Krašovec Rok, Richards Huw, Gifford Danna R, Hatcher Charlie, Faulkner Katy J, Belavkin Roman V, Channon Alastair, Aston Elizabeth, McBain Andrew J, Knight Christopher G
Faculty of Science and Engineering, The University of Manchester, Manchester, United Kingdom.
Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
PLoS Biol. 2017 Aug 24;15(8):e2002731. doi: 10.1371/journal.pbio.2002731. eCollection 2017 Aug.
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.
随机自发突变率可以根据环境灵活变化。这种可塑性会影响进化轨迹，并且可能具有适应性。我们最近在一种细菌的一个位点上发现了突变率与种群密度之间呈反向可塑性关联。尚不清楚这种关联有多普遍，是否在不同生物体之间存在差异，以及这种突变率可塑性需要哪些诱变或修复的分子机制。在此，我们回答这三个问题。我们通过对70年发表文献的研究，确定了突变率与种群密度之间存在强烈的负相关，这些文献包含了利用来自生命各领域和病毒的突变表型标记（波动测试）估算的数百个突变率。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），在较高种群密度下突变率可降低至23倍。我们发现可塑性程度存在差异，即使在亲缘关系密切的生物体之间也是如此。尽管如此，在每个测试领域中，DAMP都需要能够清除诱变氧化核苷酸8-氧代-dGTP的蛋白质。这意味着表型标记对突变率的反映比之前认为的更精确：在考虑了其他影响突变率的已知因素后，控制种群密度可使突变率估计值的变化减少93%。我们在不同生物体中通过基因操作实现的广泛的DAMP，也为对抗抗菌药物耐药性的进化提供了一种新特性。这种普遍的环境关联和保守机制表明，自生命起源早期以来，突变就随着种群密度发生了灵活变化。
