Spontaneous modulation of a dynamic balance between bacterial genomic stability and mutability: roles and molecular mechanisms of the genetic switch

Bacteria need a high degree of genetic stability to maintain their species identities over long evolutionary times while retaining some mutability to adapt to the changing environment. It is a long unanswered question that how bacteria reconcile these seemingly contradictory biological properties. We hypothesized that certain mechanisms must maintain a dynamic balance between genetic stability and mutability for the survival and evolution of bacterial species. To identify such mechanisms, we analyzed bacterial genomes, focusing on the Salmonella mismatch repair (MMR) system. We found that the MMR gene mutL functions as a genetic switch through a slipped-strand mispairing mechanism, modulating and maintaining a dynamic balance between genetic stability and mutability during bacterial evolution. This mechanism allows bacteria to maintain their phylogenetic status, while also adapting to changing environments by acquiring novel traits. In this review, we outline the history of research into this genetic switch, from its discovery to the latest findings, and discuss its potential roles in the genomic evolution of bacteria.