tgagaaacct gtatatgggc ctgacaagca gcttcatgcg 1560
gaaaagactg gaagccccta cactgaaaag atacctgcgg gacaatattt ctaatatcct 1620
gcctaaagag gtgcctggca cctccgatga cagcacagag gaacctgtca tgaagaaacg 1680
gacctactgt acctactgcc ctagtaagat ccgcagaaag gccagcgcct cttgcaagaa 1740
gtgcaagaaa gtgatctgca gagagcacaa tatcgacatg tgccagtcct gtttctgata 1800
actcgag 1807
<210> 73
<211> 594
<212> PRT
<213> 人工序列
<400> 73
Met Gly Ser Ser Leu Asp Asp Glu His Ile Leu Ser Ala Leu Leu Gln
1 5 10 15
Ser Asp Asp Glu Leu Val Gly Glu Asp Ser Asp Ser Glu Ile Ser Asp
20 25 30
His Val Ser Glu Asp Asp Val Gln Ser Asp Thr Glu Glu Ala Phe Ile
35 40 45
Asp Glu Val His Glu Val Gln Pro Thr Ser Ser Gly Ser Glu Ile Leu
50 55 60
Asp Glu Gln Asn Val Ile Glu Gln Pro Gly Ser Ser Leu Ala Ser Asn
65 70 75 80
Lys Ile Leu Thr Leu Pro Gln Arg Thr Ile Arg Gly Lys Asn Lys His
85 90 95
Cys Trp Ser Thr Ser Lys Ser Thr Arg Arg Ser Arg Val Ser Ala Leu
100 105 110
Asn His Val Arg Ser Gln Arg Gly Pro Thr Arg Met Cys Arg Asn Ile
115 120 125
Tyr Asp Pro Leu Leu Cys Phe Lys Leu Phe Phe Thr Asp Glu Ile Ile
130 135 140
Ser Glu Ile Val Lys Trp Thr Asn Ala Glu Ile Ser Leu Lys Arg Arg
145 150 155 160
Glu Ser Met Thr Gly Ala Thr Phe Arg Asp Thr Asn Glu Asp Glu Ile
165 170 175
Tyr Ala Phe Phe Gly Ile Leu Val Met Thr Ala Val Arg Lys Asp Asn
180 185 190
His Met Ser Thr Asp Asp Leu Phe Asp Arg Ser Leu Ser Met Val Tyr
195 200 205
Val Ser Val Met Ser Arg Asp Arg Phe Asp Phe Leu Ile Arg Cys Leu
210 215 220
Arg Met Asp Asp Lys Ser Ile Arg Pro Thr Leu Arg Glu Asn Asp Val
225 230 235 240
Phe Thr Pro Val Arg Lys Ile Trp Asp Leu Phe Ile His Gln Cys Ile
245 250 255
Gln Asn Tyr Thr Pro Gly Ala His Leu Thr Ile Asp Glu Gln Leu Leu
260 265 270
Gly Phe Arg Gly Arg Cys Pro Phe Arg Met Tyr Ile Pro Asn Lys Pro
275 280 285
Ser Lys Tyr Gly Ile Lys Ile Leu Met Met Cys Asp Ser Gly Thr Lys
290 295 300
Tyr Met Ile Asn Gly Met Pro Tyr Leu Gly Arg Gly Thr Gln Thr Asn
305 310 315 320
Gly Val Pro Leu Gly Glu Tyr Tyr Val Lys Glu Leu Ser Lys Pro Val
325 330 335
His Gly Ser Cys Arg Asn Ile Thr Cys Asp Asn Trp Phe Thr Ser Ile
340 345 350
Pro Leu Ala Lys Asn Leu Leu Gln Glu Pro Tyr Lys Leu Thr Ile Val
355 360 365
Gly Thr Val Arg Ser Asn Lys Arg Glu Ile Pro Glu Val Leu Lys Asn
370 375 380
Ser Arg Ser Arg Pro Val Gly Thr Ser Met Phe Cys Phe Asp Gly Pro
385 390 395 400
Leu Thr Leu Val Ser Tyr Lys Pro Lys Pro Ala Lys Met Val Tyr Leu
405 410 415
Leu Ser Ser Cys Asp Glu Asp Ala Ser Ile Asn Glu Ser Thr Gly Lys
420 425 430
Pro Gln Met Val Met Tyr Tyr Asn Gln Thr Lys Gly Gly Val Asp Thr
435 440 445
Leu Asp Gln Met Cys Ser Val Met Thr Cys Ser Arg Lys Thr Asn Arg
450 455 460
Trp Pro Met Ala Leu Leu Tyr Gly Met Ile Asn Ile Ala Cys Ile Asn
465 470 475 480
Ser Phe Ile Ile Tyr Ser His Asn Val Ser Ser Lys Gly Glu Lys Val
485 490 495
Gln Ser Arg Lys Lys Phe Met Arg Asn Leu Tyr Met Ser Leu Thr Ser
500 505 510
Ser Phe Met Arg Lys Arg Leu Glu Ala Pro Thr Leu Lys Arg Tyr Leu
515 520 525
Arg Asp Asn Ile Ser Asn Ile Leu Pro Asn Glu Val Pro Gly Thr Ser
530 535 540
Asp Asp Ser Thr Glu Glu Pro Val Thr Lys Lys Arg Thr Tyr Cys Thr
545 550 555 560
Tyr Cys Pro Ser Lys Ile Arg Arg Lys Ala Asn Ala Ser Cys Lys Lys
565 570 575
Cys Lys Lys Val Ile Cys Arg Glu His Asn Ile Asp Met Cys Gln Ser
580 585 590
Cys Phe
<210> 74
<211> 36
<212> DNA
<213> 人工序列
<400> 74
gcatgcgtca attttacgca gactatcttt ctaggg 36
<210> 75
<211> 63
<212> DNA
<213> 人工序列
<400> 75
ccctagaaag ataatcatat tgtgacgtac gttaaagata atcatgcgta aaattgacgc 60
atg 63
<210> 76
<211> 150
<212> DNA
<213> 人工序列
<400> 76
gcggccgctt aaccctagaa agataatcat attgtgacgt acgttaaaga taatcatgcg 60
taaaattgac gcatgcctgc aggtacgatc aagcggcgcg ccgcatgcgt caattttacg 120
cagactatct ttctagggtt aagcgatcgc 150
<210> 77
<211> 612
<212> DNA
<213> 人工序列
<400> 77
gcggccgcaa cacgcagcta gattaaccct agaaagataa tcatattgtg acgtacgtta 60
aagataatca tgcgtaaaat tgacgcatgt gttttatcgg tctgtatatc gaggtttatt 120
tattaatttg aatagatatt aagttttatt atatttacac ttacatacta ataataaatt 180
caacaaacaa tttatttatg tttatttatt tattaaaaaa aaacaaaaac tcaaaatttc 240
ttctataaag taacaaaact tttacctgca ggtacgatca agcggcgcgc ccatatctat 300
aacaagaaaa tatatatata ataagttatc acgtaagtag aacacgaaat aacaatataa 360
ttatcgtatg agttaaatct taaaagtcac gtaaaagata atcatgcgtc attttgactc 420
acgcggttgt tatagttcaa aatcagtgac acttaccgca ttgacaagca cgcctcacgg 480
gagctccaag cggcgactga gatgtcctaa atgcacagcg acggattcgc gctatttaga 540
aagagagagc aatatttcaa gaatgcatgc gtcaatttta cgcagactat ctttctaggg 600
ttaagcgatc gc 612
<210> 78
<211> 1044
<212> DNA
<213> 人工序列
<400> 78
ggatccgcca ccatgggcaa gtccaaggag atctctcagg acctgagaaa gaggatcgtg 60
gatctgcaca agagcggcag ctccctggga gcaatctcca agcgcctggc agtgcctcgg 120
tctagcgtgc agaccatcgt gcgcaagtac aagcaccacg gcaccacaca gccttcttat 180
cggagcggcc ggagaagggt gctgagccca cgcgacgagc ggacactggt gcgcaaggtg 240
cagatcaacc cccggaccac agccaaggat ctggtgaaga tgctggagga gaccggcaca 300
aaggtgtcca tctctaccgt gaagagagtg ctgtacaggc acaacctgaa gggccactcc 360
gccagaaaga agcctctgct gcagaatagg cacaagaagg caaggctgag gttcgcaacc 420
gcacacggcg acaaggatcg cacattttgg cggaacgtgc tgtggtctga cgagaccaag 480
atcgagctgt tcggccacaa tgatcacaga tacgtgtgga ggaagaaggg cgaggcctgc 540
aagcccaaga ataccatccc tacagtgaag cacggaggag gctccatcat gctgtgggga 600
tgttttgcag caggaggaac aggcgccctg cacaagatcg acggcatcat ggatgccgtg 660
cagtatgtgg acatcctgaa gcagcacctg aagacctctg tgagaaagct gaagctgggc 720
aggaagtggg tgttccagca cgacaacgat ccaaagcaca caagcaaggt ggtggccaag 780
tggctgaagg acaataaggt gaaggtgctg gagtggccca gccagtcccc tgatctgaac 840
ccaatcgaga atctgtgggc cgagctgaag aagagagtga gggcccggag acccaccaac 900
ctgacacagc tgcaccagct gtgccaggag gagtgggcca agatccaccc aaattactgt 960
ggcaagctgg tggagggcta tcccaagagg ctgacccagg tgaagcagtt taagggcaac 1020
gccacaaagt attgataact cgag 1044
<210> 79
<211> 340
<212> PRT
<213> 人工序列
<400> 79
Met Gly Lys Ser Lys Glu Ile Ser Gln Asp Leu Arg Lys Arg Ile Val
1 5 10 15
Asp Leu His Lys Ser Gly Ser Ser Leu Gly Ala Ile Ser Lys Arg Leu
20 25 30
Ala Val Pro Arg Ser Ser Val Gln Thr Ile Val Arg Lys Tyr Lys His
35 40 45
His Gly Thr Thr Gln Pro Ser Tyr Arg Ser Gly Arg Arg Arg Val Leu
50 55 60
Ser Pro Arg Asp Glu Arg Thr Leu Val Arg Lys Val Gln Ile Asn Pro
65 70 75 80
Arg Thr Thr Ala Lys Asp Leu Val Lys Met Leu Glu Glu Thr Gly Thr
85 90 95
Lys Val Ser Ile Ser Thr Val Lys Arg Val Leu Tyr Arg His Asn Leu
100 105 110
Lys Gly His Ser Ala Arg Lys Lys Pro Leu Leu Gln Asn Arg His Lys
115 120 125
Lys Ala Arg Leu Arg Phe Ala Thr Ala His Gly Asp Lys Asp Arg Thr
130 135 140
Phe Trp Arg Asn Val Leu Trp Ser Asp Glu Thr Lys Ile Glu Leu Phe
145 150 155 160
Gly His Asn Asp His Arg Tyr Val Trp Arg Lys Lys Gly Glu Ala Cys
165 170 175
Lys Pro Lys Asn Thr Ile Pro Thr Val Lys His Gly Gly Gly Ser Ile
180 185 190
Met Leu Trp Gly Cys Phe Ala Ala Gly Gly Thr Gly Ala Leu His Lys
195 200 205
Ile Asp Gly Ile Met Asp Ala Val Gln Tyr Val Asp Ile Leu Lys Gln
210 215 220
His Leu Lys Thr Ser Val Arg Lys Leu Lys Leu Gly Arg Lys Trp Val
225 230 235 240
Phe Gln His Asp Asn Asp Pro Lys His Thr Ser Lys Val Val Ala Lys
245 250 255
Trp Leu Lys Asp Asn Lys Val Lys Val Leu Glu Trp Pro Ser Gln Ser
260 265 270
Pro Asp Leu Asn Pro Ile Glu Asn Leu Trp Ala Glu Leu Lys Lys Arg
275 280 285
Val Arg Ala Arg Arg Pro Thr Asn Leu Thr Gln Leu His Gln Leu Cys
290 295 300
Gln Glu Glu Trp Ala Lys Ile His Pro Asn Tyr Cys Gly Lys Leu Val
305 310 315 320
Glu Gly Tyr Pro Lys Arg Leu Thr Gln Val Lys Gln Phe Lys Gly Asn
325 330 335
Ala Thr Lys Tyr
340
<210> 80
<211> 340
<212> PRT
<213> 人工序列
<400> 80
Met Gly Lys Ser Lys Glu Ile Ser Gln Asp Leu Arg Lys Lys Ile Val
1 5 10 15
Asp Leu His Lys Ser Gly Ser Ser Leu Gly Ala Ile Ser Lys Arg Leu
20 25 30
Lys Val Pro Arg Ser Ser Val Gln Thr Ile Val Arg Lys Tyr Lys His
35 40 45
His Gly Thr Thr Gln Pro Ser Tyr Arg Ser Gly Arg Arg Arg Val Leu
50 55 60
Ser Pro Arg Asp Glu Arg Thr Leu Val Arg Lys Val Gln Ile Asn Pro
65 70 75 80
Arg Thr Thr Ala Lys Asp Leu Val Lys Met Leu Glu Glu Thr Gly Thr
85 90 95
Lys Val Ser Ile Ser Thr Val Lys Arg Val Leu Tyr Arg His Asn Leu
100 105 110
Lys Gly Arg Ser Ala Arg Lys Lys Pro Leu Leu Gln Asn Arg His Lys
115 120 125
