遗传学 11 Population Genetics学习资料

1/77Chapter11.Populationand

EvolutionaryGeneticsThelady-birdbeetlesinArizonaPopulationgeneticsgeneticstructureofapopulationgroupofindividualsofthesamespeciesthatcaninterbreedallelesgenotypesPatternsofgeneticvariationinpopulationsChangesingeneticstructurethroughtime3/77IntroductionIndividualscancarryonlytwodifferentallelesofagivengene.Agroupofindividualscancarryalargernumberofdifferentalleles,givingrisetoareservoirofgeneticdiversity.ThediversitycontainedinthepopulationcanbemeasuredbytheHardy-WeinbergLaw.Mutationistheultimatesourceofgeneticvariation,andotherfactorsuchasdrift,migration,andselectioncanaltertheamountofgeneticvariationinpopulation.Populationgenetics–OutlineWhatispopulationgenetics?CalculateWhyisgeneticvariationimportant?genotypefrequenciesallelefrequenciesHowdoesgeneticstructurechange?

5/77群体遗传学(populationgenetics)：研究群体的遗传结构及其变化规律的遗传学分支学科。研究特点以群体为基本研究单位。用基因频率和基因型频率描述群体遗传结构。采用数学和统计学的方法进行研究。6/77Maincontents11.1Geneticvariation11.2TheHardy-Weinberglaw11.3Hardy-Weinberglawforhumanpopulation11.4Naturalselectionforallelechanges11.5Mutationfornewalleles11.6Migrationandgeneflow11.7GeneticDriftinsmallpopulation11.8Nonrandommating11.9Speciation11.10Reconstructionofevolutionaryhistory7/7711.1Geneticvariationandgenepools

Apopulationisagroupofindividualsfromthesamespeciesthatlivesinthesamegeographicarea,andthatactuallyorpotentiallyinterbreeds.Agenepoolconsistsofallgametesmadebyallthebreedingmembersofapopulationinsinglegeneration.8/77Genotypefrequency基因型个体数基因型频率AAD'D=D'/NAaH'H=H'/NaaR'R=R'/NN1基因型频率（genotypefrequency）：指群体中某一性状的某一基因型占该性状所有基因型的比率，或某一性状的某一基因型在群体中出现的概率。P4859/7710/7711/7712/77CCR5genotypeandphenotype1/1SusceptibletosexuallytransmittedstrainsofHIV-11/Δ32Susceptible,butmayprogresstoAIDSslowlyΔ32/Δ32ResistancetomostsexuallytransmittedstrainofHIV-113/77ThefrequencyofCCR-Δ32allelein18Europeanpopulation14/7711.2CalculatingAlleleFrequency)基因频率（genefrequency）：又叫等位基因频率（allelesfrequency），是指一个群体内特定基因座上某一等位基因占该座位全部等位基因总数的比率，即该等位基因在群体内出现的概率。

基因频率是决定一个群体性质的基本因素，当环境条件和遗传结构不变时，一个群体某一基因的频率是相对恒定的。不同群体中同一基因的频率往往不同。如，有的牛群大多数有角，而有的牛群几乎全无角。15/77基因频率和基因型频率间的关系（以一对等位基因为例）设某一基因座上有一对等位基因：A和a这对等位基因的频率分别为：pq由这对等位基因构成的基因型有：AAAaaa各基因型的个体数为：D’H’R’由这三种基因型构成的群体总数为：N（=D’+H’+R’）则各基因型频率分别为：D=D’/N，H=H’/N，R=R’/NN个个体所包含的基因总数为：2N故基因频率为：Describinggeneticstructuregenotypefrequenciesallelefrequencies rr=white Rr=pink

RR=red 200white 500pink

300redgenotypefrequenciesallelefrequencies200/1000=0.2rr500/1000=0.5Rr300/1000=0.3RRtotal=1000flowersgenotypefrequencies:Describinggeneticstructure 200rr 500Rr

300RRgenotypefrequencies

allelefrequencies900/2000=0.45r1100/2000=0.55Rtotal=2000allelesallelefrequencies:=400r=500r=

500R=600RDescribinggeneticstructureforapopulation

withgenotypes:100GG160Gg140ggGenotypefrequenciesPhenotypefrequenciesAllelefrequenciescalculate:forapopulation

withgenotypes:100GG160Gg140ggGenotypefrequenciesPhenotypefrequenciesAllelefrequencies100/400=0.25GG160/400=0.40Gg140/400=0.35gg260/400=0.65green140/400=0.35brown360/800=0.45G440/800=0.55g0.65260calculate:anotherwaytocalculate

allelefrequencies:100GG160Gg140ggGenotypefrequenciesAllelefrequencies0.25GG0.40Gg0.35gg360/800=0.45G440/800=0.55gOR

