M1 Mackay- Population genetics I: Population structure

what calculations can we use to assess sequence variation at single nucleotide polymorphisms?

• proportion of variable sites (number of polymorphic sites/total number of bases)

• pairwise differences (PD) between each pair of sequences

• average pairwise difference

• average pairwise difference per site (PD/total number of bases)

what are microsatellites?

• small insertions of simple sequence length polymorphisms (SSLPs), often repeated many times for variable amounts

what is heterozygosity and average heterozygosity and how do we calculate them?

h is calculated as 1 minus the sum of each of the squared allele frequencies

what is the hardy-weinberg principle and what are its assumptions?

• in the absence of evolutionary forces (null model), the genotype frequencies are in equilibrium, and will be reached after only one generation of random mating

• if genotype frequencies change from those predicted, then at least one evolutionary force is acting (if there is significant F, the departure of observed heterozygosity from expected heterozygosity → F = 1 - (H₀/H_E))

what evolutionary forces act on population genetics at different levels? how do they affect allele frequencies + heterozygosity?

molecular level:

• mutations- rare but are the driving force of diversity

• recombination- transmission of genes on the same chromosome is not independent (linkage disequilibrium) but is reduced in populations due to recombination producing novel gametes (or gets preserved by selective sweeps)- doesn’t affect allele frequencies but increases heterozygosity

population level:

• non-random mating- does not affect allele frequencies but decreases heterozygosity

  • inbreeding- individuals mate with relatives more often than chance → inbreeding depression due to increasing homozygosity in recessive deleterious alleles reduces fitness

  • positive assortative mating- individuals mate based on having similar phenotypes

• random genetic drift- changes allele frequencies and decreases heterozygosity due to chance alone, strongest in small populations and hence often after a bottleneck → founder effects (increasing homozygosity of recessive deleterious alleles)

• migration (gene inflow/outflow)- increases diversity within sub-populations but decreases diversity between them

• natural selection/adaptation- selection acting on the whole organism, specifically on phenotypes that are associated with fitness (different kinds/directions have different effects on the population)

what is the fixation index and how is it calculated?

• the fixation index (F_ST) is a measure of how much migration has caused differences in genetic diversity between populations vs within them

• ie. an F_ST of 1 indicates no migration, so the populations are completely diverged (low heterozygosity in each population)

• ie. an F_ST of 0 indicates frequent migration, so the populations are highly similar (high heterozygosity in each population)

• H_T is the total heterozygosity pooled across all populations

• H_S is the heterozygosity averaged across each population

• F_ST = (H_T - H_S)/H_T

what is the effective population size?

• the effective population size, N_e, accounts for the fact that not all individuals within a population have an equal propensity to reproduce

• this means it is almost always smaller than the census (real) population size, N

• effectively, the population that evolutionary forces are acting on is smaller than the actual population size

what are the different kinds of selection in single and multi locus models? how is fitness expressed?

• eg. of balancing selection- with sickle cell anaemia, the homozygous recessives suffer from anaemia but heterozygotes are protected against malaria

two additional kinds:

• frequency dependent selection (fitness is high when the allele is rare, and low when the allele is common)

• fluctuation selection (fitness changes dependent on a rapidly + constantly changing environmental factor) also maintain genetic variation

how can the change in allele frequency be quantified in haploids?

• s is the selection coefficient, the fitness of an allele relative to a reference allele (with a fitness of 1)

• if s = 0.3, an allele has 30% greater fitness than a reference allele

• if s = -0.6, an allele has 60% lower fitness than a reference allele

therefore q increases when s is positive and decreases when s is negative, the rate of change being proportional to the magnitude of s

how can the change in allele frequency be quantified in diploids?

• s is the selection coefficient, the fitness of an allele relative to a reference allele (with a fitness of 1)

• if s = 0.3, an allele has 30% greater fitness than a reference allele

• if s = -0.6, an allele has 60% lower fitness than a reference allele

how do allele frequencies change in single-locus models depending on the degree of dominance?

what is neutral evolution theory?