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On the Origins of Omicron’s Unique Spike Gene Insertion

The emergence of a heavily mutated SARS-CoV-2 variant (Omicron; Pango lineage B.1.1.529 and BA sublineages) and its rapid spread to over 75 countries raised a global public health alarm. Characterizing the mutational profile of Omicron is necessary to interpret its clinical phenotypes which are shar...

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Autores principales: Venkatakrishnan, A. J., Anand, Praveen, Lenehan, Patrick J., Suratekar, Rohit, Raghunathan, Bharathwaj, Niesen, Michiel J. M., Soundararajan, Venky
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504260/
https://www.ncbi.nlm.nih.gov/pubmed/36146586
http://dx.doi.org/10.3390/vaccines10091509
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author Venkatakrishnan, A. J.
Anand, Praveen
Lenehan, Patrick J.
Suratekar, Rohit
Raghunathan, Bharathwaj
Niesen, Michiel J. M.
Soundararajan, Venky
author_facet Venkatakrishnan, A. J.
Anand, Praveen
Lenehan, Patrick J.
Suratekar, Rohit
Raghunathan, Bharathwaj
Niesen, Michiel J. M.
Soundararajan, Venky
author_sort Venkatakrishnan, A. J.
collection PubMed
description The emergence of a heavily mutated SARS-CoV-2 variant (Omicron; Pango lineage B.1.1.529 and BA sublineages) and its rapid spread to over 75 countries raised a global public health alarm. Characterizing the mutational profile of Omicron is necessary to interpret its clinical phenotypes which are shared with or distinctive from those of other SARS-CoV-2 variants. We compared the mutations of the initially circulating Omicron variant (now known as BA.1) with prior variants of concern (Alpha, Beta, Gamma, and Delta), variants of interest (Lambda, Mu, Eta, Iota, and Kappa), and ~1500 SARS-CoV-2 lineages constituting ~5.8 million SARS-CoV-2 genomes. Omicron’s Spike protein harbors 26 amino acid mutations (23 substitutions, 2 deletions, and 1 insertion) that are distinct compared to other variants of concern. While the substitution and deletion mutations appeared in previous SARS-CoV-2 lineages, the insertion mutation (ins214EPE) was not previously observed in any other SARS-CoV-2 lineage. Here, we consider and discuss various mechanisms through which the nucleotide sequence encoding for ins214EPE could have been acquired, including local duplication, polymerase slippage, and template switching. Although we are not able to definitively determine the mechanism, we highlight the plausibility of template switching. Analysis of the homology of the inserted nucleotide sequence and flanking regions suggests that this template-switching event could have involved the genomes of SARS-CoV-2 variants (e.g., the B.1.1 strain), other human coronaviruses that infect the same host cells as SARS-CoV-2 (e.g., HCoV-OC43 or HCoV-229E), or a human transcript expressed in a host cell that was infected by the Omicron precursor.
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spelling pubmed-95042602022-09-24 On the Origins of Omicron’s Unique Spike Gene Insertion Venkatakrishnan, A. J. Anand, Praveen Lenehan, Patrick J. Suratekar, Rohit Raghunathan, Bharathwaj Niesen, Michiel J. M. Soundararajan, Venky Vaccines (Basel) Perspective The emergence of a heavily mutated SARS-CoV-2 variant (Omicron; Pango lineage B.1.1.529 and BA sublineages) and its rapid spread to over 75 countries raised a global public health alarm. Characterizing the mutational profile of Omicron is necessary to interpret its clinical phenotypes which are shared with or distinctive from those of other SARS-CoV-2 variants. We compared the mutations of the initially circulating Omicron variant (now known as BA.1) with prior variants of concern (Alpha, Beta, Gamma, and Delta), variants of interest (Lambda, Mu, Eta, Iota, and Kappa), and ~1500 SARS-CoV-2 lineages constituting ~5.8 million SARS-CoV-2 genomes. Omicron’s Spike protein harbors 26 amino acid mutations (23 substitutions, 2 deletions, and 1 insertion) that are distinct compared to other variants of concern. While the substitution and deletion mutations appeared in previous SARS-CoV-2 lineages, the insertion mutation (ins214EPE) was not previously observed in any other SARS-CoV-2 lineage. Here, we consider and discuss various mechanisms through which the nucleotide sequence encoding for ins214EPE could have been acquired, including local duplication, polymerase slippage, and template switching. Although we are not able to definitively determine the mechanism, we highlight the plausibility of template switching. Analysis of the homology of the inserted nucleotide sequence and flanking regions suggests that this template-switching event could have involved the genomes of SARS-CoV-2 variants (e.g., the B.1.1 strain), other human coronaviruses that infect the same host cells as SARS-CoV-2 (e.g., HCoV-OC43 or HCoV-229E), or a human transcript expressed in a host cell that was infected by the Omicron precursor. MDPI 2022-09-09 /pmc/articles/PMC9504260/ /pubmed/36146586 http://dx.doi.org/10.3390/vaccines10091509 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Perspective
Venkatakrishnan, A. J.
Anand, Praveen
Lenehan, Patrick J.
Suratekar, Rohit
Raghunathan, Bharathwaj
Niesen, Michiel J. M.
Soundararajan, Venky
On the Origins of Omicron’s Unique Spike Gene Insertion
title On the Origins of Omicron’s Unique Spike Gene Insertion
title_full On the Origins of Omicron’s Unique Spike Gene Insertion
title_fullStr On the Origins of Omicron’s Unique Spike Gene Insertion
title_full_unstemmed On the Origins of Omicron’s Unique Spike Gene Insertion
title_short On the Origins of Omicron’s Unique Spike Gene Insertion
title_sort on the origins of omicron’s unique spike gene insertion
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504260/
https://www.ncbi.nlm.nih.gov/pubmed/36146586
http://dx.doi.org/10.3390/vaccines10091509
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