Lys Ala Arg Leu Arg Phe Ala Thr Ala His Gly Asp Lys Asp Arg Thr
130 135 140
Phe Trp Arg Asn Val Leu Trp Ser Asp Glu Thr Lys Ile Glu Leu Phe
145 150 155 160
Gly His Asn Asp His Arg Tyr Val Trp Arg Lys Lys Gly Glu Ala Cys
165 170 175
Lys Pro Lys Asn Thr Ile Pro Thr Val Lys His Gly Gly Gly Ser Ile
180 185 190
Met Leu Trp Gly Cys Phe Ala Ala Gly Gly Thr Gly Ala Leu His Lys
195 200 205
Ile Asp Gly Ile Met Arg Lys Glu Asn Tyr Val Asp Ile Leu Lys Gln
210 215 220
His Leu Lys Thr Ser Val Arg Lys Leu Lys Leu Gly Arg Lys Trp Val
225 230 235 240
Phe Gln Met Asp Asn Asp Pro Lys His Thr Ser Lys Val Val Ala Lys
245 250 255
Trp Leu Lys Asp Asn Lys Val Lys Val Leu Glu Trp Pro Ser Gln Ser
260 265 270
Pro Asp Leu Asn Pro Ile Glu Asn Leu Trp Ala Glu Leu Lys Lys Arg
275 280 285
Val Arg Ala Arg Arg Pro Thr Asn Leu Thr Gln Leu His Gln Leu Cys
290 295 300
Gln Glu Glu Trp Ala Lys Ile His Pro Thr Tyr Cys Gly Lys Leu Val
305 310 315 320
Glu Gly Tyr Pro Lys Arg Leu Thr Gln Val Lys Gln Phe Lys Gly Asn
325 330 335
Ala Thr Lys Tyr
340
<210> 81
<211> 226
<212> DNA
<213> 人工序列
<400> 81
agttgaagtc ggaagtttac atacacttaa gttggagtca ttaaaactcg tttttcaact 60
acaccacaaa tttcttgtta acaaacaata gttttggcaa gtcagttagg acatctactt 120
tgtgcatgac acaagtcatt tttccaacaa ttgtttacag acagattatt tcacttataa 180
ttcactgtat cacaattcca gtgggtcaga agtttacata cactaa 226
<210> 82
<211> 228
<212> DNA
<213> 人工序列
<400> 82
ttgagtgtat gttaacttct gacccactgg gaatgtgatg aaagaaataa aagctgaaat 60
gaatcattct ctctactatt attctgatat ttcacattct taaaataaag tggtgatcct 120
aactgacctt aagacaggga atctttactc ggattaaatg tcaggaattg tgaaaaagtg 180
agtttaaatg tatttggcta aggtgtatgt aaacttccga cttcaact 228
<210> 83
<211> 227
<212> DNA
<213> 人工序列
<400> 83
cagttgaagt cggaagttta catacactta agttggagtc attaaaactc gtttttcaac 60
tactccacaa atttcttgtt aacaaacaat agttttggca agtcagttag gacatctact 120
ttgtgcatga cacaagtcat ttttccaaca attgtttaca gacagattat ttcacttata 180
attcactgta tcacaattcc agtgggtcag aagtttacat acactaa 227
<210> 84
<211> 228
<212> DNA
<213> 人工序列
<400> 84
ttgagtgtat gtaaacttct gacccactgg gaatgtgatg aaagaaataa aagctgaaat 60
gaatcattct ctctactatt attctgatat ttcacattct taaaataaag tggtgatcct 120
aactgaccta agacagggaa tttttactag gattaaatgt caggaattgt gaaaaagtga 180
gtttaaatgt atttggctaa ggtgtatgta aacttccgac ttcaactg 228
<210> 85
<211> 227
<212> DNA
<213> 人工序列
<400> 85
cagttgaagt cggaagttta catacactta agttggagtc attaaaactc gtttttcaac 60
tactccacaa atttcttgtt aacaaacaat agttttggca agtcagttag gacatctact 120
ttgtgcatga cacaagtcat ttttccaaca attgtttaca gacagattat ttcacttata 180
attcactgta tcacaattcc agtgggtcag aagtttacat acactaa 227
<210> 86
<211> 227
<212> DNA
<213> 人工序列
<400> 86
cagttgaagt cggaagttta catacactta agttggagtc attaaaactc gtttttcaac 60
tactccacaa atttcttgtt aacaaacaat agttttggca agtcagttag gacatctact 120
ttgtgcatga cacaagtcat ttttccaaca attgtttaca gacagattat ttcacttata 180
attcactgta tcacaattcc agtgggtcag aagtgtacat acacgcg 227
<210> 87
<211> 229
<212> DNA
<213> 人工序列
<400> 87
gcgcgtgtat gtacacttct gacccactgg gaatgtgatg aaagaaataa aagctgaaat 60
gaatcattct ctctactatt attctgatat ttcacattct taaaataaag tggtgatcct 120
aactgacctt aagacaggga atctttactc ggattaaatg tcaggaattg tgaaaaagtg 180
agtttaaatg tatttggcta aggtgtatgt aaacttccga cttcaactg 229
<210> 88
<211> 622
<212> DNA
<213> 人工序列
<400> 88
gcggccgcat ctatacagtt gaagtcggaa gtttacatac acttaagttg gagtcattaa 60
aactcgtttt tcaactactc cacaaatttc ttgttaacaa acaatagttt tggcaagtca 120
gttaggacat ctactttgtg catgacacaa gtcatttttc caacaattgt ttacagacag 180
attatttcac ttataattca ctgtatcaca attccagtgg gtcagaagtt tacatacact 240
aagttgactg tgcctttaaa cagcttggaa aattccagaa aatgatgtca tggctttagc 300
ctgcaggtac gatcaagcgg cgcgccctaa agccatgaca tcattttctg gaattttcca 360
agctgtttaa aggcacagtc aacttagtgt atgtaaactt ctgacccact ggaattgtga 420
tacagtgaat tataagtgaa ataatctgtc tgtaaacaat tgttggaaaa atgacttgtg 480
tcatgcacaa agtagatgtc ctaactgact tgccaaaact attgtttgtt aacaagaaat 540
ttgtggagta gttgaaaaac gagttttaat gactccaact taagtgtatg taaacttccg 600
acttcaactg tatagcgatc gc 622
<210> 89
<211> 507
<212> DNA
<213> 人工序列
<400> 89
gcggccgcta tacagttgaa gtcggaagtt tacatacact taagttggag tcattaaaac 60
tcgtttttca actactccac aaatttcttg ttaacaaaca atagttttgg caagtcagtt 120
aggacatcta ctttgtgcat gacacaagtc atttttccaa caattgttta cagacagatt 180
atttcactta taattcactg tatcacaatt ccagtgggtc agaagtgtac atacacgcgc 240
ctgcaggtac gatcaagcgg cgcgccgcgc gtgtatgtac acttctgacc cactgggaat 300
gtgatgaaag aaataaaagc tgaaatgaat cattctctct actattattc tgatatttca 360
cattcttaaa ataaagtggt gatcctaact gaccttaaga cagggaatct ttactcggat 420
taaatgtcag gaattgtgaa aaagtgagtt taaatgtatt tggctaaggt gtatgtaaac 480
ttccgacttc aactgtatag cgatcgc 507
<210> 90
<211> 4830
<212> DNA
<213> 人工序列
<400> 90
actgcggccg ccctgcaggt caactagtga cgtcttaatt aattgccggc tggaacgcgt 60
ctagttatta atagtaatca attacggggt cattagttca tagcccatat atggagttcc 120
gcgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat 180
tgacgtcaat aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc 240
aatgggtgga gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc 300
caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt 360
acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta 420
ccatggtgat gcggttttgg cagtacatca atgggcgtgg atagcggttt gactcacggg 480
gatttccaag tctccacccc attgacgtca atgggagttt gttttggcac caaaatcaac 540
gggactttcc aaaatgtcgt aacaactccg ccccattgac gcaaatgggc ggtaggcgtg 600
tacggtggga ggtctatata agcagagctc gtttagtgaa ccgtcagatc gcctggagac 660
gccatccacg ctgttttgac ctccatagaa gacaccggga ccgatccagc ctccgcggat 720
tcgaatcccg gccgggaacg gtgcattgga acgcggattc cccgtgccaa gagtgacgta 780
agtaccgcct atagagtcta taggcccaca aaaaatgctt tcttctttta atatactttt 840
ttgtttatct tatttctaat actttcccta atctctttct ttcagggcaa taatgataca 900
atgtatcatg cctctttgca ccattctaaa gaataacagt gataatttct gggttaaggc 960
aatagcaata tttctgcata taaatatttc tgcatataaa ttgtaactga tgtaagaggt 1020
ttcatattgc taatagcagc tacaatccag ctaccattct gcttttattt tatggttggg 1080
ataaggctgg attattctga gtccaagcta ggcccttttg ctaatcatgt tcatacctct 1140
tatcttcctc ccacagctcc tgggcaacgt gctggtctgt gtgctggccc atcactttgg 1200
caaagaattg ggattcgaac atcgattgaa ttctggccag gatccgctag ctctagagtc 1260
gacggtacca gtactaagct tgcctcgagg cccctctccc tccccccccc ctaacgttac 1320
tggccgaagc cgcttggaat aaggccggtg tgcgtttgtc tatatgttat tttccaccat 1380
attgccgtct tttggcaatg tgagggcccg gaaacctggc cctgtcttct tgacgagcat 1440
tcctaggggt ctttcccctc tcgccaaagg aatgcaaggt ctgttgaatg tcgtgaagga 1500
agcagttcct ctggaagctt cttgaagaca aacaacgtct gtagcgaccc tttgcaggca 1560
gcggaacccc ccacctggcg acaggtgcct ctgcggccaa aagccacgtg tataagatac 1620
acctgcaaag gcggcacaac cccagtgcca cgttgtgagt tggatagttg tggaaagagt 1680
caaatggctc tcctcaagcg tattcaacaa ggggctgaag gatgcccaga aggtacccca 1740
ttgtatggga tctgatctgg ggcctcggtg cacatgcttt acatgtgttt agtcgaggtt 1800
aaaaaaacgt ctaggccccc cgaaccacgg ggacgtggtt ttcctttgaa aaacacgatg 1860
ataatatggc cacaaccatg gtgagcaagg gcgaggagct gttcaccggg gtggtgccca 1920
tcctggtcga gctggacggc gacgtaaacg gccacaagtt cagcgtgtcc ggcgagggcg 1980
agggcgatgc cacctacggc aagctgaccc tgaagttcat ctgcaccacc ggcaagctgc 2040
ccgtgccctg gcccaccctc gtgaccaccc tgacctgggg cgtgcagtgc ttcagccgct 2100
accccgacca catgaagcag cacgacttct tcaagtccgc catgcccgaa ggctacgtcc 2160
aggagcgcac catcttcttc aaggacgacg gcaactacaa gacccgcgcc gaggtgaagt 2220
tcgagggcga caccctggtg aaccgcatcg agctgaaggg catcgacttc aaggaggacg 2280
gcaacatcct ggggcacaag ctggagtaca actacatcag ccacaacgtc tatatcaccg 2340
ccgacaagca gaagaacggc atcaaggcca acttcaagat ccgccacaac atcgaggacg 2400
gcagcgtgca gctcgccgac cactaccagc agaacacccc catcggcgac ggccccgtgc 2460
tgctgcccga caaccactac ctgagcaccc agtccgccct gagcaaagac cccaacgaga 2520
agcgcgatca catggtcctg ctggagttcg tgaccgccgc cgggatcact ctcggcatgg 2580
acgagctgta caagtaaaga tctacgggtg gcatccctgt gacccctccc cagtgcctct 2640
cctggccctg gaagttgcca ctccagtgcc caccagcctt gtcctaataa aattaagttg 2700
catcattttg tctgactagg tgtccttcta taatattatg gggtggaggg gggtggtatg 2760
gagcaagggg caagttggga agacaacctg tagggcctgc ggggtctatt gggaaccaag 2820