[0.25+(0.40)/2]=0.45

[0.35+(0.40)/2]=0.65GgGg0.250.40/2=0.200.40/2=0.200.3522/7711.3TheHardy-WinbergLaw1Thefrequencyofallelesdoesnotchangefromgenerationtogeneration;inotherwords,thepopulationdoesnotevolve.2Afteronegenerationofrandommating,offspringgenotypefrequenciescanbepredictedfromtheparentallelefrequencies.23/77AsetofsimpleassumptionsThereisnoselectionThereisnomutationThereisnomigrationThepopulationisinfinitelylargeIndividualsinthepopulationmaterandomlyD=p2，H=2pq，R=q2Hardy-Weinberg定律揭示了基因频率与基因型频率之间的关系及其遗传规律。24/77Thegeneralcaseofalleleandgenotypefrequencies

25/7711.4ExtensionoftheHardy-WeinberglawABOsystemmulti-allele26/7711.5UsingtheHardy-weinberglaw:calculatingheterozygotefrequencyGeneticvariationinspaceandtimeFrequencyofMdh-1allelesinsnailcoloniesintwocityblocksChangesinfrequencyofalleleFattheLaplocusinprairievolepopulationsover20generationsGeneticvariationinspaceandtimeWhyisgeneticvariationimportant?potentialforchangeingeneticstructureadaptationtoenvironmentalchange -conservationGeneticvariationinspaceandtimedivergenceofpopulations -biodiversityWhyisgeneticvariationimportant?variationnovariationEXTINCTION!!globalwarmingsurvivalWhyisgeneticvariationimportant?variationnovariationnorthsouthnorthsouthWhyisgeneticvariationimportant?variationnovariationdivergenceNODIVERGENCE!!northsouthnorthsouthHowdoesgeneticstructurechange?changesinallelefrequenciesand/orgenotypefrequenciesthroughtimeHowdoesgeneticstructurechange?mutationnaturalselectionMigrationgeneticdriftnon-randommatingHowdoesgeneticstructurechange?changesin

allelefrequenciesand/orgenotypefrequenciesthroughtime36/7711.6FactorsThatalterallelefrequenciesinpopulationInnature,populationaredynamic,andchangeinsizeandgenepoolarecommon，whichmeetdifficultlytheassumptionsofrandommating,absenceofselectionandmutation,andequalviabilityandfertility.mutationnaturalselectionmigrationgeneticdriftnon-randommatingspontaneouschangeinDNAcreatesnewallelesultimatesourceofall geneticvariationHowdoesgeneticstructurechange?38/7711.7Mutation39/77Forwardandreverse-wardmutation在没有其他因素影响时：设某一世代中，等位基因A,a的频率分别为P(A)=p,P(a)=q正反突变率分别为u,v，则：uA=======av在某一世代中：Aa的频率为pu(正突变压)aA的频率为qv(反突变压)40/77Mutationlaterallelesfrequency经过一个世代，基因频率的改变为：Δp=pu-qv即子代群体：P(A)=p-ΔpP(a)=q+Δp当群体达到平衡时，基因频率保持不变，即：Δp=pu-qv=0(正反突变压相等)因此在平衡状态下：differencesinsurvivalorreproductioncertaingenotypesproducemoreoffspringleadstoadaptationdifferencesin“fitness”Howdoesgeneticstructurechange?

mutationnaturalselection

migrationgeneticdriftnon-randommating42/7711.8NaturalSelectionChangeinthefrequencyofalethalrecessivealleleNaturalselectionResistancetoantibacterialsoapGeneration1: 1.00notresistant

0.00resistantNaturalselectionGeneration1: 1.00notresistant

0.00resistantResistancetoantibacterialsoapNaturalselectionResistancetoantibacterialsoapmutation!Generation1: 1.00notresistant

0.00resistantGeneration2: 0.96notresistant

0.04resistantNaturalselectionResistancetoantibacterialsoapGeneration1: 1.00notresistant

0.00resistantGeneration2: 0.96notresistant

0.04resistantGeneration3: 0.76notresistant

0.24resistantNaturalselectionResistancetoantibacterialsoapGeneration1: 1.00notresistant

