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六种新冠病毒变异株中同义突变的结构影响

Structural impact of synonymous mutations in six SARS-CoV-2 Variants of Concern.

作者信息

Ziesel Alison, Jabbari Hosna

机构信息

Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.

出版信息

PLoS One. 2025 Jul 1;20(7):e0325858. doi: 10.1371/journal.pone.0325858. eCollection 2025.

Abstract

SARS-CoV-2 continues to spread and infect people worldwide. While most effort into characterizing variants of this virus have focused on non-synonymous changes, accumulation of synonymous mutations in different viral variants has also occurred. Here we characterize six Variants of Concern in terms of their mutational content, and make predictions regarding the impact of those mutations on potential genomic RNA secondary structure and stability. Our hypothesis is that if non-protein changing, yet RNA structure-changing mutations impact viral fitness by imposing deleterious change to predicted RNA structure, we would expect to those mutations to be less abundant, while if those synonymous mutations do not impact viral fitness through influence of RNA structure, we would see them more frequently than non-synonymous mutations. We find that synonymous mutations typically have no or modest impact to RNA secondary structure. As synonymous mutations are free from the selective pressure imposed on protein-altering mutations, the impact of synonymous mutations is largely limited to RNA secondary structure considerations. The absence of major, structure-altering synonymous mutations emphasize the importance of RNA structure, including within coding regions, to viral fitness. Synonymous mutations should be included in the characterization of emerging RNA viruses as these mutations may confer effects to viral fitness via RNA secondary structural modifications.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)继续在全球范围内传播并感染人群。虽然对该病毒变体的特征描述大多集中在非同义变化上,但不同病毒变体中同义突变的积累也已出现。在此,我们根据突变内容对六个关注变体进行了特征描述,并对这些突变对潜在基因组RNA二级结构和稳定性的影响进行了预测。我们的假设是,如果不改变蛋白质但改变RNA结构的突变通过对预测的RNA结构施加有害变化来影响病毒适应性,我们预计这些突变的丰度较低,而如果这些同义突变不通过影响RNA结构来影响病毒适应性,我们会比非同义突变更频繁地看到它们。我们发现同义突变通常对RNA二级结构没有或只有适度影响。由于同义突变不受施加于改变蛋白质的突变的选择压力影响,同义突变的影响在很大程度上仅限于RNA二级结构方面的考虑。缺乏主要的、改变结构的同义突变强调了RNA结构(包括编码区域内的结构)对病毒适应性的重要性。新兴RNA病毒的特征描述应包括同义突变,因为这些突变可能通过RNA二级结构修饰对病毒适应性产生影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d7b/12212874/bf381ecf82c5/pone.0325858.g001.jpg

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