Robert PageDoctoral Student in Dr. Voss LabE-mail: robert.page@uky.eduPopulation Genetics

Why study population genetic structure?In general, provides perspective on adaptation and speciation.

Can reveal the recent demographic history of a population and the role of:

Gene flowGenetic driftInbreedingNatural selectionPopulation size

Can reveal the history of population structuring over deeper time.e.g. Phylogeography

Why do we expect population genetic structures to vary within and among organisms?1)Differences in mobility/dispersal ability 2)Differences in reproductive attributes/system3)Differences in life history attributes4)Differences in behavioral attributesDifferences in geographic distributionHabitat patchiness or variabilityHistorical reasonse.g. See Table 6.3 and 6.4

One of the first idealized models of a populationFrom J. Hey, 2003, Nature Reviews Genetics, 4:535-544.

a. Island modelb. Stepping stonec. Isolation by distanced. MetapopulationIdealized Population ModelsModels of population structure that allow for migration (Gene Flow)

F-Statistics: Classical Descriptors of Hierarchical Population Genetic Structure

What do We Mean by Hierarchy?Total PopSubpopB/wn SubpopsW/in SubpopB/wn Populations (2nd pop not shown)

FIS Is the Inbreeding Coefficient FIS measures the deviation of genotypes within a sub-population from those expected under HWE FIS is conceptualized in terms of heterozygote deficiency or heterozygote excess FIS = (HS - HI) / HS- HS = Mean expected heterozygosity within panmictic subpopulations - HI = Mean observed heterozygosity per individual within subpopulations FIS varies between -1 and 1... a FIS of 0 implies that the observed values agree perfectly with the expected values... an FIS of 1 implies strong inbreeding... an FIS of -1 implies strong outbreeding

FST Measures Population Subdivision

Sub-population level: FST

FST = Vp / p (1 - p)

This is a measure of the observed variation in allele frequencies among sub-populations (regardless of how the variation arose).FST can be conceptualized as the discrepancy between randomly pulling alleles from a subpopulation and randomly pulling alleles from the entire population

Another way from Avise: FST = (HT - HS) / HTHS = mean expected heterozygosity at a locus within subpops under HWEHT = overall expected heterozygosity in total population (given allele freq & HWE)FST :Ranges from 1.0 to 0.0subpopulations fixed foralternate allelessubpopulations have samealleles frequencies structurednot structured

From Selander (1970): An analysis of mouse population structure within and among barns in Texas. Estimated Number of Mean Allele Variance ofPopulation Size Pops Sampled FrequencyAllele FrequencySmall ~10 290.4180.8490.0506 0.1883Large ~200 130.372 0.843 0.0125 0.0083Es-3b Hbb Es-3b Hbb FST = Vp / p (1 - p)FST = 0.0506/(0.418)(0.582) = 0.208 for small popsFST = 0.0125/(0.372)(0.628) = 0.054 for large pops * Note that this method requires calculating FST separately for each locus (Es-3b & Hbb)

Consider the joint effects of genetic drift and gene flow on population structureIn the absence of migration, finite populations become more inbred and diverge from one another at random (with respect to allele frequencies) as a result of drift.

The probability of autozygosity (that an individual carries IBD allelesat a locus) increases faster, the smaller the population.

FST provides a measure of divergence under drift. At some pointin time, as a population approaches FST = 1, the increase inautozygosity will be balanced by the rate of migration (and/or mutation also, in reality). An equilibrium is struck.

Migration rates (Gene Flow) can be estimated assumingan equilibrium FST has been reached:FST = 1 / (4Nm + 1)~ For neutral alleles in an island model, the equilibrium value of FST :or, Nm = [(1/FST) - 1] / 4~This is interpreted as the absolute number of individuals exchanged between populations.As Nm increases, FSTdecreases.

If Nm = 1, Subpopulations are 20% more structured (inbred) than if all subpopulations essentiallycomprised a single, randomly mating populationGene Flow is a powerful thingFST = 0.20.

FSTNm1.0

0.8

06.

0.4

0.2

0.0However, FST is not very a precise measure. At best it can onlyprovide qualitative perspective.

FIT Measures Inbreeding Relative to the Entire Population FIT captures the effects of mating between close relatives within a subpopulation and the accumulated inbreeding resulting from mating between remote relatives at all levels of the population hierarchy

FIT = (HT - HI) / HT

HT = Expected heterozygosity in panmictic total popualtionHI = Mean observed heterozygosity per individual within subpopulations

Summary of F-statisticsI = Individual, S = SubpopulationT = Total

Analysis of Molecular Variance (AMOVA) Another way to describe where the variation within a dataset lies within the hierarchy Allows for partitioning this variance into components associated with the following hierarchical levels(1) Between populations(2) Between subpopulations within populations(3) Within subpopulations

More recently, there has been development of DNA sequence variation approaches to characterize population structure.However, all summarystatistic approaches liveand die by the assumeddemographic model.

The model specifies meaningto the parameters and theassumptions that underliethem.

A summary statistic doesntnecessarily provide insight.

Clustering & Assignment Approaches Different algorithms can be used... we will not belabor the differences but rather will focus on the similarities Likelihood and maximum likelihood methods are most common There are two main approaches(1) Assigning individuals to subpopulations based on how likely it is that they belong to each subpopulation given the available data on each subpopulation... The agreement between these post-hoc assignments and the subpopulation that each individual was sampled from yields insight into population structure(2) Clustering individuals into arbitrary groups by maximizing fit with expected Hardy-Weinberg proportions... If the groups recovered reflect the sampling scheme, then there is evidence of population genetic structure

Applications of Population Genetics TheoryConservationHuman AncestryWild-life ManagementAgriculture

This list is far from exhaustive

Next ClassAssigned Reading: Cabe et al. Fine-scale Population Differentiation and Gene Flow in a Terrestrial Salamander (Plethodon cinereus) Living in Continuous Habitat