0.00resistantGeneration2: 0.96notresistant

0.04resistantGeneration3: 0.76notresistant

0.24resistantGeneration4: 0.12notresistant

0.88resistantNaturalselectioncancausepopulationstodivergedivergencenorthsouthSelectiononsickle-cellalleleaa–abnormalßhemoglobinsickle-cellanemiaverylowfitnessintermed.fitnesshighfitnessSelectionfavorsheterozygotes(Aa).Bothallelesmaintainedinpopulation(aatlowlevel).Aa–bothßhemoglobinsresistanttomalariaAA–normalßhemoglobinvulnerabletomalariaintroducesnewallelesindividualsmoveintopopulationHowdoesgeneticstructurechange?mutationnaturalselectionmigration

geneticdriftnon-randommating“geneflow”51/7711.9MigrationBalleleofABOlocusispresentinagradientfromeasttowest52/77Migration迁移指生物个体从一个居群进入另一个居群如果迁入个体的基因频率与原群体不同，将改变基因频率在没有其它因素影响下：设一群体的基因频率为p0,q0。若从另一群体(基因频率为pm,qm)迁入若干个体，占新群体比例(迁入率)为m，则：迁入后新群体的基因频率为：p1=(1-m)p0+mpmq1=(1-m)q0+mqm基因频率的改变为：Δp=p1-p0=(1-m)p0+mpm-p0=m(pm-p0)Δq=q1-q0=(1-m)q0+mqm-q0=m(qm-q0)53/77samplingerrorgeneticchangebychancealonemisrepresentationsmallpopulationsHowdoesgeneticstructurechange?mutationnaturalselectionmigrationgeneticdriftnon-randommatingGeneticdrift8RR8rrBefore:After:2RR6rr0.50R0.50r0.25R0.75rmutationnaturalselectionmigrationgeneticdriftnon-randommatingcausechangesinallelefrequenciesHowdoesgeneticstructurechange?mutationnaturalselectionmigrationgeneticdriftnon-randommatingnon-randommatingnon-randomallelecombinationsmatingcombinesallelesintogenotypesHowdoesgeneticstructurechange?

AAxAAAAaaxaaaaAA0.8x0.8Aa0.8x0.2aA0.2x0.8A0.8A0.8a0.2a0.2aa0.2x0.2genotypefrequencies:AA=0.8x0.8=0.64Aa=2(0.8x0.2)=0.32aa=0.2x0.2=0.04allelefrequencies:A=0.8A=0.2AAAAAAAAaadifferencesinsurvivalorreproductioncertaingenotypesproducemoreoffspringleadstoadaptationdifferencesin“fitness”Howdoesgeneticstructurechange?

mutationmigrationnaturalselection

geneticdriftnon-randommatingsamplingerrorgeneticchangebychancealonemisrepresentationsmallpopulationsHowdoesgeneticstructurechange?

mutationmigrationnaturalselectiongeneticdrift

non-randommating61/7711.10Geneticdrift遗传漂变Insmallpopulations,significantrandomfluctuationsinallelefrequenciesarepossiblebychancedeviation.Thedegreeoffluctuationincreasesasthepopulationsizedecreases,asituationknownasgeneticdrift.群体遗传平衡的前提条件是随机交配的大群体。小群体相当于大群体的一个样本，样本容量越小，样本与总体间存在的

偏差就越大，从而造成样本(小群体)与总体(大群体)基因频率的差异。漂变发生在基因频率为0～1的群体中，群体越小，漂变的可能性就越大。62/77GeneticdriftGeneticdrift8RR8rrBefore:After:2RR6rr0.50R0.50r0.25R0.75r64/77randomgeneticdrift遗传漂变没有确定的方向，世代群体间基因频率变化是随机的，因此又称为随机遗传漂变。遗传漂变可以解释中性突变(无适应能力差异的突变)频率在不同世代群体间的变化。mutationmigrationnaturalselectiongeneticdriftnon-randommatingcausechangesinallelefrequenciesHowdoesgeneticstructurechange?mutationmigrationnaturalselectiongeneticdriftnon-randommatingnon-randommatingnon-randomallelecombinationsmatingcombinesallelesintogenotypesHowdoesgeneticstructurechange?

