polygenic adaptation

Lynch M 2010 Scaling expectations for the time to establishment of complex adaptations. PNAS 107:16577-16582.

  • one strategy has been to ignore all deleterious mutations and to assume that selection is strong enough and mutation weak enough relative to the power of random genetic drift and recombination that evolution always proceeds by the sequential fixation of single mutations
  • a broad subset of adaptations cannot be accommodated by the sequential model, most notably those in which multiple mutations must be acquired to confer a benefit
  • the routes by which such evolutionary novelties can be procured include sojourns through one or more deleterious intermediate states
  • because such intermediate haplotypes are expected to be kept at low frequencies by selection, evolutionary progress would be impeded in large populations were sequential fixation the only path to adaptation
  • complex adaptations appear to be achieved by the fortuitous appearance of combinations of mutations within single individuals before fixation of any intermediate steps at the population level
  • neutral intermediates
  • the overall influence of recombination on te is a function of the two opposing ways in which the AB haplotype is influenced
  • the rate of origin of AB gametes by recombination within doubly heterozygous (aB/Ab) parents is proportional to c
  • the net selective advantage of the resultant AB haplotypes is discounted to s − c by subsequent recombinational breakdown (whereas ab haplotypes still predominate)
  • the product c(s − c) is maximized at c = s/2
  • two-site adaptations with neutral intermediate steps are expected to emerge most rapidly in chromosomal settings where the recombination rate is half the selective advantage of the final adaptation
  • deleterious intermediates
  • the ratio of rates of establishment with and without recombination in large populations is −(s − c)[2 + (c/δ)]/(2s)
  • provided s > c, we can again anticipate that the rate of advancement of the adaptive combination will be maximized when c ≈ s/2
  • these results are inconsistent with the conclusion obtained under the assumption of an infinite population size, where recombination always prevents fixation of the double mutant
  • if the rate of recombination exceeds the selective advantage of the AB haplotype, recombinational breakdown to deleterious intermediates will present an extremely strong barrier to establishment of the AB type
  • even though mildly deleterious intermediate-state alleles are much less likely to drift to high frequency in large populations, and mutation rates are depressed, the larger number of mutational targets results in an overall elevation in the rate of progression toward adaptation by stochastic tunneling
  • such scaling is inconsistent with the classical view that populations must be small and/or fragmented to progress from one adaptive peak to another
  • which ignores the fact that stochastic tunneling of secondary mutations allows populations to navigate adaptive valleys with only negligible decline in mean population fitness