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Biased mutation and selection in RNA viruses
Molecular Biology and Evolution ( IF 10.7 ) Pub Date : 2020-09-28 , DOI: 10.1093/molbev/msaa247
Talia Kustin 1 , Adi Stern 1, 2
Affiliation  

RNA viruses are responsible for some of the worst pandemics known to mankind, including outbreaks of Influenza, Ebola, and the recent 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 dataset 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 towards 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 towards 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.

中文翻译:

RNA病毒的偏向突变和选择

RNA病毒是人类已知的一些最严重的大流行的原因,包括流感,埃博拉病毒和最近的COVID-19的爆发。应对RNA病毒的一个主要挑战是它们在遗传上极为不同。然而,它们具有共同的特征,包括它们对复制宿主细胞的依赖性以及高突变率。我们着手寻找可能有助于获得对RNA病毒进化的更广泛理解的共享进化特征,并构建了一个基于系统发育的数据集,涵盖了来自动物不同单链RNA病毒的数千个序列。令人惊讶地,我们发现这些病毒中的绝大多数具有偏斜的核苷酸组成,表现为富含腺嘌呤(富含A)的编码序列。为了测试A丰富性是由选择驱动还是由偏向突变过程驱动,我们利用了病毒系统发生过程中不完全纯化选择的影响。我们的结果表明,在所有病毒的基因组中,一致的突变偏向于U,而不是A。在+ ssRNA病毒中,我们发现这种偏倚可以通过针对U的选择和针对A的选择得到补偿,从而导致了富含A的基因组。在-ssRNA病毒中,负链上针对U的基因组突变偏向表现为正链上富含A的编码序列。我们研究了富含A序列的优势的可能原因,包括减弱的RNA二级结构,密码子使用偏倚以及对特定氨基酸组成的选择,
更新日期:2020-09-28
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