转座子转座机制.docx

转座子转座机制.docx

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转座子转座机制

BacterialTransposons

•Atransposableelement转座因子movesfromoneDNAaddresstoanother

•Originallydiscoveredinmaize,transposonshavebeenfoundinallkindsoforganisms

–Bacteria

–Plants

–Humans

DiscoveryofBacterialTransposons

•Phagecoatismadeofprotein

•Alwayshasthesamevolume同体积

•DNAismuchdenserthanproteinDNA密度大

•MoreDNAinphage,denserphage若DNA含量高，其密度就大

•ExtraDNAsthatcaninactivateagenebyinsertingintoitwerethefirsttransposonsdiscoveredinbacteria发现gal基因的失活是因为插入了一段野

生型基因中没有的DNA，这确实是转座子

•Thesetransposonsarecalledinsertionsequences（ISs）插入序列

InsertionSequences

•InsertionsequencesarethesimplesttypeofbacterialtransposonIS是最简单的细菌转座子

•Theycontainonlytheelementsnecessaryfortheirowntransposition仅包括知足自身转座需要的因子：

–Shortinvertedrepeatsattheirends结尾短的反向重复序列

–Atleast2genescodingforanenzyme,transposasethatcarriesouttransposition由至少两个基因编码的转座酶

•Transpositioninvolves:

–DuplicationofashortsequenceinthetargetDNA复制靶DNA的一段短序列

–Onecopyofthissequenceflankstheinsertionsequenceoneachsideaftertransposition转座后插入序列侧翼各有一个拷贝

GeneratingHostDNADirectRepeats

ComplexTransposons

•Theterm“selfishDNA”impliesthatinsertionsequencesandothertransposonsreplicateattheexpenseoftheirhosts,providingnovalueinreturn插入

序列或其它转座子是自私的

•Sometransposonsdocarrygenesthatarevaluabletotheirhosts,antibiotic

resistanceisamongmostfamiliar但有的转座子可以为宿主提供有利的东西，如抗生素抗性基因

AntibioticResistanceandTransposons

TranspositionMechanisms

•Transposonsaresometimescalled“jumpinggenes”,DNAdoesn’talwaysleaveoneplaceforanother转座子也被叫作跳跃基因（但有误导）

•Whenitdoes,nonreplicativetransposition非复制式转座

–“Cutandpaste”

–BothstrandsoforiginalDNAmovetogetherfrom1placetoanotherwithoutreplicating

•TranspositionfrequentlyinvolvesDNA

replication

–1copyremainsatoriginalsite

–Newcopyinsertsatthenewsite

–Replicativetransposition复制式转座

–“Copyandpaste”

ReplicativeTranspositionofTn3

23-11

DetailedTn3Transposition

NonreplicativeTransposition

EukaryoticTransposons

•Transposonshavepowerfulselectiveforcesontheirside转座子会给予寄主壮大的选择压

•Transposonscarrygenesthatareanadvantagetotheirhosts转座子携带有利的基因

–Theirhostcanmultiplyattheexpenseofcompletingorganisms因此寄主能在竞争中繁衍自己

–CanmultiplythetransposonsalongwithrestoftheirDNA并与寄主DNA的其它部份一路繁衍转座子

•Iftransposonsdonothavehostadvantage,canreplicatethemselveswithintheirhosts即便对宿主不利，它们能够自私的复制

ExamplesofTransposableElements

•VariegationinthecolorofmaizekernelsiscausedbymultiplereversionsofanunstablemutationintheClocus,responsibleforkernelcolor玉米籽粒色班是由C位点的非

稳固突变的多次答复突变引发的，C位点操纵籽粒的颜色

•MutationanditsreversionresultfromDs

（dissociation）elementDs因子

–TransposesintotheCgene转座到C基因中

–Mutatesit使其突变

–Transposesoutagain,reverttowildtype再从C基因中转座出去，答复成野生型

DsandAcofMaize

•DscannottransposeonitsownDs自身并非能发生转座

•Musthavehelpfromanautonomoustransposon,Ac（foractivator）必需由自主因子Ac才能转座

–Acsuppliestransposase提供转座酶

–DsisanAcelementwithmostofitsmiddleremovedDs因子或多或少缺失Ac因子中的一部份片段

–Dsneeds

•Apairofinvertedterminalrepeats一对结尾反向重复序列

•AdjacentshortsequencesthatActransposasecanrecognize与其相连的一段短的能够被Ac转座酶所识别的序列

TransposableElementsinMaize

StructuresofAcandDs

PElements

•TheP-MsystemofhybriddysgenesisinDrosophilaiscausedbyconjunctionof2factors果蝇杂种败育的P-M系统是由两个相连的因子引发的:

