Models of coding sequence evolution

Abstract

Probabilistic models of sequence evolution are in widespread use in phylogenetics and molecular sequence evolution. These models have become increasingly sophisticated and combined with statistical model comparison techniques have helped to shed light on how genes and proteins evolve. Models of codon evolution have been particularly useful, because, in addition to providing a significant improvement in model realism for protein-coding sequences, codon models can also be designed to test hypotheses about the selective pressures that shape the evolution of the sequences. Such models typically assume a phylogeny and can be used to identify sites or lineages that have evolved adaptively. Recently some of the key assumptions that underlie phylogenetic tests of selection have been questioned, such as the assumption that the rate of synonymous changes is constant across sites or that a single phylogenetic tree can be assumed at all sites for recombining sequences. While some of these issues have been addressed through the development of novel methods, others remain as caveats that need to be considered on a case-by-case basis. Here, we outline the theory of codon models and their application to the detection of positive selection. We review some of the more recent developments that have improved their power and utility, laying a foundation for further advances in the modeling of coding sequence evolution.

Figure 1:

The relationship between the recombination rate and the rate of false inference of positive selection in an example data set consisting of 10 taxa (using a population-scaled substitution rate of μ = 3.6, and a population-scaled recombination rate varying from ρ = 0 to 0.1 with increments of 0.002). Recombination rates are measured as ρ = 2Nr, where N is the effective population size and r is the number of recombination events per inter-codon link per lineage per generation. Hence, a recombination rate of ρ = 0.004 means that a given inter-codon link at a given lineage experiences, on average, one recombination event every 500N generations.