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新型冠状病毒之谜:印度境内传播的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒共同进化突变的系统发育及分析

The Novel Coronavirus Enigma: Phylogeny and Analyses of Coevolving Mutations Among the SARS-CoV-2 Viruses Circulating in India.

作者信息

Banerjee Anindita, Sarkar Rakesh, Mitra Suvrotoa, Lo Mahadeb, Dutta Shanta, Chawla-Sarkar Mamta

机构信息

Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases Kolkata India.

出版信息

JMIR Bioinform Biotechnol. 2020 Sep 7;1(1):e20735. doi: 10.2196/20735. eCollection 2020.

DOI:10.2196/20735
PMID:33496683
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7720937/
Abstract

BACKGROUND

The RNA genome of the emerging novel coronavirus is rapidly mutating, and its human-to-human transmission rate is increasing. Hence, temporal dissection of their evolutionary dynamics, the nature of variations among different strains, and understanding the single nucleotide polymorphisms in the endemic settings are crucial. Delineating the heterogeneous genomic constellations of this novel virus will help us understand its complex behavior in a particular geographical region.

OBJECTIVE

This is a comprehensive analysis of 95 Indian SARS-CoV-2 genome sequences available from the Global Initiative on Sharing All Influenza Data (GISAID) repository during the first 6 months of 2020 (January through June). Evolutionary dynamics, gene-specific phylogeny, and the emergence of the novel coevolving mutations in 9 structural and nonstructural genes among circulating SARS-CoV-2 strains across 12 different Indian states were analyzed.

METHODS

A total of 95 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID database. Molecular Evolutionary Genetics Analysis, version X software was used to construct the 9 phylogenetic dendrograms based on nucleotide sequences of the SARS-CoV-2 genes. Analyses of the coevolving mutations were done in comparison to the prototype SARS-CoV-2 from Wuhan, China. The secondary structure of the RNA-dependent RNA polymerase/nonstructural protein NSP12 was predicted with respect to the novel A97V mutation.

RESULTS

Phylogenetic analyses revealed the evolution of "genome-type clusters" and adaptive selection of "L"-type SARS-CoV-2 strains with genetic closeness to the bat severe acute respiratory syndrome-like coronaviruses. These strains were distant to pangolin or Middle East respiratory syndrome-related coronavirus strains. With regard to the novel coevolving mutations, 2 groups have been seen circulating in India at present, the "major group" (66/95, 69.4%) and the "minor group" (21/95, 22.1%) , harboring 4 and 5 coexisting mutations, respectively. The "major group" mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6 gene), were unique to the Indian isolates.

CONCLUSIONS

This study highlights the rapidly evolving SARS-CoV-2 virus and the cocirculation of multiple clades and subclades. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, interpreting changes in viral pathogenesis, and designing vaccines or other therapeutics.

摘要

背景

新型冠状病毒的RNA基因组正在迅速变异,其人际传播率也在上升。因此,对其进化动态进行时间剖析、不同毒株间变异的性质以及了解地方流行环境中的单核苷酸多态性至关重要。描绘这种新型病毒的异质基因组结构将有助于我们了解其在特定地理区域的复杂行为。

目的

这是一项对2020年上半年(1月至6月)从全球共享流感数据倡议组织(GISAID)数据库中获取的95个印度严重急性呼吸综合征冠状病毒2(SARS-CoV-2)基因组序列的综合分析。分析了12个不同印度邦流行的SARS-CoV-2毒株中9个结构和非结构基因的进化动态、基因特异性系统发育以及新出现的共同进化突变。

方法

从GISAID数据库下载了总共95个来自印度提交的SARS-CoV-2核苷酸序列。使用分子进化遗传学分析X版软件,根据SARS-CoV-2基因的核苷酸序列构建9个系统发育树状图。与来自中国武汉的SARS-CoV-2原型相比,对共同进化突变进行了分析。针对新出现的A97V突变,预测了RNA依赖性RNA聚合酶/非结构蛋白NSP12的二级结构。

结果

系统发育分析揭示了“基因组类型簇”的进化以及与蝙蝠严重急性呼吸综合征样冠状病毒基因相近的“L”型SARS-CoV-2毒株的适应性选择。这些毒株与穿山甲或中东呼吸综合征相关冠状病毒毒株距离较远。关于新出现的共同进化突变,目前在印度发现有两组在传播,即“主要组”(66/95,69.4%)和“次要组”(21/95,22.1%),分别含有4个和5个共存突变。“主要组”突变属于A2a进化枝。除了11083G>T(L37F,NSP6基因)外,所有次要组突变都是印度分离株所特有的。

结论

本研究突出了SARS-CoV-2病毒的快速进化以及多个进化枝和亚进化枝的共同传播。这项综合研究是监测病毒基因组新突变、解释病毒致病机制变化以及设计疫苗或其他治疗方法的潜在资源。

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