RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.
RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.
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DOI：
10.1016/j.chom.2016.03.009
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发表时间：
2016-04-13
影响因子：
30.3
通讯作者：
Andino R
中科院分区：
文献类型：
--
作者：
Xiao Y;Rouzine IM;Bianco S;Acevedo A;Goldstein EF;Farkov M;Brodsky L;Andino R
突变和重组是驱动微生物进化的中心过程。高突变率会促进适应，但也会产生有害的突变。两个不同基因组之间的融合可以解决这个矛盾，减轻克隆干扰的影响，清除有害的突变。在这里，我们证明了重组显着加速适应和进化过程中的急性病毒感染。我们确定了脊髓灰质炎病毒重组决定簇内的病毒聚合酶，突变，而不改变复制保真度降低重组率。通过产生一组具有不同突变率和重组能力的变体，我们证明了重组对于富集有益突变的群体和清除有害突变是必不可少的。突变和重组的协同活动是病毒在感染动物中传播和毒力的关键。这些发现为数学模型提供了信息，以证明脊髓灰质炎病毒在由选择和有害突变积累之间的权衡决定的最佳突变率下适应得最快。在感染过程中，病毒不断适应不同的细胞类型和组织，代谢和免疫条件的变化等。在RNA病毒中观察到的高突变率驱使它们快速适应，但也产生有害的突变。重组的作用是打破不同基因座上等位基因之间的关联，以清除群体中的有害突变，并将单个基因组中的有益突变联合收割机组合起来，这样它们就不会相互竞争。因此，突变率和重组之间的相互作用使病毒能够最大限度地利用少数有益突变，而不会被许多有害突变所压倒（穆勒棘轮）。RNA病毒已经将其突变率进化到最佳适应率，该最佳适应率是针对在感染和适应宿主的现实进化情景期间起作用的竞争性进化力量而定制的。
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. During infection viruses undergo constant adaptation to different cell types and tissues, variation in metabolic and immunological conditions, etc. The high mutation rates observed in RNA viruses drives their rapid adaptation, but also generate deleterious mutations. The effect of recombination is to break up associations between alleles at different loci to purge the population from detrimental mutations, and to combine beneficial mutation in single genomes, so they do not compete with each other. Thus, the interplay between mutation rate and recombination allows viruses to take maximal advantage of few beneficial mutations without being overwhelmed by many deleterious mutations (Muller’s ratchet). RNA viruses have evolved their mutation rate towards an optimal adaptation rate that is tailored to the competing evolutionary forces acting during a realistic evolution scenario of infection and adaptation to a host.