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在 COVID-19 大流行期间积累的风疹病毒和 SARS-CoV-2 基因组的高突变基因组中的突变谱之间的相似性。

Similarity between mutation spectra in hypermutated genomes of rubella virus and in SARS-CoV-2 genomes accumulated during the COVID-19 pandemic.

机构信息

Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, United State of America.

Mechanisms of Genome Dynamics Group, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, United State of America.

出版信息

PLoS One. 2020 Oct 2;15(10):e0237689. doi: 10.1371/journal.pone.0237689. eCollection 2020.

Abstract

Genomes of tens of thousands of SARS-CoV2 isolates have been sequenced across the world and the total number of changes (predominantly single base substitutions) in these isolates exceeds ten thousand. We compared the mutational spectrum in the new SARS-CoV-2 mutation dataset with the previously published mutation spectrum in hypermutated genomes of rubella-another positive single stranded (ss) RNA virus. Each of the rubella virus isolates arose by accumulation of hundreds of mutations during propagation in a single subject, while SARS-CoV-2 mutation spectrum represents a collection events in multiple virus isolates from individuals across the world. We found a clear similarity between the spectra of single base substitutions in rubella and in SARS-CoV-2, with C to U as well as A to G and U to C being the most prominent in plus strand genomic RNA of each virus. Of those, U to C changes universally showed preference for loops versus stems in predicted RNA secondary structure. Similarly, to what was previously reported for rubella virus, C to U changes showed enrichment in the uCn motif, which suggested a subclass of APOBEC cytidine deaminase being a source of these substitutions. We also found enrichment of several other trinucleotide-centered mutation motifs only in SARS-CoV-2-likely indicative of a mutation process characteristic to this virus. Altogether, the results of this analysis suggest that the mutation mechanisms that lead to hypermutation of the rubella vaccine virus in a rare pathological condition may also operate in the background of the SARS-CoV-2 viruses currently propagating in the human population.

摘要

已对来自世界各地的数万种 SARS-CoV2 分离株的基因组进行了测序,这些分离株中的总突变数(主要是单个碱基替换)超过了一万个。我们比较了新 SARS-CoV-2 突变数据集的突变谱与先前在风疹(另一种正链单链 (ss) RNA 病毒)高度突变基因组中发表的突变谱。每个风疹病毒分离株都是在单个个体中传播时积累了数百个突变而产生的,而 SARS-CoV-2 突变谱代表了来自世界各地个体的多个病毒分离株中的一系列事件。我们发现风疹和 SARS-CoV-2 中单个碱基替换的谱之间存在明显的相似性,每个病毒的正链基因组 RNA 中最突出的是 C 到 U 以及 A 到 G 和 U 到 C。在这些变化中,U 到 C 的变化普遍倾向于在预测的 RNA 二级结构中取代环而不是茎。同样,与先前报道的风疹病毒一样,C 到 U 的变化在 uCn 基序中富集,这表明 APOBEC 胞嘧啶脱氨酶的亚类是这些替换的来源。我们还发现仅在 SARS-CoV-2 中富集了几个其他三核苷酸中心的突变基序,这可能表明该病毒的突变过程具有特征。总之,该分析的结果表明,导致风疹疫苗病毒在罕见病理条件下高度突变的突变机制也可能在当前在人群中传播的 SARS-CoV-2 病毒的背景下起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f68c/7531822/f3e0fc98a285/pone.0237689.g001.jpg

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