title: RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Igor M
authors.initials: IM
authors.lastname: Rouzine
authors.affiliation: Department of Industrial and Applied Genomics, Accelerated Discovery Lab, IBM Almaden Research Center, 650 Harry Road, San Jose, CA 95120-6099, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Bianco
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Acevedo
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Elizabeth Faul
authors.initials: EF
authors.lastname: Goldstein
authors.affiliation: Tauber Bioinformatics Research Center and Department of Evolutionary and Environmental Biology, University of Haifa, Mount Carmel, Haifa 31905, Israel.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Farkov
authors.affiliation: Tauber Bioinformatics Research Center and Department of Evolutionary and Environmental Biology, University of Haifa, Mount Carmel, Haifa 31905, Israel.
authors.forename: Leonid
authors.initials: L
authors.lastname: Brodsky
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: raul.andino@ucsf.edu.
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D011051:Poliomyelitis / Q000821:virology*; D017955:Poliovirus / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D012641:Selection, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases