Correlation Between Mutation Rate and Genome Size in Riboviruses: Mutation Rate of Bacteriophage Qβ
Correlation Between Mutation Rate and Genome Size in Riboviruses: Mutation Rate of Bacteriophage Qβ
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DOI：
10.1534/genetics.113.154963
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发表时间：
2013-09-01
期刊：
影响因子：
3.3
通讯作者：
Sanjuan, Rafael
中科院分区：
文献类型：
--
作者：
Bradwell, Katie;Combe, Marine;Sanjuan, Rafael
基因组的大小和突变率在生命的所有领域都是共同变化的。在单细胞生物和DNA病毒中，它们表现出被称为德雷克规则的反比关系。然而，目前尚不清楚基因组大小和RNA基因组突变率之间是否存在类似的关系。冠状病毒是基因组最大（约30 kb）的RNA病毒，它编码一种校对3'外切酶，使其能够提高复制保真度。然而，是否相反，具有最小基因组的RNA病毒往往表现出特别高的突变率尚不清楚。为了验证这一点，我们测量了噬菌体Q β的突变率，这是一种4.2 kb的利维病毒。基于琥珀还原的Luria-Delbruck波动试验结合突变测序，估计每轮复制每个核苷酸有1.4 x 10（-4）个替换，这是使用该方法报道的任何病毒的最高突变率。这一估计是通过直接斑块测序方法和对先前发表的噬菌体估计进行再分析后得到证实的。与其他核病毒（除逆转录病毒外的所有RNA病毒）的比较提供了突变率与基因组大小负相关的统计支持。我们认为RNA病毒的突变率可能被优化以获得最大的适应性，而这个最优值可能反过来与基因组大小成反比。
Genome sizes and mutation rates covary across all domains of life. In unicellular organisms and DNA viruses, they show an inverse relationship known as Drake's rule. However, it is still unclear whether a similar relationship exists between genome sizes and mutation rates in RNA genomes. Coronaviruses, the RNA viruses with the largest genomes (similar to 30 kb), encode a proofreading 3' exonuclease that allows them to increase replication fidelity. However, it is unknown whether, conversely, the RNA viruses with the smallest genomes tend to show particularly high mutation rates. To test this, we measured the mutation rate of bacteriophage Q beta, a 4.2-kb levivirus. Amber reversion-based Luria-Delbruck fluctuation tests combined with mutant sequencing gave an estimate of 1.4 x 10(-4) substitutions per nucleotide per round of copying, the highest mutation rate reported for any virus using this method. This estimate was confirmed using a direct plaque sequencing approach and after reanalysis of previously published estimates for this phage. Comparison with other riboviruses (all RNA viruses except retroviruses) provided statistical support for a negative correlation between mutation rates and genome sizes. We suggest that the mutation rates of RNA viruses might be optimized for maximal adaptability and that the value of this optimum may in turn depend inversely on genome size.