mutL as a genetic switch of bacterial mutability: turned on or off through repeat copy number changes

Area of Science:

• Microbiology
• Genetics
• Evolutionary Biology

Background:

• Bacterial adaptation relies on genetic novelty via mutations and gene recombination.
• The mismatch repair (MMR) system is a key inhibitor of these genetic changes.
• A defective MMR genotype (6bpΔmutL) was previously associated with high bacterial mutability in Salmonella typhimurium.

Purpose of the Study:

• To experimentally validate the association between the 6bpΔmutL genotype and elevated bacterial mutability.
• To investigate the reversibility of this hypermutability.
• To explore the potential of MMR gene conversion as a population-level adaptation mechanism.

Main Methods:

• Experimental conversion of the mutL gene between wild-type and 6bpΔmutL genotypes in Salmonella typhimurium.
• Assessment of bacterial mutability status following genetic conversion.
• Monitoring population dynamics to observe the replacement of 6bpΔmutL cells by mutL cells.

Main Results:

• Conversion of 6bpΔmutL to wild-type mutL restored genetic stability in Salmonella strains.
• Conversion of wild-type mutL to 6bpΔmutL resulted in a 100-fold increase in mutability.
• Populations of mutL cells were observed to outcompete and replace 6bpΔmutL cells.

Conclusions:

• The mutL gene conversion mechanism can readily modulate bacterial mutability at the population level.
• This provides a dynamic way for bacteria to respond to environmental changes.
• It allows rapid adaptation while mitigating the risks of persistent hypermutability.