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 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, 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.

中文翻译：

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风疹病毒超突变基因组中突变谱与在COVID-19大流行期间积累的SARS-CoV-2基因组突变谱之间相似。

全世界已对数以万计的SARS-CoV2分离株的基因组进行了测序，这些分离株的变化总数（主要是单碱基取代）超过了10,000。我们将新的SARS-CoV-2突变数据集中的突变谱与风疹超突变基因组（另一种阳性单链（ss）RNA病毒）的先前发布的突变谱进行了比较。每个风疹分离株都是通过在单个受试者中繁殖期间积累数百个突变而产生的，而SARS-CoV-2突变谱则代表了来自世界各地的多个病毒分离株中的采集事件。我们发现风疹和SARS-CoV-2中单碱基取代的光谱之间存在明显的相似性，在每种病毒的正链基因组RNA中，C到U以及A到G和U到C是最突出的。其中，从U到C的变化普遍显示在预测的RNA二级结构中相对于茎环而言更喜欢环。类似地，对于先前报道的风疹，从C到U的变化表明uCn基序富集，这表明APOBEC胞苷脱氨酶的一个亚类是这些取代的来源。我们还发现仅在SARS-CoV-2中富集了其他几个以三核苷酸为中心的突变基序-可能表明该病毒具有突变过程特征。共，