The Population Genetics of dN/dS

PLoS Genet. 2008 Dec;4(12):e1000304. doi: 10.1371/journal.pgen.1000304. Epub 2008 Dec 12.

Abstract

Evolutionary pressures on proteins are often quantified by the ratio of substitution rates at non-synonymous and synonymous sites. The dN/dS ratio was originally developed for application to distantly diverged sequences, the differences among which represent substitutions that have fixed along independent lineages. Nevertheless, the dN/dS measure is often applied to sequences sampled from a single population, the differences among which represent segregating polymorphisms. Here, we study the expected dN/dS ratio for samples drawn from a single population under selection, and we find that in this context, dN/dS is relatively insensitive to the selection coefficient. Moreover, the hallmark signature of positive selection over divergent lineages, dN/dS>1, is violated within a population. For population samples, the relationship between selection and dN/dS does not follow a monotonic function, and so it may be impossible to infer selection pressures from dN/dS. These results have significant implications for the interpretation of dN/dS measurements among population-genetic samples.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Substitution*
  • Evolution, Molecular
  • Genetic Variation
  • Genetics, Population*
  • Models, Genetic*
  • Models, Statistical
  • Proteins / genetics*
  • Selection, Genetic*

Substances

  • Proteins