Population Genetics CCR5 CCR5 32 Macrophage 1 What accounts for this variation Random Past epidemics plague smallpox What will happen to this variation in the future Will 32 allele increase in frequency These are the questions that population genetics is designed to address Hardy Weinberg Principle 1 Allele frequencies remain constant from generation to generation unless some outside force is acting to change them 2 When an allele is rare there are many more heterozygotes than homozygotes if p is small then is very small 2 Assumptions of H W 1 Mating is random across the entire population 2 All genotypes have equal viability and fertility no selection 3 Migration into the population can be ignored 4 Mutation does not occur or is so rare it can be ignored 5 Population is large enough that the allele frequencies do not change from generation to generation due to chance random genetic drift 6 Allele frequencies are the same in females and males Usefulness of H W If you know the frequency of one of the homozygous genotypes you can estimate allele frequencies and predict the frequencies of the other genotypes Q Among individuals of European descent 1 1700 newborns have cystic fibrosis a recessive genetic disorder What proportion of this population are heterozygous carriers Usefulness of H W If you know the allele frequencies you can predict the genotype frequencies AA Aa aa p2 2pq q2 Q In S France the frequency of the 32 allele is 10 i e q 0 10 What proportion of individuals will be homozygous for the allele What proportion will be heterozygous Multiple Alleles ABO blood types p freq of A allele q freq of B allele r freq of O allele Expansion of p q r 2 p2 q2 r2 2pq 2pr 2qr Hint q2 1 1700 0 00059 A 3 Assumptions of H W 1 Mating is random across the entire population 2 All genotypes have equal viability and fertility no selection 3 Migration into the population can be ignored 4 Mutation does not occur or is so rare it can be ignored 5 Population is large enough that the allele frequencies do not change from generation to generation due to chance random genetic drift 6 Allele frequencies are the same in females and males How can we detect deviation from H W expectations What happens when any of these assumptions are violated Selection Mutation Non random mating Do observed genotype frequencies match HW expectations q 4575 p 5425 MM p2 0 294 Do observed genotype frequencies match HW expectations If any of these processes are occurring will tend to get from H W expected proportions Ge not y p es MM MN NN MN 2pq 0 496 Ex p ect e d 294 3 496 4 209 3 NN q2 0 209 O bse rv ed 298 489 213 4 Test for H W Genotype Frequencies Ge not y p es MM MN NN Ex p ect e d 294 3 496 4 209 3 O bse rv ed 298 489 213 Change in allele frequencies over generations Evolution is defined as a change in allele or genotype frequencies over generations and evolution will be caused by violation of any of the assumptions of H W Importance of H W H W is an important tool for population genetics If assumptions are met we can use it to estimate allele and genotype frequencies that would otherwise be difficult to measure If assumptions are not met can be tested statistically then we know that some outside force is perturbing allele or genotype frequencies Forces that cause deviation from H W evolution 1 2 3 4 5 Selection Mutation Genetic Drift Nonrandom Mating Gene Flow Migration 5 Genotype A has a constitutive mutation for enzyme production in the lactose operon B is the normal inducible lactose operon A and B grown together in environment with limited lactose p 0 5 q 0 5 Genotypes Number AA 25 Aa 50 aa 25 Survival to reproduction 25 100 1 50 100 1 20 80 0 8 Gamete contribution 25 95 A 25 95 A 25 95 a 20 95 a New allele frequencies p q New genotype frequencies assume random mating AA Aa aa 0 28 0 50 0 22 6 Consistent differences in survival or reproduction between genotypes genotypic specific differences in fitness When fitness values are expressed on a scale such that highest fitness 1 then the values are called relative fitness To conveniently calculate change in allele frequency due to selection need concept of average fitness Change in allele frequency Genotype AA Aa aa Genotype Frequency p2 2pq q2 Relative Fitness WAA WAa Waa W average fitness p2WAA 2pqWAa q2WAa Freq of A after one gen of selection p p2 WAA W pqWAa W Freq of a after one gen of selection 1 p or q q2 Waa W pqWAa W CCR5 Example p 0 9 q 32 0 1 Genotype frequency Relative Fitness 32 32 32 2pq 0 18 p2 0 81 q2 0 01 W 0 99 W 32 0 99 W 32 32 1 0 Average fitness W 0 81 0 99 0 18 0 99 0 01 1 0 9901 q q2 q q2 W 32 32 W pqW 32 W 0 01009 0 089991 0 100091 p 1 q 0 89999 Next generation genotype freq p2 0 80998 2pq 0 18016 q2 0 01002 7 Selection will increase the frequency of 32 allele Selection is relatively weak The favored allele is recessive and the favored genotype is very rare The change in allele frequency response to selection will be relatively slow Response to selection can be fast Selection is strong Favored allele is partially dominant Both alleles are common Selection is not always Directional Heterozygote advantage Frequency dependence Selection varying in space or time 8 Heterozygote advantage Relative fitness of hemoglobin genotypes in Yorubans Fitness AA Aa aa Relative Fitness HbA HbA HbA HbS 0 88 1 0 Fitness in symbols 1 t Selection coefficients t 0 12 HbS HbS 0 14 1 1 s s 0 86 Equilibrium frequencies peq s s t 0 86 0 12 0 86 0 88 qeq t s t 0 12 0 12 0 86 0 12 Predict the genotype frequencies at birth HW proportions 0 774 0 211 Variable selection genotypes have different fitness effects in different environments 0 0144 Frequency dependent selection Fitness 9 Other Examples of Freq dep Selection 10
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