Shifts in mutation bias promote mutators by altering the distribution of fitness effects

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 wildtype. 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 under-sampled beneficial mutations., ,

最近的实验证据表明，突变偏向性的改变（例如颠换频率的增加）能够改变突变的适合度效应分布（distribution of fitness effects of mutations，DFE）。具体而言，减弱或逆转主导性偏向性可提高新生突变（de novo mutation）具有有益效应的概率。研究还显示，若突变体细菌产生的有益突变具有比野生型中观察到的更大的效应大小，则此类细菌更易出现。本文将这两项结果关联起来，证明了那些减弱或逆转主导性偏向性的突变体菌株具有正向偏移的DFE，而这反过来可显著提高其出现概率。由于突变率和偏向性的改变通常通过DNA修复酶的获得与丢失而耦合，我们的结果预测，若突变偏向性的改变能让菌株更易获得此前未充分取样的有益突变，则会促进突变体菌株的入侵。