A nutrient-driven tRNA modification alters translational fidelity and genome-wide protein coding across an animal genus

• Published in: PLoS biology 2014-12, Vol.12 (12), p.e1002015-e1002015
• Main Authors: Zaborske, John M, DuMont, Vanessa L Bauer, Wallace, Edward W J, Pan, Tao, Aquadro, Charles F, Drummond, D Allan
• Format: Article
• Language: English
• Subjects: Accuracy; Amino acids; Animals; Anticodon - genetics; Base Sequence; Biology and Life Sciences; Codon; Competition; Drosophila - genetics; Drosophila melanogaster - genetics; Gene expression; Genetic translation; Genome, Insect; Genome-wide association studies; Genomes; Health aspects; Insects; Kinetics; Medical research; Models, Genetic; Molecular Sequence Data; Natural selection; Nucleoside Q - chemistry; Nucleoside Q - metabolism; Open Reading Frames - genetics; Phylogeny; Protein Biosynthesis; Protein folding; RNA, Transfer - metabolism; Selection, Genetic; Transfer RNA
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1002015

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.