医学遗传学基因的群体行为

医学遗传学基因的群体行为第一页，共三十三页，2022年，8月28日第二页，共三十三页，2022年，8月28日第三页，共三十三页，2022年，8月28日Whatisapopulationfromageneticperspective?

Apopulationinthegeneticsense,isnotjustagroupofindividuals,butabreedinggroup第四页，共三十三页，2022年，8月28日Thegeneticsofapopulationisconcernednotonlywiththegeneticconstitutionoftheindividualsbutalsowiththetransmissionofthegenesfromonegenerationtothenext.第五页，共三十三页，2022年，8月28日Inthetransmissionthegenotypesoftheparentsarebrokendownandanewsetofgenotypesisconstitutedintheprogeny,fromthegenestransmittedinthegametes.Thegenescarriedbythepopulationthushavecontinuityfromgenerationtogeneration,butthegenotypesinwhichtheyappeardonot.Thegeneticconstitutionofapopulation,referringtothegenesitcarries,isdescribedbythearrayofgenefrequencies,thatisbyspecificationoftheallelespresentateverylocusandthenumbersorproportionsofthedifferentallelesateachlocus."第六页，共三十三页，2022年，8月28日GoalsofPopulationGenetics

Todescribehowthefrequencyofanallelewhichcontrolsatraitchangesovertime；Toanalyzethefactorsthatleadtochangesingene(allele)frequencies；Todeterminehowchangesingene(allele)frequenciesaffectevolutionandspeciation.第七页，共三十三页，2022年，8月28日WhyStudyPopulationsandGeneFrequencies

Geneticvariabilitynecessaryforevolutionarysuccess;Measuringgeneticvariabilityatmanylocicancharacterizeapopulation;Variabilityofphenotypicandmoleculartraitsareanalyzed.第八页，共三十三页，2022年，8月28日1.VariabilityandGene(orAllelic)Frequencies

Geneticdataforapopulationcanbeexpressedasgeneorallelicfrequencies;Allgeneshaveatleasttwoalleles;Summationofalltheallelicfrequenciesforapopulationcanbeconsideredadescriptionofthepopulation;Frequenciescanvarywidelyamongtheallelesinapopulation;Twopopulationsofthesamespeciesdonothavetohavethesameallelicfrequencies.第九页，共三十三页，2022年，8月28日GenotypicfrequenciesItdescribesthedistributionofgenotypesinapopulation.

第十页，共三十三页，2022年，8月28日Example

Bloodtypelocus;twoalleles,MorN,andthreeMM,MN,NNgenotypesarepossible(thefollowingdatawascollectedfromasinglehumanpopulation).第十一页，共三十三页，2022年，8月28日Genotye#ofIndividualsGenotypicFrequenciesMM

1787MM=1787/6129=0.289MN

3039MN=3039/6129=0.50NN

1303NN=1303/6129=0.21Total6129第十二页，共三十三页，2022年，8月28日DerivingGene(orAllelic)FrequenciesTodeterminetheallelicfrequencieswesimplycountthenumberofMorNallelesanddividebythetotalnumberofalleles.

f(M)=[(2x1787)+3039]/12,258=0.5395

f(N)=[(2x1303)+3039]/12,258=0.4605

Byconventiononeoftheallelesisgiventhedesignationpandtheotherq.Alsop+q=1.

p=0.5395andq=0.4605

Furthermore,apopulationisconsideredbypopulationgeneticiststobepolymorphiciftwoallelesaresegregatingandthefrequencyofthemostfrequentalleleislessthan0.99.第十三页，共三十三页，2022年，8月28日DerivingallelicfrequenciesfromgenotypicfrequenciesThefollowingexamplewillillustratehowtocalculateallelicfrequenciesfromgenotypicfrequencies.Itwillalsodemonstratethattwodifferentpopulationsfromthesamespeciesdonothavetohavethesameallelicfrequencies.第十四页，共三十三页，2022年，8月28日Let:p=f(M)andq=f(N)Thus:p=f(MM)+½

f(MN)andq=f(NN)+½

f(MN)..PercentAllelicFrequenciesLocationMM

MN

NN

p

q

Greenland83.515.6

0.900.9130.087Iceland31.251.517.300.5690.431第十五页，共三十三页，2022年，8月28日Sotheresultsoftheabovedataare:Greenland:p=0.835+½(0.156)=0.913andq=0.009+½(0.156)=0.087

Iceland:p=0.312+½(0.515)=0.569andq=0.173+½(0.515)=0.431Clearlytheallelicfrequenciesvarybetweenthesepopulations.

第十六页，共三十三页，2022年，8月28日2.TheHardy-WeinbergLawTheHardy-WeinbergLawTheunifyingconceptofpopulationgeneticsNamedafterthetwoscientistswhosimultaneouslydiscoveredthelawThelawpredictshowgenefrequencieswillbetransmittedfromgenerationtogenerationgivenaspecificsetofassumptions.第十七页，共三十三页，2022年，8月28日If

aninfinitelylarge,randommatingpopulationisfreefromoutsideevolutionaryforces(i.e.mutation,migrationandnaturalselection),then

thegenefrequencieswillnotchangeovertime,andthefrequenciesinthenextgenerationwillbe:

p2forthe

AAgenotype

2pqfortheAagenotype,and

q2fortheaagenotype.第十八页，共三十三页，2022年，8月28日Let'sexaminetheassumptionsandconclusionsinmoredetailstartingfirstwiththeassumptions.第十九页，共三十三页，2022年，8月28日A.Infinitelylargepopulation

