The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins.

The unprecedented pace of the sequencing of the SARS-CoV-2 virus genomes provides us with unique information about the genetic changes in a single pathogen during ongoing pandemic. By the analysis of close to 200,000 genomes we show that the patterns of the SARS-CoV-2 virus mutations along its genom...

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Main Authors: Lukasz Jaroszewski, Mallika Iyer, Arghavan Alisoltani, Mayya Sedova, Adam Godzik
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-07-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009147&type=printable
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author Lukasz Jaroszewski
Mallika Iyer
Arghavan Alisoltani
Mayya Sedova
Adam Godzik
author_facet Lukasz Jaroszewski
Mallika Iyer
Arghavan Alisoltani
Mayya Sedova
Adam Godzik
author_sort Lukasz Jaroszewski
collection DOAJ
description The unprecedented pace of the sequencing of the SARS-CoV-2 virus genomes provides us with unique information about the genetic changes in a single pathogen during ongoing pandemic. By the analysis of close to 200,000 genomes we show that the patterns of the SARS-CoV-2 virus mutations along its genome are closely correlated with the structural and functional features of the encoded proteins. Requirements of foldability of proteins' 3D structures and the conservation of their key functional regions, such as protein-protein interaction interfaces, are the dominant factors driving evolutionary selection in protein-coding genes. At the same time, avoidance of the host immunity leads to the abundance of mutations in other regions, resulting in high variability of the missense mutation rate along the genome. "Unexplained" peaks and valleys in the mutation rate provide hints on function for yet uncharacterized genomic regions and specific protein structural and functional features they code for. Some of these observations have immediate practical implications for the selection of target regions for PCR-based COVID-19 tests and for evaluating the risk of mutations in epitopes targeted by specific antibodies and vaccine design strategies.
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spelling doaj-art-e9620fa4572c46c2b648e6a17add128f2025-08-20T02:18:04ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-07-01177e100914710.1371/journal.pcbi.1009147The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins.Lukasz JaroszewskiMallika IyerArghavan AlisoltaniMayya SedovaAdam GodzikThe unprecedented pace of the sequencing of the SARS-CoV-2 virus genomes provides us with unique information about the genetic changes in a single pathogen during ongoing pandemic. By the analysis of close to 200,000 genomes we show that the patterns of the SARS-CoV-2 virus mutations along its genome are closely correlated with the structural and functional features of the encoded proteins. Requirements of foldability of proteins' 3D structures and the conservation of their key functional regions, such as protein-protein interaction interfaces, are the dominant factors driving evolutionary selection in protein-coding genes. At the same time, avoidance of the host immunity leads to the abundance of mutations in other regions, resulting in high variability of the missense mutation rate along the genome. "Unexplained" peaks and valleys in the mutation rate provide hints on function for yet uncharacterized genomic regions and specific protein structural and functional features they code for. Some of these observations have immediate practical implications for the selection of target regions for PCR-based COVID-19 tests and for evaluating the risk of mutations in epitopes targeted by specific antibodies and vaccine design strategies.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009147&type=printable
spellingShingle Lukasz Jaroszewski
Mallika Iyer
Arghavan Alisoltani
Mayya Sedova
Adam Godzik
The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins.
PLoS Computational Biology
title The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins.
title_full The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins.
title_fullStr The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins.
title_full_unstemmed The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins.
title_short The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins.
title_sort interplay of sars cov 2 evolution and constraints imposed by the structure and functionality of its proteins
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009147&type=printable
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