The Population Genetics of dN/dS

By Sergey Kryazhimskiy, Joshua B. Plotkin. PLoS Genetics, 2008

927 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9e7df94639494e44a1c6dabc341f100a6e02b7c2

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Citations in the corpus

Universal Patterns of Selection in Cancer and Somatic Tissues (2018, positive): “Second, while some concerns exist regarding the use of dN/dS within a highly-recombining population (Kryazhimskiy and Plotkin, 2008), these considerations do not apply to somatic mutations accumulated in a cancer sample.”
Prevalence of Epistasis in the Evolution of Influenza A Surface Proteins (2011, background): “Thus, an average dN/dS value at a site may be well below 1 even if this site occasionally evolves under strong immune selection [78].”
Functional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality (2015, background): “In fact, it has been shown that when the genetic diversity is low, as is the case of PA protein sequences from type A influenza virus, dN/dS becomes less sensitive to purifying selection [68], and may not be able to identify functional residues.”