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RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence
Open accessAbstract
Mutation and recombination are central processes driving microbial evolution. A high mutation rate fuels adaptation but also generates deleterious mutations. Recombination between two different genomes may resolve this paradox, alleviating effects of clonal interference and purging deleterious mutations. Here we demonstrate that recombination significantly accelerates adaptation and evolution during acute virus infection. We identified a poliovirus recombination determinant within the virus polymerase, mutation of which reduces recombination rates without altering replication fidelity. By generating a panel of variants with distinct mutation rates and recombination ability, we demonstrate that recombination is essential to enrich the population in beneficial mutations and purge it from deleterious mutations. The concerted activities of mutation and recombination are key to virus spread and virulence in infected animals. These findings inform a mathematical model to demonstrate that poliovirus adapts most rapidly at an optimal mutation rate determined by the trade-off between selection and accumulation of detrimental mutations.
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“Indeed, viral populations with reduced adaptation capacity yield viruses that are tissue restricted, and thus attenuated (Xiao et al., 2017a, Xiao et al., 2016).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Xiao et al., 2016
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Metadata
- Authors
- Xiao, Y., Rouzine, I. M., Bianco, S., Acevedo, A., Goldstein, E. F., Farkov, M., Brodsky, L., & Andino, R.
- Affiliations
- University of California, San Francisco (US)
- IBM Research - Almaden (US)
- University of Haifa (IL)
- Corresponding author
- Andino, Raul
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 19
- Issue
- 4
- Pages
- 493-503
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC4840895
- OpenAlex
- W2335860311
- Cited by
- 157
- References
- 57
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 14 · 2023: 19 · 2022: 13 · 2021: 17 · 2020: 20 · 2019: 16 · 2018: 21 · 2017: 11 · 2016: 6
- FWCI
- 14.53
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-09-13)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (R01, AI36178, AI40085, P01 AI091575)
- University of California
- DoD-DARPA
- Irvin “Tack” Kuntz
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- RNA recombination, poliovirus, viral adaptation, mutation rate, deleterious mutations, clonal interference, purging of deleterious mutations, viral virulence, viral spread, acute viral infection
- MeSH terms
- Adaptation, Physiological, Animals, Humans, Poliomyelitis, Recombination, Genetic, DNA-Directed RNA Polymerases, RNA, Viral, Selection, Genetic, Viral Proteins, Virulence, Virus Replication, Poliovirus, Evolution, Molecular
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