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Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein D614G mutation became the predominant globally circulating variant after its emergence in the early coronavirus disease 2019 (COVID-19) pandemic. Studies showed that this mutation results in an open conformation...

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Autores principales: Huang, Szu-Wei, Miller, Sorin O., Yen, Chia-Hung, Wang, Sheng-Fan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824201/
https://www.ncbi.nlm.nih.gov/pubmed/33374416
http://dx.doi.org/10.3390/genes12010016
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author Huang, Szu-Wei
Miller, Sorin O.
Yen, Chia-Hung
Wang, Sheng-Fan
author_facet Huang, Szu-Wei
Miller, Sorin O.
Yen, Chia-Hung
Wang, Sheng-Fan
author_sort Huang, Szu-Wei
collection PubMed
description The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein D614G mutation became the predominant globally circulating variant after its emergence in the early coronavirus disease 2019 (COVID-19) pandemic. Studies showed that this mutation results in an open conformation of the S glycoprotein receptor-binding domain (RBD), and increased angiotensin 1-converting enzyme 2 (ACE2) binding and fusion, which result in an increase in SARS-CoV-2 transmissibility and infectivity. Dynamic tracking of SARS-CoV-2 showed that the D614G variant became predominant after emergence in Europe and North America, but not in China. The current absence of selective pressures from antiviral treatment suggests that the driving force for viral evolution could be variations in human population genetics. Results show that ACE2 expression is higher in Asian populations than that in European, North American, and African populations. This supports the idea that lower ACE2 expression is a driving force in the positive selection for the D614G mutation. This study suggests that the dynamics of the SARS-CoV-2 D614G mutation during the early-to-mid pandemic is associated with enhanced transmission efficiency in populations with lower ACE2 expression. Understanding the role that human genetic diversity plays in the adaptive evolution of SARS-CoV-2 may have an important impact on public health and measures to control the pandemic.
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spelling pubmed-78242012021-01-24 Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation Huang, Szu-Wei Miller, Sorin O. Yen, Chia-Hung Wang, Sheng-Fan Genes (Basel) Communication The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein D614G mutation became the predominant globally circulating variant after its emergence in the early coronavirus disease 2019 (COVID-19) pandemic. Studies showed that this mutation results in an open conformation of the S glycoprotein receptor-binding domain (RBD), and increased angiotensin 1-converting enzyme 2 (ACE2) binding and fusion, which result in an increase in SARS-CoV-2 transmissibility and infectivity. Dynamic tracking of SARS-CoV-2 showed that the D614G variant became predominant after emergence in Europe and North America, but not in China. The current absence of selective pressures from antiviral treatment suggests that the driving force for viral evolution could be variations in human population genetics. Results show that ACE2 expression is higher in Asian populations than that in European, North American, and African populations. This supports the idea that lower ACE2 expression is a driving force in the positive selection for the D614G mutation. This study suggests that the dynamics of the SARS-CoV-2 D614G mutation during the early-to-mid pandemic is associated with enhanced transmission efficiency in populations with lower ACE2 expression. Understanding the role that human genetic diversity plays in the adaptive evolution of SARS-CoV-2 may have an important impact on public health and measures to control the pandemic. MDPI 2020-12-24 /pmc/articles/PMC7824201/ /pubmed/33374416 http://dx.doi.org/10.3390/genes12010016 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Huang, Szu-Wei
Miller, Sorin O.
Yen, Chia-Hung
Wang, Sheng-Fan
Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation
title Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation
title_full Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation
title_fullStr Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation
title_full_unstemmed Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation
title_short Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation
title_sort impact of genetic variability in ace2 expression on the evolutionary dynamics of sars-cov-2 spike d614g mutation
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824201/
https://www.ncbi.nlm.nih.gov/pubmed/33374416
http://dx.doi.org/10.3390/genes12010016
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