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

被引:109
作者
Xiao, Yinghong [1 ]
Rouzine, Igor M. [1 ,2 ]
Bianco, Simone [3 ]
Acevedo, Ashley [1 ]
Goldstein, Elizabeth Faul [1 ]
Farkov, Mikhail [4 ,5 ]
Brodsky, Leonid [4 ,5 ]
Andino, Raul [1 ]
机构
[1] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94158 USA
[2] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA
[3] IBM Almaden Res Ctr, Accelerated Discovery Lab, Dept Ind & Appl Genom, 650 Harry Rd, San Jose, CA 95120 USA
[4] Univ Haifa, Tauber Bioinformat Res Ctr, IL-31905 Haifa, Israel
[5] Univ Haifa, Dept Evolutionary & Environm Biol, IL-31905 Haifa, Israel
关键词
BENEFICIAL MUTATIONS; ASEXUAL POPULATIONS; RAPID EVOLUTION; MULLER RATCHET; ADAPTATION; POLIOVIRUS; SELECTION; FITNESS; PATHOGENESIS; REPLICATION;
D O I
10.1016/j.chom.2016.03.009
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:493 / 503
页数:11
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