Nov 24, 2015

One-rate models outperform two-rate models in site-specific dN/dS estimation

BioRxiv : the Preprint Server for Biology
Stephanie SpielmanClaus O Wilke


Methods that infer site-specific dN/dS, the ratio of nonsynonymous to synonymous substi- tution rates, from coding data have been developed primarily to identify positively selected sites (dN/dS > 1). As a consequence, it is largely unknown how well different inference methods can infer dN/dS point estimates at individual sites. In particular, dN/dS may be estimated using either a one-rate approach, where dN/dS is parameterized as a single parameter, or a two-rate approach, in which dN and dS are estimated separately. While some have suggested that the two-rate paradigm may be preferred for positive-selection inference, the relative merits of these two paradigms for site-specific dN/dS estimation remain largely untested. Here, we systematically assess how accurately several popular inference frameworks infer site-specific dN/dS values using alignments simulated within a mutation-selection framework rather than within a dN/dS-based framework. As mutation-selection models describe long-term evolutionary constraints, our simulation approach further allows us to study under what conditions inferred dN/dS captures the underlying equilibrium evolutionary process. We find that one-rate inference models universally outperform two-rate ...Continue Reading

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