A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome

A model of DNA sequence evolution applicable to coding regions ispresented. This represents the first evolutionary model that accounts fordependencies among nucleotides within a codon. The model uses the codon, asopposed to the nucleotide, as the unit of evolution, and is parameterizedin terms of synonymous and nonsynonymous nucleotide substitution rates. Oneof the model's advantages over those used in methods for estimatingsynonymous and nonsynonymous substitution rates is that it completelycorrects for multiple hits at a codon, rather than taking a parsimonyapproach and considering only pathways of minimum change between homologouscodons. Likelihood-ratio versions of the relative-rate test are constructedand applied to data from the complete chloroplast DNA sequences of Oryzasativa, Nicotiana tabacum, and Marchantia polymorpha. Results of thesetests confirm previous findings that substitution rates in the chloroplastgenome are subject to both lineage-specific and locus-specific effects.Additionally, the new tests suggest tha the rate heterogeneity is dueprimarily to differences in nonsynonymous substitution rates. Simulationshelp confirm previous suggestions that silent sites are saturated, leavingno evidence of heterogeneity in synonymous substitution rates.