The contribution of epistasis to the architecture of fitness in an RNA virus
Open accessAbstract
The tendency for genetic architectures to exhibit epistasis among mutations plays a central role in the modern synthesis of evolutionary biology and in theoretical descriptions of many evolutionary processes. Nevertheless, few studies unquestionably show whether, and how, mutations typically interact. Beneficial mutations are especially difficult to identify because of their scarcity. Consequently, epistasis among pairs of this important class of mutations has, to our knowledge, never before been explored. Interactions among genome components should be of special relevance in compacted genomes such as those of RNA viruses. To tackle these issues, we first generated 47 genotypes of vesicular stomatitis virus carrying pairs of nucleotide substitution mutations whose separated and combined deleterious effects on fitness were determined. Several pairs exhibited significant interactions for fitness, including antagonistic and synergistic epistasis. Synthetic lethals represented 50% of the latter. In a second set of experiments, 15 genotypes carrying pairs of beneficial mutations were also created. In this case, all significant interactions were antagonistic. Our results show that the architecture of the fitness depends on complex interactions among genome components.
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The error threshold is changed by only [small] when [condition], and this result does not change even if epistasis observed in [30] is taken into account.
“Putting , we find that the error threshold is changed by only . This result does not change even if we take into account the epistasis, observed in [30].”
From Lethal mutants and truncated selection together solve a paradox of the origin of life (2011) · cites this paper as [30]
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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 Valencia, 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
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-10-18
- Volume
- 101
- Issue
- 43
- Pages
- 15376-15379
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC524436
- OpenAlex
- W2108670087
- Cited by
- 233
- References
- 31
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 7 · 2017: 8 · 2016: 14 · 2015: 11 · 2014: 14 · 2013: 9 · 2012: 15
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- 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
- Social Sciences › Arts and Humanities › History and Philosophy of Science › Philosophy and History of Science
- Keywords
- epistasis, RNA viruses, vesicular stomatitis virus, beneficial mutations, deleterious mutations, synergistic epistasis, synthetic lethality, genome organization
- MeSH terms
- Cloning, Molecular, Epistasis, Genetic, RNA Viruses, Mutagenesis, Site-Directed, DNA, Complementary
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