Open Evolution Highlights - the Population Genetics of dN/dS

An interesting new paper in PLoS Genetics (PLoS Genetics: The Population Genetics of dN/dS) by Sergey Kryazhimskiy and Josh Plotkin that discusses the use of the widely used parameter dN/dS (in essence a measure of the ratio of non synonymous to synonymous substitutions in protein coding genes). This parameter is commonly used to estimate the type of selection that has occurred in a protein coding gene.

Here is their summary of their article:

Since the time of Darwin, biologists have worked to identify instances of evolutionary adaptation. At the molecular scale, it is understood that adaptation should induce more genetic changes at amino acid altering sites in the genome, compared to amino acid–preserving sites. The ratio of substitution rates at such sites, denoted dN/dS, is therefore commonly used to detect proteins undergoing adaptation. This test was originally developed for application to distantly diverged genetic sequences, the differences among which represent substitutions along independent evolutionary lineages. Nonetheless, the dN/dS statistics are also frequently applied to genetic sequences sampled from a single population, the differences among which represent transient polymorphisms, not substitutions. Here, we show that the behavior of the dN/dS statistic is very different in these two cases. In particular, when applied to sequences from a single population, the dN/dS ratio is relatively insensitive to the strength of natural selection, and the anticipated signature of adaptive evolution, dN/dS>1, is violated. These results have implications for the interpretation of genetic variation sampled from a population. In particular, these results suggest that microbes may experience substantially stronger selective forces than previously thought.

The key to me is that it seems that many may have been using dN/dS ratios inappropriately when comparing samples within a species. For more, well, see the paper.