Optimization of DNA polymerase mutation rates during bacterial evolution
Optimization of DNA polymerase mutation rates during bacterial evolution
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DOI：
10.1073/pnas.0912451107
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发表时间：
2010-01-19
影响因子：
11.1
通讯作者：
Loeb, Lawrence A.
中科院分区：
文献类型：
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作者：
Loh, Ern;Salk, Jesse J.;Loeb, Lawrence A.
突变率是进化性的一个重要决定因素。在进化过程中，不同生物体的最佳突变率已经在计算机中建模并在体内进行测试，主要是通过成对比较。为了在广泛的突变率范围内表征适应度景观，我们在大肠杆菌中产生了一组66个DNA聚合酶I突变体，这些突变体具有可比的生长特性，但具有不同的DNA复制能力，比野生型高和低10（3）倍。这些菌株在两种不同环境中的六个重复培养物中竞争了350代。一个狭窄的范围内的突变率，10- 47倍大于野生型，占主导地位后，连续通过。未检测到突变率较高的突变体，也未检测到野生型或抗突变菌株。获胜的克隆表现出较短的倍增时间，更大的最大培养密度，并在成对竞争相对于他们的竞争前的祖先的生长优势，表明收购的适应性表型。为了研究突变体选择的基础，我们在大多数情况下，一种菌株在18天内完全超过培养物的条件下进行了一系列突变体和野生型菌株之间的成对竞争。突变体是最常见的赢家，但也观察到野生型菌株获胜，这表明突变体的竞争优势是由于更大的概率发展选择性有利的突变，而不是从初始的生长优势赋予聚合酶变异体本身。我们的研究结果表明，在生物体的适应性尚未最大化的条件下，一个特定的环境，竞争性适应可能会促进增强诱变。
Mutation rate is an important determinant of evolvability. The optimal mutation rate for different organisms during evolution has been modeled in silico and tested in vivo, predominantly through pairwise comparisons. To characterize the fitness landscape across a broad range of mutation rates, we generated a panel of 66 DNA polymerase I mutants in Escherichia coli with comparable growth properties, yet with differing DNA replication fidelities, spanning 10(3)-fold higher and lower than that of wild type. These strains were competed for 350 generations in six replicate cultures in two different environments. A narrow range of mutation rates, 10- to 47-fold greater than that of wild type, predominated after serial passage. Mutants exhibiting higher mutation rates were not detected, nor were wild-type or antimutator strains. Winning clones exhibited shorter doubling times, greater maximum culture densities, and a growth advantages in pairwise competition relative to their precompetition ancestors, indicating the acquisition of adaptive phenotypes. To investigate the basis for mutator selection, we undertook a large series of pairwise competitions between mutator and wildtype strains under conditions where, in most cases, one strain completely overtook the culture within 18 days. Mutators were the most frequent winners but wild-type strains were also observed winning, suggesting that the competitive advantage of mutators is due to a greater probability of developing selectably advantageous mutations rather than from an initial growth advantage conferred by the polymerase variant itself. Our results indicate that under conditions where organism fitness is not yet maximized for a particular environment, competitive adaptation may be facilitated by enhanced mutagenesis.