–Transposableelement（P）contributedbythemale父本提供的转座因子P

–McytoplasmcontributedbythefemaleallowstranspositionofthePelement母本提供的M细胞质，这种细胞质

能使P因子发生转座

•HybridoffspringofPmalesandMfemalessuffermultipletranspositionsofPelementP系雄性和M系雌性杂

交后代中P因子多次发生转座

•Damagingchromosomalmutationsarecausedthatrenderthehybridssterile转座引发染色体的损伤突变，导

致杂种后代不育

RearrangementofImmunoglobulinGenes

免疫球蛋白基因的重排

•Mammaliangenesuseaprocessthatcloselyresemblestranspositionfor与转座相似的进程产生:

–BcellantibodiesB细胞抗体

–TcellreceptorsT细胞受体

•Recombinasesinvolvedintheseprocesseshavesimilarstructures两个进程中的重组酶也很相似

AntibodyStructure

ImmuneSystem

•Enormousdiversityofimmunesystemisgeneratedby3basicmechanisms产生10亿种抗体与外来物质发生作用，这些免疫系统通过3个大体机制产生了庞大的多样性:

–Assemblinggenesforantibodylightchainsandheavychainsfrom2or3componentparts2个或3个部份被用于组装抗体的重链和轻链

–Joiningthegenepartsbyanimprecisemechanismthatcandeletebasesoraddextrabases通过减少乃至增加碱基对的非精准连接机制来重组基因的各

部份从而改变基因

–Causingahighrateofsomaticmutations,probablyduringproliferationofacloneifimmunecells可能在免疫细胞的增殖进程中引发体细胞的高额突变，产

生不同轻微的基因

RearrangementofAntibodyLightChainGene

AntibodyHeavyChainCodingRegions

RecombinationSignals重组信号

•Therecombinationsignalsequences

（RSSs）inV（D）Jrecombinationconsistof重组信号序列包括:

–Heptamer7聚体

–Nonamer9聚体

–Separatedby12-bpor23-bpspacers距离12bp或

23bp

•Recombinationoccursonlybetweena12signalanda23signal重组只能发生在12信号和23信号之间

•Guaranteesthatonly1ofeachcodingregionisincorporatedintotherearrangedgene以确保重组基因中仅整合每一个编码区中的一个

TheRecombinase

•Recombination-activatinggene（RAG-1）

stimulatedV（D）Jjoiningactivityinvivo

•AnothergenetightlylikedtoRAG-1alsoworksinV（D）Jjoining,RAG-2

•Thesegenes,RAG-1andRAG-2,areexpressedonlyinpre-Bandpre-Tcells

MechanismofV（D）JRecombination

•RAG1andRAG2introducesingle-strandnicksintoDNAadjacenttoeithera12signalor23signal在DNA单链上切口

•Resultsintransesterificationwherenewlycreated3’-OHgroup转酯反映发生

•Hairpinsthenbreakinanimprecisewaythatallowsjoiningofcodingregionswithlossofbasesorgainofextrabases形成发夹结

构以非精准的方式断裂，通过碱基的增减连接编码区

重组信号序列

Retrotransposons反转录转座子

•Retrotransposonsreplicatethroughan

RNAintermediate反转录转座子通过一个RNA中间体进行复制

•Retrotransposonsresembleretroviruses类似于反转录病毒

–Retrovirusescancausetumorsinvertebrates

引发脊椎动物的肿瘤

–Someretrovirusescausediseasessuchas

AIDS或爱滋

•Beforestudyingretrotransposons,lookatreplicationoftheretroviruses

Retroviruses

•ClassofvirusisnamedforitsabilitytomakeaDNAcopyofitsRNAgenome

•Thisreactionisthereverseofthetranscriptionreaction–reversetranscription

•Virusparticlescontainanenzymethatcatalyzesreversetranscriptionreaction

RetrovirusReplication

Retrotransposons

•Severaleukaryotictransposonstransposeinawaysimilartoretroviruses一些真核生物转座子的转座方

式是相似的

–Tyofyeast

–copiaofDrosophila

•StartwithDNAinthehostgenome

–MakeanRNAcopy产生RNA

–Reversetranscribeitwithinavirus-likeparticleintoDNAthatcaninsertintonewlocation可能在一个

类病毒中反转录，最后插入基因的新位点

TyTranscription