BACKGROUND Mutators are common in bacterial populations, both in natural isolates and in the lab. The fate of these lineages, which mutation rate is increased up to 100 ×, has long been studied using population genetics models, showing that they can spread in a population following an environmental change. However in stable conditions, they suffer from the increased mutational load, hence being overcome by non-mutators. However, these results don't take into account the fact that an elevated mutation rate can impact the genetic structure, hence changing the sensitivity of the population to mutations. Here we used Aevol, an in silico experimental evolution platform in which genomic structures are free to evolve, in order to study the fate of mutator populations evolving for a long time in constant conditions. RESULTS Starting from wild-types that were pre-evolved for 300,000 generations, we let 100 mutator populations (point mutation rate ×100) evolve for 100,000 further generations in constant conditions. As expected all populations initially undergo a fitness loss. However, after that the mutator populations started to recover. Most populations ultimately recovered their ancestors fitness, and a significant fraction became even fitter than the non-mutator control clones that evolved in parallel. By analyzing the genomes of the mutators, we show that the fitness recovery is due to two mechanisms: i. an increase in robustness through compaction of the coding part of the mutator genomes, ii. an increase of the selection coefficient that decreases the mean-fitness of the population. Strikingly the latter is due to the accumulation of non-coding sequences in the mutators genomes. CONCLUSION Our results show that the mutational burden that is classically thought to be associated with mutator phenotype is escapable. On the long run mutators adapted their genomes and reshaped the distribution of mutation effects. Therewith the lineage is able to recover fitness even though the population still suffers the elevated mutation rate. Overall these results change our view of mutator dynamics: by being able to reduce the deleterious effect of the elevated mutation rate, mutator populations may be able to last for a very long time; A situation commonly observed in nature.

中文翻译：

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使引擎适应燃料：突变体种群可以通过重组其基因组结构来减少突变负荷。

背景技术突变体在细菌种群中是很常见的，无论是在自然分离物中还是在实验室中。长期以来，使用群体遗传学模型研究了这些谱系的命运，其突变率提高到了100倍，表明它们可以随着环境变化而在人群中传播。然而，在稳定的条件下，它们承受突变负载增加的困扰，因此被非突变者克服。但是，这些结果没有考虑到突变率升高会影响遗传结构的事实，从而改变了人群对突变的敏感性。在这里，我们使用了Aevol，这是一个计算机模拟实验演化平台，在其中可以自由进化基因组结构，以研究在恒定条件下长时间进化的突变体种群的命运。结果从预先进化了300,000代的野生型开始，我们使100个突变体种群（点突变率×100）在恒定条件下又进化了100,000代。不出所料，所有人群最初都会遭受健康损失。但是，此后，突变者种群开始恢复。大多数种群最终都恢复了祖先的适应能力，并且相当一部分人比并行进化的非突变体对照克隆更适合。通过分析突变体的基因组，我们表明适应度恢复归因于两个机制：i。通过压缩突变体基因组的编码部分来提高鲁棒性； ii。选择系数的增加会降低总体的平均适应度。令人惊讶的是，后者是由于突变体基因组中非编码序列的积累。结论我们的结果表明，传统上认为与突变体表型相关的突变负担是可以避免的。从长远来看，突变者适应了他们的基因组并重塑了突变效应的分布。这样，即使种群仍然遭受突变率升高，血统也能够恢复健康。总的来说，这些结果改变了我们对突变体动力学的看法：通过减少突变率升高的有害影响，突变体群体可能能够持续很长时间。自然界中通常观察到的一种情况。从长远来看，突变者适应了他们的基因组并重塑了突变效应的分布。这样，即使种群仍然遭受突变率升高，血统也能够恢复健康。总的来说，这些结果改变了我们对突变体动力学的看法：通过减少突变率升高的有害影响，突变体群体可能能够持续很长时间。自然界中通常观察到的一种情况。从长远来看，突变者适应了他们的基因组并重塑了突变效应的分布。这样，即使种群仍然遭受突变率升高，血统也能够恢复健康。总的来说，这些结果改变了我们对突变体动力学的看法：通过减少突变率升高的有害影响，突变体群体可能能够持续很长时间。自然界中通常观察到的一种情况。突变种群可能会持续很长时间。自然界中通常观察到的一种情况。突变种群可能会持续很长时间。自然界中通常观察到的一种情况。