title: mutL as a genetic switch of bacterial mutability: turned on or off through repeat copy number changes.
abstract: 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, 6bpΔmutL, with greatly elevated bacterial mutability in Salmonella typhimurium. To validate these observations, we experimentally converted the mutL gene between the wild-type and 6bpΔmutL in S. typhimurium and inspected the bacterial mutability status. When 6bpΔmutL was converted to mutL, the originally highly mutable Salmonella strains regained genetic stability; when mutL was converted to 6bpΔmutL, the mutability was elevated 100-fold. Interestingly, mutL cells were found to grow out of 6bpΔmutL cells; the new mutL cells eventually replaced the original 6bpΔmutL population. As conversion between mutL and 6bpΔmutL 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.
authors.affiliation: Genomics Research Center, Harbin Medical University, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Wei-Qiao
authors.initials: WQ
authors.lastname: Liu
authors.forename: Zhen-Hong
authors.initials: ZH
authors.lastname: Liu
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Zou
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong-Guo
authors.initials: YG
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Abraham
authors.initials: A
authors.lastname: Eisenstark
authors.forename: Randal N
authors.initials: RN
authors.lastname: Johnston
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Liu
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Liu
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D056915:DNA Copy Number Variations; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D055786:Gene Knockout Techniques; D014644:Genetic Variation; D016680:Genome, Bacterial; D042822:Genomic Instability; D008958:Models, Molecular; D009154:Mutation; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism; D020080:Tandem Repeat Sequences
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases