title: The population genetics of dN/dS.
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.
authors.affiliation: Biology Department, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Kryazhimskiy
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Plotkin
mesh_terms: D019943:Amino Acid Substitution; D019143:Evolution, Molecular; D014644:Genetic Variation; D005828:Genetics, Population; D008957:Models, Genetic; D015233:Models, Statistical; D011506:Proteins / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D011506:Proteins