Relaxing the Molecular Clock to Different Degrees for Different Substitution Types

Rates of molecular evolution can vary over time. Diverse statistical techniques for divergence time estimation have been developed to accommodate this variation. These typically require that all sequence (or codon) positions at a locus change independently of one another. They also generally assume that the rates of different types of nucleotide substitutions vary across a phylogeny in the same way. This permits divergence time estimation procedures to employ an instantaneous rate matrix with relative rates that do not differ among branches. However, previous studies have suggested that some substitution types (e.g., CpG to TpG changes in mammals) are more clock-like than others. As has been previously noted, this is biologically plausible given the mutational mechanism of CpG to TpG changes. Through stochastic mapping of sequence histories from context-independent substitution models, our approach allows for context-dependent nucleotide substitutions to change their relative rates over time. We apply our approach to the analysis of a 0.15 Mb intergenic region from eight primates. In accord with previous findings, we find comparatively little rate variation over time for CpG to TpG substitutions but we find more for other substitution types. We conclude by discussing the limitations and prospects of our approach.