Inferring parameters of mutation, selection and demography from patterns of synonymous site evolution in drosophila

Selection acting on codon usage can cause patterns of synonymous evolution to deviate considerably from those expected under neutrality. To investigat e the quantitative relationship between parameters of mutation, selection, and demography, and patterns of synonymous site divergence, we have develop ed a novel combination of population genetic models and likelihood methods of phylogenetic sequence analysis. Comparing 50 orthologous gene pairs from Drosophila melanogaster and D. virilis and 27 from D. melanogaster and D. simulans, we show considerable variation between amino acids and genes in t he strength of selection acting on codon usage and. find evidence for both long-term and short-term changes in the strength of selection between speci es. Remarkably, D. melanogaster shows no evidence of current selection on c odon usage, while its sister species D. simulans experiences only half the selection pressure for codon usage of their common ancestor. We also find e vidence for considerable base asymmetries in the rate of mutation, such tha t the average synonymous mutation rate is 20-30% higher than in noncoding r egions. A Bayesian approach is adopted to investigate how accounting for se lection on codon usage influences estimates of tho parameters of mutation.