Unique cost dynamics elucidate the role of frameshifting errors in promoting translational robustness.
Unique cost dynamics elucidate the role of frameshifting errors in promoting translational robustness.
复制标题
独特的成本动态阐明了移码错误在促进翻译鲁棒性方面的作用。
DOI：
10.1093/gbe/evq049
复制
发表时间：
2010
影响因子：
3.3
通讯作者：
Hurst,LaurenceD
中科院分区：
文献类型：
--
作者：
Warnecke,Tobias;Huang,Yang;Przytycka,TeresaM;Hurst,LaurenceD
现在有相当多的证据支持的观点，密码子的使用经常选择翻译的准确性。然而，存在多种形式的不准确性（误义、过早终止和移帧错误），并且在明显自适应的mRNA解剖结构背后确定特定的错误过程很少是直截了当的。了解与不同类型的翻译错误相关的适应度成本的差异，可以帮助我们设计出关键的测试，可以将一个错误过程排除在其他错误过程之外。为此，我们提出了一个模型，捕捉帧移成本的不同特征，并将其应用于641个原核生物基因组。我们证明，尽管通常认为核糖体在移码后很快就会遇到帧外停止密码子，因此错误延伸的成本有限，但高GC含量的基因组通常会产生更大的每次错误成本。我们继续推导出预测，独特的帧移误差，基因的5 ‘和3 ’端之间的翻译稳健性差异应该是不太明显的基因组具有较高的GC含量。我们证明这个预测是正确的。令人惊讶的是，这并不意味着富含gc的生物体必然会因为偶然的帧移而承担更大的适应性负担。事实上，由于富含gc的基因组中反密码子的多样性，每次错误成本的增加往往被较低的预测错误率所抵消。因此，我们建议对tRNA库的选择可以减少帧移误差。
There is now considerable evidence supporting the view that codon usage is frequently under selection for translational accuracy. There are, however, multiple forms of inaccuracy (missense, premature termination, and frameshifting errors) and pinpointing a particular error process behind apparently adaptive mRNA anatomy is rarely straightforward. Understanding differences in the fitness costs associated with different types of translational error can help us devise critical tests that can implicate one error process to the exclusion of others. To this end, we present a model that captures distinct features of frameshifting cost and apply this to 641 prokaryotic genomes. We demonstrate that, although it is commonly assumed that the ribosome encounters an off-frame stop codon soon after the frameshift and costs of mis-elongation are therefore limited, genomes with high GC content typically incur much larger per-error costs. We go on to derive the prediction, unique to frameshifting errors, that differences in translational robustness between the 5′ and 3′ ends of genes should be less pronounced in genomes with higher GC content. This prediction we show to be correct. Surprisingly, this does not mean that GC-rich organisms necessarily carry a greater fitness burden as a consequence of accidental frameshifting. Indeed, increased per-error costs are often more than counterbalanced by lower predicted error rates owing to more diverse anticodon repertoires in GC-rich genomes. We therefore propose that selection on tRNA repertoires may operate to reduce frameshifting errors.