Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins-A Possible Signature of Adaptive Selection.

Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins-A Possible Signature of Adaptive Selection.
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SARS-COV-2蛋白质高变量区域中indels的频率增加 - 自适应选择的可能标志。

DOI:
10.3389/fgene.2022.875406
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发表时间:
2022
影响因子:
3.7
通讯作者:
Godzik, Adam
Godzik, Adam
中科院分区:
生物学3区
文献类型:
--
作者:
Alisoltani, Arghavan;Jaroszewski, Lukasz;Iyer, Mallika;Iranzadeh, Arash;Godzik, Adam

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在SARS-CoV-2基因组进化的监测中,大多数注意力集中在刺突糖蛋白的核苷酸替换上。我们发现,随着大流行持续到第二年,具有框内插入和缺失(indels)的基因组的数量和比例显着增加,特别是在关注的变体(VOC)中。对SARS-CoV-2基因组进化的监测显示,插入/缺失(尤其是刺突N-末端结构域和非结构蛋白6(NSP 6)上的缺失)是若干VOC如α、β、δ和0微米中的共有特征。插入缺失分布与免疫逃逸相关的尖峰突变相关,并且具有插入缺失的基因组数量的增长与由于疫苗接种和先前感染而增加的群体抗性相一致。插入缺失最常出现在刺突中,但也出现在其他蛋白质中,特别是那些参与与宿主免疫系统相互作用的蛋白质中。我们还发现,插入缺失集中在被称为高变区(HVR)的单个SARS-CoV-2蛋白的区域,这些区域主要位于特定的环区域。结构分析表明,插入缺失在共同表位和相互作用界面处重塑病毒蛋白质的表面,影响病毒与宿主蛋白质的相互作用。我们假设,indels的频率增加,它们的非随机分布及其在几种VOC中的独立共存是对全球人群免疫力提高的另一种反应机制。
Most attention in the surveillance of evolving SARS-CoV-2 genome has been centered on nucleotide substitutions in the spike glycoprotein. We show that, as the pandemic extends into its second year, the numbers and ratio of genomes with in-frame insertions and deletions (indels) increases significantly, especially among the variants of concern (VOCs). Monitoring of the SARS-CoV-2 genome evolution shows that co-occurrence (i.e., highly correlated presence) of indels, especially deletions on spike N-terminal domain and non-structural protein 6 (NSP6) is a shared feature in several VOCs such as Alpha, Beta, Delta, and Omicron. Indels distribution is correlated with spike mutations associated with immune escape and growth in the number of genomes with indels coincides with the increasing population resistance due to vaccination and previous infections. Indels occur most frequently in the spike, but also in other proteins, especially those involved in interactions with the host immune system. We also showed that indels concentrate in regions of individual SARS-CoV-2 proteins known as hypervariable regions (HVRs) that are mostly located in specific loop regions. Structural analysis suggests that indels remodel viral proteins’ surfaces at common epitopes and interaction interfaces, affecting the virus’ interactions with host proteins. We hypothesize that the increased frequency of indels, the non-random distribution of them and their independent co-occurrence in several VOCs is another mechanism of response to elevated global population immunity.
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