ctggagtgca gtggcacaat cttggctcac tgcaatctcc gcctcctggg ttcaagcgat 2880
tctcctgcct cagcctcccg agttgttggg attccaggca agcatgacca ggctcagcta 2940
atttttgttt ttttggtaga gacggggttt caccatattg gccaggctgg tctccaactc 3000
ctaatctcag gtgatctacc caccttggcc tcccaaattg ctgggattac aggcgtgaac 3060
cactgctccc ttccctgtcc ttgcatgccc taggtccgga accggttggc gcgccatctg 3120
gcagcgatcg ccgcggaacc cctatttgtt tatttttcta aatacattca aatatgtatc 3180
cgctcatgag acaataaccc tgataaatgc ttcaataata ttgaaaaagg aagagtatga 3240
gtattcaaca tttccgtgtc gcccttattc ccttttttgc ggcattttgc cttcctgttt 3300
ttgctcaccc agaaacgctg gtgaaagtaa aagatgctga agatcagttg ggtgcacgag 3360
tgggttacat cgaactggat ctcaacagcg gtaagatcct tgagagtttt cgccccgaag 3420
aacgttttcc aatgatgagc acttttaaag ttctgctatg tggcgcggta ttatcccgta 3480
ttgacgccgg gcaagagcaa ctcggtcgcc gcatacacta ttctcagaat gacttggttg 3540
agtactcacc agtcacagaa aagcatctta cggatggcat gacagtaaga gaattatgca 3600
gtgctgccat aaccatgagt gataacactg cggccaactt acttctgaca acgatcggag 3660
gaccgaagga gctaaccgct tttttgcaca acatggggga tcatgtaact cgccttgatc 3720
gttgggaacc ggagctgaat gaagccatac caaacgacga gcgtgacacc acgatgcctg 3780
tagcaatggc aacaacgttg cgcaaactat taactggcga actacttact ctagcttccc 3840
ggcaacaatt aatagactgg atggaggcgg ataaagttgc aggaccactt ctgcgctcgg 3900
cccttccggc tggctggttt attgctgata aatctggagc cggtgagcgt gggtctcgcg 3960
gtatcattgc agcactgggg ccagatggta agccctcccg tatcgtagtt atctacacga 4020
cggggagtca ggcaactatg gatgaacgaa atagacagat cgctgagata ggtgcctcac 4080
tgattaagca ttggtaacgt acggaagtta gagaaaaggc ataagtagaa aagatcaaag 4140
gatcttcttg agatcctttt tttctgcgcg taatctgctg cttgcaaaca aaaaaaccac 4200
cgctaccagc ggtggtttgt ttgccggatc aagagctacc aactcttttt ccgaaggtaa 4260
ctggcttcag cagagcgcag ataccaaata ctgttcttct agtgtagccg tagttaggcc 4320
accacttcaa gaactctgta gcaccgccta catacctcgc tctgctaatc ctgttaccag 4380
tggctgctgc cagtggcgat aagtcgtgtc ttaccgggtt ggactcaaga cgatagttac 4440
cggataaggc gcagcggtcg ggctgaacgg ggggttcgtg cacacagccc agcttggagc 4500
gaacgaccta caccgaactg agatacctac agcgtgagct atgagaaagc gccacgcttc 4560
ccgaagggag aaaggcggac aggtatccgg taagcggcag ggtcggaaca ggagagcgca 4620
cgagggagct tccaggggga aacgcctggt atctttatag tcctgtcggg tttcgccacc 4680
tctgacttga gcgtcgattt ttgtgatgct cgtcaggggg gcggagccta tggaaaaacg 4740
ccagcaacgc ggccttttta cggttcctgg ccttttgctg gccttttgct catctcatga 4800
aaattatgca aattgagcca gtcaggcagt 4830
<210> 91
<211> 1830
<212> DNA
<213> 人工序列
<400> 91
actgcggccg ccctgcaggt caactagtga cgtcttaatt aattgccggc tggaacgcgt 60
ttcgaacatc gattgaattc tggccaagtg gatccgctag ctctagagtc gacggtacca 120
agcttgcctc gagccatgga gatctgcatg ccctaggtcc ggaaccggtt ggcgcgccat 180
ctggcagcga tcgccgcgga acccctattt gtttattttt ctaaatacat tcaaatatgt 240
atccgctcat gagacaataa ccctgataaa tgcttcaata atattgaaaa aggaagagta 300
tgattgaaca agatggattg cacgcaggtt ctccggccgc ttgggtggag aggctattcg 360
gctatgactg ggcacaacag acaatcggct gctctgatgc cgccgtgttc cggctgtcag 420
cgcaggggcg cccggttctt tttgtcaaga ccgacctgtc cggtgccctg aatgaactgc 480
aagacgaggc agcgcggcta tcgtggctgg cgacgacggg cgttccttgc gccgctgtgc 540
tcgacgttgt cactgaagcg ggaagggact ggctgctatt gggcgaagtg ccggggcagg 600
atctcctgtc atctcacctt gctcctgccg agaaagtatc catcatggct gatgcaatgc 660
ggcggctgca tacgcttgat ccggctacct gcccattcga ccaccaagcg aaacatcgca 720
tcgagcgagc acgtactcgg atggaagccg gtcttgtcga tcaggatgat ctggacgaag 780
agcatcaggg gctcgcgcca gccgaactgt tcgccaggct caaggcgtct atgcccgacg 840
gcgaggatct cgtcgtgact catggcgatg cctgcttgcc gaatatcatg gtggaaaatg 900
gccgcttttc tggattcatc gactgtggtc ggctgggtgt ggcggatcgc tatcaggaca 960
tagcgttggc tacccgtgat attgctgaag agcttggcgg cgaatgggct gaccgcttcc 1020
tcgtgcttta cggtatcgcc gctcccgatt cgcagcgcat cgccttctat cgccttcttg 1080
acgagttctt ctgataacgt acggaagtta gagaaaaggc ataagtagaa aagatcaaag 1140
gatcttcttg agatcctttt tttctgcgcg taatctgctg cttgcaaaca aaaaaaccac 1200
cgctaccagc ggtggtttgt ttgccggatc aagagctacc aactcttttt ccgaaggtaa 1260
ctggcttcag cagagcgcag ataccaaata ctgttcttct agtgtagccg tagttaggcc 1320
accacttcaa gaactctgta gcaccgccta catacctcgc tctgctaatc ctgttaccag 1380
tggctgctgc cagtggcgat aagtcgtgtc ttaccgggtt ggactcaaga cgatagttac 1440
cggataaggc gcagcggtcg ggctgaacgg ggggttcgtg cacacagccc agcttggagc 1500
gaacgaccta caccgaactg agatacctac agcgtgagct atgagaaagc gccacgcttc 1560
ccgaagggag aaaggcggac aggtatccgg taagcggcag ggtcggaaca ggagagcgca 1620
cgagggagct tccaggggga aacgcctggt atctttatag tcctgtcggg tttcgccacc 1680
tctgacttga gcgtcgattt ttgtgatgct cgtcaggggg gcggagccta tggaaaaacg 1740
ccagcaacgc ggccttttta cggttcctgg ccttttgctg gccttttgct catctcatga 1800
aaattatgca aattgagcca gtcaggcagt 1830
<210> 92
<211> 4689
<212> DNA
<213> 人工序列
<400> 92
ttaattaatt gccggctgga acgcgttgcg ccttttccaa ggcagccctg ggtttgcgca 60
gggacgcggc tgctctgggc gtggttccgg gaaacgcagc ggcgccgacc ctgggtctcg 120
cacattcttc acgtccgttc gcagcgtcac ccggatcttc gccgctaccc ttgtgggccc 180
cccggcgacg cttcctgctc cgcccctaag tcgggaaggt tccttgcggt tcgcggcgtg 240
ccggacgtga caaacggaag ccgcacgtct ctctagtacc ctcgcagacg gacagcgcca 300
gggagcaatg gcagcgcgcc gaccgcgatg ggctgtggcc aatagcggct gctcagcagg 360
gcgcgcggag agcagcggcc gggaaggggc ggtgcgggag gcggggtgtg gggcggtagt 420
gtgggccctg ttcctgcccg cgcggtgttc cgcattctgc aagcctccgg agcgcacgtc 480
ggcagtcggc tccctcgttg accgaatcac cgacctctct ccccagttcg aacatcgatg 540
ccaccatgga agacgccaaa aacataaaga aaggcccggc gccattctat ccgctggaag 600
atggaaccgc tggagagcaa ctgcataagg ctatgaagag atacgccctg gttcctggaa 660
caattgcttt tacagatgca catatcgagg tggacatcac ttacgctgag tacttcgaaa 720
tgtccgttcg gttggcagaa gctatgaaac gatatgggct gaatacaaat cacagaatcg 780
tcgtatgcag tgaaaactct cttcaattct ttatgccggt gttgggcgcg ttatttatcg 840
gagttgcagt tgcgcccgcg aacgacattt ataatgaacg tgaattgctc aacagtatgg 900
gcatttcgca gcctaccgtg gtgttcgttt ccaaaaaggg gttgcaaaaa attttgaacg 960
tgcaaaaaaa gctcccaatc atccaaaaaa ttattatcat ggattctaaa acggattacc 1020
agggatttca gtcgatgtac acgttcgtca catctcatct acctcccggt tttaatgaat 1080
acgattttgt gccagagtcc ttcgataggg acaagacaat tgcactgatc atgaactcct 1140
ctggatctac tggtctgcct aaaggtgtcg ctctgcctca tagaactgcc tgcgtgagat 1200
tctcgcatgc cagagatcct atttttggca atcaaatcat tccggatact gcgattttaa 1260
gtgttgttcc attccatcac ggttttggaa tgtttactac actcggatat ttgatatgtg 1320
gatttcgagt cgtcttaatg tatagatttg aagaagagct gtttctgagg agccttcagg 1380
attacaagat tcaaagtgcg ctgctggtgc caaccctatt ctccttcttc gccaaaagca 1440
ctctgattga caaatacgat ttatctaatt tacacgaaat tgcttctggt ggcgctcccc 1500
tctctaagga agtcggggaa gcggttgcca agaggttcca tctgccaggt atcaggcaag 1560
gatatgggct cactgagact acatcagcta ttctgattac acccgagggg gatgataaac 1620
cgggcgcggt cggtaaagtt gttccatttt ttgaagcgaa ggttgtggat ctggataccg 1680
ggaaaacgct gggcgttaat caaagaggcg aactgtgtgt gagaggtcct atgattatgt 1740
ccggttatgt aaacaatccg gaagcgacca acgccttgat tgacaaggat ggatggctac 1800
attctggaga catagcttac tgggacgaag acgaacactt cttcatcgtt gaccgcctga 1860
agtctctgat taagtacaaa ggctatcagg tggctcccgc tgaattggaa tccatcttgc 1920
tccaacaccc caacatcttc gacgcaggtg tcgcaggtct tcccgacgat gacgccggtg 1980
aacttcccgc cgccgttgtt gttttggagc acggaaagac gatgacggaa aaagagatcg 2040
tggattacgt cgccagtcaa gtaacaaccg cgaaaaagtt gcgcggagga gttgtgtttg 2100
tggacgaagt accgaaaggt cttaccggaa aactcgacgc aagaaaaatc agagagatcc 2160
tcataaaggc caagaagggc ggaaagatcg ccgtgtaatt ctagctcgag gcccctctcc 2220
ctcccccccc cctaacgtta ctggccgaag ccgcttggaa taaggccggt gtgcgtttgt 2280
ctatatgtta ttttccacca tattgccgtc ttttggcaat gtgagggccc ggaaacctgg 2340
ccctgtcttc ttgacgagca ttcctagggg tctttcccct ctcgccaaag gaatgcaagg 2400
tctgttgaat gtcgtgaagg aagcagttcc tctggaagct tcttgaagac aaacaacgtc 2460
tgtagcgacc ctttgcaggc agcggaaccc cccacctggc gacaggtgcc tctgcggcca 2520
aaagccacgt gtataagata cacctgcaaa ggcggcacaa ccccagtgcc acgttgtgag 2580
ttggatagtt gtggaaagag tcaaatggct ctcctcaagc gtattcaaca aggggctgaa 2640
ggatgcccag aaggtacccc attgtatggg atctgatctg gggcctcggt acacatgctt 2700
tacatgtgtt tagtcgaggt taaaaaaacg tctaggcccc ccgaaccacg gggacgtggt 2760
tttcctttga aaaacacgat gataatatgg ccacaaccat ggtgagcaag ggcgaggagc 2820
tgttcaccgg ggtggtgccc atcctggtcg agctggacgg cgacgtaaac ggccacaagt 2880
