population expansion

Lohmueller KE 2014 The impact of population demography and selection on the genetic architecture of complex traits. PLoS Genet 10:e1004379.

  • recent population growth increases the input of deleterious mutations into the population, directly causing a proportional excess of deleterious genetic variation segregating in the population
  • the first model includes a brief, but severe, reduction in population size
  • the second model of population history also includes the same Out-of-Africa population bottleneck, but now includes an instantaneous, 100-fold population expansion in the last 80 generations, or the last 2000 years, assuming 25 years/generation
  • forward simulations
  • selection coefficients for new mutations are drawn from a gamma distribution with the parameters as inferred in Boyko et al. [46]
  • for computational efficiency, I divided the population size by 2 and rescaled all times to be two-fold smaller than under the specified model
  • I keep the population scaled mutation rate (θ), and the population scaled selection coefficient (γ = 2Ns), equal to the same values as for the larger population
  • in the diffusion limit, patterns of genetic variation only depend on the scaled parameters
  • such a rescaling is customary in other forward simulation programs
  • the median length of coding regions of human genes is 1335 bp
  • a random gene would have approximately 934 nonsynonymous sites (assuming 70% of the coding sites are nonsynonymous)
  • it will take approximately 4Ne (where Ne is the current effective population size) generations for the proportion of deleterious SNPs to reach the equilibrium value for the larger population size
  • unlike the average selection coefficient, the genetic load is not affected by the demographic history of the population
  • similar results have recently been reported by Simons et al. [38]
  • the recent population growth increases the number of deleterious SNPs segregating in the population
  • this increase in load is offset by the fact that most of these new deleterious mutations are kept at very low frequency in the population
  • put another way, while the load appears to be the same across demographic models, the way in which the populations arrive at that load differs across demographies