Week 7 Pop Gen, HWE, Population change 2023.pptx

Population Genetics, HWE, and Changes to Populations Dr. Jan E. Janecka [email protected] 236 Mellon Hall Important Concepts Lesson 1 • • • • Intro to population genetics What are populations Hardy Weinberg equilibrium Calculating allele and genotype frequencies What makes a species unique? vs...

Population Genetics, HWE, and Changes to Populations Dr. Jan E. Janecka [email protected] 236 Mellon Hall Important Concepts Lesson 1 • • • • Intro to population genetics What are populations Hardy Weinberg equilibrium Calculating allele and genotype frequencies What makes a species unique? vs Carnivora Wolverine Molecular Evolution focuses on fixed differences between species What makes a population unique? Population Genetics focuses on differences in frequencies between populations of one species Janecka et al. 2017 J. of Heredity Evolutionary Genetics - Variation Between Species • Whales diverged from deer around the same time as gophers from rats Meredith, Janecka et al. 2011 Science • What fixed mutations make them so different? • What processes drive these differences? Population Genetics - Variation Within Species • Wolves are continuously distributed in western Canada, but there are more black wolves in the Rockies • What variants make the populations different? • How are the populations structured? • What is the history of these wolves? • What processes drive their evolution? Anderson et al. 2009 Molecular, population, and evolutionary processes are linked MOLECULAR MOLECULAR GENETICS GENETICS Population POPULATION processes GENETICS determine fixation of alleles that ultimately differentiate species EVOLUTIONARY EVOLUTIONARY GENETICS GENETICS Population Genetics • Application of genetic principles to a group of individuals from the same species • Foundation for linking genetics to population inferences, disease, management, forensics, etc Population Structure Population – group of individuals of one species living in the same geographical area Subpopulations – local population within which most individuals find their mates Migration – Movement of individuals between populations followed by breeding Population Genetics Now think of these three subpopulations in terms of their genetic variation • Gene pool - all genetic variation within a population • Allele frequency - proportion of any specific allele in a population Allele = variant of a locus, comes from a mutation Locus = independent location on a chromosome, can be a gene • Genotype frequency - proportion of individuals in a population with a specific genotype – In diploid, the genotype is the combination of two alleles in individual Population parameters will affect the gene pool in a predicted way One Population AA AA Aa aa AA Aa Aa AA Collection of Individuals Collection of Genotypes AAAAA AAAAA Aaaaaa Collection of Alleles Genetic Variation In a Population AaAAa AAAaA AaAaa Generation 1 aa AA AA Aa AA aaAAa AAaAA AaAaA Generation 2 Aa Mating What determines the alleles in the offspring? Remember Mendel.... .... extending Mendel’s law of inheritance to populations yields Hardy–Weinberg equilibrium Frequency in Offspring from Mendel’s Laws f(A) = p • • f(a) = q p is typically assigned to the frequency of the wild type allele is Frequency in female gene pool Frequency in male gene pool wild type – the most common allele (or The frequency of genotypes in next generation determined by the frequency of alleles in the gametes (if mating is random) Hardy–Weinberg equilibrium When gametes containing either of two alleles, A or a, unite at random to form the next generation, the genotype frequencies in offspring (zygote) is: f(AA) : f(Aa) : f(aa) p2 : 2pq : q2 p = f(A) = frequency of allele A q = f(a) = frequency of allele a p + q =1 Modeling populations AaA a AAAa A AaAaa f(A) = 3 x 2AA inds + 2 x 1Aa inds = 0.57 2 x 7 ind f(a) = 2 x 2aa inds + 2 x 1Aa inds = 0.43 Generation 1 2 x 7 ind aa f(A) = 8 A alleles/ 14 total alleles = 0.57 f(a) = 6 a alleles/ 14 total alleles = 0.43 aaAAa AAaAA AaAaA Mating AA AA Aa AA Generation 2 f(A) = 8 A alleles/ 14 total alleles = 0.57 f(a) = 6 a alleles/ 14 total alleles = 0.43 Aa aa Probability and frequency AaaAa aAAaA AaAaa aAaaa A Our population Probability of a randomly choosing an A allele is 0.4 Probability of a randomly choosing any allele is the frequency of that allele (p or q) Modeling populations AaaAa