AUTHOR=Kim Byoung-Jun , Kim Bo-Ram , Kook Yoon-Hoh , Kim Bum-Joon 

TITLE=Role of the DNA Mismatch Repair Gene MutS4 in Driving the Evolution of Mycobacterium yongonense Type I via Homologous Recombination

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02578

DOI=10.3389/fmicb.2017.02578

ISSN=1664-302X

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