mutL as a genetic switch of bacterial mutability: turned on or off through repeat copy number changes
mutL as a genetic switch of bacterial mutability: turned on or off through repeat copy number changes
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mutL 作为细菌突变性的遗传开关：通过重复拷贝数变化打开或关闭。
DOI：
10.1111/j.1574-6968.2010.02107.x
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发表时间：
2010-11-01
影响因子：
2.1
通讯作者：
Liu, Shu-Lin
中科院分区：
文献类型：
--
作者：
Chen, Fang;Liu, Wei-Qiao;Liu, Shu-Lin
细菌对环境变化的适应可以通过突变的积累和横向转移基因重组到基因组中获得遗传新奇来实现，但错配修复（MMR）系统强烈抑制这两种类型的遗传变化。由于突变和重组确实发生在细菌中，因此了解在MMR存在下如何实现遗传新奇是令人感兴趣的。以前，我们观察到一个有缺陷的MMR基因型，6 bp Δ mutL，大大提高了细菌的突变性，在鼠伤寒沙门氏菌的协会。为了验证这些观察结果，我们实验性地在S.鼠伤寒沙门氏菌，并检查细菌的突变状态。当6 bp delta mutL转化为mutL时，原本高度突变的沙门氏菌菌株恢复了遗传稳定性;当mutL转化为6 bp delta mutL时，突变性提高了100倍。有趣的是，发现mutL细胞从6 bp Δ mutL细胞中生长出来;新的mutL细胞最终取代了原始的6 bp Δ mutL群体。由于mutL和6 bp delta mutL之间的转换可能在DNA复制过程中容易发生，因此它可能代表了一种以前未被认识到的在群体水平上调节细菌突变性的机制，使细菌能够快速响应变化的环境，同时最大限度地减少与持续超变相关的风险。
Bacterial adaptation to changing environments can be achieved through the acquisition of genetic novelty by accumulation of mutations and recombination of laterally transferred genes into the genome, but the mismatch repair (MMR) system strongly inhibits both these types of genetic changes. As mutation and recombination do occur in bacteria, it is of interest to understand how genetic novelty may be achieved in the presence of MMR. Previously, we observed associations of a defective MMR genotype, 6bp delta mutL, with greatly elevated bacterial mutability in Salmonella typhimurium. To validate these observations, we experimentally converted the mutL gene between the wild-type and 6bp delta mutL in S. typhimurium and inspected the bacterial mutability status. When 6bp delta mutL was converted to mutL, the originally highly mutable Salmonella strains regained genetic stability; when mutL was converted to 6bp delta mutL, the mutability was elevated 100-fold. Interestingly, mutL cells were found to grow out of 6bp delta mutL cells; the new mutL cells eventually replaced the original 6bp delta mutL population. As conversion between mutL and 6bp delta mutL may occur readily during DNA replication, it may represent a previously unrecognized mechanism to modulate bacterial mutability at the population level, allowing bacteria to respond rapidly to changing environments while minimizing the risks associated with persistent hypermutability.