aAAaA AaAaa aAaaa ‘gene pool’ aa Aa AA Aa Probability of making an AA is the probability of randomly choosing an A, and then randomly choosing A again. In the next generation: f(AA) = p2 f(Aa) = 2pq f(aa) = q2 Modeling populations – Disease risk Individual with a = recessive disease allele AaaAa aAAaA AaAaa aAaaa disease ‘gene pool’ aa Aa AA Aa Carriers For heritable recessive disorder • Recessive homozygotes have the he disease • Heterozygotes are carriers Under HWE f(AA) = p2 f(Aa) = 2pq f(aa) = q2 Carriers Individuals with disease Can estimate number of carriers in a population by solving for q from incidence rate, calculating f(Aa), and multiplying by population size Activity 5 – HWE, Disease, and Drift Do Part A and B only 20 Hardy–Weinberg equilibrium • KEY IMPLICATION: Allele frequencies will remain constant over time if the following assumptions are met:      Infinite population size (No genetic drift) No mutation No migration Radom Mating No selection Violations to these assumptions have predicted effects on allele and genotype frequencies Lesson 2 • Modeling populations • Violations to Hardy Weinberg equilibrium • How processes can interact 22 Violations to HWE These cause change in allele frequencies leading to evolution of populations: • Genetic Drift (Small pop size) • Mutation • Migration • Non-Random Mating (example of inbreeding) • Selection Populations as collections of alleles Here is our population How do the 5 forces change allele frequencies? Freq(A) = p = 0.90 Freq(a) = q = 0.10 2N = 100 Genetic Drift Generation 1 p = 0.90 q = 0.10 Generation 10 p = 1.00 q = 0.00 1 • Genetic drift reduces diversity p 0 1 2 3 4 5 6 7 8 9 10 generations • Leads to random fixation of one allele Genetic Drift Generation 1 p = 0.90 q = 0.10 Generation 10 p = 0.10 q = 0.90 • Genetic drift stronger in smaller populations Genetic Drift • Genetic drift is a random process and outcomes will differ • The probability of which allele is fixed depends on its initial frequency Probability of fixation of allele A = f(A) Activity 5 – HWE, Disease, and Do Part C Drift 28 Genetic Drift - Bottleneck • Bottleneck is a special case of genetic drift due to a temporary reduction of population size Large, genetically diverse population Bottleneck – pop crash to few individuals reduces diversity Population expands and becomes large again, but diversity remains low due A bottlenecktooccurs when a population is reduced in size, past bottleneck changing allele frequencies in the future generations with of variation a loss Mutation • New mutations introduce variation into a population mutation p=1 q=0 p = 0.99 q = 0.01 • Probability mutation will be fixed in this population is q = 0.01 • Most new mutations are usually lost from populations Migration • Migration is dispersal followed by breeding with offspring • homogenizes alleles frequencies in populations If this is between previously isolated populations lead to admixture – combining two or more populations with different alleles frequencies into one group p = 0.90 q = 0.10 Migration Less migration More migration Pop 3 p = 0.85 q = 0.15 p = 0.11 q = 0.89 • Migration makes allele frequencies more similar • Less migration = more divergence • Population structure: When subpopulations have different alleles frequencies Estimating Population Structure • One common index Fixation index (Fst) is an estimate of genetics divergence between populations • Fst compare how alleles are distributed among versus within populations Fst = AP / (WI + AI + AP) AP = Estimated variance in allele frequencies among populations AI = Estimated variance in allele frequencies among individuals WI = Estimated variance in allele frequencies within individuals Fst = 0.0 to 0.05, no to low structure Fst = 0.05 to 0.25, moderate structure Fst = 0.25 to 0.50, high structure Fst = 0.50 to 0.75, very high structure Fst = 0.75 to 1.0, virtually no migration, completely different alleles Pop 1 p = 0.90 q = 0.10 Migration low migration allele freq. different high Fst Pop 2 Pop 3 p = 0.85 q = 0.15 high migration p = 0.11 allele freq. similar q = 0.89 low Fst • Fixation index (Fst) is an estimate of genetics divergence between populations • Fst is higher between population with less migration between them • Estimate of connectivity Non-Random Mating • Assortative mating is when pair bonding is based on an observable phenotype • Alleles associated with the