State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences, Peking University, Beijing, China.
Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Nat Commun. 2024 Sep 27;15(1):8329. doi: 10.1038/s41467-024-52660-4.
Accuracy and efficiency are fundamental to mRNA translation. Codon usage bias is widespread across species. Despite the long-standing association between optimized codon usage and improved translation, our understanding of its evolutionary basis and functional effects remains limited. Drosophila is widely used to study codon usage bias, but genome-scale experimental data are scarce. Using high-resolution mass spectrometry data from Drosophila melanogaster, we show that optimal codons have lower translation errors than nonoptimal codons after accounting for these biases. Genomic-scale analysis of ribosome profiling data shows that optimal codons are translated more rapidly than nonoptimal codons. Although we find no long-term selection favoring synonymous mutations in D. melanogaster after diverging from D. simulans, we identify signatures of positive selection driving codon optimization in the D. melanogaster population. These findings expand our understanding of the functional consequences of codon optimization and serve as a foundation for future investigations.
准确性和效率是 mRNA 翻译的基础。密码子使用偏性在物种中广泛存在。尽管优化的密码子使用与提高翻译效率之间存在长期关联，但我们对其进化基础和功能影响的理解仍然有限。果蝇被广泛用于研究密码子使用偏性，但基因组规模的实验数据却很少。利用来自黑腹果蝇的高分辨率质谱数据，我们表明，在考虑这些偏性后，最优密码子的翻译错误率低于非最优密码子。核糖体分析数据的基因组规模分析表明，最优密码子的翻译速度快于非最优密码子。尽管我们没有发现黑腹果蝇从模拟果蝇分化后有利于同义突变的长期选择，但我们鉴定出了正选择驱动黑腹果蝇群体中密码子优化的特征。这些发现扩展了我们对密码子优化功能后果的理解，并为未来的研究奠定了基础。
