polygenic adaptation

Coop G, Pickrell JK, Novembre J, Kudaravalli S, Li J, Absher D, Myers RM, Cavalli-Sforza LL, Feldman MW & Pritchard JK 2009 The role of geography in human adaptation. PLoS Genet 5:e1000500.

  • there are surprisingly few fixed or nearly fixed differences between human populations
  • among the nearly fixed differences that do exist, nearly all are due to fixation events that occurred outside of Africa
  • most appear in East Asia
  • selection is often weak enough that neutral processes − especially population history, migration, and drift − exert powerful influences over the fate and geographic distribution of selected alleles
  • properties of selection pressures themselves may contribute to the observed low rate of rapid fixation events (and small number of high- FST signals)
  • it is likely that selection pressures fluctuate through time
  • mutations may be driven to intermediate frequency by strong selection, but subsequently drift to loss or fixation when the selective pressure weakens
  • it is likely that most selected phenotypes are influenced by mutations at multiple genes (as seen for skin pigmentation, for example)
  • if favored mutations increase in frequency at several genes simultaneously, then this can shift the phenotype of typical individuals of a quantitative trait towards an adaptive optimum, thus reducing the overall strength of selection on each favored mutation
  • this is a form of epistasis on fitness
  • favored mutations may increase in frequency rapidly at first, and then start to drift as the strength of selection becomes weaker
  • strong, sustained selection that drives alleles from low frequency to near fixation has been relatively rare during the past ~70 KY of human evolution
  • there might be many more partial sweeps than completed sweeps
  • this could occur if selection pressures tend to be highly variable so that favored alleles often rise to intermediate frequency and then start to drift as a result of fluctuating selection pressures or polygenic adaptation
  • perhaps the most important current challenge in selection studies is to obtain better estimates of the fraction of true positive selection signals in different types of analyses
  • this is especially pressing since we have shown that even extreme signals of the data have patterns that are predictable from neutral loci
  • one important unknown is the extent and strength of background selection
  • since high- FST SNPs are rare in the human genome, our study raises the question of whether human populations can effectively adapt to new environments or new selective pressures over time-scales of, say, ten thousand years or so
  • rapid adaptation generally does not occur by (nearly) complete sweeps at single loci
  • if human populations can adapt quickly to new environments, then we propose that this might instead occur by partial sweeps simultaneously at many loci