phenotype will increase in frequency Non-Random Mating • Inbreeding - mating between relatives • Results in excess homozygotes Inbreeding does not change allele frequencies, only reduces the number of heterozygotes • In most species, inbreeding is harmful due to rare recessive detrimental alleles that become homozygous • Increased chance of rare genetic disorders Non-Random Mating • Inbreeding Depression is caused by an excess of homozygous genotypes with recessive detrimental alleles in individuals • In Florida Panthers inbreeding depression linked to • Decreased survival • Increased mortality of cubs • Reduced number of offspring by females • Increased sperm abnormalities Natural Selection Species can co-evolve American cheetah went extinct 8,000 BC, about 35,000 years after Clovis civilizations spread across North America Natural Selection • First proposed by Charles Darwin in 1859 • Consequence of:  Hereditary differences among organisms  Different ability to survive and reproduce • The driving force behind adaptive evolution selection Adaptation progressive genetic improvement in populations due to natural selection Number of nests There Can be Different Kinds of Selection Starting population Number of nests Few In another population, it may be advantageous to have more eggs, so thisMany would shift the curve to the Number of eggs right towards “Many”. This is Stabilizing Selection referred to as “directional” selection. Population after stabilizing selection Few Number of eggs Many Selection • Fitness is the relative ability of genotypes to survive and reproduce • It is sometimes referred to as the number of children of your children” to place importance on future descendants • Relative fitness measures the comparative contribution of each parental genotype to the pool of offspring genotypes, in each generation • Selection coefficient (S) refers to selective disadvantage of a disfavored genotype Predicting the future No natural selection: next generation (N = 40) our population (N = 40) Calculate allele freqs = AA freq(AA) = 0.25 = Aa freq(Aa) = 0.50 = aa freq(aa) = 0.25 p = 0.5 q = 0.5 mate Under no selection, allele frequencies stay the same between generations freq(AA) = 0.25 freq(Aa) = 0.50 freq(aa) = 0.25 Predicting the future How can we use W to predict the change in allele frequencies? With natural selection: our population (N = 40) NATURAL SELECTION IN PARENTAL POPULATION W = relative fitness, probability the genotype will reproduce reproducing individuals (N = 30) Calculate allele freqs WAA = 1 WAa = 1 Waa = 0 = AA freq(AA) = 0.25 (10) = Aa freq(Aa) = 0.50 (20) = aa freq(aa) = 0.25 (10) freq(AA) = 0.33 (10) freq(Aa) = 0.67 (20) freq(aa) = 0.0 (0) • With complete selection against the aa genotype, allele frequency of A increases in next generation p = 0.67 q = 0.33 mate Next generation freq(AA) = 0.45 freq(Aa) = 0.44 freq(aa) = 0.11 Mutation, Drift, and Selection all Interact New mutation drift p=1 q=0 migration mutation p = 0.99 q = 0.01 Evolution of new phenotype in a new species Mutation becomes beneficial in new environment Selection Over 1000s of generations p=0 q=1 p=1 q=0 p = 0.95 q = 0.05 The Power of Pop Gen You can also go the other way! .... If you know the allele and genotype frequencies you can estimate: • • • • • • • • inbreeding rates population size effective population size (number of breeders) migration/dispersal population structure/gene flow recent changes in population sizes selection coefficients genotype-phenotype associations Review – Population Genetics, HWE, and Violations Main Concepts Lesson 1 • The perspective population genetics uses to examine variation • Parameters that are estimated for populaitons • The basics of Hardy Weinberg equilibrium and its assumptions • Calculating allele and genotype frequencies Lesson 2 • How violating HWE assumptions affects allele and genotype frequencies • Genetic drift • Mutation • Migration • Non-random mating Review – Population Structure, Genotype-Phenotype Interactions, and GWAS Main Terms Lesson 1 • Populations, subpopulations, gene pool, • Allele frequency, genotype frequency • Hardy Weinberg equilibrium, Gregory Mendel Lesson 2 • Genetic drift, bottleneck • Migration, admixture, Fixation Index (Fst) • Non-random mating, Assortative mating, Inbreeding • Natural selection, adaptation, balancing selection, directional selection, relative fitness, selection coefficient