tcagcgtgtc cggcgagggc gagggcgatg ccacctacgg caagctgacc ctgaagttca 2940
tctgcaccac cggcaagctg cccgtgccct ggcccaccct cgtgaccacc ctgacctacg 3000
gcgtgcagtg cttcagccgc taccccgacc acatgaagca gcacgacttc ttcaagtccg 3060
ccatgcccga aggctacgtc caggagcgca ccatcttctt caaggacgac ggcaactaca 3120
agacccgcgc cgaggtgaag ttcgagggcg acaccctggt gaaccgcatc gagctgaagg 3180
gcatcgactt caaggaggac ggcaacatcc tggggcacaa gctggagtac aactacaaca 3240
gccacaacgt ctatatcatg gccgacaagc agaagaacgg catcaaggtg aacttcaaga 3300
tccgccacaa catcgaggac ggcagcgtgc agctcgccga ccactaccag cagaacaccc 3360
ccatcggcga cggccccgtg ctgctgcccg acaaccacta cctgagcacc cagtccgccc 3420
tgagcaaaga ccccaacgag aagcgcgatc acatggtcct gctggagttc gtgaccgccg 3480
ccgggatcac tctcggcatg gacgagctgt acaagtaaag atccgatatc atatgaatca 3540
acctctggat tacaaaattt gtgaaagatt gactggtatt cttaactatg ttgctccttt 3600
tacgctatgt ggatacgctg ctttaatgcc tttgtatcat gctattgctt cccgtatggc 3660
tttcattttc tcctccttgt ataaatcctg gttgctgtct ctttatgagg agttgtggcc 3720
cgttgtcagg caacgtggcg tggtgtgcac tgtgtttgct gacgcaaccc ccactggttg 3780
gggcattgcc accacctgtc agctcctttc cgggactttc gctttccccc tccctattgc 3840
cacggcggaa ctcatcgccg cctgccttgc ccgctgctgg acaggggctc ggctgttggg 3900
cactgacaat tccgtggtgt tgtcggggaa gctgacgtcc tttccatggc tgctcgcctg 3960
tgttgccacc tggattctgc gcgggacgtc cttctgctac gtcccttcgg ccctcaatcc 4020
agcggacctt ccttcccgcg gcctgctgcc ggctctgcgg cctcttccgc gtcttcgcct 4080
tcgccctcag acgagtcgga tctccctttg ggccgcctcc ccgcctgtct agagtcgacg 4140
gtaccagtac taagcttgcc tcgagccatg gagatctacg ggtggcatcc ctgtgacccc 4200
tccccagtgc ctctcctggc cctggaagtt gccactccag tgcccaccag ccttgtccta 4260
ataaaattaa gttgcatcat tttgtctgac taggtgtcct tctataatat tatggggtgg 4320
aggggggtgg tatggagcaa ggggcaagtt gggaagacaa cctgtagggc ctgcggggtc 4380
tattgggaac caagctggag tgcagtggca caatcttggc tcactgcaat ctccgcctcc 4440
tgggttcaag cgattctcct gcctcagcct cccgagttgt tgggattcca ggcaagcatg 4500
accaggctca gctaattttt gtttttttgg tagagacggg gtttcaccat attggccagg 4560
ctggtctcca actcctaatc tcaggtgatc tacccacctt ggcctcccaa attgctggga 4620
ttacaggcgt gaaccactgc tcccttccct gtccttgcat gccctaggtc cggaaccggt 4680
tggcgcgcc 4689
<210> 93
<211> 1083
<212> DNA
<213> 人工序列
<400> 93
cctgcaggtc aactagttaa gatacattga tgagtttgga caaaccacaa ctagaatgca 60
gtgaaaaaaa tgctttattt gtgaaatttg tgatgctatt gctttatttg taaccattat 120
aagctgcaat aaacaagttt caggcaccgg gcttgcgggt catgcaccag gtacgcggtc 180
cttcgggcac ctcgacatcg gcggtgacgg tgaagccgag ccgctcgtag aaggggaggt 240
tgcggggcgc ggaggtttcc agaaaggcgg gcaccccggc tctctcggct gcctccactc 300
cggggagaac gacggcggag cccagaccct tgccctggtg gtcgggcgag acaccgacgg 360
tagccaggaa ccacgcgggc tccttgggtc ggtgcggtgc cagaagtccc tccatctgtt 420
gctgcgcggc cagccgggaa ccgctcaact cggccatgcg cgggccgatc tcggcgaaca 480
ccgcccccgc ttcgacgctc tccggcgtgg tccagaccgc caccgctgcg ccgtcgtccg 540
cgacccacac cttgccgatg tcgagcccga cgcgcgtgag aaacagctct tgcagctctg 600
tgaccctctc gatgtggcgg tcagggtcta cggtgtggcg cgtggcgggg tagtcggcga 660
acgcggcggc gagggtgcgg acggctctag gaacatcgtc gcgggtggcg aggcgcaccg 720
tgggcttgta ctcagtcata gctttttgca aaagcctatg gcctccaaaa aagcctcctc 780
actacttctg gaatagctca gaggcagagg cggcctcggc ctctgcataa ataaaaaaaa 840
ttagtcagcc atggggcgga gaatgggcgg aactgggcgg agttaggggc gggatgggcg 900
gagttagggg cgggactatg gttgctgact aattgagatg catgctttgc atacttctgc 960
ctgctgggga gcctggggac tttccacacc tggttgctga ctaattgaga tgcatgcttt 1020
gcatacttct gcctgctggg gagcctgggg actttccaca ccctaactga cacacttaat 1080
taa 1083
<210> 94
<211> 1509
<212> DNA
<213> 人工序列
<400> 94
cctgcaggtc aactagttaa gatacattga tgagtttgga caaaccacaa ctagaatgca 60
gtgaaaaaaa tgctttattt gtgaaatttg tgatgctatt gctttatttg taaccattat 120
aagctgcaat aaacaagttc tattcctttg ccctcggacg agtagagggg cgtctgtttc 180
cactatcggc gagaacttct acacagccat cggtccagac ggctgcgctt ctgcgggcga 240
tttgtgttcg cccgacagtc ccggctccac ttcggacgat tgcatcacat cgaccctgcg 300
cccaagcagc atcatcgaaa ttgccgtcca ccaagctctg atagagttgg tcaagaccaa 360
tgcggagcat atacgcccgg agccgaggcg atcctgcaag ctctggatgt cgtctttcaa 420
agtagcgcgt ttgctgctcc atacaagcca accaaggacg ccagaaaaag atgttagcga 480
cctcgtattg ggaatccccg aacatagctt cgctccaatc aatgaccgct gttatgcggc 540
cattatctgt caggacattg ttgctgccga aatccgcgtg gaccaagtgg cgaacttcgg 600
ggcaatcctc ggcccaaagc atcagctcat cgagagcctg cgcgacactc gcgctgacgg 660
tatcatccat cacagtttgc caatgataca catggggatc agcaatcgcg caaatgaaat 720
cacgccatgt agtgtattga ccgattcctt gcggtccaaa tgggccgaac ccggaagtct 780
gggaaagatc ggcagcagca atagcgtcca tagcctccgc gacaggttgt agaacagcgg 840
gcagttcggt ttcagggagg tcttgcaaag ttacgccctg tgcgcggcgg gagatgcaat 900
aggtcaggct ctcgctgaac tccccaatgt caagcacttc gggaatcggg agcgcagccg 960
atgcaaagtg ccgataaaca taacgatctt tgtagaaacc atcggcgcag ctatttaccc 1020
gcaggacata tccacgccct cctacatcga agctgaaagc cctagattcc tcgccctccg 1080
agagctgcat caggtcgcta acgctgtcga acttttcgat cagaaacttc tcaacagaag 1140
tcgctgtgag ttcaggcttt ttcatagctt tttgcaaaag cctatggcct ccaaaaaagc 1200
ctcctcacta cttctggaat agctcagagg cagaggcggc ctcggcctct gcataaataa 1260
aaaaaattag tcagccatgg ggcggagaat gggcggaact gggcggagtt aggggcggga 1320
tgggcggagt taggggcggg actatggttg ctgactaatt gagatgcatg ctttgcatac 1380
ttctgcctgc tggggagcct ggggactttc cacacctggt tgctgactaa ttgagatgca 1440
tgctttgcat acttctgcct gctggggagc ctggggactt tccacaccct aactgacaca 1500
cttaattaa 1509
<210> 95
<211> 882
<212> DNA
<213> 人工序列
<400> 95
cctgcaggtc aactagttaa gatacattga tgagtttgga caaaccacaa ctagaatgca 60
gtgaaaaaaa tgctttattt gtgaaatttg tgatgctatt gctttatttg taaccattat 120
aagctgcaat aaacaagttt tagccctccc acacataacc agagggcagc aattcacgaa 180
tcccaactgc cgtcggctgt ccatcactgt ctttcactat ggctttgata ccaggatgga 240
ggtcaagaag cacctgtcgg catcttccgc agggacttaa aatgcccctg ttctcatttc 300
cgatagcgac tatacaagtc aggttgcctg ctgccgccgc cgccgcagtt ccaagcacca 360
caagttcagc acatggtcct cctgtaaaat gatatacatt gacacctgta aaaatacgac 420
catcactaga gagagcagca gaagcgacag aataatcttc gctgatagga atactattga 480
ttgtagcagt tgctctttca atgagggtgc tttcctcttg ggacaatggt ttagccatag 540
ctttttgcaa aagcctatgg cctccaaaaa agcctcctca ctacttctgg aatagctcag 600
aggcagaggc ggcctcggcc tctgcataaa taaaaaaaat tagtcagcca tggggcggag 660
aatgggcgga actgggcgga gttaggggcg ggatgggcgg agttaggggc gggactatgg 720
ttgctgacta attgagatgc atgctttgca tacttctgcc tgctggggag cctggggact 780
ttccacacct ggttgctgac taattgagat gcatgctttg catacttctg cctgctgggg 840
agcctgggga ctttccacac cctaactgac acacttaatt aa 882
<210> 96
<211> 6391
<212> DNA
<213> 人工序列
<400> 96
cctgcaggcg cgtctagtta ttaatagtaa tcaattacgg ggtcattagt tcatagccca 60
tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg accgcccaac 120
gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc aatagggact 180
ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc agtacatcaa 240
gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg gcccgcctgg 300
cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat ctacgtatta 360
gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg tggatagcgg 420
tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag tttgttttgg 480
caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt gacgcaaatg 540
ggcggtaggc gtgtacggtg ggaggtctat ataagcagag ctcgtttagt gaaccgtcag 600
atcgcctgga gacgccatcc acgctgtttt gacctccata gaagacaccg ggaccgatcc 660
agcctccgcg gattcgaatc ccggccggga acggtgcatt ggaacgcgga ttccccgtgc 720
caagagtgac gtaagtaccg cctatagagt ctataggccc acaaaaaatg ctttcttctt 780
ttaatatact tttttgttta tcttatttct aatactttcc ctaatctctt tctttcaggg 840
caataatgat acaatgtatc atgcctcttt gcaccattct aaagaataac agtgataatt 900
tctgggttaa ggcaatagca atatttctgc atataaatat ttctgcatat aaattgtaac 960
tgatgtaaga ggtttcatat tgctaatagc agctacaatc cagctaccat tctgctttta 1020
ttttatggtt gggataaggc tggattattc tgagtccaag ctaggccctt ttgctaatca 1080
tgttcatacc tcttatcttc ctcccacagc tcctgggcaa cgtgctggtc tgtgtgctgg 1140
cccatcactt tggcaaagaa ttgggattcg aacatcgatt gaattcgcca ccatgggtgc 1200
gagagcgtca gtattaagcg ggggagaatt agatcgatgg gaaaaaattc ggttaaggcc 1260
agggggaaag aaaaaatata aattaaaaca tatagtatgg gcaagcaggg agctagaacg 1320
