Mapping of long stretches of highly conserved sequences in over 6 million SARS-CoV-2 genomes.

IF 2.5 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Akhil Kumar, Rishika Kaushal, Himanshi Sharma, Khushboo Sharma, Manoj B Menon, Vivekanandan P
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引用次数: 0

Abstract

We identified 11 conserved stretches in over 6.3 million SARS-CoV-2 genomes including all the major variants of concerns. Each conserved stretch is ≥100 nucleotides in length with ≥99.9% conservation at each nucleotide position. Interestingly, six of the eight conserved stretches in ORF1ab overlapped significantly with well-folded experimentally verified RNA secondary structures. Furthermore, two of the conserved stretches were mapped to regions within the S2-subunit that undergo dynamic structural rearrangements during viral fusion. In addition, the conserved stretches were significantly depleted for zinc-finger antiviral protein (ZAP) binding sites, which facilitated the recognition and degradation of viral RNA. These highly conserved stretches in the SARS-CoV-2 genome were poorly conserved at the nucleotide level among closely related β-coronaviruses, thus representing ideal targets for highly specific and discriminatory diagnostic assays. Our findings highlight the role of structural constraints at both RNA and protein levels that contribute to the sequence conservation of specific genomic regions in SARS-CoV-2.

在 600 多万个 SARS-CoV-2 基因组中绘制高度保守的长序列图。
我们在超过630万个SARS-CoV-2基因组中发现了11个保守区段,包括所有主要的关注变体。每个保守区段的长度≥100个核苷酸,每个核苷酸位置的保守性≥99.9%。有趣的是,ORF1ab 的 8 个保守片段中有 6 个与实验验证的折叠良好的 RNA 二级结构明显重叠。此外,其中两个保守片段被映射到了S2亚基中的区域,这些区域在病毒融合过程中会发生动态结构重排。此外,这些保守区段的锌指抗病毒蛋白(ZAP)结合位点明显减少,这有利于病毒 RNA 的识别和降解。SARS-CoV-2基因组中的这些高度保守区段在核苷酸水平上与近缘的β-冠状病毒保守性很低,因此是高度特异性和鉴别性诊断检测的理想目标。我们的研究结果突显了 RNA 和蛋白质水平上的结构限制对 SARS-CoV-2 基因组特定区域的序列保守性所起的作用。
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来源期刊
Briefings in Functional Genomics
Briefings in Functional Genomics BIOTECHNOLOGY & APPLIED MICROBIOLOGY-GENETICS & HEREDITY
CiteScore
6.30
自引率
2.50%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Briefings in Functional Genomics publishes high quality peer reviewed articles that focus on the use, development or exploitation of genomic approaches, and their application to all areas of biological research. As well as exploring thematic areas where these techniques and protocols are being used, articles review the impact that these approaches have had, or are likely to have, on their field. Subjects covered by the Journal include but are not restricted to: the identification and functional characterisation of coding and non-coding features in genomes, microarray technologies, gene expression profiling, next generation sequencing, pharmacogenomics, phenomics, SNP technologies, transgenic systems, mutation screens and genotyping. Articles range in scope and depth from the introductory level to specific details of protocols and analyses, encompassing bacterial, fungal, plant, animal and human data. The editorial board welcome the submission of review articles for publication. Essential criteria for the publication of papers is that they do not contain primary data, and that they are high quality, clearly written review articles which provide a balanced, highly informative and up to date perspective to researchers in the field of functional genomics.
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