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Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation.
Genes (Basel). 2020 12 24; 12(1)G

Abstract

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.

Authors+Show Affiliations

Model Development Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.Model Development Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. National Natural Product Libraries and High-Throughput Screening Core Facility, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33374416

Citation

Huang, Szu-Wei, et al. "Impact of Genetic Variability in ACE2 Expression On the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation." Genes, vol. 12, no. 1, 2020.
Huang SW, Miller SO, Yen CH, et al. Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation. Genes (Basel). 2020;12(1).
Huang, S. W., Miller, S. O., Yen, C. H., & Wang, S. F. (2020). Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation. Genes, 12(1). https://doi.org/10.3390/genes12010016
Huang SW, et al. Impact of Genetic Variability in ACE2 Expression On the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation. Genes (Basel). 2020 12 24;12(1) PubMed PMID: 33374416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation. AU - Huang,Szu-Wei, AU - Miller,Sorin O, AU - Yen,Chia-Hung, AU - Wang,Sheng-Fan, Y1 - 2020/12/24/ PY - 2020/11/24/received PY - 2020/12/11/revised PY - 2020/12/22/accepted PY - 2020/12/30/entrez PY - 2020/12/31/pubmed PY - 2021/1/12/medline KW - ACE2 KW - D 614G KW - SARS-CoV-2 KW - evolution KW - genetic variation KW - spike JF - Genes JO - Genes (Basel) VL - 12 IS - 1 N2 - 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. SN - 2073-4425 UR - https://www.unboundmedicine.com/medline/citation/33374416/Impact_of_Genetic_Variability_in_ACE2_Expression_on_the_Evolutionary_Dynamics_of_SARS_CoV_2_Spike_D614G_Mutation_ L2 - https://www.mdpi.com/resolver?pii=genes12010016 DB - PRIME DP - Unbound Medicine ER -