Gene-X-ppt(Gene10-基因十)--Chapter08

Chapter8GenomeEvolution8.2DNASequencesEvolvebyMutationandaSortingMechanism•Theprobabilityofamutationisinfluencedbythelikelihoodthattheparticularerrorwilloccurandthelikelihoodthatitwillberepaired.•synonymousmutation–AchangeinDNAsequenceinacodingregionthatdoesnotaltertheaminoacidthatisencoded.•nonsynonymousmutation–AchangeinDNAsequenceinacodingregionthatalterstheaminoacidthatisencoded.8.2DNASequencesEvolvebyMutationandaSortingMechanism•Insmallpopulations,thefrequencyofamutationwillchangerandomlyandnewmutationsarelikelytobeeliminatedbychance.•fixation–Theprocessbywhichanewallelereplacestheallelethatwaspreviouslypredominantinapopulation.8.2DNASequencesEvolvebyMutationandaSortingMechanism•Thefrequencyofaneutralmutationlargelydependsongeneticdrift,thestrengthofwhichdependsonthesizeofthepopulation.•Thefrequencyofamutationthataffectsphenotypewillbeinfluencedbynegativeorpositiveselection.DatacourtesyofKentE.Holsinger,UniversityofConnecticut[]FIGURE02:Thefixationorlossofallelesbyrandomgeneticdriftoccursmorerapidlyin(A)populationsof10thanin(B)populationsof1008.3SelectionCanBeDetectedbyMeasuringSequenceVariation•Theratioofnonsynonymoustosynonymoussubstitutionsintheevolutionaryhistoryofageneisameasureofpositiveornegativeselection.•Lowheterozygosityofagenemayindicaterecentselectiveevents.•genetichitchhiking–Thechangeinfrequencyofageneticvariantduetoitslinkagetoaselectedvariantatanotherlocus.8.3SelectionCanBeDetectedbyMeasuringSequenceVariation•Comparingtheratesofsubstitutionamongrelatedspeciescanindicatewhetherselectiononthegenehasoccurred.•linkagedisequilibrium–Anonrandomassociationbetweenallelesattwodifferentloci,oftenasaresultoflinkage.AdaptedfromN.H.Barton,etal.Evolution.ColdSpringHarborLaboratoryPress,2007.OriginalfigureappearedinJ.H.Gillespie,TheCausesofMolecularEvolution.OxfordUniversityPress,1991.FIGURE04:Ahighernumberofnonsynonymoussubstitutionsinlysozymesequencesinthecow/deerlineageascomparedtothepiglineage8.3SelectionCanBeDetectedbyMeasuringSequenceVariationReproducedfromR.M.Clark,etal.,Proc.Natl.Acad.Sci.USA101(2004):700-707.Copyright©2004NationalAcademyofSciences,U.S.A.CourtesyofJohnF.Doebley,UniversityofWisconsin,MadisonFIGURE05:Nucleotidediversity(pi)ofthetb1regionindomesticatedmaizeismuchlowerthaninwildteosinte,indicatingstrongselectiononthislocusinmaize8.3SelectionCanBeDetectedbyMeasuringSequenceVariationAdaptedfromE.T.Wang,etal.,Proc.Natl.Acad.Sci.USA103(2006):135-140.FIGURE06:TheG6PDallelehasrapidlyincreasedinfrequencybypositiveselection8.4AConstantRateofSequenceDivergenceIsaMolecularClock•Thesequencesoforthologousgenesindifferentspeciesvaryatnonsynonymoussites(wheremutationshavecausedaminoacidsubstitutions)andsynonymoussites(wheremutationhasnotaffectedtheaminoacidsequence).•Synonymoussubstitutionsaccumulate~10×fasterthannonsynonymoussubstitutions.8.4AConstantRateofSequenceDivergenceIsaMolecularClockReproducedwithkindpermissionfromSpringerScience+BusinessMedia:J.Mol.Evol.,Thestructureofcytochromeandtheratesofmolecularevolution,vol.1,1971,pp.26-45,R.E.Dickerson,fig.3.CourtesyofRichardDickerson,UniversityofCaliforniFIGURE07:Therateofevolutionofthreetypesofproteinsovertime8.4AConstantRateofSequenceDivergenceIsaMolecularClock•TheevolutionarydivergencebetweentwoDNAsequencesismeasuredbythecorrectedpercentofpositionsatwhichthecorrespondingnucleotidesdiffer.•Substitutionsmayaccumulateatamoreorlessconstantrateaftergenesseparate,sothatthedivergencebetweenanypairofglobinsequencesisproportionaltothetimesincetheysharedcommonancestry.8.4AConstantRateofSequenceDivergenceIsaMolecularClockFIGURE08:DivergenceofDNAsequencesdependsonevolutionaryseparation8.4AConstantRateofSequenceDivergenceIsaMolecularClockFIGURE09:Allglobingeneshaveevolvedbyaseriesofduplications,transpositions,andmutationsfromasingleancestralgene8.4AConstantRateofSequenceDivergenceIsaMolecularClockFIGURE10:Nonsynonymoussitedivergencesbetweenpairsofbeta-globingenesallowthehistoryofthehumanclustertobereconstructed8.4AConstantRateofSequenceDivergenceIsaMolecularClock•codonbias–Ahigherusageofonecodoningenestoencodeaminoacidsforwhichthereareseveralsynonymouscodons.8.5TheRateofNeutralSubstitutionCanBeMeasuredfromDivergenceofRepeatedSequences•Therateofsubstitutionperyearatneutralsitesisgreaterinthemousegenomethaninthehumangenome,probablybecauseofahighermutationrate.FIGURE11:Anancestralconsensussequenceforafamilyiscalculatedbytakingthemostcommonbaseateachposition8.6HowDidInterruptedGenesEvolve?•Amajorevolutionaryquestioniswhethergenesoriginatedwithintronsorwhethertheywereoriginallyuninterrupted.•“intronslate”model–Thehypothesisthattheearliestgenesdidnotcontainintrons,andthatintronsweresubsequentlyaddedtosomegenes.8.6HowDidInterruptedGenesEvolve?•Interruptedgenesthatcorrespondeithertoproteinsortoindependentlyfunctioningnonprotein-encodingRNAsprobablyoriginatedinaninterruptedform(the“intronsearly”hypothesis).•exonshuffling–Thehypothesisthatgeneshaveevolvedbytherecombinationofvariousexonscodingforfunctionalproteindomains.8.6HowDidInterrup