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 is pres ented. This represents the first evolutionary model that accounts for dependencies among nucleotides within a codon. The model uses the codo n, as opposed to the nucleotide, as the unit of evolution, and is para meterized in terms of synonymous and nonsynonymous nucleotide substitu tion rates. One of the model's advantages over those used in methods f or estimating synonymous and nonsynonymous substitution rates is that it completely corrects for multiple hits at a codon, rather than takin g a parsimony approach and considering only pathways of minimum change between homologous codons. Likelihood-ratio versions of the relative- rate test are constructed and applied to data from the complete chloro plast DNA sequences of Oryza sativa, Nicotiana tabacum, and Marchantia polymorpha. Results of these tests confirm previous findings that sub stitution rates in the chloroplast genome are subject to both lineage- specific and locus-specific effects. Additionally, the new tests sugge st that the rate heterogeneity is due primarily to differences in nons ynonymous substitution rates. Simulations help confirm previous sugges tions that silent sites are saturated, leaving no evidence of heteroge neity in synonymous substitution rates.