群体的遗传平衡.ppt

Chapter 11 Population Genetics 第十一章 群体的遗传平衡 11.1 Concept 11.1.1 Gene frequency 11.1.2 Genotype frequency 11.2 Hardy-Weinberg law 哈迪温伯格平衡 11.2.1 Equilibrium in gene frequencies 基因频率的恒定 11.2.2 Equilibrium in genotype frequencies 基因型频率的恒定,11.3 Calculating multi-allele frequencies 复等位基因频率的计算 11.4 Genotype frequencies in the self-crossing population 自交群体中基因型频率的变化11.5 Transfer of recessive lethal gene in the random mating population 互交群体中隐性致死基因的传递,Genes in populations:hardy-weinberg equilibrium 群体中的基因:哈迪 温伯格平衡Population genetics 群体遗传学Deme 同类群Frequency 频率Gene pool 基因库 Randomly 随机地Random mating 随机交配Selection 选择Migration 迁移,11.1 Concept Population genetics is the study of alleles of genes in populations,and the force which maintain or change the frequencies of particular alleles and genotypes in populations.The total genetic stock of the population is its gene pool.Individuals have a selection of alleles from that gene pool,possibly taken randomly.,群体：随机交配(异交)，产生可育后代的动态个体群 dynamic,孟德尔氏群体：基因遗传表现符合孟德尔遗传规律的 群体。,群体遗传组成变化 物种进化。研究群体遗传学 阐明物种进化机制,群体基因库-群体中遗传物质总和,群体遗传学 研究群体中维持或改变特定等位基因及 基因型频率的作用力的学科。,研究基因在群体中的传递情况和基因频率、基因型频率变化的科学。,研究群体遗传结构及其变化规律的遗传学分支学科。,Gene/allele frequencies 基因频率 某群体中某一等位基因数与位点上出现的基因总数之比（该位点上可能出现的所有基因类型的频率之 和等于1，p+q=1）,14.1.2 Genotype frequencies 基因型频率 同一基因座上某种基因型个体数与总群体数之比（群体中某基因座上所有基因型频率之和等于1，P+H+Q=1）,Eg.100个体 AA 30，Aa 60，aa 10 基因型频率为：AA Aa aa 30%60%10%,设:P H Q(P+H+Q=100%）基因数：A 60 60 0=120 a 0 60 20=80 总基因数=60+60+60+20=200 基因频率：p(A)=120/200 100%=60%q(a)=80/200100%=40%(p+q=100%),即：p(A)=(2P+H)/(2P+H+H+2Q)=(2P+H)/2(P+H+Q)=P+1/2 H q(a)=(H+2Q)/(2P+H+H+2Q)=(2Q+H)/2(P+H+Q)=Q+1/2H 即：p+q=P+1/2H+Q+1/2H=P+H+Q=1,11.2 Hardy-Weinberg law(哈迪温伯格平衡定律)Hardy and Weinberg independently developed this calculation to show that an equilibrium in genotype frequencies will occur after one generation of random mating,and those genotype can be calculated from allele frequencies.The equilibrium frequencies will be maintained from generation to generation unless some force changes the allele frequencies,1908年，英国数学家Hardy、德国内科医生Weinberg分别得出该定律,Hardy和Weinberg各自独立提出此平衡式:经过一个世代的随机交配，群体中基因型频率恒定，其频率可由等位基因频率推算。这种衡定代代保持，除非某种因素改变等位基因的频率。,在一个无限大的随机交配的群体中，基因频率和基因型频率在没有迁移、突变、自然选择的条件下，世代相传不发生变化。