Nosuchpopulationactuallyexists.Theeffectthatisofconcernisgeneticdrift(achangeingenefrequencythatistheresultofchancedeviationfromexpectedgenotypicfrequencies)aprobleminsmallpopulations.第二十页，共三十三页，2022年，8月28日B.Randommating

Randommating-matingsinapopulationthatoccurinproportiontotheirallelicfrequencies.第二十一页，共三十三页，2022年，8月28日Forexample,iftheallelicfrequenciesinapopulationare:f(M)=0.91

f(N)=0.09thentheprobabilityofMMindividualsoccurringis0.91x0.91=0.828.Ifasignificantdeviationoccurred,thenrandommatingdidnothappeninthispopulation.第二十二页，共三十三页，2022年，8月28日Withinapopulation,randommatingcanbeoccurringatsomelocibutnotatothers.Examplesofrandommatingloci-bloodtype,RFLPpatternsExamplesofnon-randommatingloci-intelligence,physicalstature第二十三页，共三十三页，2022年，8月28日C.Noevolutionaryforcesaffectingthepopulation

Theprincipalforcesare:MutationMigrationSelectionSomelociinapopulationmaybeaffectedbytheseforces,andothersmaynot;thoselocinotaffectedbytheforcescanbyanalyzedasaHardy-Weinbergpopulation第二十四页，共三十三页，2022年，8月28日MathematicalDerivationoftheHardy-WeinbergLaw

IfpequalsthefrequencyofalleleAinapopulationandqisthefrequencyofalleleainthesamepopulation,unionofgameteswouldoccurwiththefollowinggenotypicfrequencies:第二十五页，共三十三页，2022年，8月28日*Thegameteandoffspringgenotypesareinparentheses.Fromthetable,itisclearthatthepredictionregardinggenotypicfrequenciesafteronegenerationofrandommatingiscorrect.

Thatis:

AA=p2;Aa=2pq;andaa=q2

FemaleGametes*

p

(A)q

(a)Male

Gametesp

(A)p2

(AA)pq

(Aa)q

(a)pq

(Aa)q2

(aa)第二十六页，共三十三页，2022年，8月28日PredictionregardingstabilityofgenefrequenciesThefollowingisamathematicalproofofthesecondprediction.Todeterminetheallelicfrequency,theycanbederivedfromthegenotypicfrequenciesasshownabove.p=f(AA)+½f(Aa)(substitutefromthetableonpreviouspage)p=p2+½(2pq)(factoroutpanddivide)p=p(p+q)(p+q=1;thereforeq=1-p;makethissubstitution)p=p[p+(1-p)](subtractandmultiply)p=p

第二十七页，共三十三页，2022年，8月28日EvolutionaryGenetics

TheHardy-WeinbergLawdescribedapopulationthatexistsingeneticequilibriumwhereallelicfrequenciesdonotchangefromgenerationtogeneration.Forevolutionofapopulationtooccur,thegenefrequenciesofthatpopulationmustundergochange.Severalfactorscanacttochangefitnessortheabilitytomaintainallelicfrequencies.Viability-abilitytosurviveFertility-abilitytoreproduceByalteringthefitnessofanindividual,thematingdistributionwillchange,andconsequentlytheallelicfrequencieswillchangeandthepopulationwillevolve.第二十八页，共三十三页，2022年，8月28日3.FactorsthatAffectStabilityofGeneFrequenciesMutationClassifiedasbeneficial,harmfulorneutral;Canoccurbypointmutations;orsmallinsertionsordeletionsofthenucleotidesequence;Harmfulmutationsarelostiftheyreducefitness;Iffitnessisimprovedbyamutation,thenthefrequencyofthatallelewillincreasefromgenerationtogeneration;Themutationcouldbeachangeinonealleletoresembleonecurrentlyinthepopulation,forexamplefromadominanttoarecessiveallele;第二十九页，共三十三页，2022年，8月28日6Themutationcouldgenerateanentirelynewallele.Mostofthesemutationsthoughwillbedetrimentalandlost.Iftheenvironmentchanges,thenewmutantallelemaybefavoredandeventuallybecomethedominantalelleinthatpopulation.Ifthemutationisbeneficialtothespeciesasawhole,migrationmustoccurforittospreadtootherpopulationsofthespecies.7Geneduplicationfavormutationalevents.Theduplicatedgenecanundergomutationstogenerateanewgenethathasasimilar,butaslightlymodifiedfunctionfortheorganism.Thistypeofevolutiongeneratesmultigenefamilies.(Examples:hemoglobinandmusclegenesinhumans,andseedstorageandphotosyntheticgenesinplants)

第三十页，共三十三页，2022年，8月28日B.Migration

TheHardy-WeinbergLawassumesthepopulationisclosed.Butformanypopulationsthisisnotthecase.Migrationwillchangegenefrequenciesbybringinginmorecopiesofanallelealreadyinthepopulationorbybringinginanewallelethathasarisenbymutation.Becausemutationsdonotoccurineverypopulation,migrationwillberequiredforthatalleletospreadthroughoutthatspecies.

第三十一页，共三十三页，2022年，8月28日4.Inageneticcontext,migrationrequirestheintroductionofnewallelesintothepopulation.Thiswillonlyoccu