Detecting Adaptation from Multi-species Protein-coding DNA Sequence Alignments

Modern methods to detecting adaptive evolution from interspecific protein-coding gene alignments rely on statistical models of sequence evolution formulated at the level of codons. By performing model comparisons, one measures the evidence for signals of adaptive substitution processes, relative to a null model that disallows any adaptive regime. In this chapter, we present the detailed form of these models of sequence evolution, and how they are applied to real data sets. The classical codon substitution models are based on evaluating the relative nonsynonymous to synonymous substitution rates, and the main focus has traditionally been placed on devising models allowing for increasingly more subtle manifestations of adaptive substitution processes. We also overview a contrasting modeling direction that has emerged in the last decade-although with roots two decades back-in which the emphasis is placed on devising a richer modeling of purifying selection. Using simulations, we expand the characterization of this latter approach, followed by a contrasting of its conclusions on real data with those of classical codon models. Finally , we discuss the numerous model violations that can lead to erroneous inferences on various tests, and potential future directions meriting attention.