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RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.

TitleRNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.
Publication TypeJournal Article
Year of Publication2016
AuthorsXiao, Y, IM Rouzine, Bianco, S, Acevedo, A, Goldstein, EFaul, Farkov, M, Brodsky, L, Andino, R
JournalCell Host Microbe
Volume19
Issue4
Pagination493-503
Date Published2016 Apr 13
ISSN1934-6069
KeywordsAdaptation, Physiological, Animals, DNA-Directed RNA Polymerases, Evolution, Molecular, Humans, Poliomyelitis, Poliovirus, Recombination, Genetic, RNA, Viral, Selection, Genetic, Viral Proteins, Virulence, Virus Replication
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.

DOI10.1016/j.chom.2016.03.009
Alternate JournalCell Host Microbe
PubMed ID27078068
PubMed Central IDPMC4840895
Grant ListR01 AI36178 / AI / NIAID NIH HHS / United States
R56 AI036178 / AI / NIAID NIH HHS / United States
R01 AI036178 / AI / NIAID NIH HHS / United States
N01AI40085 / AI / NIAID NIH HHS / United States
R01 AI040085 / AI / NIAID NIH HHS / United States
R21 AI036178 / AI / NIAID NIH HHS / United States
P01 AI091575 / AI / NIAID NIH HHS / United States