Selection for robustness in mutagenized RNA viruses
Selection for robustness in mutagenized RNA viruses
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DOI：
10.1371/journal.pgen.0030093
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发表时间：
2007-06-01
期刊：
影响因子：
4.5
通讯作者：
Moya, Andrés
中科院分区：
文献类型：
--
作者：
Sanjuán, Rafael;Cuevas, José M.;Moya, Andrés
突变稳健性被定义为面对有害突变时表型的稳定性。自然选择是否直接有利于健壮性仍然存在争议。理论和计算机实验预测，在高突变率的情况下，如果复制缓慢的基因型受益于更高的稳健性，它们就有可能胜过快速复制的基因型。在这里，我们通过实验验证了这一假设，称为“最平坦的生存”，使用两个水疱性口炎RNA病毒种群。适应度分布和遗传变异特征表明，一个种群具有较高的复制率，而另一个种群具有较强的突变能力。在标准的竞争分析中，速度更快的复制子的生长速度超过了健壮的复制子，但在化学诱变剂的存在下，结果却相反。这些结果表明，选择可以直接促进突变稳健性，并揭示了一种新的病毒抵抗致命诱变治疗的机制。
Mutational robustness is defined as the constancy of a phenotype in the face of deleterious mutations. Whether robustness can be directly favored by natural selection remains controversial. Theory and in silico experiments predict that, at high mutation rates, slow-replicating genotypes can potentially outcompete faster counterparts if they benefit from a higher robustness. Here, we experimentally validate this hypothesis, dubbed the "survival of the flattest,'' using two populations of the vesicular stomatitis RNA virus. Characterization of fitness distributions and genetic variability indicated that one population showed a higher replication rate, whereas the other was more robust to mutation. The faster replicator outgrew its robust counterpart in standard competition assays, but the outcome was reversed in the presence of chemical mutagens. These results show that selection can directly favor mutational robustness and reveal a novel viral resistance mechanism against treatment by lethal mutagenesis.