Role of the DNA Mismatch Repair Gene in Driving the Evolution of Type I via Homologous Recombination.

We recently showed that could be divided into two genotypes: Type I, in which the gene has been transferred from , and Type II, in which the gene has not been transferred. Comparative genome analysis of three Type I, two Type II and type strains were performed in this study to gain insight into gene transfer from into Type I strains. We found two genome regions transferred from : one contained 3 consecutive genes, including the operon, and the other contained 57 consecutive genes that had been transferred into Type I genomes via homologous recombination. Further comparison between the Type I and II genomes revealed that Type I, but not Type II has a distinct DNA mismatch repair gene ( subfamily) that was possibly transferred via non-homologous recombination from other actinomycetes. We hypothesized that it could facilitate homologous recombination from the to the Type I genomes. We therefore generated recombinant containing a operon of . We found that the fragment with a rifampin resistance-conferring mutation was more frequently inserted into recombinant than the wild type, suggesting that MutS4 is a driving force in the gene transfer from to Type I strains via homologous recombination. In conclusion, our data indicated that MutS4 in Type I genomes may drive gene transfer from via homologous recombination, resulting in division of into two genotypes, Type I and II.