attcgcagtt aatcctggcc tgttagaaac atcagaaggc tgtagacaaa tactgggaca 1380
gctacaacca tcccttcaga caggatcaga agaacttaga tcattatata atacagtagc 1440
aaccctctat tgtgtgcatc aaaggataga gataaaagac accaaggaag ctttagacaa 1500
gatagaggaa gagcaaaaca aaagtaagaa aaaagcacag caagcagcag ctgacacagg 1560
acacagcaat caggtcagcc aaaattaccc tatagtgcag aacatccagg ggcaaatggt 1620
acatcaggcc atatcaccta gaactttaaa tgcatgggta aaagtagtag aagagaaggc 1680
tttcagccca gaagtgatac ccatgttttc agcattatca gaaggagcca ccccacaaga 1740
tttaaacacc atgctaaaca cagtgggggg acatcaagca gccatgcaaa tgttaaaaga 1800
gaccatcaat gaggaagctg cagaatggga tagagtgcat ccagtgcatg cagggcctat 1860
tgcaccaggc cagatgagag aaccaagggg aagtgacata gcaggaacta ctagtaccct 1920
tcaggaacaa ataggatgga tgacacataa tccacctatc ccagtaggag aaatctataa 1980
aagatggata atcctgggat taaataaaat agtaagaatg tatagcccta ccagcattct 2040
ggacataaga caaggaccaa aggaaccctt tagagactat gtagaccgat tctataaaac 2100
tctaagagcc gagcaagctt cacaagaggt aaaaaattgg atgacagaaa ccttgttggt 2160
ccaaaatgcg aacccagatt gtaagactat tttaaaagca ttgggaccag gagcgacact 2220
agaagaaatg atgacagcat gtcagggagt ggggggaccc ggccataaag caagagtttt 2280
ggctgaagca atgagccaag taacaaatcc agctaccata atgatacaga aaggcaattt 2340
taggaaccaa agaaagactg ttaagtgttt caattgtggc aaagaagggc acatagccaa 2400
aaattgcagg gcccctagga aaaagggctg ttggaaatgt ggaaaggaag gacaccaaat 2460
gaaagattgt actgagagac aggctaattt tttagggaag atctggcctt cccacaaggg 2520
aaggccaggg aattttcttc agagcagacc agagccaaca gccccaccag aagagagctt 2580
caggtttggg gaagagacaa caactccctc tcagaagcag gagccgatag acaaggaact 2640
gtatccttta gcttccctca gatcactctt tggcagcgac ccctcgtcac aataaagata 2700
ggggggcaat taaaggaagc tctattagat acaggagcag atgatacagt attagaagaa 2760
atgaatttgc caggaagatg gaaaccaaaa atgatagggg gaattggagg ttttatcaaa 2820
gtaagacagt atgatcagat actcatagaa atctgcggac ataaagctat aggtacagta 2880
ttagtaggac ctacacctgt caacataatt ggaagaaatc tgttgactca gattggctgc 2940
actttaaatt ttcccattag tcctattgag actgtaccag taaaattaaa gccaggaatg 3000
gatggcccaa aagttaaaca atggccattg acagaagaaa aaataaaagc attagtagaa 3060
atttgtacag aaatggaaaa ggaaggaaaa atttcaaaaa ttgggcctga aaatccatac 3120
aatactccag tatttgccat aaagaaaaaa gacagtacta aatggagaaa attagtagat 3180
ttcagagaac ttaataagag aactcaagat ttctgggaag ttcaattagg aataccacat 3240
cctgccgggt taaaacagaa aaaatcagta acagtactgg atgtgggcga tgcatatttt 3300
tcagttccct tagataaaga cttcaggaag tatactgcat ttaccatacc tagtataaac 3360
aatgagacac cagggattag atatcagtac aatgtgcttc cacagggatg gaaaggatca 3420
ccagcaatat tccagtgtag catgacaaaa atcttagagc cttttagaaa acaaaatcca 3480
gacatagtca tctatcaata catggatgat ttgtatgtag gatctgactt agaaataggg 3540
cagcatagaa caaaaataga ggaactgaga caacatctgt tgaggtgggg atttaccaca 3600
ccagacaaaa aacatcagaa agaacctcca ttcctttgga tgggttatga actccatcct 3660
gataaatgga cagtacagcc tatagtgctg ccagaaaagg acagctggac tgtcaatgac 3720
atacagaaat tagtgggaaa attgaattgg gcaagtcaga tttatgcagg gattaaagta 3780
aggcaattat gtaaacttct taggggaacc aaagcactaa cagaagtagt accactaaca 3840
gaagaagcag agctagaact ggcagaaaac agggagattc taaaagaacc ggtacatgga 3900
gtgtattatg acccatcaaa agacttaata gcagaaatac agaagcaggg gcaaggccaa 3960
tggacatatc aaatttatca agagccattt aaaaatctga aaacaggaaa gtatgcaaga 4020
atgaagggtg cccacactaa tgatgtgaaa caattaacag aggcagtaca aaaaatagcc 4080
acagaaagca tagtaatatg gggaaagact cctaaattta aattacccat acaaaaggaa 4140
acatgggaag catggtggac agagtattgg caagccacct ggattcctga gtgggagttt 4200
gtcaataccc ctcccttagt gaagttatgg taccagttag agaaagaacc cataatagga 4260
gcagaaactt tctatgtaga tggggcagcc aatagggaaa ctaaattagg aaaagcagga 4320
tatgtaactg acagaggaag acaaaaagtt gtccccctaa cggacacaac aaatcagaag 4380
actgagttac aagcaattca tctagctttg caggattcgg gattagaagt aaacatagtg 4440
acagactcac aatatgcatt gggaatcatt caagcacaac cagataagag tgaatcagag 4500
ttagtcagtc aaataataga gcagttaata aaaaaggaaa aagtctacct ggcatgggta 4560
ccagcacaca aaggaattgg aggaaatgaa caagtagata aattggtcag tgctggaatc 4620
aggaaagtac tatttttaga tggaatagat aaggcccaag aagaacatga gaaatatcac 4680
agtaattgga gagcaatggc tagtgatttt aacctaccac ctgtagtagc aaaagaaata 4740
gtagccagct gtgataaatg tcagctaaaa ggggaagcca tgcatggaca agtagactgt 4800
agcccaggaa tatggcagct agattgtaca catttagaag gaaaagttat cttggtagca 4860
gttcatgtag ccagtggata tatagaagca gaagtaattc cagcagagac agggcaagaa 4920
acagcatact tcctcttaaa attagcagga agatggccag taaaaacagt acatacagac 4980
aatggcagca atttcaccag tactacagtt aaggccgcct gttggtgggc ggggatcaag 5040
caggaatttg gcattcccta caatccccaa agtcaaggag taatagaatc tatgaataaa 5100
gaattaaaga aaattatagg acaggtaaga gatcaggctg aacatcttaa gacagcagta 5160
caaatggcag tattcatcca caattttaaa agaaaagggg ggattggggg gtacagtgca 5220
ggggaaagaa tagtagacat aatagcaaca gacatacaaa ctaaagaatt acaaaaacaa 5280
attacaaaaa ttcaaaattt tcgggtttat tacagggaca gcagagatcc agtttggaaa 5340
ggaccagcaa agctcctctg gaaaggtgaa ggggcagtag taatacaaga taatagtgac 5400
ataaaagtag tgccaagaag aaaagcaaag atcatcaggg attatggaaa acagatggca 5460
ggtgatgatt gtgtggcaag tagacaggat gaggattaat agtctagaag gagctttgtt 5520
ccttgggttc ttgggagcag caggaagcac tatgggcgca gcgtcaatga cgctgacggt 5580
acaggccaga caattattgt ctggtatagt gcagcagcag aacaatttgc tgagggctat 5640
tgaggcgcaa cagcatctgt tgcaactcac agtctggggc atcaagcagc tccaggcaag 5700
aatcctggct gtggaaagat acctaaagga tcaacagctc ctggggattt ggggttgctc 5760
tggaaaactc atttgcacca ctgctgtgcc ttggaatgct agttggagta ataaatctct 5820
ggaacagatt tggaatcaca cgacctggat ggagtgggac agagaaatta acaattacac 5880
aagcttctcg agccatggag atctacgggt ggcatccctg tgacccctcc ccagtgcctc 5940
tcctggccct ggaagttgcc actccagtgc ccaccagcct tgtcctaata aaattaagtt 6000
gcatcatttt gtctgactag gtgtccttct ataatattat ggggtggagg ggggtggtat 6060
ggagcaaggg gcaagttggg aagacaacct gtagggcctg cggggtctat tgggaaccaa 6120
gctggagtgc agtggcacaa tcttggctca ctgcaatctc cgcctcctgg gttcaagcga 6180
ttctcctgcc tcagcctccc gagttgttgg gattccaggc aagcatgacc aggctcagct 6240
aatttttgtt tttttggtag agacggggtt tcaccatatt ggccaggctg gtctccaact 6300
cctaatctca ggtgatctac ccaccttggc ctcccaaatt gctgggatta caggcgtgaa 6360
ccactgctcc cttccctgtc cttggcgcgc c 6391
<210> 97
<211> 1282
<212> DNA
<213> 人工序列
<400> 97
cctgcaggtt actccctatc agtgatagag aacgtatgaa gagtttactc cctatcagtg 60
atagagaacg tatgcagact ttactcccta tcagtgatag agaacgtata aggagtttac 120
tccctatcag tgatagagaa cgtatgacca gtttactccc tatcagtgat agagaacgta 180
tctacagttt actccctatc agtgatagag aacgtatatc cagtttactc cctatcagtg 240
atagagaacg tattaggcgt gtacggtggg cgcctataaa agcagagctc gtttagtgaa 300
ccgtcagatc gcctggagca attccacata caaacagacc agattgtctg tttgttacac 360
ttttgtctta taccaacttt ccgtaccact tcctaccctc gtaaattcga aatcgatgcc 420
accatggcag gaagaagcgg agacagcgac gaagacctcc tcaaggcagt cagactcatc 480
aagtttctct atcaaagcaa cccacctccc aatcccgagg ggacccgaca ggcccgaagg 540
aatagaagaa gaaggtggag agagagacag agacagatcc attcgattag tgaacggatc 600
cttagcactt atctgggacg atctgcggag cctgtgcctc ttcagctacc accgcttgag 660
agacttactc ttgattgtaa cgaggattgt ggaacttctg ggacgcaggg ggtgggaagc 720
cctcaaatat tggtggaatc tcctacaata ttggagtcag gagctaaaga atagtaactc 780
gagccatgga gatctacggg tggcatccct gtgacccctc cccagtgcct ctcctggccc 840
tggaagttgc cactccagtg cccaccagcc ttgtcctaat aaaattaagt tgcatcattt 900
tgtctgacta ggtgtccttc tataatatta tggggtggag gggggtggta tggagcaagg 960
ggcaagttgg gaagacaacc tgtagggcct gcggggtcta ttgggaacca agctggagtg 1020
cagtggcaca atcttggctc actgcaatct ccgcctcctg ggttcaagcg attctcctgc 1080
ctcagcctcc cgagttgttg ggattccagg caagcatgac caggctcagc taatttttgt 1140
ttttttggta gagacggggt ttcaccatat tggccaggct ggtctccaac tcctaatctc 1200
aggtgatcta cccaccttgg cctcccaaat tgctgggatt acaggcgtga accactgctc 1260
ccttccctgt ccttggcgcg cc 1282
<210> 98
<211> 2961
<212> DNA
<213> 人工序列
<400> 98
cctgcaggtt actccctatc agtgatagag aacgtatgaa gagtttactc cctatcagtg 60
atagagaacg tatgcagact ttactcccta tcagtgatag agaacgtata aggagtttac 120
tccctatcag tgatagagaa cgtatgacca gtttactccc tatcagtgat agagaacgta 180
tctacagttt actccctatc agtgatagag aacgtatatc cagtttactc cctatcagtg 240
atagagaacg tattaggcgt gtacggtggg cgcctataaa agcagagctc gtttagtgaa 300
ccgtcagatc gcctggagca attccacata caaacagacc agattgtctg tttgttacac 360