,大群体 Large population 无限大 无遗传漂变,无迁移 No immigration 不发生迁入迁出,随机交配 Random mating 有性交配（泛交）机会均等且随机,基因频率和基因型频率恒定的五大条件：,无突变 No mutation 无频发和非频发突变,无选择 No selection 无自然选择作用,Populations that satisfy all five assumptions above are said to be at Hardy-Weinberg equilibrium.,11.2.1 Equilibrium in gene frequencies 基因频率的恒定Allele frequencies is found by adding up the number of copies of each allele in a population and expressing it as a frequency.A population of diploid individuals has 2N alleles.Each Aa heterozygote has one A allele and one a allele,each AA homozygote has two A alleles,each aa has two a alleles.,基因频率的恒定：假设亲本交配产生精、卵配子，各 配子中基因频率p(A)和q(a)；配子随机组合形成合子，其基因型：,基因型之比：p2AA:2pqAa:q2aa=p2:2pq:q2=1:2:1,子一代配子基因频率：A=(2p2+2pq)/(2p2+2pq+2pq+2q2)=p2+pq=p(p+q)=p 或=P+1/2H=p2+1/22pq=p(p+q)=p a=(2q2+2pq)/(2p2+2pq+2pq+2q2)=q2+pq=q(p+q)=q 或 Q+1/2H=q2+1/22pq=q(p+q)=q,F1 基因A频率=p；基因a频率=q；且世代相传-基因频率的恒定,e.g.亲本配子中p=0.7,q=0.3，求子代形成配子的基因频率？,lets see the answer,合子基因型：,子代形成配子的基因频率：A=(2p2+2pq)/(2p2+2pq+2pq+2q2)=p2+pq=0.49+0.21=0.70a=(2q2+2pq)/(2p2+2pq+2pq+2q2)=q2+pq=0.09+0.21=0.30,A、a频率仍分别为0.7和0.3群体该基因座上 基因频率总和=0.7+0.3=1 基因型频率总和=0.49+20.21+0.09=1,p2(AA)+2pq(Aa)+q2(aa)=p(A)+q(a)2=P+H+Q=1,11.2.2 Equilibrium in genotype frequencies 基因型频率的恒定Equilibrium in genotype frequencies will be reached in zygotes after one round of random mating.The total expected genotype frequencies are predicted by the Hardy-Weinberg equation:p2(AA)+2pq(Aa)+q2(aa)If there are two alleles,A and a,with frequencies p and q respectively,then the expected frequency of AA homozygotes is p2,of Aa heterozygotes is 2pq,and of aa homozygotes is q2.,三种基因型个体间随机交配，产生的不同基因型频率为：,父本基因型及频率,母本基因型及频率,AA Aa aa,全部后代的基因型频率为：P2+2PH+2PQ+H2+2HQ+Q2=P2+PH+1/4H2+PH+2PQ+1/2H2+HQ+1/4H2+HQ+Q2=(P+1/2H)2+2(1/2PH+PQ+1/4H2+1/2HQ)+(Q+1/2H)2=(P+1/2H)2+2P(1/2H+Q)+1/2H(1/2H+Q)+(Q+1/2H)2=(P+1/2H)2+2(Q+1/2H)(P+1/2H)+(Q+1/2H)2 AA Aa aa=p2+2pq+q2=1,后代基因型频率与亲本一致相同基因位点上的基因型频率总和为1,e.g.苯丙酮尿症隐性遗传病患者在美国的发病率为 1/10000，问美国人群中，该隐性基因频率和携带该隐性基因的杂合子基因型频率是多少？,The frequency of homozygous recessiveness is q2,so the frequency of the recessive allele is q,and the frequency of the dominant allele p=(1-q),解：设该隐性基因为a，杂合子基因型为Aa，发病率即纯合隐性aa基因型频率为：1/10000 aa=q2=1/10000 q=1/10000=0.01 p+q=1 p=1-0.01=0.99 Aa=2pq Aa=20.990.01=0.0198 答:q=1%Aa=1.98%,e.g.根据实际调查数据判断是否遗传平衡群体 上海中心血站1977年对500个上海居民进行M、N血型调查，发现M血型为111人，MN血型的为241人，N型的为148人，问上海人群中M、N基因频率各是多少？该群体是否处于遗传平衡状态？,血型 基因型 人数 M基因数 N基因数 M MM 111 222 0 MN MN 241 241 241 N NN 148 0 296,基因频率：p=0.463 q=0.537 预期平衡群体的基因型频率和人数为：P(MM)=p2=0.4632=0.2144 500=108人 H(MN)=2pq=20.4630.537=0.4973 500=249人 Q(NN)=q2=0.5372=0.2884 500=145人 与实际人数不符，x2测验是否在允许误差范围之内,MM MN NN 实际人数 111 241 148 预期数 108 249 145 差数 3 8 3 x2=(d2/e)=0.33 自由度取1 查表得0.5p0.7为差异不显著，说明上海居民MN血型基因座位上的基因型频率处于平衡状态，为平衡群体,所以处于遗传平衡状态下的群体，一对等位基因的基因频率与基因型频率的关系为：,p=q=0.5时，AA(P)=aa(Q)=0.25 Aa(H)=0.5 P:H:Q=1:2:1 p q,PQ;pq PQ,Judgement of equilibrium population:AA Aa aa1 0.50 0.25 0.252 0.25 0.25 0.503 0.64 0.32 0.044 560 340 100,11.3 复等位基因的频率计算：,e.g.