Improved inference of site-specific positive selection under a generalized parametric codon model when there are multinucleotide mutations and multiple nonsynonymous rates.

We suggest GPP models should be used alongside traditional codon models. Further, all codon models should be deployed within an experimental design that includes (i) assessing robustness to model assumptions, and (ii) investigation of non-standard behaviour of MLEs. As the goal of every analysis is to avoid false conclusions, more work is needed on model selection methods that consider both the increase in fit engendered by a model parameter and the degree to which that parameter is affected by un-modelled evolutionary processes.