A comparison of one-rate and two-rate inference frameworks for site-specific dN/dS estimation

Two broad paradigms exist for inferring dN/dS, the ratio of nonsynonymous to synonymous substitution rates, from coding sequences: i) a one-rate approach, where dN/dS is represented with a single parameter, or ii) a two-rate approach, where dN and dS are estimated separately. The performances of these two approaches have been well-studied in the specific context of proper model specification, i.e. when the inference model matches the simulation model. By contrast, the relative performances of one-rate vs. two-rate parameterizations when applied to data generated according to a different mechanism remains unclear. Here, we compare the relative merits of one-rate and two-rate approaches in the