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Progressive Evolutionary Dynamics of Gene-Specific ω Led to the Emergence of Novel SARS-CoV-2 Strains Having Super-Infectivity and Virulence with Vaccine Neutralization.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Jun 07; Vol. 25 (12). Date of Electronic Publication: 2024 Jun 07. - Publication Year :
- 2024
-
Abstract
- An estimation of the proportion of nonsynonymous to synonymous mutation (dn/ds, ω) of the SARS-CoV-2 genome would indicate the evolutionary dynamics necessary to evolve into novel strains with increased infection, virulence, and vaccine neutralization. A temporal estimation of ω of the whole genome, and all twenty-nine SARS-CoV-2 genes of major virulent strains of alpha, delta and omicron demonstrates that the SARS-CoV-2 genome originally emerged (ω ~ 0.04) with a strong purifying selection (ω < 1) and reached (ω ~ 0.85) in omicron towards diversifying selection (ω > 1). A marked increase in the ω occurred in the spike gene from alpha (ω = 0.2) to omicron (ω = 1.97). The ω of the replication machinery genes including RDRP , NSP3 , NSP4 , NSP7 , NSP8 , NSP10 , NSP13 , NSP14 , and ORF9 are markedly increased, indicating that these genes/proteins are yet to be evolutionary stabilized and are contributing to the evolution of novel virulent strains. The delta-specific maximum increase in ω in the immunomodulatory genes of NSP8 , NSP10 , NSP16 , ORF4 , ORF5 , ORF6 , ORF7A , and ORF8 compared to alpha or omicron indicates delta-specific vulnerabilities for severe COVID-19 related hospitalization and death. The maximum values of ω are observed for spike ( S ), NSP4 , ORF8 and NSP15 , which indicates that the gene-specific temporal estimation of ω identifies specific genes for its super-infectivity and virulency that could be targeted for drug development.
- Subjects :
- Humans
Virulence genetics
Spike Glycoprotein, Coronavirus genetics
Spike Glycoprotein, Coronavirus immunology
Spike Glycoprotein, Coronavirus metabolism
Mutation
Phylogeny
SARS-CoV-2 genetics
SARS-CoV-2 pathogenicity
SARS-CoV-2 immunology
Evolution, Molecular
COVID-19 Vaccines immunology
COVID-19 virology
COVID-19 immunology
Genome, Viral
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 38928018
- Full Text :
- https://doi.org/10.3390/ijms25126306