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Cited by 582Evolution and Genetic DynamicsRNA and protein synthesis mechanismsMathematical and Theoretical Epidemiology and Ecology Models

The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus.

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Sanjuán, Rafael, Moya, Andrés, Elena, Santiago F.·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0400146101PMC PMC420405
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Abstract

Little is known about the mutational fitness effects associated with single-nucleotide substitutions on RNA viral genomes. Here, we used site-directed mutagenesis to create 91 single mutant clones of vesicular stomatitis virus derived from a common ancestral cDNA and performed competition experiments to measure the relative fitness of each mutant. The distribution of nonlethal deleterious effects was highly skewed and had a long, flat tail. As expected, fitness effects depended on whether mutations were chosen at random or reproduced previously described ones. The effect of random deleterious mutations was well described by a log-normal distribution, with -19% reduction of average fitness; the effects distribution of preobserved deleterious mutations was better explained by a β model. The fit of both models was improved when combined with a uniform distribution. Up to 40% of random mutations were lethal. The proportion of beneficial mutations was unexpectedly high. Beneficial effects followed a γ distribution, with expected fitness increases of 1% for random mutations and 5% for preobserved mutations.

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Authors
Sanjuán, R., Moya, A., & Elena, S. F.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de València, P.O. Box 22085, 46071 Valencia, Spain; and Instituto de Biología Molecular y Celular de Plantas, Consejo Superior de Investigaciones Científicas, Universidad Politécnica de Valencia, 46022 Valencia, Spain
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2004-05-24
Volume
101
Issue
22
Pages
8396-8401
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0400146101
PMC
PMC420405
OpenAlex
W2142391696
Cited by
582
References
56
Citations by year
2026: 10 · 2025: 13 · 2024: 38 · 2023: 20 · 2022: 25 · 2021: 38 · 2020: 16 · 2019: 23 · 2018: 33 · 2017: 31 · 2016: 30 · 2015: 30 · 2014: 32 · 2013: 38 · 2012: 39
FWCI
11.96
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
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
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mathematical and Theoretical Epidemiology and Ecology Models
Keywords
distribution of fitness effects, single nucleotide substitution, vesicular stomatitis virus, RNA virus evolution, deleterious mutations, beneficial mutations, lognormal distribution, beta model, gamma distribution, lethal mutations, competition experiments, site-directed mutagenesis
MeSH terms
Animals, Biological Evolution, Genetics, Population, Genetic Variation, Vesicular stomatitis Indiana virus, Mutagenesis, Site-Directed, Point Mutation

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