From Drift to Draft: How Much Do Beneficial Mutations Actually Contribute to Predictions of Ohta's Slightly Deleterious Model of Molecular Evolution?

Genetics. 2020 Apr;214(4):1005-1018. doi: 10.1534/genetics.119.302869. Epub 2020 Feb 3.


Since its inception in 1973, the slightly deleterious model of molecular evolution, also known as the nearly neutral theory of molecular evolution, remains a central model to explain the main patterns of DNA polymorphism in natural populations. This is not to say that the quantitative fit to data are perfect. A recent study used polymorphism data from Drosophila melanogaster to test whether, as predicted by the nearly neutral theory, the proportion of effectively neutral mutations depends on the effective population size (Ne ). It showed that a nearly neutral model simply scaling with Ne variation across the genome could not alone explain the data, but that consideration of linked positive selection improves the fit between observations and predictions. In the present article, we extended the work in two main directions. First, we confirmed the observed pattern on a set of 59 species, including high-quality genomic data from 11 animal and plant species with different mating systems and effective population sizes, hence a priori different levels of linked selection. Second, for the 11 species with high-quality genomic data we also estimated the full distribution of fitness effects (DFE) of mutations, and not solely the DFE of deleterious mutations. Both Ne and beneficial mutations contributed to the relationship between the proportion of effectively neutral mutations and local Ne across the genome. In conclusion, the predictions of the slightly deleterious model of molecular evolution hold well for species with small Ne , but for species with large Ne , the fit is improved by incorporating linked positive selection to the model.

Keywords: beneficial mutations; distribution of fitness effects; linked selection; nearly neutral theory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila melanogaster
  • Evolution, Molecular*
  • Genetic Drift*
  • Genetic Fitness*
  • Genetic Linkage
  • Genome, Insect
  • Genome, Plant
  • Models, Genetic*
  • Mutation*
  • Selection, Genetic