Department of Biophysical Chemistry and Molecular Oncology, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic.
National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic.
Brief Bioinform. 2021 Mar 22;22(2):1338-1345. doi: 10.1093/bib/bbaa385.
SARS-CoV-2 is an intensively investigated virus from the order Nidovirales (Coronaviridae family) that causes COVID-19 disease in humans. Through enormous scientific effort, thousands of viral strains have been sequenced to date, thereby creating a strong background for deep bioinformatics studies of the SARS-CoV-2 genome. In this study, we inspected high-frequency mutations of SARS-CoV-2 and carried out systematic analyses of their overlay with inverted repeat (IR) loci and CpG islands. The main conclusion of our study is that SARS-CoV-2 hot-spot mutations are significantly enriched within both IRs and CpG island loci. This points to their role in genomic instability and may predict further mutational drive of the SARS-CoV-2 genome. Moreover, CpG islands are strongly enriched upstream from viral ORFs and thus could play important roles in transcription and the viral life cycle. We hypothesize that hypermethylation of these loci will decrease the transcription of viral ORFs and could therefore limit the progression of the disease.
SARS-CoV-2 是一种来自套式病毒目（冠状病毒科）的病毒，可引起人类 COVID-19 疾病。通过巨大的科学努力，迄今为止已对数千种病毒株进行了测序，从而为 SARS-CoV-2 基因组的深入生物信息学研究奠定了坚实的基础。在这项研究中，我们检查了 SARS-CoV-2 的高频突变，并对其与反向重复（IR）基因座和 CpG 岛的重叠进行了系统分析。我们研究的主要结论是，SARS-CoV-2 的热点突变在 IR 和 CpG 岛基因座中均明显富集。这表明它们在基因组不稳定性中的作用，并可能预测 SARS-CoV-2 基因组的进一步突变驱动。此外，CpG 岛在上游强烈富集病毒 ORFs，因此可能在转录和病毒生命周期中发挥重要作用。我们假设这些基因座的过度甲基化将降低病毒 ORFs 的转录，从而可能限制疾病的进展。
