polygenic adaptation

Hernandez RD, Kelley JL, Melton SC, Auton A, McVean G, 1000 Genomes Project, Sella G & Przeworski M 2011 Classic selective sweeps were rare in recent human evolution. Science 331:920-924.

  • two main lines of evidence have been advanced in support of the hypothesis that classic selective sweeps were common
  • these patterns are informative but are only indirectly related to theoretical predictions
  • some―possibly all―of these patterns may instead result from purifying selection acting on deleterious mutations at linked sites ("background selection")
  • in the fly Drosophila simulans, diversity levels ... suggest that ~13% of amino acid substitutions involved classic sweeps
  • human diversity levels around amino acid substitutions are not lower than around synonymous substitutions
  • the similar troughs indicate ..., more plausibly, that few amino acid substitutions resulted from classic sweeps
  • simulations suggest that even if only 10% of human-specific amino acid substitutions were strongly favored or if 25% of amino acid fixations were favored with weak effects, there should be a significant decrease in the diversity levels relative to what would be expected if all fixations were neutral
  • amino acid substitutions are more clustered with one another than with synonymous substitutions
  • patterns of diversity around genic substitutions and of highly differentiated alleles are inconsistent with the expectation for frequent classic sweeps, but could result, at least in part, from background selection
  • although some substitutions in proteins and regulatory positions undoubtedly involved classic sweeps, they were too infrequent within the past 250,000 years to have had discernible effects on genomic diversity
  • this conclusion does not imply that humans have experienced few phenotypic adaptations, or that adaptations have not shaped genomic patterns of diversity
  • comparisons of diversity and divergence levels at putatively functional versus neutral sites, for example, suggest that 10 to 15% [and possibly as many as 40% (29)] of amino acid differences between humans and chimpanzees were adaptive [e.g., (30)], as were 5% of substitutions in conserved noncoding regions (22, 29) and ~20% in UTRs (22)
  • an excess of functional divergence would point to the importance of other modes of adaptation
  • classic sweeps bring new alleles to fixation
  • selection on standing variation or on multiple beneficial alleles brings rare or intermediate frequency alleles to fixation
  • other forms of adaptation, such as selection on polygenic traits, increase or decrease allele frequencies to a lesser extent