The role of mismatch repair in bacterial evolution

Experimental (directed) evolution is a study of evolution under defined and reproducible conditions, particularly on model laboratory populations of bacteria. Recently, remarkable success of directed evolution has been reported, ranging from industrial enzymes, with substantially improved activities and thermostabilities, to vaccines and pharmaceuticals as well as a generation of novel microorganisms with desired properties. It has become clear that the major process influencing evolution is DNA Mismatch Repair (MMR). The MMR system controls genome stability of the species and is highly conserved from bacteria to humans. It maintains the integrity of DNA by repairing errors made during the replication process and by preventing genetic recombination between diverged DNAs. Inactivation of MMR results in the generation of hereditary mutators with highly increased mutation rates as well as in abolishment of genetic barriers between species. Most of the mutations are deleterious, but some of them are beneficial and enable mutators to survive environmental stress. In the stable environment mutators lose their advantage because of accumulating deleterious mutations. Strains with beneficial mutations could survive by reacquiring MMR wild type alleles in horizontal gene transfer through hyperrecombination phenotype of MMR mutators. During evolutionary history, MMR functions have been repeatedly lost and reacquired by horizontal gene transfer, which gives rise to the mosaic gene structure of MMR genes. This mosaicism is a hallmark of the evolutionary process.