Aug 19, 2016

A Comparison of One-Rate and Two-Rate Inference Frameworks for Site-Specific dN/dS Estimation

Stephanie J SpielmanClaus O Wilke


Two broad paradigms exist for inferring [Formula: see text] the ratio of nonsynonymous to synonymous substitution rates, from coding sequences: (i) a one-rate approach, where [Formula: see text] is represented with a single parameter, or (ii) a two-rate approach, where [Formula: see text] and [Formula: see text] 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 remain unclear. Here, we compare the relative merits of one-rate and two-rate approaches in the specific context of model misspecification by simulating alignments with mutation-selection models rather than with [Formula: see text]-based models. We find that one-rate frameworks generally infer more accurate [Formula: see text] point estimates, even when [Formula: see text] varies among sites. In other words, modeling [Formula: see text] variation may substantially reduce accuracy of [Formula: see text] point estimates. These results appear to depend on the selective constr...Continue Reading

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