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Cited by 331Evolution and Genetic DynamicsMathematical and Theoretical Epidemiology and Ecology ModelsRNA and protein synthesis mechanisms

Rapid fitness losses in mammalian RNA virus clones due to Muller’s ratchet

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Duarte, E, Clarke, D, Moya, A, Domingo, E, Holland, J·1992·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.89.13.6015PMC PMC402129
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Abstract

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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  • Selection of beneficial mutations requires breaking the linkage between detrimental and beneficial mutations and avoiding competition between beneficial mutations ("clonal interference" effect).

    “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

    The Abstract (page not supplied) says that deleterious mutations accumulate in small asexual populations and that recombination may stop or reverse this loss of fitness. It does not say that selecting beneficial mutations requires breaking their linkage to detrimental mutations. The clonal-interference clause is cited to other sources, not Duarte et al. (LLM, conf=0.76)

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2 of the 21 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. Domingo, E., Holland, J. J. & Ahlquist, P. (CRC, Boca Raton, FL), pp. 3-36.
  2. Domingo, E., Holland, J. J. & Ahlquist, P. (CRC, Boca Raton, FL), Vol. 3, pp. 211-245.
  3. Zimmern, D. (1988) in RNA Genetics, eds. Domingo, E., Holland, J. J. & Ahlquist, P. (CRC, Boca Raton, FL), Vol. 2, pp. 211-240.
  4. Holland, J. J. & Cords, C. E. (1964) Proc. Natl. Acad. Sci. USA 51, 1082-1085.

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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
DOI
10.1073/pnas.89.13.6015
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
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
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › 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

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