These data are consistent with previous findings on mutL (e.g. Zahrt et al., 1994); here,

we repeated the same kind of experiments to demonstrate the association of greatly elevated mutability with the specific 6-bp lesion of mutL, which will be the basis for the proposal of spontaneous conversion between mutL and 6bpΔmutL as a genetic switch in bacterial evolution. In particular, these experimental results support the presumption that the 6bpΔmutL genotype facilitates homologous recombination and thus provides the bacteria many more chances to incorporate Selleckchem Caspase inhibitor beneficial DNA of foreign sources. To further confirm differences in homologous DNA recombination efficiency between 6bpΔmutL and mutL cells, we carried out crosses between S. typhimurium LT7 (SGSC1417 and 8608F2 series) and E. coli Hfr cells by conjugation, using E. coli Hfr 3000 as the donor (Low, 1973;

Theze et al., 1974). With SGSC1417 or 8608F2mutL as the recipient, the conjugation frequencies were <10−8 per Hfr; with SGSC14176bpΔmutL, 8608F2 or the ΔmutL strain of SGSC1417 as the recipient, the conjugation frequencies were >10−6 per Hfr (Fig. 3). As the 6bpΔmutL genotype significantly facilitated mutability, as shown above, and because the 6-bp tandem repeat structure easily leads to copy number changes through slipped-strand mispairing (Streisinger et al., 1966; Cell Cycle inhibitor Levinson & Gutman, 1987), we hypothesized that bacterial populations dominated with 6bpΔmutL cells under some kind of selective pressure may begin having mutL cells when the pressure is no longer present, and the mutL cells may continuously increase in number or even replace the original 6bpΔmutL population. As the S. typhimurium LT7 mutants had suffered from starvation during stock in sealed agar stab cultures under room temperature

for over 40 years, we cultured the bacteria on LB plates to ‘remove’ such starvation pressures. We started with strain 9052D1, which was the first strain to have the MMR genes sequenced in our laboratory and was found to have the 6bpΔmutL genotype (Gong et al., 2007). During the first plating, a minority of colonies contained both 6bpΔmutL and mutL cells (Fig. 4a, lane 9). When such colonies were restreaked, most of them made only mutL cells (data not shown). The 6bpΔmutL cells continued making both 6bpΔmutL and mutL cells, but very few mutL cells made 6bpΔmutL cells (Fig. 4b), which demonstrates a much crotamiton stronger tendency of the 6bpΔmutL allele to convert to mutL than in the opposite direction. Bacteria use several strategies to increase mutability for acquiring genetic novelty in adaptation to changing environments, involving, in addition to allele conversion of the MMR genes as reported in this paper, the RpoS regulon, SOS responses, DinB error-prone DNA polymerase, RecA, etc., as has been documented widely (Bjedov et al., 2003; Friedman et al., 2005; Ponder et al., 2005; Finkel, 2006; Galhardo et al., 2007, 2009; Sundin & Weigand, 2007; Weigand & Sundin, 2009).