polygenic adaptation

Novembre J & Barton NH 2018 Tread lightly interpreting polygenic tests of selection. Genetics 208:1351-1355.

  • by aggregating small signals of change across many such loci, directional natural selection is now in principle detectable using genetic data, even for highly polygenic traits
  • we can now study selection in what may be its most prevalent mode
  • every new GWAS is an opportunity for an accompanying test of polygenic selection
  • these studies may easily be misinterpreted both in and outside the evolutionary genetics community
  • the mean phenotypic value of a trait in a population can shift substantially and quickly via very subtle shifts in frequencies at the many QTL that underlie a trait
  • modern polygenic tests use the QTL discovered by GWAS and detect shifts in their frequencies across time or across populations
  • the first polygenic selection study to use human GWAS results was based on a commonly studied trait, human height
  • a subsequent foundational paper by Berg and Coop (2014) gave a more formal analysis, by establishing a null model for how polygenic scores should vary across populations
  • this approach generalized and modernized a traditional pre-GWAS approach [comparison of Qst vs. Fst, Whitlock and Guillaume 2009] and has itself been extended to consider multiple traits
  • caution is needed as these results are discussed or considered in an applied context
  • correcting GWAS studies to avoid stratification has become standard using PCA and mixed model-based approaches
  • the concern of residual stratification still persists
  • some studies of polygenic evolution have relied on family-based estimates of effect sizes
  • SNPs identified by GWAS for traits of interest may be associated with regions that show "signatures" of selection simply because detection depends on allele frequencies, or less trivially, because SNPs that affect the trait also tend to affect fitness, for reasons that have nothing to do with the trait
  • at the core there is a major challenge for interpretation in untangling the connection between measured traits (e.g., height) and components of fitness (e.g., increased success in survival, finding a mate, successful reproduction upon mating)
  • they still are complicated by the fundamental problem of missing, unmeasured traits
  • the challenges of trait covariance are complicated, even for the interpretation for some of the strongest single-locus signatures of selection
  • authors of polygenic studies ... are careful to say they have detected selection on "variants associated with trait X"
  • not "selection on trait X"
  • to truly say a trait is selected, i.e., that it causes a difference in fitness, requires more direct evidence and extended study than allele frequency shifts alone can provide