Lecture 10LECTURE 10POPULATION GENETICSSEPTEMBER 17, 2014Reading: Chapter 25.0-25.3. Next: 25.4-25.8Homework: Illustrate Summary Points (p. 721) #1-5.Solved problem 1.Questions Ch 25 Q 5-10. A. Genetic variation in populations; allele frequenciesCase study: Sickle cell anemiaDefinitions: Population, gene pool, allele frequencyVariation in DNA sequence (alleles; polymorphisms)Visualizing variation (‘markers’)Immunological tests (ABO bloodtype)Protein based tests (hemoglobin electrophoresis)DNA sequence based tests (VNTRs, SNPs, microsatellites)Measuring and tallying allele frequencies (ex: MN blood type)B. The Hardy-Weinberg equilibrium ('HW law')p2 + 2pq + q2 = 1; p + q = 1Observations based on HW > Rare recessive alleles ‘hide’ in heterozygotes. > If HW applies, then allele and genotype frequencies remain stable over timeC. The assumptions underlying the Hardy-Weinberg lawNo mutationNo selection (i.e. difference in reproductive success/fitness)No migrationA large population (no sampling error)No assortative mating or inbreedingD. How does assortative mating / inbreeding affect the HW law?Trend toward homozygotes and against heterozygotesHomozygosity of ‘hidden’ detrimental alleles => Inbreeding depression > Inbreeding alone does NOT change allele frequenciesKey concepts of Population Genetics:-> Population genetics centers on the gene pool of a population (a group of interbreeding individuals), a higher level of biological organization as compared to transmission genetics and molecular genetics. -> The genetic makeup of a population can be described quantitatively by recording phenotypes, measuring the underlying genotypic frequencies and allele frequencies. -> The Hardy-Weinberg law is a simple mathematical representation of a gene pool. It states: Given allele frequencies p (for A) and q (for a), and given a closed system that obeys a number of additional constraints ('HW conditions'), the genotype frequencies are expected to equal p2 (AA), 2pq (Aa), and q2(aa).-> HW conditions are: population size (large), mate choice (not affected by allele), migration (none), mutation (none), fitness (equal)/selection. -> Specific deviations from Hardy-Weinberg conditions cause predictable deviations in genotype frequencies. -> Conversely, if experimental observations from a natural population are in conflict with the Hardy-Weinberg law, one can – under certain circumstances - decipher how a particular parameter has shaped the gene pool of a natural population. Population genetics can answer questions like: How much selection pressure from malaria morbidity is necessary to maintain the Hb-S sickle cell allele in a human population? If we discourage partnerships between carriers of the allele for the lethal Tay-Sachs disease (nerve cell death), is the frequency of the Tay-Sachs allele in the human population going to decrease over time? Once a new allele has been generated by mutation, what determines the frequency of the new allele over time in a population? How does enhanced reproductive success (fitness) of one genotype over another lead to changes in the gene pool over time (evolution)? As population sizes of endangered animals become smaller, how will this affect the genetic diversity of the population or the chances of survival of the species?Interestingly, for some of these questions the answer is not intuitive.Food for thoughtQ: What is the frequency of the recessive albinism allele in a Hopi Indian population of 6,000 people with26 phenotypic albinos (q2 = 0.0043)? A: Assuming that all relevant HW assumptions apply (no assortative mating etc.) the frequency of the albinism allele is q= 0.0043 1/2 = 0.065 = 6.5%. Q: If humans could propagate by self-fertilization, would this be a good idea from a genetic standpoint? What will happen?Q: Why is the Hardy-Weinberg equilibrium called an 'equilibrium'?Q: Why do population geneticists prefer 'molecular' traits over visual traits (white eyes, etc.)? A: Molecular traits are less sensitive to confounding factors such as multi-genic inheritance, pleiotropic effects, gene-environment interaction, and epistasis. Second, molecular traits often behave in a co-dominant fashion. ---Study guide for specific topics (see next lectures for details)E.1 Consequences of non-random (assortative) mating – inbreedingCase study: Star-bellied sneetches3 generations of sneetches.A1=no stars A2-A4=star-belliedAssume III is A1/- and p(A1)=0.001. What is the probability that III is A1/A1 if (i) its mother and father were siblings: 1/4(ii) if they were unrelated: 1/1000. Case study: Repeated self-fertilization (in plants) is an extreme case of inbreeding. Result: A population in HW equilibrium is split into 100% homozygous (AA) and 100% (aa) lines. At every generation, half of all heterozygosity is lost. => Implication: A shift from hetero- to homozygosity can be achieved by repeated selfing/inbreeding (recombinant inbred lines). => Implication: Inbreeding increases the exposure of recessive alleles to natural selection.=> Implication: In small populations, where inbreeding becomes inevitable, recessive alleles tend to become homozygous = inbreeding depressionNote: Assortative mating does not increase the frequency q of the a allele; however, it does increase the frequency of the aa genotype over what is expected according to HW.Q: If humans could propagate by self-fertilization, would this be a good idea from a genetic standpoint?A: Absolutely not. Every individual carries several recessive defective alleles in his/her genome. Cystic fibrosis is the most frequent one at q=1/25 in caucasians, but there are many others. If we selfed ourselves, one quarter of our children would be afflicted with homozygous disease alleles. E.2. Sources of variation in allele frequency - Selection:Assumption: All genotypes have equal reproductive success. Reproductive success is called 'fitness'. In practice, this assumption holds very well for certain traits (e.g. blood type) and not at all for others (lethal alleles). Fitness is often measured in a relative way (Darwinian fitness) by setting the fitness (W)of the most successful genotype to 1.0. W=1.0 Offspring of the fittest genotype s=0W=0.0 No offspring. s=1The selection coefficient (s) is simply the complementary value: s=1-W. How does selection change allele frequencies over time? - Perhaps the most informative case is that of a recessive deleterious allele (d). In this case:W (DD)