Spontaneous mutation rate is a plastic trait associated with population density across domains of life.
Spontaneous mutation rate is a plastic trait associated with population density across domains of life.
复制标题
自发突变率是一种塑性性状，与生命领域的种群密度相关。
DOI：
10.1371/journal.pbio.2002731
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发表时间：
2017-08
期刊：
影响因子：
9.8
通讯作者：
Knight CG
中科院分区：
文献类型：
--
作者：
Krašovec R;Richards H;Gifford DR;Hatcher C;Faulkner KJ;Belavkin RV;Channon A;Aston E;McBain AJ;Knight CG
随机自发突变的速率可以根据环境的可塑性而变化。这种可塑性影响进化轨迹，可能是适应性的。最近，我们发现了一个逆塑性之间的关联突变率和人口密度在1个位点的1种细菌。目前还不清楚这种关联有多普遍，它是否在生物体中变化，以及这种突变率可塑性需要什么样的诱变或修复分子机制。在这里，我们解决所有三个问题。我们在70年的已发表文献中确定了突变率与人口密度之间的强负相关性，其中包括使用来自生命和病毒所有领域的突变表型标记（波动测试）估计的数百个突变率。我们通过实验测试了这种关系，确定在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），在较高的人口密度下，突变率降低了23倍。我们发现，可塑性的程度各不相同，即使在密切相关的生物体。尽管如此，在每个测试的结构域中，DAMP需要蛋白质清除诱变氧化的核苷酸8-氧代-dGTP。这意味着表型标记比以前认为的更精确地观察突变率：考虑到影响突变率的其他已知因素，控制种群密度可以将突变率估计值的变化减少93%。我们在不同的生物体中对广泛分布的DAMP进行遗传操纵，也提供了一种新的特性，可用于对抗抗菌素耐药性的进化。这种普遍的环境关联和保守的机制表明，自生命早期起源以来，突变已随人口密度发生可塑性变化。自发突变促进了进化，但是它们发生的速率对于特定的有机体来说会因其环境而异，这种现象被称为突变速率可塑性。对于在液体中生长的微生物来说，种群可以生长的密度是环境的一个关键特征。我们发现生物的突变率与它们生长的密度有关，因此较高的人口密度与较低的突变率有关。最初，我们在从已发表的文献中挑选的数据中确定了这种密度相关的突变率可塑性（DAMP）：除了生物体之间众所周知的突变率变化模式之外，我们还看到了不同生物体内的大量变化，其中大部分与人口密度有关。我们在实验室中测试了这种关联，在细菌（大肠杆菌）和真核生物（酵母，酿酒酵母）的基因组中的不同位点发现DAMP。在每种情况下，DAMP都需要一种蛋白质，通过清除细胞中氧化损伤的鸟嘌呤核苷酸来避免突变（大肠杆菌中的MutT）。coli和酵母中的Pcd 1）。在我们的测定中，DAMP导致在较高的人口密度下看到抗生素耐药性演变的可能性较低。我们预计DAMP会更普遍地影响进化过程，理解其原因和影响将有助于我们理解和控制进化轨迹。
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. Spontaneous mutations fuel evolution, but the rate at which they occur can vary for a particular organism depending on its environment—a phenomenon known as mutation-rate plasticity. For microbes growing in liquid, the density to which a population can grow is a key feature of the environment. We find that organisms’ mutation rates are associated with the density to which they grow, such that higher population densities are associated with lower mutation rates. Initially we identify this density-associated mutation-rate plasticity (DAMP) in data culled from the published literature: beyond well-known patterns of mutation-rate variation among organisms, we see substantial variation within diverse organisms, the large majority of which is associated with population densities. We test this association in the laboratory, finding DAMP at different sites in the genomes of both bacteria (Escherichia coli) and eukaryotes (the yeast, Saccharomyces cerevisiae). In each case, DAMP requires a protein that avoids mutation by cleaning cells of oxidatively damaged guanine nucleotides (MutT in E. coli and Pcd1 in yeast). In our assays, DAMP results in a lower probability of seeing the evolution of antibiotic resistance at higher population densities. We anticipate that DAMP affects the course of evolution more generally and that understanding its causes and effects will help us to understand and control evolutionary trajectories.
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DOI：
10.15698/mic2014.07.158
发表时间：
2014-06-25
期刊：
Microbial cell (Graz, Austria)
影响因子：
--
作者：
Krašovec R;Belavkin RV;Aston JA;Channon A;Aston E;Rash BM;Kadirvel M;Forbes S;Knight CG
通讯作者：
Knight CG
影响因子：
64.8
作者：
Kong A;Frigge ML;Masson G;Besenbacher S;Sulem P;Magnusson G;Gudjonsson SA;Sigurdsson A;Jonasdottir A;Jonasdottir A;Wong WS;Sigurdsson G;Walters GB;Steinberg S;Helgason H;Thorleifsson G;Gudbjartsson DF;Helgason A;Magnusson OT;Thorsteinsdottir U;Stefansson K
通讯作者：
Stefansson K
影响因子：
2.9
作者：
LENSKI, RE;ROSE, MR;TADLER, SC
通讯作者：
TADLER, SC
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
30.8
作者：
通讯作者：
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