Rates of random, spontaneous mutation can vary plastically, dependent upon the environment. Such plasticity affects evolutionary trajectories and may be adaptive. We recently identified an inverse plastic association between mutation rate and population density at 1 locus in 1 species of bacterium. It is unknown how widespread this association is, whether it varies among organisms, and what molecular mechanisms of mutagenesis or repair are required for this mutation-rate plasticity. Here, we address all 3 questions. We identify a strong negative association between mutation rate and population density across 70 years of published literature, comprising hundreds of mutation rates estimated using phenotypic markers of mutation (fluctuation tests) from all domains of life and viruses. We test this relationship experimentally, determining that there is indeed density-associated mutation-rate plasticity (DAMP) at multiple loci in both eukaryotes and bacteria, with up to 23-fold lower mutation rates at higher population densities. We find that the degree of plasticity varies, even among closely related organisms. Nonetheless, in each domain tested, DAMP requires proteins scavenging the mutagenic oxidised nucleotide 8-oxo-dGTP. This implies that phenotypic markers give a more precise view of mutation rate than previously believed: having accounted for other known factors affecting mutation rate, controlling for population density can reduce variation in mutation-rate estimates by 93%. Widespread DAMP, which we manipulate genetically in disparate organisms, also provides a novel trait to use in the fight against the evolution of antimicrobial resistance. Such a prevalent environmental association and conserved mechanism suggest that mutation has varied plastically with population density since the early origins of life.

随机、自发突变的速率可以塑性地变化，这取决于环境。这种可塑性会影响进化轨迹，并且可能具有适应性。我们最近在 1 种细菌的 1 个基因座处发现了突变率和种群密度之间的反向塑性关联。目前尚不清楚这种关联有多广泛，它是否在生物体中有所不同，以及这种突变率可塑性需要哪些诱变或修复的分子机制。在这里，我们解决了所有 3 个问题。我们在 70 年的已发表文献中发现突变率与人口密度之间存在强烈的负相关关系，其中包括数百个使用来自所有生命领域和病毒领域的突变表型标记（波动测试）估计的突变率。我们通过实验测试这种关系，确定真核生物和细菌的多个位点确实存在密度相关的突变率可塑性（DAMP），在较高的种群密度下突变率降低了 23 倍。我们发现可塑性程度各不相同，即使在密切相关的生物中也是如此。尽管如此，在每个测试域中，DAMP 都需要蛋白质来清除诱变的氧化核苷酸 8-oxo-dGTP。这意味着表型标记比以前认为的更精确地了解突变率：考虑到影响突变率的其他已知因素，控制人口密度可以将突变率估计的变化减少 93%。我们在不同的生物体中进行基因操作的广泛 DAMP 也提供了一种新的特性，可用于对抗抗菌素耐药性的演变。