Dissimilation of synonymous codon usage bias in virus-host coevolution due to translational selection
Dissimilation of synonymous codon usage bias in virus-host coevolution due to translational selection
复制标题
由于翻译选择导致病毒-宿主协同进化中同义密码子使用偏差的异化
DOI：
10.1038/s41559-020-1124-7
复制
发表时间：
2020-03-02
影响因子：
16.8
通讯作者：
Yang, Jian-Rong
中科院分区：
文献类型：
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作者：
Chen, Feng;Wu, Peng;Yang, Jian-Rong
这项研究表明，当病毒和宿主密码子使用过于相似时，由于病毒表达增加导致tRNA消耗水平阻碍宿主翻译，两者之间存在排斥。20个氨基酸中的18个都由一个以上的同义密码子编码。由于细胞内的差异转移RNA供应，同义密码子的使用频率不同，这种现象被称为密码子使用偏向(CUB)。以前的研究已经证明，内源基因的CUB反式调节其他基因的翻译效率。我们假设外源基因对宿主翻译的幼崽有类似的影响，并在病毒感染的情况下进行了测试，病毒感染是自然发生的外源基因翻译的一种常见形式。我们分析了来自感染病毒的酵母和人类细胞的公共Ribo-Seq数据集，结果表明，病毒幼体反式调节tRNA的可用性，从而调节密码子的相对解码时间。在酵母中使用37个同义荧光蛋白的操纵实验证实，带有与宿主更相似的CUB的外源基因将在每单位表达中对宿主施加更少的翻译负荷，而外源基因的表达增加。这两种效应的共同作用是，带有与寄主过于相似的幼体的外源基因严重阻碍了寄主的翻译。最后，使用人工整理的病毒和自然宿主和症状宿主的列表，我们发现病毒幼体与症状宿主的幼体往往比自然宿主的幼体更相似，这支持了病毒与宿主之间幼体过度相似的一般有害影响。我们的工作揭示了当病毒和宿主幼崽过于相似时，它们之间的排斥，这是以前在病毒和宿主的共同进化中未知的复杂性。
This study shows repulsion between virus and host codon usage bias when they are too similar, due to increased viral expression leading to levels of tRNA consumption that impede host translation.Eighteen of the 20 amino acids are each encoded by more than one synonymous codon. Due to differential transfer RNA supply within the cell, synonymous codons are not used with equal frequency, a phenomenon termed codon usage bias (CUB). Previous studies have demonstrated that CUB of endogenous genes trans-regulates the translational efficiency of other genes. We hypothesized similar effects for CUB of exogenous genes on host translation, and tested it in the case of viral infection, a common form of naturally occurring exogenous gene translation. We analysed public Ribo-Seq datasets from virus-infected yeast and human cells and showed that virus CUB trans-regulated tRNA availability, and therefore the relative decoding time of codons. Manipulative experiments in yeast using 37 synonymous fluorescent proteins confirmed that an exogenous gene with CUB more similar to that of the host would apply decreased translational load on the host per unit of expression, whereas expression of the exogenous gene was elevated. The combination of these two effects was that exogenous genes with CUB overly similar to that of the host severely impeded host translation. Finally, using a manually curated list of viruses and natural and symptomatic hosts, we found that virus CUB tended to be more similar to that of symptomatic hosts than that of natural hosts, supporting a general deleterious effect of excessive CUB similarity between virus and host. Our work revealed repulsion between virus and host CUBs when they are overly similar, a previously unrecognized complexity in the coevolution of virus and host.