Biased Mutation and Selection in RNA Viruses.
Biased Mutation and Selection in RNA Viruses.
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DOI：
10.1093/molbev/msaa247
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发表时间：
2021-01-23
影响因子：
10.7
通讯作者：
Stern A
中科院分区：
文献类型：
--
作者：
Kustin T;Stern A
RNA病毒是人类已知的一些最严重的流行病的罪魁祸首，包括流感，埃博拉和COVID-19的爆发。对付RNA病毒的一个主要挑战是它们的遗传多样性。然而，它们有共同的特征，包括它们对宿主细胞的复制依赖和高突变率。我们开始寻找共同的进化特征，这可能有助于更广泛地了解RNA病毒的进化，并构建了一个基于遗传学的数据集，涵盖了来自动物的不同单链RNA病毒的数千个序列。引人注目的是，我们发现这些病毒中的绝大多数具有倾斜的核苷酸组成，表现为富含腺嘌呤（富含A）的编码序列。为了测试A丰富度是由选择还是由偏向突变过程驱动，我们利用了病毒复制过程中不完全纯化选择的影响。我们的研究结果揭示了所有病毒基因组中一致的突变偏向U而不是A。在+ssRNA病毒中，我们发现这种偏好通过对U的选择和对A的选择来补偿，这导致了富含A的基因组。在−ssRNA病毒中，基因组突变偏向负链上的U，表现为正链上富含A的编码序列。我们研究了富含A的序列的优势的可能原因，包括弱化的RNA二级结构，密码子使用偏好，以及对特定氨基酸组成的选择，并得出结论，宿主免疫压力可能导致编码序列组成在非常不同的RNA病毒中存在类似的偏好。
RNA viruses are responsible for some of the worst pandemics known to mankind, including outbreaks of Influenza, Ebola, and COVID-19. One major challenge in tackling RNA viruses is the fact they are extremely genetically diverse. Nevertheless, they share common features that include their dependence on host cells for replication, and high mutation rates. We set out to search for shared evolutionary characteristics that may aid in gaining a broader understanding of RNA virus evolution, and constructed a phylogeny-based data set spanning thousands of sequences from diverse single-stranded RNA viruses of animals. Strikingly, we found that the vast majority of these viruses have a skewed nucleotide composition, manifested as adenine rich (A-rich) coding sequences. In order to test whether A-richness is driven by selection or by biased mutation processes, we harnessed the effects of incomplete purifying selection at the tips of virus phylogenies. Our results revealed consistent mutational biases toward U rather than A in genomes of all viruses. In +ssRNA viruses, we found that this bias is compensated by selection against U and selection for A, which leads to A-rich genomes. In −ssRNA viruses, the genomic mutational bias toward U on the negative strand manifests as A-rich coding sequences, on the positive strand. We investigated possible reasons for the advantage of A-rich sequences including weakened RNA secondary structures, codon usage bias, and selection for a particular amino acid composition, and conclude that host immune pressures may have led to similar biases in coding sequence composition across very divergent RNA viruses.
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