Analysis of Emerging Variants in Structured Regions of the SARS-CoV-2 Genome
UMass Chan Affiliations
Graduate School of Biomedical SciencesDepartment of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2021-05-05Keywords
COVID-19RNA structure
SARS
coronavirus
phylogeny
Bioinformatics
Computational Biology
Genomics
Immunology and Infectious Disease
Infectious Disease
Microbiology
Nucleic Acids, Nucleotides, and Nucleosides
Population Biology
Structural Biology
Virus Diseases
Metadata
Show full item recordAbstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers of SARS-CoV-2 genome sequences in curated repositories, which have been useful in mapping the spread of the virus around the globe. They also provide a unique opportunity to observe virus evolution in real time. Here, we evaluate two sets of SARS-CoV-2 genomic sequences to identify emerging variants within structured cis-regulatory elements of the SARS-CoV-2 genome. Overall, 20 variants are present at a minor allele frequency of at least 0.5%. Several enhance the stability of Stem Loop 1 in the 5' untranslated region (UTR), including a group of co-occurring variants that extend its length. One appears to modulate the stability of the frameshifting pseudoknot between ORF1a and ORF1b, and another perturbs a bi-ss molecular switch in the 3'UTR. Finally, 5 variants destabilize structured elements within the 3'UTR hypervariable region, including the S2M (stem loop 2 m) selfish genetic element, raising questions as to the functional relevance of these structures in viral replication. Two of the most abundant variants appear to be caused by RNA editing, suggesting host-viral defense contributes to SARS-CoV-2 genome heterogeneity. Our analysis has implications for the development of therapeutics that target viral cis-regulatory RNA structures or sequences.Source
Ryder SP, Morgan BR, Coskun P, Antkowiak K, Massi F. Analysis of Emerging Variants in Structured Regions of the SARS-CoV-2 Genome. Evol Bioinform Online. 2021 May 5;17:11769343211014167. doi: 10.1177/11769343211014167. PMID: 34017166; PMCID: PMC8114311. Link to article on publisher's site
DOI
10.1177/11769343211014167Permanent Link to this Item
http://hdl.handle.net/20.500.14038/27450PubMed ID
34017166Related Resources
Rights
Copyright © The Author(s) 2021. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Distribution License
http://creativecommons.org/licenses/by-nc/4.0/ae974a485f413a2113503eed53cd6c53
10.1177/11769343211014167
Scopus Count
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2021. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).