从大猩猩的基因组序列深入了解人类进化

--------------------------------1Insightsintohominidevolution2fromthegorillagenomesequence3从大猩猩的基因组序列深入了解人类进化4----------------------------------------------------------5AylwynScally1,JulienY.Dutheil2{,LaDeanaW.Hillier3,GregoryE.Jordan4,Ian6Goodhead1{,JavierHerrero4,AsgerHobolth2,TuuliLappalainen5,ThomasMailund2,7TomasMarques-Bonet3,6,7,ShaneMcCarthy1,StephenH.Montgomery8,PetraC.8Schwalie4,Y.AmyTang1,MichelleC.Ward9,10,YaliXue1,BryndisYngvadottir1{,9CanAlkan3,11,LarsN.Andersen2,QasimAyub1,EdwardV.Ball12,KathrynBeal4,10BrendaJ.Bradley8,13,YuanChen1,ChrisM.Clee1,StephenFitzgerald4,TinaA.11Graves14,YongGu1,PaulHeath1,AndreasHeger15,EmreKarakoc3,Anja12Kolb-Kokocinski1,GavinK.Laird1,GertonLunter16,StephenMeader15,Matthew13Mort12,JamesC.Mullikin17,KasperMunch2,TimothyD.O’Connor8,AndrewD.14Phillips12,JavierPrado-Martinez6,AnthonyS.Rogers1{,SabaSajjadian3,Dominic15Schmidt9,10,KatyShaw12,JaredT.Simpson1,PeterD.Stenson12,DanielJ.Turner1{,16LindaVigilant18,AlbertJ.Vilella4,WeldonWhitener1,BaoliZhu19{,17DavidN.Cooper12,PieterdeJong19,EmmanouilT.Dermitzakis5,EvanE.Eichler3,11,18PaulFlicek4,NickGoldman4,NicholasI.Mundy8,ZeminNing1,DuncanT.Odom1,9,10,19ChrisP.Ponting15,MichaelA.Quail1,OliverA.Ryder20,StephenM.Searle1,Wesley20C.Warren14,RichardK.Wilson14,MikkelH.Schierup2,JaneRogers1{,Chris21Tyler-Smith1&RichardDurbin122人名23------------------------------------------------------------------------------2425Gorillasarehumans’closestlivingrelativesafterchimpanzees,and26areofcomparableimportanceforthestudyofhumanoriginsandevolution.27Herewepresenttheassemblyandanalysisofagenomesequenceforthe28westernlowlandgorilla,andcomparethewholegenomesofallextantgreat29apegenera.Weproposeasynthesisofgeneticandfossilevidence30consistentwithplacingthehuman–chimpanzeeandhuman–chimpanzee–31gorillaspeciationeventsatapproximately6and10millionyearsago.32In30%ofthegenome,gorillaisclosertohumanorchimpanzeethanthe33latteraretoeachother;thisisrareraroundcodinggenes,indicating34pervasiveselectionthroughoutgreatapeevolution,andhasfunctional35consequencesingeneexpression.Acomparisonofproteincodinggenes36revealsapproximately500genesshowingacceleratedevolutiononeach37ofthegorilla,humanandchimpanzeelineages,andevidenceforparallel38acceleration,particularlyofgenesinvolvedinhearing.Wealsocompare39thewesternandeasterngorillaspecies,estimatinganaveragesequence40divergencetime1.75millionyearsago,butwithevidenceformorerecent41geneticexchangeandapopulationbottleneckintheeasternspecies.The42useofthegenomesequenceintheseandfutureanalyseswillpromotea43deeperunderstandingofgreatapebiologyandevolution.4445大猩猩是人类除了黑猩猩之外的又一近亲，并且在研究人类起源以及进化46方面有着重要作用。现在，我们对西部低地大猩猩的基因组进行组装和分析，47而后，和现存的巨猿属的所有基因组进行比较。我们提出一个符合大约在6百万48到1千万年前人类—黑猩猩和人类—黑猩猩—大猩猩形态事件的基因和化石的综49合证据。30%的基因组中，大猩猩接近于人类或者黑猩猩的程度较之于黑猩猩接50近于人类或者大猩猩更高，这在编码基因中是非常罕见地，表明普遍选择在巨51猿时演变以及基因表达的功能性后果。比较蛋白质的编码基因我们发现，大约52500个基因表现出加速人类，大猩猩，黑猩猩的血统的进化，并且这种进化是并53行加速的，而基因的参与则更加特别。我们还比较东西部的大猩猩物种，估算54出平均的基因序列差异是在175万年前。但最近的证据表明遗传交换和物种数量55的瓶颈是在东部的物种。对基因组序列的现在和未来的分析的利用将促进更深56入的了解巨猿的生物与进化。5758--------------------------------------------------------------------59-60Humanssharemanyelementsoftheiranatomyandphysiologywithboth61gorillasandchimpanzees,andoursimilaritytothesespecieswas62emphasizedbyDarwinandHuxleyinthefirstevolutionaryaccountsof63humanorigins1.Molecularstudiesconfirmedthatweareclosertothe64Africanapesthantoorang-utans,andonaverageclosertochimpanzees65thangorillas2(Fig.1a).Subsequentanalyseshaveexploredfunctional66differencesbetweenthegreatapesandtheirrelevancetohuman67evolution,68assistedrecentlybyreferencegenomesequencesforchimpanzee3and69orang-utan4.Hereweprovideareferenceassemblyandinitialanalysis70ofthegorillagenomesequence,establishingafoundationforthefurther71studyofgreatapeevolutionandgenetics.7273人类与大星星和黑猩猩有着许多共有的解剖和生理学原理，我们和这些物种74的相似强调了达尔文和赫胥黎的第一次人类起源进化理论。分子研究证实，和75接近猩猩相比，我们更接近于非洲人猿；和大猩猩相比，平均上，我们更接近76于黑猩猩（图1）。随后的分析，根据对于黑猩猩与猩猩基因组序列的辅助参考，77探讨了巨猿以及他们与人类进化之间的关系上的功能性差异。在这里我们提供78了组装和初步分析大猩猩基因组序列的参考，为进一步研究巨猿的进化与遗传79学建立了一个基础。8081-------------------------------------------------------------------8283Recenttechnologicaldevelopmentshavesubstantiallyreducedthe84costsofsequencing,buttheassemblyofawholevertebrategenomeremains85achallengingcomputationalproblem.Wegeneratedareferenceassembly86fromasinglefemalewesternlowlandgorilla(Gorillagorillagorilla)87namedKamilah,using5.43109basepairs(5.4Gbp)ofcapillarysequence88combinedwith166.8GbpofIlluminareadpairs(MethodsSummary).Genes,89transcriptsandpredictionsofgeneorthologuesandparalogueswere90annotatedbyEnsembl,andadditionalanalysisfoundevidencefor49891functionallong(.200-bp)intergenicRNAtranscripts.Table1summarizes92theassemblyandannotationproperties.Anassessmentofassemblyquality93usingfinishedfosmidsequencesfoundthattypical(N50;seeTable1for94definition)stretchesoferror-freesequenceare7.2kbpinlength,with95errorstendingtobeclusteredinrepetitiveregions.Outsiderepeat96maskedregionsandawayfromcontigends,thetotalrateofsingle-base97andindelerrorsis0.13perkbp.SeeSupplementaryInformationfor98furtherdetail