Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function.
Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function.
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作者：
Berrio A;Gartner V;Wray GA
一种与严重急性呼吸道疾病(新冠肺炎)相关的新型冠状病毒(SARS-CoV-2)的出现促使人们努力了解其独特特征的遗传基础及其从非灵长类宿主向人类的传播。正向选择测试可以识别基因组中突变积累的明显非随机模式，突出显示在物种起源期间分子功能可能发生变化的区域。最近对SARS-CoV-2基因组的几项研究发现，根据同义替换与非同义替换的比率，在编码Spike蛋白的基因中存在保守和正选择的信号。然而，这样的测试无法检测到RNA分子功能的变化。在这里，我们应用了一种在基因组的狭窄窗口内对突变的分支特定过度替换的测试，而不参考遗传密码。我们总结了这一发现，即编码Spike蛋白的基因一直是纯化和正选择的目标。此外，我们在SARS-CoV-2基因组中发现了其他可能的正选择靶点，特别是在编码NSP4和NSP16的基因中。同源定向建模表明，相对于最近的共同祖先，NSP4或NSP16的蛋白质结构没有变化。这些SARS-CoV-2特异性突变可能影响由正性或负性RNA分子介导的分子过程，包括转录、翻译、RNA稳定性和逃避宿主天然免疫系统。我们的结果强调了考虑病毒基因组突变的重要性，不仅从它们对蛋白质结构的影响的角度，而且从它们可能如何影响对病毒生命周期至关重要的其他分子过程的角度来考虑。
The emergence of a novel coronavirus (SARS-CoV-2) associated with severe acute respiratory disease (COVID-19) has prompted efforts to understand the genetic basis for its unique characteristics and its jump from non-primate hosts to humans. Tests for positive selection can identify apparently nonrandom patterns of mutation accumulation within genomes, highlighting regions where molecular function may have changed during the origin of a species. Several recent studies of the SARS-CoV-2 genome have identified signals of conservation and positive selection within the gene encoding Spike protein based on the ratio of synonymous to nonsynonymous substitution. Such tests cannot, however, detect changes in the function of RNA molecules. Here we apply a test for branch-specific oversubstitution of mutations within narrow windows of the genome without reference to the genetic code. We recapitulate the finding that the gene encoding Spike protein has been a target of both purifying and positive selection. In addition, we find other likely targets of positive selection within the genome of SARS-CoV-2, specifically within the genes encoding Nsp4 and Nsp16. Homology-directed modeling indicates no change in either Nsp4 or Nsp16 protein structure relative to the most recent common ancestor. These SARS-CoV-2-specific mutations may affect molecular processes mediated by the positive or negative RNA molecules, including transcription, translation, RNA stability, and evasion of the host innate immune system. Our results highlight the importance of considering mutations in viral genomes not only from the perspective of their impact on protein structure, but also how they may impact other molecular processes critical to the viral life cycle.
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影响因子：
11
作者：
Chaw, Shu-Miaw;Tai, Jui-Hung;Wang, Hurng-Yi
通讯作者：
Wang, Hurng-Yi
DOI：
10.3390/v3091739
发表时间：
2011-09
期刊：
Viruses
影响因子：
--
作者：
Gebhard LG;Filomatori CV;Gamarnik AV
通讯作者：
Gamarnik AV
影响因子：
4.1
作者：
Armijos-Jaramillo, Vinicio;Yeager, Justin;Perez-Castillo, Yunierkis
通讯作者：
Perez-Castillo, Yunierkis
DOI：
10.3109/08977194.2012.669382
发表时间：
2012-06
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Fuchs SY
通讯作者：
Fuchs SY
影响因子：
7.6
作者：
Báez-Santos YM;St John SE;Mesecar AD
通讯作者：
Mesecar AD