Xiao Yinghong, Rouzine Igor M, Bianco Simone, Acevedo Ashley, Goldstein Elizabeth Faul, Farkov Mikhail, Brodsky Leonid, Andino Raul
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
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.
Cell Host Microbe. 2016 Apr 13;19(4):493-503. doi: 10.1016/j.chom.2016.03.009.
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.
突变和重组是推动微生物进化的核心过程。高突变率促进了适应性,但也会产生有害突变。两个不同基因组之间的重组可能解决这一矛盾,减轻克隆干扰的影响并清除有害突变。在这里,我们证明重组在急性病毒感染期间显著加速了适应性和进化。我们在病毒聚合酶中鉴定出一个脊髓灰质炎病毒重组决定因素,其突变会降低重组率而不改变复制保真度。通过生成一组具有不同突变率和重组能力的变体,我们证明重组对于在有益突变中富集群体并从有害突变中清除群体至关重要。突变和重组的协同活动是病毒在受感染动物中传播和毒力的关键。这些发现为一个数学模型提供了依据,以证明脊髓灰质炎病毒在由有害突变的选择和积累之间的权衡所决定的最佳突变率下适应最快。