Recent codon preference reversals in the Drosophila melanogaster lineage

Nearly neutral evolutionary dynamics may be prevalent in genome evolution but the functional effects of weakly selected mutations generally lie outside the range of direct measurement. Synonymous codon usage bias is well-suited for population genetic inference; under major codon preference, translationally superior “major” codons confer fitness benefits relative to their less efficiently and/or accurately decoded synonymous counterparts. The fitness benefits of major codons are likely vanishingly small, but common selective forces among genes justify pooling of mutations with predicted fitness effects to confer statistical power to detect footprints of directional forces. In naturally occurring variation from Drosophila simulans, minor to major codon mutations segregate at higher frequencies within populations than major to minor changes. In contrast, in Drosophila melanogaster , codon family-specific polymorphism patterns reveal a reduced efficacy of natural selection in most synonymous families, but surprisingly, support reversals of favored states in the four codon families encoded by NAY. These codon families show accelerated synonymous fixations in favor of NAT codons deeper in the gene tree, within the ancestral D. melanogaster lineage. Differences for both allele frequencies and fixation rates are greater among X-linked, relative to autosomal, loci. These four lines of evidence are best explained by fitness effect reversals and illustrate how fine-scale sequence pattern analyses can reveal ongoing genome-wide adaptation and motivate experimental investigations of novel function. The correspondence between reversed selection and wobble position queuosine modification in NAY cognate tRNAs is intriguing, but the phenotypic basis of reversals remains unclear.