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首页> 外文期刊>PLoS Biology >A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus
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A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus

机译：营养驱动的tRNA修饰改变整个动物属的翻译保真度和全基因组蛋白编码。

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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.
机译：自然选择有利于编码蛋白的有效表达，但是进化的编码变化的原因，机制和适应性后果仍然是积极研究的领域。我们报告果蝇/ Sophophora属中的12个蝇种的密码子的相对翻译准确性的大规模逆转。因为逆转涉及相同基因组编码的tRNA读取的密码子对，所以我们假设并通过直接测量显示，从鸟苷到queussine的tRNA反密码子修饰与这些基因组变化共同进化。在大多数生物中都存在Queuosine修饰，但其功能尚不清楚。修饰水平随黑腹果蝇的发育阶段而变化，并且与因果效应一致，在每个阶段最大表达的基因显示出选择密码子的选择，这些密码子在给定特定阶段的queossine修饰水平的情况下最准确。在动力学模型中，已知奎松修饰的tRNA对核糖体的亲和力增加，从而提高了同源密码子的准确性，同时降低了近同源密码子的准确性。 D. melanogaster中queuosine修饰的水平反映了前体queuine的生物利用度，其是真核生物从细菌的tRNA清除并在肠道中吸收。这些结果揭示了一个惊人的直接机制，通过该机制可以通过营养物利用的变化来对整个基因组进行编码。

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