67/7711.11Non-randommating非随机交配只改变群体的基因型频率，而不影响基因频率。AAxAAAAaaxaaaaAA0.8x0.8Aa0.8x0.2aA0.2x0.8A0.8A0.8a0.2a0.2aa0.2x0.2genotypefrequencies:AA=0.8x0.8=0.64Aa=2(0.8x0.2)=0.32aa=0.2x0.2=0.04allelefrequencies:A=0.8A=0.2AAAAAAAAaa69/77Calculatingthecoefficientofinbreeding70/77Hybridvigor(heterosis)Inmembersoftwofavorableinbredlinesareoftenmorevigorousindesirabletraitsthaneitheroftheparentallines.Thephenomenoniscalledhybridvigor.Why?71/77Dominanceandover-dominanceDominanthypothesis:TheF1hybridsareheterozygotesatalllocishown.Thedeleteriousrecessiveallelespresentinthehomozygousformintheparentsismaskedbythemorefavorabledominantallelesinthehybrids.Over-dominanthypothesis:Itholdsthatinmanycasestheheterozygoteissuperiortoeitherhomozygote.Thismayrelatetothefactthatintheheterozygotetwoformsofageneproductmaybepresent,providingaformofbiochemicaldiversity.Thus,thecumulativeeffectofheterozygosityatmanylociaccountsforthehybridvigor.72/77SummaryStudyobjectiveone:tounderstandtheconceptofpopulation-levelgeneticprocesses.Inalarge,randomlymatingpopulationofsexuallyreproducingdiploidorganisms,notsubjecttotheinfluencesofmutation,migration,orselection,anequilibriumwillbeachievedforanautosomallocuswithtwoalleles.Studyobjectivetwo:TolearntheassumptionsandnatureoftheHardy-Weinbergequilibriumanditsextensions.TheHardly-Weinbergequilibriumpredictthat(1)allelicfrequencies(p,q)willnotchangefromgenerationtogeneration;(2)Genotypeswilloccuraccordingtothebinomialdistribution;(3)ifperturbed,equilibriumwillreestablishitselfinjustonegenerationofrandommating.EvolutionaryGeneticsAdaptedfromnotesofElvisNunezCharlesDarwinandAlfredWallace/images2/darwin.jpg/html/evolution98/2.JPEGEvolution

Microevolution

-evolutionaryprocesseswithinaspecies.Changesinallelefrequency.Macroevolution-evolutionaryeventsleadingtotheemergenceofnewspeciesandothertaxonomicgroups(e.g.speciationandextinction)/images/gene_synth.jpg/resources/phyletic.gifConceptofNaturalSelectionVariationsinphenotypeamongindividualsofaspecies.Manyvariationsareheritableandpassedontooffspring.Organismsreproduceinanexponentialfashion(moreoffspringthancansurvive).Struggleforsurvival.Moresuccessfulonessurviveandreproduce.UnknownstoWallaceandDarwinOriginofvariationsMechanismsofinheritance20thCentury(Neo-Darwinism)1)ApplicationofMendeliangeneticstopopulations2)Sourceofvariation(mutations)3)Mechanismofinheritance(segregationofalleles)OrganizationoftheAdhlocusofDrosophilaThelocationofdisease-causingmutationsincysticfibrosisgene囊性纤维化Reducedgeneflow,selectionandgenedriftcanleadtospeciationAllelesofLDH-BEnzymeSpeciationInSomeCases,NotMuch!Controlledbyasmallnumberofgenes!DrosophilaontheBigIsland,HI(300,00yrsago)StrongMorphologicalandbehavioraldivergenceOnly0.55%proteinsequencediversityOnly15-19locimayberesponsibleformorphologicaldifferences.UseofrepetitiveDNAelementstotracespeciesincichlidsfromlakeTanganyika丽鱼科鱼ExamplesofSpeciation

(IntheWild)Pairedsnappingshrimps鼓虾fromtheCaribbean加勒比andthePacific.Pairsmoresimilartoeachother(morphology/alleles).Butstilllesslikelytomateandonly1%viableclutchesofeggs.AverageminimalmutationdistanceCytochromecaminoacidMtDNAphylogenetictreeofNeanderthaland2000modernhumanHIVpatientphylogenetictreeevolutionNeutralTheoryofMolecularEvolutionMostnewmutationsareunconditionallydeleteriousandarerapidlylost.Segregatingvariationinthepopulationtendstobeselectivelyneutral.Differencesbetweenspeciesareoftenselectivelyneutralandresultfromgeneticdrift.Beneficialmutations(i.e.adaptation)arepossible,butvanishinglyrare.ImplicationsofNeutralTheoryMolecularClockIngeneral,itexplainsmostofthevariationwesee.Currentcontroversyaboutfractionofaminoacidsubstitutionsthatareadaptive.SpeciationWhatisaspecies?Whataresomemodesofspeciation?/.../2007/07/05/0102090491100.jpg

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