Dec 13, 2007

Joint inference of the distribution of fitness effects of deleterious mutations and population demography based on nucleotide polymorphism frequencies

Peter D Keightley, Adam Eyre-Walker


The distribution of fitness effects of new mutations (DFE) is important for addressing several questions in genetics, including the nature of quantitative variation and the evolutionary fate of small populations. Properties of the DFE can be inferred by comparing the distributions of the frequencies of segregating nucleotide polymorphisms at selected and neutral sites in a population sample, but demographic changes alter the spectrum of allele frequencies at both neutral and selected sites, so can bias estimates of the DFE if not accounted for. We have developed a maximum-likelihood approach, based on the expected allele-frequency distribution generated by transition matrix methods, to estimate parameters of the DFE while simultaneously estimating parameters of a demographic model that allows a population size change at some time in the past. We tested the method using simulations and found that it accurately recovers simulated parameter values, even if the simulated demography differs substantially from that assumed in our analysis. We use our method to estimate parameters of the DFE for amino acid-changing mutations in humans and Drosophila melanogaster. For a model of unconditionally deleterious mutations, with effects sampl...Continue Reading

  • References26
  • Citations159


  • References26
  • Citations159

Mentioned in this Paper

Likelihood Functions
Genetic Equilibrium
Genetic Polymorphism
Drosophila melanogaster
Amino Acid [EPC]

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