Locus-Specific Decoupling of Base Composition Evolution at Synonymous Sites and Introns along the Drosophila melanogaster and Drosophila sechellia Lineages

Selection is thought to be partially responsible for patterns of molecular evolution at synonymous sites within numerous Drosophila species. Recently, “per-site” and likelihood methods have been developed to detect loci for which positive selection is a major component of synonymous site evolution. An underlying assumption of these methods, however, is a homogeneous mutation process. To address this potential shortcoming, we perform a complementary analysis making gene-by-gene comparisons of paired synonymous site and intron substitution rates toward and away from the nucleotides G and C because preferred codons are G or C ending in Drosophila. This comparison may reduce both the false-positive rate (due to broadscale heterogeneity in mutation) and false-negative rate (due to lack of power comparing small numbers of sites) of the per-site and likelihood methods. We detect loci with patterns of evolution suggestive of synonymous site selection pressures predominately favoring unpreferred and preferred codons along the Drosophila melanogaster and Drosophila sechellia lineages, respectively. Intron selection pressures do not appear sufficient to explain all these results as the magnitude of the difference in synonymous and intron evolution is dependent on recombination environment and chromosomal location in a direction supporting the hypothesis of selectively driven synonymous fixations. This comparison identifies 101 loci with an apparent switch in codon preference between D. melanogaster and D. sechellia, a pattern previously only observed at the Notch locus

A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus

<div><p>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 <i>Drosophila</i>/<i>Sophophora</i> 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 <i>D. melanogaster</i>, 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 <i>D. melanogaster</i> 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.</p></div

Self-harm and attachment in adolescents: what is the role of emotion dysregulation?

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

A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus

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.</p

Drosophilid Akashi selection scores

A tar/bz2 file containing 22 files: 12 reporting Akashi selection scores over 12 drosophilid species, 8 reporting Akashi selection scores over 6 developmental stages plus two merged stages (embryo and adult), one reporting all-stage information, and one readme.txt file

Queuosine tRNA modification covaries with relative codon accuracy across the drosophilid phylogeny.

<p>(A) Northern blot of total <i>D. melanogaster</i> third-instar larval tRNA using tRNA^Tyr-specific probe resolves two major bands (left) after electrophoretic separation on an acryloyl aminophenylboronic acid gel (APB gel); when <i>cis</i>-diols are oxidized with periodate, tRNA runs as a single band (right). (B) APB gel measurements of Q modification produce similar stage-specific results to an independent method in <i>D. melanogaster</i>. (C) Separation of total tRNA from four species at two developmental stages by APB gel followed by Northern blotting using probes specific for each species' tRNA^His, tRNA^Asn, and tRNA^Tyr reveals shifts in Q modification (<i>mel</i>, <i>D. melanogaster</i>; <i>pse</i>, <i>D. pseudoobscura</i>; <i>wil</i>, <i>D. willistoni</i>; <i>vir</i>, <i>D. virilis</i>). (D) Quantification of the data in (C) (cf. <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002015#pbio.1002015.s005" target="_blank">Data S1</a>); error bars show standard error in measurement. (E) The Akashi selection scores for NAU to NAC, over all genes, track the proportion of Q-modified tRNA in adult flies across species. Colors as in (D). Bars show standard error of the mean (SEM) for modification levels and 95% confidence interval for selection scores. Spearman rank correlation <i>r</i> = 0.61, <i>p</i><0.05 for raw values, and <i>r</i> = 0.73, <i>p</i><0.01 after subtracting means from each synonymous family.</p