假设 ABO血型在某一群体中各血型基因型频率:A 0.45 B 0.13 O 0.36 AB 0.06 计算复等位基因 IA、IB、i的基因频率？,A-IAIA，IAi B-IBIB,IBi O-ii AB-IAIB,设:p为IA 基因频率，q 为IB 基因频率，r为i基因频率 A:IAIA=p2,IAi=2pr p2+2pr=0.45(a)B:IBIB=q2,IBi=2qr q2+2qr=0.13(b)O:ii=r2 r2=0.36(c)AB:IAIB=2pq 2pq=0.06 解方程得：p=0.3 q=0.1 r=0.6,11.4 自交群体中基因型频率的变化：,杂合体的连续自交 纯合基因型频率上升 杂合基因型频率下降,Aa 自交 P0-0世代杂合基因型频率，P0=1n=1 P0 Aa 自交n=2 P0 Aan P0/2n-自交n代后杂合基因型频率 1-P0/2n-纯合基因型频率,自交-增加遗传稳定性杂交-增加遗传变异性,11.5 互交群体中隐性致死基因的传递,The unifying concept of population genetics is the Hardy-Weinberg Law.The law predicts how gene frequencies will be transmitted from generation to generation given a specific set of assumptions.Specifically,If an infinitely large,random mating population is free from outside evolutionary forces(i.e.mutation,migration and natural selection),As a check of your arithmetic p2(AA)+2pq(Aa)+q2(aa)when the frequency q of an allele is low,the frequency of occurrence of homozygotes,q2,is very low.Uncommon alleles are usually present in heterozygotes,so cannot be identified if they are recessive and are not expressed,so selection cannot act against them.,e.g.玉米白化病隐性致死基因型aa设 A、a 频率分别p、q，起始值皆1/2，即杂合态Aa,P1 F1P2 1/2A 1/2a1/2A 1/4AA 1/4Aa1/2a 1/4Aa 1/4aaF1基因 0.25AA:0.5Aa型之比=AA:2Aa p=2/3 q=1/3,F2 2/3A 1/3a2/3A 4/9AA 2/9Aa1/3a 2/9Aa 1/9aaF2基因 1AA:1Aa 型之比 p=3/4 q=1/4,在隐性纯合致死效应下，显性基因频率以 n+1/n+2 的规律逐代递增，隐性基因频率以 1/n+2 的规律递减 n-互交代数,crossing,群体中隐性致死基因的频率越低,显性基因的频率越高,选择系数（S-selective coefficient）-某一基因型在群体中被自然选择淘汰的程度 S=1 每传一代，该基因型全部被淘汰(如玉米白化隐性纯合个体),适合度(-fitness）-生物体将基因传给下一代的能力=1,S=0;=0,S=1,qn=q0/(1+nq0),e.g.隐性基因频率起始值为，隐性纯合致死，经 过几代后，群体中该基因频率降为 1/8？,Inbreeding depression(近交衰退)Inbreeding is mating between relatives and showing effects of this on the population.It increases the frequency of homozygotes above that expected for a random breeding population in Hardy-Weinberg equilibrium.Inbreeding increase the rate at which recessive deleterious alleles become homozygous and are removed by selection,so they have a lower frequency in inbred populations.,近交-亲缘种间的交配，使群体中纯合子频率 高于平衡群体预期的频率。,近交-增加隐形有害基因纯和的频率，也增加 其被选择淘汰的速率，所以隐性有害基 因在近交群体中的频率较低。,Medical importanceThe majority of the rarest human genetic disease occur as a result of consanguineous marriages.Studies suggest that marriages between cousins have at least two times,and up to ten times the rates of miscarriage and neonatal mortality as marriages between unrelated parents.,