ttttgtctta taccaacttt ccgtaccact tcctaccctc gtaaattcga atcccggccg 420
ggaacggtgc attggaacgc ggattccccg tgccaagagt gacgtaagta ccgcctatag 480
agtctatagg cccacaaaaa atgctttctt cttttaatat acttttttgt ttatcttatt 540
tctaatactt tccctaatct ctttctttca gggcaataat gatacaatgt atcatgcctc 600
tttgcaccat tctaaagaat aacagtgata atttctgggt taaggcaata gcaatatttc 660
tgcatataaa tatttctgca tataaattgt aactgatgta agaggtttca tattgctaat 720
agcagctaca atccagctac cattctgctt ttattttatg gttgggataa ggctggatta 780
ttctgagtcc aagctaggcc cttttgctaa tcatgttcat acctcttatc ttcctcccac 840
agctcctggg caacgtgctg gtctgtgtgc tggcccatca ctttggcaaa gaattgggat 900
tcgaaatcga tgccaccatg aagtgccttt tgtacttagc ctttttattc attggggtga 960
attgcaagtt caccatagtt tttccacaca accaaaaagg aaactggaaa aatgttcctt 1020
ctaattacca ttattgcccg tcaagctcag atttaaattg gcataatgac ttaataggca 1080
cagccttaca agtcaaaatg cccaagagtc acaaggctat tcaagcagac ggttggatgt 1140
gtcatgcttc caaatgggtc actacttgtg atttccgctg gtatggaccg aagtatataa 1200
cacattccat ccgatccttc actccatctg tagaacaatg caaggaaagc attgaacaaa 1260
cgaaacaagg aacttggctg aatccaggct tccctcctca aagttgtgga tatgcaactg 1320
tgacggatgc cgaagcagtg attgtccagg tgactcctca ccatgtgctg gttgatgaat 1380
acacaggaga atgggttgat tcacagttca tcaacggaaa atgcagcaat tacatatgcc 1440
ccactgtcca taactctaca acctggcatt ctgactataa ggtcaaaggg ctatgtgatt 1500
ctaacctcat ttccatggac atcaccttct tctcagagga cggagagcta tcatccctgg 1560
gaaaggaggg cacagggttc agaagtaact actttgctta tgaaactgga ggcaaggcct 1620
gcaaaatgca atactgcaag cattggggag tcagactccc atcaggtgtc tggttcgaga 1680
tggctgataa ggatctcttt gctgcagcca gattccctga atgcccagaa gggtcaagta 1740
tctctgctcc atctcagacc tcagtggatg taagtctaat tcaggacgtt gagaggatct 1800
tggattattc cctctgccaa gaaacctgga gcaaaatcag agcgggtctt ccaatctctc 1860
cagtggatct cagctatctt gctcctaaaa acccaggaac cggtcctgct ttcaccataa 1920
tcaatggtac cctaaaatac tttgagacca gatacatcag agtcgatatt gctgctccaa 1980
tcctctcaag aatggtcgga atgatcagtg gaactaccac agaaagggaa ctgtgggatg 2040
actgggcacc atatgaagac gtggaaattg gacccaatgg agttctgagg accagttcag 2100
gatataagtt tcctttatac atgattggac atggtatgtt ggactccgat cttcatctta 2160
gctcaaaggc tcaggtgttc gaacatcctc acattcaaga cgctgcttcg caacttcctg 2220
atgatgagag tttatttttt ggtgatactg ggctatccaa aaatccaatc gagcttgtag 2280
aaggttggtt cagtagttgg aaaagctcta ttgcctcttt tttctttatc atagggttaa 2340
tcattggact attcttggtt ctccgagttg gtatccatct ttgcattaaa ttaaagcaca 2400
ccaagaaaag acagatttat acagacatag agatgaaccg acttggaaag taatagctcg 2460
agccatggag atctacgggt ggcatccctg tgacccctcc ccagtgcctc tcctggccct 2520
ggaagttgcc actccagtgc ccaccagcct tgtcctaata aaattaagtt gcatcatttt 2580
gtctgactag gtgtccttct ataatattat ggggtggagg ggggtggtat ggagcaaggg 2640
gcaagttggg aagacaacct gtagggcctg cggggtctat tgggaaccaa gctggagtgc 2700
agtggcacaa tcttggctca ctgcaatctc cgcctcctgg gttcaagcga ttctcctgcc 2760
tcagcctccc gagttgttgg gattccaggc aagcatgacc aggctcagct aatttttgtt 2820
tttttggtag agacggggtt tcaccatatt ggccaggctg gtctccaact cctaatctca 2880
ggtgatctac ccaccttggc ctcccaaatt gctgggatta caggcgtgaa ccactgctcc 2940
cttccctgtc cttggcgcgc c 2961
<210> 99
<211> 6439
<212> DNA
<213> 人工序列
<400> 99
cctgcaggga cattgattat tgacatgtta ttaatagtaa tcaattacgg ggtcattagt 60
tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 120
accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 180
aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 240
agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 300
gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 360
ctacgtatta gtcatcgcta ttaccatggt cgaggtgagc cccacgttct gcttcactct 420
ccccatctcc cccccctccc cacccccaat tttgtattta tttatttttt aattattttg 480
tgcagcgatg ggggcggggg gggggggggg gcgcgcgcca ggcggggcgg ggcggggcga 540
ggggcggggc ggggcgaggc ggagaggtgc ggcggcagcc aatcagagcg gcgcgctccg 600
aaagtttcct tttatggcga ggcggcggcg gcggcggccc tataaaaagc gaagcgcgcg 660
gcgggcgttc gaaggagtcg ctgcgacgct gccttcgccc cgtgccccgc tccgccgccg 720
cctcgcgccg cccgccccgg ctctgactga ccgcgttact cccacaggtg agcgggcggg 780
acggcccttc tcctccgggc tgtaattagc gcttggttta atgacggctt gtttcttttc 840
tgtggctgcg tgaaagcctt gaggggctcc gggagggccc tttgtgcggg gggagcggct 900
cggggggtgc gtgcgtgtgt gtgtgcgtgg ggagcgccgc gtgcggctcc gcgctgcccg 960
gcggctgtga gcgctgcggg cgcggcgcgg ggctttgtgc gctccgcagt gtgcgcgagg 1020
ggagcgcggc cgggggcggt gccccgcggt gcgggggggg ctgcgagggg aacaaaggct 1080
gcgtgcgggg tgtgtgcgtg ggggggtgag cagggggtgt gggcgcgtcg gtcgggctgc 1140
aaccccccct gcacccccct ccccgagttg ctgagcacgg cccggcttcg ggtgcggggc 1200
tccgtacggg gcgtggcgcg gggctcgccg tgccgggcgg ggggtggcgg caggtggggg 1260
tgccgggcgg ggcggggccg cctcgggccg gggagggctc gggggagggg cgcggcggcc 1320
cccggagcgc cggcggctgt cgaggcgcgg cgagccgcag ccattgcctt ttatggtaat 1380
cgtgcgagag ggcgcaggga cttcctttgt cccaaatctg tgcggagccg aaatctggga 1440
ggcgccgccg caccccctct agcgggcgcg gggcgaagcg gtgcggcgcc ggcaggaagg 1500
aaatgggcgg ggagggcctt cgtgcgtcgc cgcgccgccg tccccttctc cctctccagc 1560
ctcggggctg tccgcggggg gacggctgcc ttcggggggg acggggcagg gcggggttcg 1620
gcttctggcg tgtgaccggc ggctcttgag cctctgctaa ccatgttcat gccttcttct 1680
ttttcctaca gcttcgaacc tgggcaacgt gctggttatt gtgctgtctc atcattttgg 1740
caaaatcgat gccaccatgt ccagactgga caagagcaaa gtcataaacg gcgctctgga 1800
attactcaat ggagtcggta tcgaaggcct gacgacaagg aaactcgctc aaaagctggg 1860
agttgagcag cctaccctgt actggcacgt gaagaacaag cgggccctgc tcgatgccct 1920
gccaatcgag atgctggaca ggcatcatac ccacttctgc cccctggaag gcgagtcatg 1980
gcaagacttt ctgcggaaca acgccaagtc attccgctgt gctctcctct cacatcgcga 2040
cggggctaaa gtgcatctcg gcacccgccc aacagagaaa cagtacgaaa ccctggaaaa 2100
tcagctcgcg ttcctgtgtc agcaaggctt ctccctggag aacgcactgt acgctctgtc 2160
cgccgtgggc cactttacac tgggctgcgt attggaggaa caggagcatc aagtagcaaa 2220
agaggaaaga gagacaccta ccaccgattc tatgccccca cttctgagac aagcaattga 2280
gctgttcgac cggcagggag ccgaacctgc cttccttttc ggcctggaac taatcatatg 2340
tggcctggag aaacagctaa agtgcgaaag cggcgggccg gccgacgccc ttgacgattt 2400
tgacttagac atgctcccag ccgatgccct tgacgacttt gaccttgata tgctgcctgc 2460
tgacgctctt gacgattttg accttgacat gctccccggg taactcgagg atatcccatg 2520
gagatctatg gggacatcat gaagcccctt gagcatctga cttctggcta ataaaggaaa 2580
tttattttca ttgcaatagt gtgttggaat tttttgtgtc tctcactcgg aaggacatat 2640
gggagccgcg tctagttatt aatagtaatc aattacgggg tcattagttc atagcccata 2700
tatggagttc cgcgttacat aacttacggt aaatggcccg cctggctgac cgcccaacga 2760
cccccgccca ttgacgtcaa taatgacgta tgttcccata gtaacgccaa tagggacttt 2820
ccattgacgt caatgggtgg agtatttacg gtaaactgcc cacttggcag tacatcaagt 2880
gtatcatatg ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca 2940
ttatgcccag tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt 3000
catcgctatt accatggtga tgcggttttg gcagtacatc aatgggcgtg gatagcggtt 3060
tgactcacgg ggatttccaa gtctccaccc cattgacgtc aatgggagtt tgttttggca 3120
ccaaaatcaa cgggactttc caaaatgtcg taacaactcc gccccattga cgcaaatggg 3180
cggtaggcgt gtacggtggg aggtctatat aagcagagct cgtttagtga accgtcagat 3240
cgcctggaga cgccatccac gctgttttga cctccataga agacaccggg accgatccag 3300
cctccgcgga ttcgaatccc ggccgggaac ggtgcattgg aacgcggatt ccccgtgcca 3360
agagtgacgt aagtaccgcc tatagagtct ataggcccac aaaaaatgct ttcttctttt 3420
aatatacttt tttgtttatc ttatttctaa tactttccct aatctctttc tttcagggca 3480
ataatgatac aatgtatcat gcctctttgc accattctaa agaataacag tgataatttc 3540
tgggttaagg caatagcaat atttctgcat ataaatattt ctgcatataa attgtaactg 3600
atgtaagagg tttcatattg ctaatagcag ctacaatcca gctaccattc tgcttttatt 3660
ttatggttgg gataaggctg gattattctg agtccaagct aggccctttt gctaatcatg 3720
ttcatacctc ttatcttcct cccacagctc ctgggcaacg tgctggtctg tgtgctggcc 3780
catcactttg gcaaagaatt gggattcgaa catcgatgcc accatgtctc caaagaggag 3840
aacccaggca gagagggcaa tggagacaca gggcaagctg atcgccgccg ccctgggcgt 3900
gctgagggag aagggatacg caggcttccg catcgccgat gtgccaggag ccgccggcgt 3960
gtcccggggc gcacagtctc accacttccc taccaagctg gagctgctgc tggccacatt 4020
tgagtggctg tatgagcaga tcaccgagag gagccgcgcc aggctggcaa agctgaagcc 4080
agaggacgat gtgatccagc agatgctgga cgatgccgcc gagttctttc tggacgatga 4140
ctttagcatc tccctggatc tgatcgtggc cgccgataga gaccccgccc tgagggaggg 4200
