Extra credit question (from last Tuesday’s lecture: Do these genotype frequencies match HW expectations?Forces that cause deviation from H-W (evolution)PowerPoint PresentationSelectionSlide 5Change in allele frequencyCCR5 Example; p(+)=0.9; q(D32)=0.1Slide 8Selection will increase the frequency of D32 alleleSlide 10Slide 11Selection is not always “Directional”Heterozygote advantageRelative fitness of hemoglobin genotypes in YorubansVariable selection: genotypes have different fitness effects in different environmentsFrequency-dependent selectionForces causing evolution: Random Genetic DriftGenetic drift eliminates genetic variation10 Populations, N=15Drift occurs even in large populations! N=10,000Forces that cause evolutionHow common is mutation?Mutation/Selection BalanceMutation-selection equilibriumMutation maintains substantial genetic variationForces causing evolution: Non-random mating: InbreedingWhat happens to genotype frequencies under inbreeding?What happens to heterozygosity under inbreeding?What happens to allele frequencies under inbreeding?F is a measure of inbreedingSlide 31Pup survival relative to InbreedingProportions of individuals w/ genetic disease who are products of first cousin marriagesEvolution is the result of violating assumptions of H-WSlide 35Practical ConsiderationsMigration between subpopulationsMigration: island modelp = 0.5, q = 0.5Extra credit question (from last Tuesday’s lecture: Do these genotype frequencies match HW expectations?MMMNNN298489213Give 2 value (df=1), P value and state whether you reject or do not reject the hypothesis that the observed frequencies match the expected frequenciesForces that cause deviation from H-W (evolution)1. Selection2. Mutation3. Genetic Drift4. Nonrandom Mating5. Gene Flow (Migration)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 fitnessTo conveniently calculate change in allele frequency due to selection, need concept of average fitnessSelectionChange in allele frequencyGenotype AA Aa aaGenotype Frequency p22pq q2Relative Fitness WAA WAa Waa(W=average fitness= p2WAA+ 2pqWAa + q2WAa)Freq of A after one gen. of selection: p' = p2 WAA/W + pqWAa/WFreq of a after one gen. of selection: (1-p’) or: q'= q2 Waa/W + pqWAa/WCCR5 Example; p(+)=0.9; q(32)=0.1Genotype frequency:+/+ p2=0.81 +/32 2pq=0.1832/32 q2=0.01 Relative Fitness W+/+=0.99 W+/32=0.99 W32/32=1.0Average fitness W = 0. 81*0.99 + 0.18*0.99 + 0.01*1 = 0.9901q'=q2W32/32/W + pqW+/32 /W=0.01009 +0.089991=0.100091p’= 1-q’ = 0.89999Next generation genotype freq.p20.809982pq0.18016q20.01002qq2Selection 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 slowResponse to selection can be fast!Selection is strongFavored allele is partially dominantBoth alleles are commonSelection is not always “Directional”•Heterozygote advantage•Frequency dependence•Selection varying in space or timeHeterozygote advantageFitnessA a a aA AHbA/HbAHbA/HbSHbS/HbSRelative Fitness 0.88 1.0 0.14Fitness (in symbols) 1-t 1 1-sSelection coefficients t=0.12 s=0.86Relative fitness of hemoglobin genotypes in YorubansEquilibrium frequencies:peq = s/(s+t) = 0.86/(0.12+0.86) = 0.88qeq = t/(s+t) = 0.12/(0.12+0.86) = 0.12Predict the genotype frequencies (at birth):HW proportions 0.774 0.211 0.0144Variable selection: genotypes have different fitness effects in different environments0.40.50.60.70.80.91Env. 1 Env. 2 Env. 3AAAaaaFitnessFrequency-dependent selectionForces causing evolution:Random Genetic DriftChanges in allele frequency due to random samplingGenetic drift eliminates genetic variation10 Populations, N=15Drift occurs even in large populations!N=10,000Forces that cause evolutionMutationHow common is mutation? •Dominant autosomal allele•Recurrent mutation rate: 3/200,000 = 0.000015 per generation•q0=0.0; q1 = 0.000015, q2 = 0.000030Achondroplastic dwarfismMutation/Selection BalanceEven highly deleterious mutations can persist at substantial frequency, especially if they are recessive:Selection against a recessive allele is sGenotype AA Aa aaFitness 1 1 1-sFor recessive lethal, s = 1Mutation-selection equilibriumRecessive deleterious alleles:qe = √(/s)If a recessive lethal (s=1) has a recurrent mutation rate of 1.5*10-5, what is it’s equilibrium frequency?qe = 0.004Mutation maintains substantial genetic variation Deleterious mutationsOrganism per genome/gener’nC. Elegans 0.04D. melanogaster 0.14Mouse 0.9Human 1.6HIV virus is thought to have mutation rate ~10 X greater than humans!Forces causing evolution:Non-random mating:InbreedingMating between relativesWhat happens to genotype frequencies under inbreeding? Most extreme form of inbreeding is selfingP: Aa x AaF1: 25% AA 50% Aa 25% aaF2: 37.5% AA 25% Aa 37.5% aaF3: 43.75% AA 12.5% Aa 43.75% aaFewer heterozygotes and more homozygotes each generationWhat happens to heterozygosity under inbreeding?Generationsof selfing Prop. of heterozygotes 0 100% Aa 1 50% Aa 2 25% Aa 3 12.5% AaWhat happens to allele frequencies under inbreeding?P: Aa x AaF1: 25% AA 50% Aa 25% aaF2: 37.5% AA 25% Aa 37.5% aaF3: 43.75% AA 12.5% Aa 43.75% aaAllele frequencies do not change under inbreedingF is a measure of inbreedingF = 1 – (Observed Het/Expected Het) F = (1 – H/2pq) H = 2pq (1 - F)Pop. allele frequencies p=q=0.5Pop. In H-W 0.25 AA 0.50 Aa 0.25 aa1 Gen Selfing: F=0.5 0.375 AA 0.25 Aa 0.375 aa0102030405060700 0.25 0.5 0.75 1Corn yield in relation to InbreedingInbreeding CoefficientPup survival relative to InbreedingInbreeding Coefficient Survival< 0.19 75%0.25-0.67 51%> 0.67 25%Proportions of individuals w/ genetic disease who are products of first cousin marriagesEvolution is the result of violating assumptions of H-W•Selection•Mutation•Non-random mating•Genetic Drift•MigrationEvolution is the result of violating assumptions of H-W•These ideas are straightforward.•Mathematics can be complicated, especially