The Origin of Mutants Under Selection: How Natural Selection Mimics Mutagenesis (Adaptive Mutation)
The Origin of Mutants Under Selection: How Natural Selection Mimics Mutagenesis (Adaptive Mutation)
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DOI：
10.1101/cshperspect.a018176
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发表时间：
2015-07-01
影响因子：
7.2
通讯作者：
Roth, John R.
中科院分区：
文献类型：
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作者：
Maisnier-Patin, Sophie;Roth, John R.
选择检测突变，但不引起突变。与这句格言相反，凯恩斯和福斯特在乳糖培养基上培养了一种漏lac突变体的大肠杆菌，并观察到随着时间的推移，在不生长的草坪上，可逆的（lac(+)）菌落逐渐积累。这一结果表明，当细菌生长受阻时，它们可能会使自己的基因组突变。然而，鉴于最近的证据表明，可逆菌落是由携带lac突变的共轭F'lac质粒的多个拷贝的预先存在的细胞发起的，因此这一结论是可疑的。一些被镀的细胞具有简单的F'lac质粒的多个拷贝。这提供了足够的LacZ活性来支持质粒复制，但不支持细胞分裂。在非生长细胞中，重复的质粒复制增加了逆转事件的可能性。还原到lac（+）触发指数细胞生长，导致稳定的lac（+）可逆菌落。在10%的细胞中，高拷贝质粒包括内部串联lac复制，这提供了更多的LacZ活性，足以支持缓慢生长和不稳定lac（+）集落的形成。具有多个F'lac质粒拷贝的细胞突变率增加，因为质粒编码容易出错（致突变）的DNA聚合酶DinB。在没有DinB的情况下，不稳定型和稳定型Lac（+）可逆型的数量相等，两种类型都不发生突变。扩增和选择是凯恩斯-福斯特系统行为的核心，而诱变是由dinB与lac共同扩增引起的系统特异性副作用或人工产物。对该系统的研究揭示了几个广泛适用的原则。在所有群体中，基因重复是频繁的稳定遗传多态性，常见的近中性突变等位基因在选择下扩增后可以获得阳性表型，当局部基因组亚区过度复制产生变异性时，自然选择可以在没有细胞分裂的情况下进行。
Selection detects mutants but does not cause mutations. Contrary to this dictum, Cairns and Foster plated a leaky lac mutant of Escherichia coli on lactose medium and saw revertant (Lac(+)) colonies accumulate with time above a nongrowing lawn. This result suggested that bacteria might mutagenize their own genome when growth is blocked. However, this conclusion is suspect in the light of recent evidence that revertant colonies are initiated by preexisting cells with multiple copies the conjugative F'lac plasmid, which carries the lac mutation. Some plated cells have multiple copies of the simple F'lac plasmid. This provides sufficient LacZ activity to support plasmid replication but not cell division. In nongrowing cells, repeated plasmid replication increases the likelihood of a reversion event. Reversion to lac(+) triggers exponential cell growth leading to a stable Lac(+) revertant colony. In 10% of these plated cells, the high-copy plasmid includes an internal tandem lac duplication, which provides even more LacZ activity-sufficient to support slow growth and formation of an unstable Lac(+) colony. Cells with multiple copies of the F'lac plasmid have an increased mutation rate, because the plasmid encodes the error-prone (mutagenic) DNA polymerase, DinB. Without DinB, unstable and stable Lac(+) revertant types form in equal numbers and both types arise with no mutagenesis. Amplification and selection are central to behavior of the Cairns-Foster system, whereas mutagenesis is a system-specific side effect or artifact caused by coamplification of dinB with lac. Study of this system has revealed several broadly applicable principles. In all populations, gene duplications are frequent stable genetic polymorphisms, common near-neutral mutant alleles can gain a positive phenotype when amplified under selection, and natural selection can operate without cell division when variability is generated by overreplication of local genome subregions.