Phylogenetic evidence for deleterious mutation load in RNA viruses and its contribution to viral evolution
Open accessAbstract
Populations of RNA viruses are often characterized by abundant genetic variation. However, the relative fitness of these mutations is largely unknown, although this information is central to our understanding of viral emergence, immune evasion, and drug resistance. Here we develop a phylogenetic method, based on the distribution of nonsynonymous and synonymous changes, to assess the relative fitness of polymorphisms in the structural genes of 143 RNA viruses. This reveals that a substantial proportion of the amino acid variation observed in natural populations of RNA viruses comprises transient deleterious mutations that are later purged by purifying selection, potentially limiting virus adaptability. We also demonstrate, for the first time, the existence of a relationship between amino acid variability and the phylogenetic distribution of polymorphisms. From this relationship, we propose an empirical threshold for the maximum viable deleterious mutation load in RNA viruses.
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Exogenous free-living RNA viruses are subject to remarkably strong purifying selection.
“Despite a reputation for rapid adaptive evolution, exogenous free-living RNA viruses are subject to remarkably strong purifying selection (Holmes 2003;Pybus et al. 2007;Wertheim and Kosakovsky Pond 2011).”
From RELAX: Detecting Relaxed Selection in a Phylogenetic Framework (2015) · cites this paper as Pybus et al. 2007
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Mutation rates among RNA viruses
Drake, J. W., & Holland, J. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13910 · Cited by 1,143 · see citing works
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Research works printed but not linked: 2
- Burnham KP, Anderson DR. 2002. Model selection and multimo- del inference. New York: Springer.
- Yang Z. 2006. Computational molecular evolution. Oxford: Oxford University Press.
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Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.012 · Cited by 1,956 · see citing works
RELAX: Detecting Relaxed Selection in a Phylogenetic Framework
Wertheim, J. O., Murrell, B., Smith, M. D., Kosakovsky Pond, S. L., & Scheffler, K. (2015) · Molecular Biology and Evolution · doi:10.1093/molbev/msu400 · Cited by 778 · see citing works
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Self-citationThe Evolutionary Pathway to Virulence of an RNA Virus
Stern, A., Yeh, M. T., Zinger, T., Smith, M., Wright, C., Ling, G., Nielsen, R., Macadam, A., & Andino, R. (2017) · Cell · doi:10.1016/j.cell.2017.03.013 · Cited by 127 · see citing works
Martin, D. P., Weaver, S., Tegally, H., San, E. J., Shank, S. D., Wilkinson, E., Lucaci, A. G., Giandhari, J., Naidoo, S., Pillay, Y., et al. (2021) · doi:10.1101/2021.02.23.21252268 · Cited by 291 · see citing works
- Authors
- Pybus, O. G., Rambaut, A., Belshaw, R., Freckleton, R. P., Drummond, A. J., & Holmes, E. C.
- Affiliations
- University of Oxford (GB)
- University of Auckland (NZ)
- National Institutes of Health (US)
- ORCID
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-01-11
- Volume
- 24
- Issue
- 3
- Pages
- 845-852
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W2099743715
- Cited by
- 140
- References
- 1
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 10 · 2017: 4 · 2016: 8 · 2015: 13 · 2014: 10 · 2013: 7 · 2012: 9
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Biology and Evolution (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Royal Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- deleterious mutation load, RNA viruses, purifying selection, amino acid sequence variation, viral evolution, structural genes, drug resistance, immune evasion
- MeSH terms
- Amino Acid Sequence, Models, Genetic, Mutation, Phylogeny, Polymorphism, Genetic, RNA Viruses, Selection, Genetic, Likelihood Functions, Evolution, Molecular, Computational Biology
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