catccagagg acagtggaga gaaacaggtt cgtggtggag gatatgtggc tgggcgtgct 4260
ggtgtctcgc ggcctgagcc gggatgacgc agaggacatc ctgtggctga tctttaacag 4320
cgtgcggggc ctggccgtga gatccctgtg gcagaaggac aaggagcggt tcgagcgcgt 4380
gcggaattcc accctggaga tcgccagaga gaggtacgcc aagtttaaga gatgataact 4440
cgagccatgg agatctacgg gtggcatccc tgtgacccct ccccagtgcc tctcctggcc 4500
ctggaagttg ccactccagt gcccaccagc cttgtcctaa taaaattaag ttgcatcatt 4560
ttgtctgact aggtgtcctt ctataatatt atggggtgga ggggggtggt atggagcaag 4620
gggcaagttg ggaagacaac ctgtagggcc tgcggggtct attgggaacc aagctggagt 4680
gcagtggcac aatcttggct cactgcaatc tccgcctcct gggttcaagc gattctcctg 4740
cctcagcctc ccgagttgtt gggattccag gcaagcatga ccaggctcag ctaatttttg 4800
tttttttggt agagacgggg tttcaccata ttggccaggc tggtctccaa ctcctaatct 4860
caggtgatct acccaccttg gcctcccaaa ttgctgggat tacaggcgtg aaccactgct 4920
cccttccctg tccttgcatg ccctagtgtg tgtcagttag ggtgtggaaa gtccccaggc 4980
tccccagcag gcagaagtat gcaaagcatg catctcaatt agtcagcaac caggtgtgga 5040
aagtccccag gctccccagc aggcagaagt atgcaaagca tgcatctcaa ttagtcagca 5100
accatagtcc cgcccctaac tccgcccatc ccgcccctaa ctccgcccag ttccgcccat 5160
tctccgcccc atggctgact aatttttttt atttatgcag aggccgaggc cgcctctgcc 5220
tctgagctat tccagaagta gtgaggaggc ttttttggag gccataggct tttgcaaaaa 5280
gctatgaaaa agcctgaact cacagcgact tctgttgaga agtttctgat cgaaaagttc 5340
gacagcgtta gcgacctgat gcagctctcg gagggcgagg aatctagggc tttcagcttc 5400
gatgtaggag ggcgtggata tgtcctgcgg gtaaatagct gcgccgatgg tttctacaaa 5460
gatcgttatg tttatcggca ctttgcatcg gctgcgctcc cgattcccga agtgcttgac 5520
attggggagt tcagcgagag cctgacctat tgcatctccc gccgcgcaca gggcgtaact 5580
ttgcaagacc tccctgaaac cgaactgccc gctgttctac aacctgtcgc ggaggctatg 5640
gacgctattg ctgctgccga tctttcccag acttccgggt tcggcccatt tggaccgcaa 5700
ggaatcggtc aatacactac atggcgtgat ttcatttgcg cgattgctga tccccatgtg 5760
tatcattggc aaactgtgat ggatgatacc gtcagcgcga gtgtcgcgca ggctctcgat 5820
gagctgatgc tttgggccga ggattgcccc gaagttcgcc acttggtcca cgcggatttc 5880
ggcagcaaca atgtcctgac agataatggc cgcataacag cggtcattga ttggagcgaa 5940
gctatgttcg gggattccca atacgaggtc gctaacatct ttttctggcg tccttggttg 6000
gcttgtatgg agcagcaaac gcgctacttt gaaagacgac atccagagct tgcaggatcg 6060
cctcggctcc gggcgtatat gctccgcatt ggtcttgacc aactctatca gagcttggtg 6120
gacggcaatt tcgatgatgc tgcttgggcg cagggtcgat gtgatgcaat cgtccgaagt 6180
ggagccggga ctgtcgggcg aacacaaatc gcccgcagaa gcgcagccgt ctggaccgat 6240
ggctgtgtag aagttctcgc cgatagtgga aacagacgcc cctctactcg tccgagggca 6300
aaggaataga acttgtttat tgcagcttat aatggttaca aataaagcaa tagcatcaca 6360
aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc caaactcatc 6420
aatgtatctt aggcgcgcc 6439
<210> 100
<211> 7091
<212> DNA
<213> 人工序列
<400> 100
cctgcaggtt aagtagtctt atgcaatact cttgtagtct tgcaacatgg taacgatgag 60
ttagcaacat gccttacaag gagagaaaaa gcaccgtgca tgccgattgg tggaagtaag 120
gtggtacgat cgtgccttat taggaaggca acagacgggt ctgacatgga ttggacgaac 180
cactgaattg ccgcattgca gagatattgt atttaagtgc ctagctcgat acataaacgg 240
gtctctctgg ttagaccaga tctgagcctg ggagctctct ggctaactag ggaacccact 300
gcttaagcct caataaagct tgccttgagt gcttcaagta gtgtgtgccc gtctgttgtg 360
tgactctggt aactagagat ccctcagacc cttttagtca gtgtggaaaa tctctagcag 420
tggcgcccga acagggactt gaaagcgaaa gggaaaccag aggagctctc tcgacgcagg 480
actcggcttg ctgaagcgcg cacggcaaga ggcgaggggc ggcgactggt gagtacgcca 540
aaaattttga ctagcggagg ctagaaggag agagatgggt gcgagagcgt cagtattaag 600
cgggggagaa ttagatcgcg atgggaaaaa attcggttaa ggccaggggg aaagaaaaaa 660
tataaattaa aacatatagt atgggcaagc agggagctag aacgattcgc agttaatcct 720
ggcctgttag aaacatcaga aggctgtaga caaatactgg gacagctaca accatccctt 780
cagacaggat cagaagaact tagatcatta tataatacag tagcaaccct ctattgtgtg 840
catcaaagga tagagataaa agacaccaag gaagctttag acaagataga ggaagagcaa 900
aacaaaagaa tcgatattag gagtagcacc caccaaggca aagagaagag tggtgcagag 960
agaaaaaaga gcagtgggaa taggagcttt gttccttggg ttcttgggag cagcaggaag 1020
cactatgggc gcagcgtcaa tgacgctgac ggtacaggcc agacaattat tgtctggtat 1080
agtgcagcag cagaacaatt tgctgagggc tattgaggcg caacagcatc tgttgcaact 1140
cacagtctgg ggcatcaagc agctccaggc aagaatcctg gctgtggaaa gatacctaaa 1200
ggatcaacag ctcctgggga tttggggttg ctctggaaaa ctcatttgca ccactgctgt 1260
gccttggaat gctagttgga gaattcttcg aaatggtacc aaggcctttt taaaagaaaa 1320
ggggggattg gggggtacag tgcaggggaa agaatagtag acataatagc aacagacata 1380
caaactaaag aattacaaaa acaaattaca aaaattcaaa attttacgcg tggggttggg 1440
gttgcgcctt ttccaaggca gccctgggtt tgcgcaggga cgcggctgct ctgggcgtgg 1500
ttccgggaaa cgcagcggcg ccgaccctgg gtctcgcaca ttcttcacgt ccgttcgcag 1560
cgtcacccgg atcttcgccg ctacccttgt gggccccccg gcgacgcttc ctgctccgcc 1620
cctaagtcgg gaaggttcct tgcggttcgc ggcgtgccgg acgtgacaaa cggaagccgc 1680
acgtctcact agtaccctcg cagacggaca gcgccaggga gcaatggcag cgcgccgacc 1740
gcgatgggct gtggccaata gcggctgctc agcagggcgc gcggagagca gcggccggga 1800
aggggcggtg cgggaggcgg ggtgtggggc ggtagtgtgg gccctgttcc tgcccgcgcg 1860
gtgttccgca ttctgcaagc ctccggagcg cacgtcggca gtcggctccc tcgttgaccg 1920
aatcaccgac ctctctcccc agggggatcc atctgcgatc taagtaagct tggcattccg 1980
gtactgttgg taaagccacc atggaagacg ccaaaaacat aaagaaaggc ccggcgccat 2040
tctatccgct ggaagatgga accgctggag agcaactgca taaggctatg aagagatacg 2100
ccctggttcc tggaacaatt gcttttacag atgcacatat cgaggtggac atcacttacg 2160
ctgagtactt cgaaatgtcc gttcggttgg cagaagctat gaaacgatat gggctgaata 2220
caaatcacag aatcgtcgta tgcagtgaaa actctcttca attctttatg ccggtgttgg 2280
gcgcgttatt tatcggagtt gcagttgcgc ccgcgaacga catttataat gaacgtgaat 2340
tgctcaacag tatgggcatt tcgcagccta ccgtggtgtt cgtttccaaa aaggggttgc 2400
aaaaaatttt gaacgtgcaa aaaaagctcc caatcatcca aaaaattatt atcatggatt 2460
ctaaaacgga ttaccaggga tttcagtcga tgtacacgtt cgtcacatct catctacctc 2520
ccggttttaa tgaatacgat tttgtgccag agtccttcga tagggacaag acaattgcac 2580
tgatcatgaa ctcctctgga tctactggtc tgcctaaagg tgtcgctctg cctcatagaa 2640
ctgcctgcgt gagattctcg catgccagag atcctatttt tggcaatcaa atcattccgg 2700
atactgcgat tttaagtgtt gttccattcc atcacggttt tggaatgttt actacactcg 2760
gatatttgat atgtggattt cgagtcgtct taatgtatag atttgaagaa gagctgtttc 2820
tgaggagcct tcaggattac aagattcaaa gtgcgctgct ggtgccaacc ctattctcct 2880
tcttcgccaa aagcactctg attgacaaat acgatttatc taatttacac gaaattgctt 2940
ctggtggcgc tcccctctct aaggaagtcg gggaagcggt tgccaagagg ttccatctgc 3000
caggtatcag gcaaggatat gggctcactg agactacatc agctattctg attacacccg 3060
agggggatga taaaccgggc gcggtcggta aagttgttcc attttttgaa gcgaaggttg 3120
tggatctgga taccgggaaa acgctgggcg ttaatcaaag aggcgaactg tgtgtgagag 3180
gtcctatgat tatgtccggt tatgtaaaca atccggaagc gaccaacgcc ttgattgaca 3240
aggatggatg gctacattct ggagacatag cttactggga cgaagacgaa cacttcttca 3300
tcgttgaccg cctgaagtct ctgattaagt acaaaggcta tcaggtggct cccgctgaat 3360
tggaatccat cttgctccaa caccccaaca tcttcgacgc aggtgtcgca ggtcttcccg 3420
acgatgacgc cggtgaactt cccgccgccg ttgttgtttt ggagcacgga aagacgatga 3480
cggaaaaaga gatcgtggat tacgtcgcca gtcaagtaac aaccgcgaaa aagttgcgcg 3540
gaggagttgt gtttgtggac gaagtaccga aaggtcttac cggaaaactc gacgcaagaa 3600
aaatcagaga gatcctcata aaggccaaga agggcggaaa gatcgccgtg taattctagc 3660
tcgaggcccc tctccctccc ccccccctaa cgttactggc cgaagccgct tggaataagg 3720
ccggtgtgcg tttgtctata tgttattttc caccatattg ccgtcttttg gcaatgtgag 3780
ggcccggaaa cctggccctg tcttcttgac gagcattcct aggggtcttt cccctctcgc 3840
caaaggaatg caaggtctgt tgaatgtcgt gaaggaagca gttcctctgg aagcttcttg 3900
aagacaaaca acgtctgtag cgaccctttg caggcagcgg aaccccccac ctggcgacag 3960
gtgcctctgc ggccaaaagc cacgtgtata agatacacct gcaaaggcgg cacaacccca 4020
gtgccacgtt gtgagttgga tagttgtgga aagagtcaaa tggctctcct caagcgtatt 4080
caacaagggg ctgaaggatg cccagaaggt accccattgt atgggatctg atctggggcc 4140
tcggtacaca tgctttacat gtgtttagtc gaggttaaaa aaacgtctag gccccccgaa 4200
ccacggggac gtggttttcc tttgaaaaac acgatgataa tatggccaca accatggtga 4260
gcaagggcga ggagctgttc accggggtgg tgcccatcct ggtcgagctg gacggcgacg 4320
taaacggcca caagttcagc gtgtccggcg agggcgaggg cgatgccacc tacggcaagc 4380
tgaccctgaa gttcatctgc accaccggca agctgcccgt gccctggccc accctcgtga 4440
ccaccctgac ctacggcgtg cagtgcttca gccgctaccc cgaccacatg aagcagcacg 4500
