Natural selection favors efficient expression of encoded proteins, but the causes, mechanisms, and fitness consequences of evolved coding changes remain an area of aggressive inquiry. We report a large-scale reversal in the relative translational accuracy of codons across 12 fly species in the Drosophila/Sophophora genus. Because the reversal involves pairs of codons that are read by the same genomically encoded tRNAs, we hypothesize, and show by direct measurement, that a tRNA anticodon modification from guanosine to queuosine has coevolved with these genomic changes. Queuosine modification is present in most organisms but its function remains unclear. Modification levels vary across developmental stages in D. melanogaster, and, consistent with a causal effect, genes maximally expressed at each stage display selection for codons that are most accurate given stage-specific queuosine modification levels. In a kinetic model, the known increased affinity of queuosine-modified tRNA for ribosomes increases the accuracy of cognate codons while reducing the accuracy of near-cognate codons. Levels of queuosine modification in D. melanogaster reflect bioavailability of the precursor queuine, which eukaryotes scavenge from the tRNAs of bacteria and absorb in the gut. These results reveal a strikingly direct mechanism by which recoding of entire genomes results from changes in utilization of a nutrient.
Ribosomes translate mRNA into protein using tRNAs, and these tRNAs often translate multiple synonymous codons. Although synonymous codons specify the same amino acid, tRNAs read codons with differing speed and accuracy, and so some codons may be more accurately translated than their synonyms. Such variation in the efficiency of translation between synonymous codons can result in costs to cellular fitness. By favoring certain coding choices over evolutionary timescales, natural selection leaves signs of pressure for translational fidelity on evolved genomes. We have found that the way in which proteins are encoded has changed systematically across several closely related fruit fly species. Surprisingly, several of these changes involve two codons both read by the same tRNA. Here we confirm experimentally that the anticodons of these tRNAs are chemically modified (from guanine to queuosine) in vivo, and that the levels of this modification in different species track the differences in protein coding. Furthermore, queuosine modification levels are known to change during fruit fly development, and we find that genes expressed maximally during a given developmental stage have codings reflecting levels of modification at that stage. Remarkably, queuosine modification depends upon acquisition of its precursor, queuine, as a nutrient that eukaryotes must obtain from bacteria through the gut. We have thus elucidated a mechanism by which availability of a nutrient can shape the coding patterns of whole genomes.