selection

Jensen JD, Payseur BA, Stephan W, Aquadro CF, Lynch M, Charlesworth D & Charlesworth B 2019 The importance of the Neutral Theory in 1968 and 50 years on: a response to Kern and Hahn 2018. Evolution 73:111-114.

  • inaccuracies can sometimes morph into an accepted narrative for those not familiar with the underlying science
  • it is now abundantly clear that the foundational ideas presented five decades ago by Kimura and Ohta are indeed correct
  • in the 1950s and 1960s, almost all evolutionary changes were attributed to directional natural selection
  • most polymorphisms with alleles at intermediate frequencies were thought to be maintained by balancing selection (e.g., Ford 1975)
  • Fisher famously rejected any significant evolutionary role for genetic drift (Fisher 1930)
  • Wright had simultaneously developed a deep appreciation for the importance of these stochastic effects that was later justified when molecular variants began to be studied (Wright 1931)
  • Kern and Hahn (2018) argue that modern data have demolished the original evidence supporting the Neutral Theory
  • this is not a new claim
  • Gillespie criticized some of the original arguments in favor of neutrality (e.g., Gillespie 1991)
  • nearly identical views were expressed in Hahn (2008)
  • the novelty of the arguments of Kern and Hahn (2018) mainly lies in their emphasis on the effects of selection at linked sites on patterns of variation within genomes
  • we focus primarily on this aspect of their paper
  • a major problem with Kern and Hahn's views arise from their narrow definition of the Neutral Theory
  • these inferred frequencies of adaptive substitutions mostly concern only the small fraction of the genome that codes for proteins
  • Kern and Hahn further overstate the pervasiveness of adaptive substitutions by highlighting studies in humans and plants that focus on the limited subset of genes that evolve rapidly
  • the circularity involved in ignoring the vast majority of neutral or nearly neutral substitutions across the genome, and then rejecting a significant role for neutrality, hardly justifies the need for the "selection theory of molecular evolution" advocated by Hahn (2008)
  • levels of polymorphism are low in the neighborhood of coding or conserved noncoding sequences and increase approximately monotonically away from them
  • these findings imply that any selective sweeps involved must have rather local effects
  • Kern and Hahn (2018) emphasize studies that invoke pervasive positive selection to explain genome‐wide patterns of variation
  • these claimed effects must be evaluated with caution owing to their failure to exclude or take proper account of the effects of the (unknown) non‐equilibrium demographic histories of the populations in question
  • a reduction in Ne causes the fixation probabilities of mutations with selective effects to be closer to those of neutral mutations
  • these hitchhiking effects only further emphasize the fundamental evolutionary role of genetic drift
  • the earliest formulations of the Neutral Theory focused on the dynamics of individual loci
  • the effects of selection in reducing the Ne values at linked loci were not studied
  • we could not have understood these patterns without the contributions of Kimura and Ohta
  • natural populations are rarely at demographic equilibrium, and commonly have undergone recent historical changes
  • these demographic histories cannot be assumed to affect patterns of variation uniformly across the genome, and indeed may produce different effects in different genomic regions, mimicking expectations under selection
  • beneficial mutations occasionally arise and some may reach fixation or high frequencies
  • localized hitchhiking effects related to such events have been convincingly described in a variety of organisms
  • the effects of these comparatively rare, localized positive selection events are best characterized and quantified as additional to the genome‐wide processes described above
  • in the absence of an appropriate null model accounting for these processes that are common to the genome as a whole, inappropriate adaptive story‐telling will be likely to proliferate
  • the transition to molecular biology has increased the importance of population genetics for our understanding of evolution
  • instead of unraveling the prior theoretical framework, the influx of molecular data has lent support to many pre‐genomic theoretical developments
  • the Neutral Theory changed how people thought about evolution at the molecular level
  • this framework appropriately continues to serve as the basis of modern evolutionary genomics