acttcttcaa gtccgccatg cccgaaggct acgtccagga gcgcaccatc ttcttcaagg 4560
acgacggcaa ctacaagacc cgcgccgagg tgaagttcga gggcgacacc ctggtgaacc 4620
gcatcgagct gaagggcatc gacttcaagg aggacggcaa catcctgggg cacaagctgg 4680
agtacaacta caacagccac aacgtctata tcatggccga caagcagaag aacggcatca 4740
aggtgaactt caagatccgc cacaacatcg aggacggcag cgtgcagctc gccgaccact 4800
accagcagaa cacccccatc ggcgacggcc ccgtgctgct gcccgacaac cactacctga 4860
gcacccagtc cgccctgagc aaagacccca acgagaagcg cgatcacatg gtcctgctgg 4920
agttcgtgac cgccgccggg atcactctcg gcatggacga gctgtacaag taaagatccg 4980
atatcatatg aatcaacctc tggattacaa aatttgtgaa agattgactg gtattcttaa 5040
ctatgttgct ccttttacgc tatgtggata cgctgcttta atgcctttgt atcatgctat 5100
tgcttcccgt atggctttca ttttctcctc cttgtataaa tcctggttgc tgtctcttta 5160
tgaggagttg tggcccgttg tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc 5220
aacccccact ggttggggca ttgccaccac ctgtcagctc ctttccggga ctttcgcttt 5280
ccccctccct attgccacgg cggaactcat cgccgcctgc cttgcccgct gctggacagg 5340
ggctcggctg ttgggcactg acaattccgt ggtgttgtcg gggaagctga cgtcctttcc 5400
atggctgctc gcctgtgttg ccacctggat tctgcgcggg acgtccttct gctacgtccc 5460
ttcggccctc aatccagcgg accttccttc ccgcggcctg ctgccggctc tgcggcctct 5520
tccgcgtctt cgccttcgcc ctcagacgag tcggatctcc ctttgggccg cctccccgcc 5580
tggcggccgc ttaagaccaa tgacttacaa ggcagctgta gatcttagcc actttttaaa 5640
agaaaagggg ggactggaag ggctaattca ctcccaacga agacaagatc tgctttttgc 5700
ttgtactggg tctctctggt tagaccagat ctgagcctgg gagctctctg gctaactagg 5760
gaacccactg cttaagcctc aataaagctt gccttgagtg cttcaagtag tgtgtgcccg 5820
tctgttgtgt gactctggta actagagatc cctcagaccc ttttagtcag tgtggaaaat 5880
ctctagcagg cgatcgcaac ttgtttattg cagcttataa tggttacaaa taaagcaata 5940
gcatcacaaa tttcacaaat aaagcatttt tttcactgca ttctagttgt ggtttgtcca 6000
aactcatcaa tgtatcttac ctagtgtgtg tcagttaggg tgtggaaagt ccccaggctc 6060
cccagcaggc agaagtatgc aaagcatgca tctcaattag tcagcaacca ggtgtggaaa 6120
gtccccaggc tccccagcag gcagaagtat gcaaagcatg catctcaatt agtcagcaac 6180
catagtcccg cccctaactc cgcccatccc gcccctaact ccgcccagtt ccgcccattc 6240
tccgccccat ggctgactaa ttttttttat ttatgcagag gccgaggccg cctctgcctc 6300
tgagctattc cagaagtagt gaggaggctt ttttggaggc cataggcttt tgcaaaaagc 6360
tatgactgag tacaagccca cggtgcgcct cgccacccgc gacgatgttc ctagagccgt 6420
ccgcaccctc gccgccgcgt tcgccgacta ccccgccacg cgccacaccg tagaccctga 6480
ccgccacatc gagagggtca cagagctgca agagctgttt ctcacgcgcg tcgggctcga 6540
catcggcaag gtgtgggtcg cggacgacgg cgcagcggtg gcggtctgga ccacgccgga 6600
gagcgtcgaa gcgggggcgg tgttcgccga gatcggcccg cgcatggccg agttgagcgg 6660
ttcccggctg gccgcgcagc aacagatgga gggacttctg gcaccgcacc gacccaagga 6720
gcccgcgtgg ttcctggcta ccgtcggtgt ctcgcccgac caccagggca agggtctggg 6780
ctccgccgtc gttctccccg gagtggaggc agccgagaga gccggggtgc ccgcctttct 6840
ggaaacctcc gcgccccgca acctcccctt ctacgagcgg ctcggcttca ccgtcaccgc 6900
cgatgtcgag gtgcccgaag gaccgcgtac ctggtgcatg acccgcaagc ccggtgcctg 6960
aaacttgttt attgcagctt ataatggtta caaataaagc aatagcatca caaatttcac 7020
aaataaagca tttttttcac tgcattctag ttgtggtttg tccaaactca tcaatgtatc 7080
ttaggcgcgc c 7091
<210> 101
<211> 20
<212> DNA
<213> 人工序列
<400> 101
attctgagtc caagctaggc 20
<210> 102
<211> 17
<212> DNA
<213> 人工序列
<400> 102
gggccctcac attgcca 17
<210> 103
<211> 22
<212> DNA
<213> 人工序列
<400> 103
gcaacagctc cctgaatcct gc 22
<210> 104
<211> 26
<212> DNA
<213> 人工序列
<400> 104
gagctgttgc tcaccacctg ttcgca 26
<210> 105
<211> 30
<212> DNA
<213> 人工序列
<400> 105
agagtgttca agctgctgtg cgacgatctg 30
<210> 106
<211> 30
<212> DNA
<213> 人工序列
<400> 106
cacagcagct tgaacactct ggcgttcaga 30
<210> 107
<211> 31
<212> DNA
<213> 人工序列
<400> 107
tcaatagcaa gaaaagcaag ctgaagctct g 31
<210> 108
<211> 34
<212> DNA
<213> 人工序列
<400> 108
cagcttgctt ttcttgctat tgattctgct gttc 34
<210> 109
<211> 39
<212> DNA
<213> 人工序列
<400> 109
ctgagagagc cgtgaagctg ctgatgcctt ttgtgacca 39
<210> 110
<211> 39
<212> DNA
<213> 人工序列
<400> 110
cagcagcttc acggctctct cagaaatctc ggggaattc 39
<210> 111
<211> 30
<212> DNA
<213> 人工序列
<400> 111
cgccaagaat gactacgtgg tcaacctgga 30
<210> 112
<211> 31
<212> DNA
<213> 人工序列
<400> 112
tgaccacgta gtcattcttg gcgtccacca g 31
<210> 113
<211> 40
<212> DNA
<213> 人工序列
<400> 113
agcagacacg tgaacgtgaa gggaagatac gtgaggtgtc 40
<210> 114
<211> 43
<212> DNA
<213> 人工序列
<400> 114
cttcccttca cgttcacgtg tctgctggaa ggctcgccca gct 43
<210> 115
<211> 38
<212> DNA
<213> 人工序列
<400> 115
gcgaatcgat gccaccatgg acatcgagag acaggaag 38
<210> 116
<211> 36
<212> DNA
<213> 人工序列
<400> 116
gcgaatcgat gccaccatgg atatcgagcg gcagga 36
<210> 117
<211> 33
<212> DNA
<213> 人工序列
<400> 117
cagaatcctc tgaccagata cgccagagca cat 33
<210> 118
<211> 33
<212> DNA
<213> 人工序列
<400> 118
tctggcgtat ctggtcagag gattctgggt cag 33
<210> 119
<211> 32
<212> DNA
<213> 人工序列
<400> 119
ctgtactgcc tgaacacacc tgcttgtggc ac 32
<210> 120
<211> 31
<212> DNA
<213> 人工序列
<400> 120
agcaggtgtg ttcaggcagt acagggcggt a 31
<210> 121
<211> 37
<212> DNA
<213> 人工序列
<400> 121
aggaagacca gacactggta caaaaaagtg ggaatct 37
<210> 122
<211> 35
<212> DNA
<213> 人工序列
<400> 122
cacttttttg taccagtgtc tggtcttcct ggtgg 35
<210> 123
<211> 73
<212> DNA
<213> 人工序列
<400> 123
gactctcgag ttatcagtag tgcagctggg tgtggtagat ctcgaaacag ggcttccggc 60
acaggccggg gtt 73
<210> 124
<211> 29
<212> DNA
<213> 人工序列
<400> 124
cagtcctgaa gatccccgtg ttctctgct 29
<210> 125
<211> 31
<212> DNA
<213> 人工序列
<400> 125
aacacgggga tcttcaggac tgttgtggtg t 31
<210> 126
<211> 37
<212> DNA
<213> 人工序列
<400> 126
gcgaatcgat gccaccatgg ccaagagatt ctacagc 37
<210> 127
<211> 36
<212> DNA
<213> 人工序列
<400> 127
gcgaatcgat gccaccatgg ccaagcggtt ctacag 36
<210> 128
<211> 31
<212> DNA
<213> 人工序列
<400> 128
agatcgacgg cagcatggat gccgtgcagt a 31
<210> 129
<211> 27
<212> DNA
<213> 人工序列
<400> 129
catccatgct gccgtcgatc ttgtgca 27
<210> 130
<211> 21
<212> DNA
<213> 人工序列
<400> 130
cctttccggg actttcgctt t 21
<210> 131
<211> 20
<212> DNA
<213> 人工序列
<400> 131
gcagaatcca ggtggcaaca 20
<210> 132
<211> 22
<212> DNA
<213> 人工序列
<400> 132
actcatcgcc gcctgccttg cc 22

Claims (9)

1.用于将一种或多种外源核苷酸序列整合到哺乳动物宿主细胞基因组中的方法，其特征在于，所述方法包括通过使用至少两种转座子系统将所述一种或多种外源核苷酸序列整合到所述哺乳动物宿主细胞基因组中。
2.根据权利要求1所述的方法，其特征在于，所述至少两种转座子系统包括：Tol1转座子系统、Tol2转座子系统、Frog Prince转座子系统、Minos转座子系统、Hsmar1转座子系统、Helraiser转座子系统、ZB转座子系统、Intruder转座子系统、SPINON转座子系统、TcBuster转座子系统、Passport转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PiggyBac(PB)转座子系统、Sleeping Beauty(SB)转座子系统，以及上述转座子系统的各种变体或衍生物；优选地，所述至少两种转座子系统包括：Tol1转座子系统、Tol2转座子系统、ZB转座子系统、Intruder转座子系统、TcBuster转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PB转座子系统和SB转座子系统，以及上述转座子系统的各种变体或衍生物。
3.根据权利要求1所述的方法，其特征在于，通过同时或相继使用所述至少两种转座子系统将所述一种或多种外源核苷酸序列整合到所述哺乳动物宿主细胞基因组中。
4.通过根据权利要求1-3中任一项所述的方法获得的包含整合在其基因组中的一种或多种外源核苷酸序列的哺乳动物细胞。
5.哺乳动物细胞，其特征在于，所述哺乳动物细胞包含整合在其基因组中的至少两种转座子。
6.根据权利要求5所述的哺乳动物细胞，其中所述至少两种转座子的序列彼此不重叠。
7.根据权利要求5或6所述的哺乳动物细胞，其中所述至少两种转座子包括：Tol1转座子、Tol2转座子、Frog Prince转座子、Minos转座子、Hsmar1转座子、Helraiser转座子、ZB转座子、Intruder转座子、SPINON转座子、TcBuster转座子、Passport转座子、Yabusame-1转座子、Uribo2转座子、PiggyBac(PB)转座子、Sleeping Beauty(SB)转座子，以及上述转座子的各种变体或衍生物；优选地，所述至少两种转座子包括：Tol1转座子、Tol2转座子、ZB转座子、Intruder转座子、TcBuster转座子、Yabusame-1转座子、Uribo2转座子、PB转座子和SB转座子，以及上述转座子的各种变体或衍生物。
8.用于构建慢病毒生产细胞系的方法，其特征在于，所述方法包括通过使用至少两种转座子系统将慢病毒的gag、pol和rev基因的序列、病毒包膜蛋白的编码序列、以及携带目的核酸片段的病毒基因组转录盒序列整合到宿主细胞基因组中；优选地，所述至少两种转座子系统包括：Tol1转座子系统、Tol2转座子系统、Frog Prince转座子系统、Minos转座子系统、Hsmar1转座子系统、Helraiser转座子系统、ZB转座子系统、Intruder转座子系统、SPINON转座子系统、TcBuster转座子系统、Passport转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PiggyBac(PB)转座子系统、Sleeping Beauty(SB)转座子系统，以及上述转座子系统的各种变体或衍生物；更优选地，所述至少两种转座子系统包括：Tol1转座子系统、Tol2转座子系统、ZB转座子、Intruder转座子、TcBuster转座子系统、Yabusame-1转座子系统、Uribo2转座子系统、PB转座子系统和SB转座子系统，以及上述转座子系统的各种变体或衍生物。
9.慢病毒生产细胞系，其特征在于，所述慢病毒生产细胞系包含整合在其基因组中的至少两种转座子；优选地，所述至少两种转座子包括：Tol1转座子、Tol2转座子、FrogPrince转座子、Minos转座子、Hsmar1转座子、Helraiser转座子、ZB转座子、Intruder转座子、SPINON转座子、TcBuster转座子、Passport转座子、Yabusame-1转座子、Uribo2转座子、PiggyBac(PB)转座子、Sleeping Beauty(SB)转座子，以及上述转座子的各种变体或衍生物；更优选地，所述至少两种转座子包括：Tol1转座子、Tol2转座子、ZB转座子、Intruder转座子、TcBuster转座子、Yabusame-1转座子、Uribo2转座子、PB转座子和SB转座子，以及上述转座子的各种变体或衍生物。
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