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Rapid fitness losses in mammalian RNA virus clones due to Muller’s ratchet
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Muller's ratchet is an important concept in population genetics. It predicts that when mutation rates are high and a significant proportion of mutations are deleterious, a kind of irreversible ratchet mechanism will gradually decrease the mean fitness of small populations of asexual organisms. In contrast, sexual recombination may stop or reverse this mutational ratchet by recombinational repair of genetic damage. Experimental support for Muller's ratchet has previously been obtained in protozoa and in a tripartite RNA bacteriophage. We now show clear evidence that Muller's ratchet can operate on a nonsegmented nonrecombining pathogenic RNA virus of animals and humans. We did genetic bottleneck passages (plaque-to-plaque transfers) of vesicular somatitis virus (VSV) and then quantitated relative fitness of the bottleneck clones by allowing direct replication competition in mixed infections in cell culture. We document variable fitness drops (some severe) following only 20 plaque-to-plaque transfers of VSV. In some clones no fitness changes (or only insignificant changes) were observed. Surprisingly, the most regular and severe fitness losses occurred during virus passages on a new host cell type. These results again demonstrate the extreme genetic and biological variability of RNA virus populations. Muller's ratchet could have significant implications for variability of disease severity during virus outbreaks, since genetic bottlenecks must often occur during respiratory droplet transmissions and during spread of low-yield RNA viruses from one body site to another (as with human immunodeficiency virus). Likewise, the lower-probability generation of increased-fitness clones during repeated genetic bottleneck transfers of RNA viruses in nature might also affect disease pathogenesis in infected individuals and in host populations. Whenever genetic bottlenecks of RNA viruses occur, enhanced biological differences among viral subpopulations may result.
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“Thus, selection of beneficial mutations requires breaking the linkage between detrimental and beneficial mutations (Chao, 1990, Duarte et al., 1992) and avoiding competition between beneficial mutations (“clonal interference” effect) (Fisher, 1930, Lenski et al., 1998, Roze and Barton, 2006, Worobey and Holmes, 1999).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Duarte et al., 1992
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Metadata
- Authors
- Duarte, E., Clarke, D., Moya, A., Domingo, E., & Holland, J.
- Affiliations
- University of California San Diego (US)
- Department of Biology, University of California, San Diego, La Jolla 92093-0116.
- ORCID
- Domingo, E
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1992-07
- Volume
- 89
- Issue
- 13
- Pages
- 6015-6019
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC402129
- OpenAlex
- W2055633360
- Cited by
- 331
- References
- 21
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 7 · 2020: 10 · 2019: 9 · 2018: 7 · 2017: 7 · 2016: 12 · 2015: 7 · 2014: 13 · 2013: 10 · 2012: 14
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI-14627)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Physical Sciences › Mathematics › Applied Mathematics › Mathematical and Theoretical Epidemiology and Ecology Models
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- Muller's ratchet, RNA viruses, vesicular stomatitis virus, population bottleneck, fitness loss, relative fitness, disease severity variability, virus transmission
- MeSH terms
- Animals, Cells, Cultured, Genetics, Population, Cricetinae, HeLa Cells, Humans, Mutation, RNA Viruses, Vesicular stomatitis Indiana virus, Virus Replication, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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