Arising from M. S. Breen, C. Kemena, P. K. Vlasov, C. Notredame & F. A. Kondrashov Nature 490, 535–538 (2012)10.1038/nature11510
An important question in molecular evolution is whether an amino acid that occurs at a given site makes an independent contribution to fitness, or whether its contribution depends on the state of other sites in the organism’s genome, a phenomenon known as epistasis1,2,3,4,5. Breen and colleagues recently argued6 that epistasis must be “pervasive throughout protein evolution” because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS)7 is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al.6 assumed that all amino acids observed at a given position in a protein alignment have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis; furthermore, for all nuclear and chloroplast genes in the Breen et al. data set, we show that the observed dN/dS values and the observed patterns of amino-acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.
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McCandlish, D., Rajon, E., Shah, P. et al. The role of epistasis in protein evolution. Nature 497, E1–E2 (2013). https://doi.org/10.1038/nature12219
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