ArticleMolecular biology and evolution2022
Selection Analysis Identifies Clusters of Unusual Mutational Changes in Omicron Lineage BA.1 That Likely Impact Spike Function.
Article in Molecular biology and evolution, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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82 citing papers in PubMed, 118 citations in OpenAlex.
- SARS-CoV-2 Omicron infection reveals imprinted antibody responses in the absence of vaccination.iScience · 2026Article
- SARS-CoV-2 intra-host viral diversity associated with host innate and vaccine-induced immunity in an obese mouse model.BMC infectious diseases · 2026Article
- Molecular evolution and spatial transmission of severe fever with thrombocytopenia syndrome virus.Nature communications · 2026Article
- From single-sequences to evolutionary trajectories: protein language models capture the evolutionary potential of SARS-CoV-2.Nature communications · 2026Article
- Chronic infections can generate SARS-CoV-2-like bursts of viral evolution without epistasis.Virus evolution · 2026Article
- Identification and genomic characterization of BA.3.2: a highly divergent BA.3-related SARS-CoV-2 lineage from southern Africa.Virus evolution · 2026Article
- Comparative systemic pathogenicity and host tropism of ancestral SARS-CoV-2, Delta, and Omicron EG.5 variants in K18-hACE2 mice.Frontiers in immunology · 2026Article
- Tradeoffs between proliferation and transmission in virus evolution- insights from evolutionary and functional analyses of SARS-CoV-2.Virology journal · 2025Article
- Pathogen genomic surveillance and the AI revolution.Journal of virology · 2025Review
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- Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic.Nature microbiology · 2025Article
- The importance of epistasis in the evolution of viral pathogens.Virus evolution · 2025Review
- Positive selection, genetic recombination, and intra-host evolution in novel equine coronavirus genomes and other members of theMicrobiology spectrum · 2024Article
- Chronic infections can generate SARS-CoV-2-like bursts of viral evolution without epistasis.bioRxiv : the preprint server for biology · 2024Article
- Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants.Nature communications · 2024Article
- Predicting human and viral protein variants affecting COVID-19 susceptibility and repurposing therapeutics.Scientific reports · 2024Article
- Article
- Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics.PLoS computational biology · 2024Article
- Correlates of Breakthrough SARS-CoV-2 Infections in People with HIV: Results from the CIHR CTN 328 Study.Vaccines · 2024Article
- A laboratory framework for ongoing optimization of amplification-based genomic surveillance programs.Microbiology spectrum · 2023Article
22 more citing papers are in PubMed but not listed here.
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39 authors at 16 institutions in 6 countries.
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Abstract
Among the 30 nonsynonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (1) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (2) interactions of Spike with ACE2 receptors, and (3) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron overall previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
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