Shifts in Mutation Bias Promote Mutators by Altering the Distribution of Fitness Effects.
Shifts in Mutation Bias Promote Mutators by Altering the Distribution of Fitness Effects.
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突变偏差的变化通过改变适应度效应的分布来促进突变。
DOI：
10.1086/726010
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Wahl,LindiM
中科院分区：
文献类型：
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作者：
Tuffaha,MarwaZ;Varakunan,Saranya;Castellano,David;Gutenkunst,RyanN;Wahl,LindiM
最近的实验证据表明，突变偏见的变化--例如，颠换频率的增加--可以改变突变的适应度效应(DFE)的分布。特别是，减少或逆转普遍存在的偏见可以增加从头开始突变有益的可能性。研究还表明，如果突变细菌产生的有益突变的影响大小大于野生型，则更有可能出现突变细菌。在这里，我们将这两个结果联系在一起，证明了减少或逆转流行偏见的突变株具有正向移位的DFE，这反过来又可以显著增加它们的出现概率。由于突变率和偏差的变化往往通过DNA修复酶的获得和丢失来耦合，我们的结果预测，突变偏见的改变将促进突变菌株的入侵，这些突变偏见提供了更好的获得先前未充分采样的有益突变的途径。
Recent experimental evidence demonstrates that shifts in mutational biases—for example, increases in transversion frequency—can change the distribution of fitness effects of mutations (DFE). In particular, reducing or reversing a prevailing bias can increase the probability that a de novo mutation is beneficial. It has also been shown that mutator bacteria are more likely to emerge if the beneficial mutations they generate have a larger effect size than observed in the wild type. Here, we connect these two results, demonstrating that mutator strains that reduce or reverse a prevailing bias have a positively shifted DFE, which in turn can dramatically increase their emergence probability. Since changes in mutation rate and bias are often coupled through the gain and loss of DNA repair enzymes, our results predict that the invasion of mutator strains will be facilitated by shifts in mutation bias that offer improved access to previously undersampled beneficial mutations.