ArticleWellcome open research2024
Phylogenetic signatures reveal multilevel selection and fitness costs in SARS-CoV-2.
Article in Wellcome open research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- From sites to structure to serology: a roadmap for structure-aware molecular evolution of antigenically evolving viruses.Journal of virology · 2026Review
- SARS-CoV-2 genomic diversity and within-host evolution in individuals with persistent infection in the UK: an observational, longitudinal, population-based surveillance study.The Lancet. Microbe · 2025Observational
- Article
- Phylogenetic signatures reveal multilevel selection and fitness costs in SARS-CoV-2.Wellcome open research · 2024Article
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Authors and funding
2 authors.
Funding
Abstract
Background: Large-scale sequencing of SARS-CoV-2 has enabled the study of viral evolution during the COVID-19 pandemic. Some viral mutations may be advantageous to viral replication within hosts but detrimental to transmission, thus carrying a transient fitness advantage. By affecting the number of descendants, persistence times and growth rates of associated clades, these mutations generate localised imbalance in phylogenies. Quantifying these features in closely-related clades with and without recurring mutations can elucidate the tradeoffs between within-host replication and between-host transmission. Methods: We implemented a novel phylogenetic clustering algorithm ( mlscluster, https://github.com/mrc-ide/mlscluster) to systematically explore time-scaled phylogenies for mutations under transient/multilevel selection. We applied this method to a SARS-CoV-2 time-calibrated phylogeny with >1.2 million sequences from England, and characterised these recurrent mutations that may influence transmission fitness across PANGO-lineages and genomic regions using Poisson regressions and summary statistics. Results: We found no major differences across two epidemic stages (before and after Omicron), PANGO-lineages, and genomic regions. However, spike, nucleocapsid, and ORF3a were proportionally more enriched for transmission fitness polymorphisms (TFP)-homoplasies than other proteins. We provide a catalog of SARS-CoV-2 sites under multilevel selection, which can guide experimental investigations within and beyond the spike protein. Conclusions: This study provides empirical evidence for the existence of important tradeoffs between within-host replication and between-host transmission shaping the fitness landscape of SARS-CoV-2. This method may be used as a fast and scalable means to shortlist large sequence databases for sites under putative multilevel selection which may warrant subsequent confirmatory analyses and experimental confirmation.
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