BIO 305 1st Edition Lecture 13 Outline of Last Lecture I. QTL Mapping and Association MappingII. Population GeneticsA. Allele FrequencyB. The Hardy Weinberg LawIII. Violations of the Hardy Weinberg Law (Part I.)A. Population StructureB. InbreedingOutline of Current Lecture I. Violations of the Hardy Weinberg Law (Part II.)A. Mating Bias, Migration, MutationB. Genetic Drift, Natural SelectionII. Introduction to Evolutionary GeneticsIII. Vocabulary and Sample QuestionsCurrent LectureI. Violations of the Hardy Weinberg Law (Part II.)Recall: 6 Laws, 5 violations1st Violation: Mating Bias – Population Structure and Inbreeding (previous lecture)2nd Violation: Migration – individuals move between two populations Island model – when allele frequencies are different from mainland, and m migrates to island, there is a change in frequency:the next generation depends on both current and mainland frequencySimple model of how migration affects allele frequencies: Ex: FY-Null*1 allele has low frequency in Africa but is very high in EuropeIn African Americans living in Detroit, NY, Pittsburgh, etc: see a rise in FY-Null*1 alleleThis is because migration of alleles INTO African American populations3rd Violation: Mutation – the generation of new allelesMutation is the ultimate source of alternate genetic variationVery random Rate is usually very low (Ex: 10^-9 per nucleotide per year in human genomes)Ex: At 0, everyone is big A: but the population of big A will decline and a will increase,Note that it takes 70,000 generations in order to reach .5 of original frequencyRecombination – does not generate new variations at each nucleotide position (recombination is not mutation) but can create new haplotypesHaplotypes: AB – is one haplotype, ab – is one haplotypeCan have four other haplotypes because the other two are generated by recombinationLinkage disequilibrium – if you have two loci and each can calculate allele frequency in a population, what would be the frequency of each haplotype?If the two loci are in ‘linkage equilibrium’, then haplotype frequency is determined by allele frequency using the product law Otherwise, the two loci are said to be in ‘linkage disequilibrium’Ex: Linkage Disequilibrium is the nonrandom association between two lociHave 8 chromosomes:a) F(A) x F (B) = .5 * .5 = .25b) Only observe two types of haplotypes: paB and pAb = 0 = disequilibrium4th Violation: Small Population – which leads to genetic driftGenetic drift – by chance, random sampling may occur: HW requires that population is infiniteEx: Extremely small population with only two individualsResult: Can see that the allele frequencies will just change by chanceFor one generation, the chance of keeping frequency constant is less than 50%!Ex: Gamete Pool exemplifies Genetic driftwhen we randomly picked 10 gametes from a pool whose population was ½ black and ½ white, you know it is unlikely to pick 5 white and 5 black:if the pool is smaller, this random fluctuation is biggerEx: Buri ExperimentKept randomly picking 8 pairs of flies to mate, generation after generation Found that genetic drift results in the loss of genetic variationThis is because the two extreme phenotypes were the two absorbing points, so the frequency of the intermediate phenotypes for bw/bw7 got lower and lowerEither lost the bw allele or the bw- alleleThe effect of genetic drift relies on the size of the populationThe effect is bigger when the population is smallerHow fast it decreases also depends on genetic size:Genetic Drift reduces genetic variationMutation and Drift can counteract each other and balance: Y-axis = heterozygosity = fraction of heterozygotes, measured at a certain lociIf population size is larger, heterozygosity is larger5th Violation: Natural selection – shifts in populations due to differences in survival and reproduction rateFitness – a measure of survivabilityEx: There are 100 individuals, where Generation 0 (under HW) – AA : 25, Aa : 50, and aa : 25If fitness = AA : 1, Aa : 0.9, and aa : 0.8Generation 1 as juveniles will still be AA : 25, Aa : 50, and aa : 25butGeneration 1 as adults will be AA*1 : 25, Aa*.9 : 45, and aa*.8 : 20Total adults = 25 + 45 +20 = 90Frequency of ‘A’ in generation 1: (25*2+45)/(90*2) = 0.528 (while p=q=.5 in G0)Natural selection is one of the major drives behind change in allele frequency but varies in strength (1-100%)This diagram shows what happens to a lethal allele over generations while allele frequencies after 10 generations can be given by this formula:Selection against partially dominant deleterious alleles The different colors show different strengths of selectionSelection is strong if aa has a small frequencySelection is weak if aa frequency decreases slowlyWhy does the speed gradually get slower or gradually become flat?aa is being eliminated and eventually there is nobody left to select forThe effect of selection is larger when ‘aa’ amount is largeOverdominant selection – often leads to maintenance of polymorphisms in an environmentEx: Sickle cell anemia – mutation in beta-globin genesheterozygotes are both resistant to malaria AND no disease phenotypeConcordance between the two maps of sickle-cell and malaria in Africa is evidence that malaria is selecting for ss allelesIf there are few mutants, cannot remove muchthus mutation-selection balance can occurA harmful recessive allele introduced by mutation into a population (u) could be eliminated by selection as sq^2Ex: If s = 1 and allele frequency = 0.02 for cystic fibrosis, then the mutation rate (u) = 0.02^2 * 1 = .0004Equilibrium frequency is calculated as: the square root of mutation rate over selection rateThere are three types of selection:Directional – selection for one extreme, thus the peak shifts to left or rightEx: Corn oil contentQuantitatively, selection can be either upward or downwardDisruptive – selects for extremes, thus two peaks in the curve gradually formEx: Artificial selection against intermediate bristle number of DrosophilaEach generation, the curve is ‘pulled apart’ and the peak flattensStabilizing – selects for the peaking phenotype, the curve narrowsEx: Infant mortality vs. Birth WeightIf you graphed percentage mortality per measure of birth weight,you would find that at a certain weight, birth weight peaks while infant mortality dips: an example of selection for a intermediate phenotype II. Introduction to Evolutionary GeneticsEvolution