Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations

ABSTRACT The currently ongoing COVID-19 pandemic caused by SARS-CoV-2 has accounted for millions of infections and deaths across the globe. Genome sequences of SARS-CoV-2 are being published daily in public databases and the availability of these genome data sets has allowed unprecedented access to...

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Autores principales:	Jobin John Jacob, Karthick Vasudevan, Agila Kumari Pragasam, Karthik Gunasekaran, Balaji Veeraraghavan, Ankur Mutreja
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	SARS-CoV-2 mutation evolution stability vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/672458a88d9c4eb297184d79ecd7c539
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spelling	oai:doaj.org-article:672458a88d9c4eb297184d79ecd7c5392021-11-10T18:37:51ZEvolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations10.1128/mBio.01188-212150-7511https://doaj.org/article/672458a88d9c4eb297184d79ecd7c5392021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01188-21https://doaj.org/toc/2150-7511ABSTRACT The currently ongoing COVID-19 pandemic caused by SARS-CoV-2 has accounted for millions of infections and deaths across the globe. Genome sequences of SARS-CoV-2 are being published daily in public databases and the availability of these genome data sets has allowed unprecedented access to the mutational patterns of SARS-CoV-2 evolution. We made use of the same genomic information for conducting phylogenetic analysis and identifying lineage-specific mutations. The catalogued lineage-defining mutations were analyzed for their stabilizing or destabilizing impact on viral proteins. We recorded persistence of D614G, S477N, A222V, and V1176F variants and a global expansion of the PANGOLIN variant B.1. In addition, a retention of Q57H (B.1.X), R203K/G204R (B.1.1.X), T85I (B.1.2-B.1.3), G15S+T428I (C.X), and I120F (D.X) variations was observed. Overall, we recorded a striking balance between stabilizing and destabilizing mutations, therefore leading to well-maintained protein structures. With selection pressures in the form of newly developed vaccines and therapeutics to mount in the coming months, the task of mapping viral mutations and recording their impact on key viral proteins should be crucial to preemptively catch any escape mechanism for which SARS-CoV-2 may evolve. IMPORTANCE Since its initial isolation in Wuhan, China, large numbers of SARS-CoV-2 genome sequences have been shared in publicly accessible repositories, thus enabling scientists to do detailed evolutionary analysis. We investigated the evolutionarily associated mutational diversity overlaid on the major phylogenetic lineages circulating globally, using 513 representative genomes. We detailed the phylogenetic persistence of key variants facilitating global expansion of the PANGOLIN variant B.1, including the recent, fast-expanding, B.1.1.7 lineage. The stabilizing or destabilizing impact of the catalogued lineage-defining mutations on viral proteins indicates their possible involvement in balancing the protein function and structure. A clear understanding of this mutational profile is of high clinical significance to catch any vaccine escape mechanism, as the same proteins make crucial components of vaccines that have recently been approved or are in development. In this vein, our study provides an imperative framework and baseline data upon which further analysis could be built as newer variants of SARS-CoV-2 continue to appear.Jobin John JacobKarthick VasudevanAgila Kumari PragasamKarthik GunasekaranBalaji VeeraraghavanAnkur MutrejaAmerican Society for MicrobiologyarticleSARS-CoV-2mutationevolutionstabilityvaccineMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 mutation evolution stability vaccine Microbiology QR1-502
spellingShingle	SARS-CoV-2 mutation evolution stability vaccine Microbiology QR1-502 Jobin John Jacob Karthick Vasudevan Agila Kumari Pragasam Karthik Gunasekaran Balaji Veeraraghavan Ankur Mutreja Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations
description	ABSTRACT The currently ongoing COVID-19 pandemic caused by SARS-CoV-2 has accounted for millions of infections and deaths across the globe. Genome sequences of SARS-CoV-2 are being published daily in public databases and the availability of these genome data sets has allowed unprecedented access to the mutational patterns of SARS-CoV-2 evolution. We made use of the same genomic information for conducting phylogenetic analysis and identifying lineage-specific mutations. The catalogued lineage-defining mutations were analyzed for their stabilizing or destabilizing impact on viral proteins. We recorded persistence of D614G, S477N, A222V, and V1176F variants and a global expansion of the PANGOLIN variant B.1. In addition, a retention of Q57H (B.1.X), R203K/G204R (B.1.1.X), T85I (B.1.2-B.1.3), G15S+T428I (C.X), and I120F (D.X) variations was observed. Overall, we recorded a striking balance between stabilizing and destabilizing mutations, therefore leading to well-maintained protein structures. With selection pressures in the form of newly developed vaccines and therapeutics to mount in the coming months, the task of mapping viral mutations and recording their impact on key viral proteins should be crucial to preemptively catch any escape mechanism for which SARS-CoV-2 may evolve. IMPORTANCE Since its initial isolation in Wuhan, China, large numbers of SARS-CoV-2 genome sequences have been shared in publicly accessible repositories, thus enabling scientists to do detailed evolutionary analysis. We investigated the evolutionarily associated mutational diversity overlaid on the major phylogenetic lineages circulating globally, using 513 representative genomes. We detailed the phylogenetic persistence of key variants facilitating global expansion of the PANGOLIN variant B.1, including the recent, fast-expanding, B.1.1.7 lineage. The stabilizing or destabilizing impact of the catalogued lineage-defining mutations on viral proteins indicates their possible involvement in balancing the protein function and structure. A clear understanding of this mutational profile is of high clinical significance to catch any vaccine escape mechanism, as the same proteins make crucial components of vaccines that have recently been approved or are in development. In this vein, our study provides an imperative framework and baseline data upon which further analysis could be built as newer variants of SARS-CoV-2 continue to appear.
format	article
author	Jobin John Jacob Karthick Vasudevan Agila Kumari Pragasam Karthik Gunasekaran Balaji Veeraraghavan Ankur Mutreja
author_facet	Jobin John Jacob Karthick Vasudevan Agila Kumari Pragasam Karthik Gunasekaran Balaji Veeraraghavan Ankur Mutreja
author_sort	Jobin John Jacob
title	Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations
title_short	Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations
title_full	Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations
title_fullStr	Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations
title_full_unstemmed	Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations
title_sort	evolutionary tracking of sars-cov-2 genetic variants highlights an intricate balance of stabilizing and destabilizing mutations
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/672458a88d9c4eb297184d79ecd7c539
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Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations

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