This is because such

Selleckchem 5-FU allele conversion occurs constantly as stochastic events among cells of the bacterial population: at any time point, there must be some cells that have the wild-type allele converted to the defective one, for example from wild-type mutL to 6bpΔmutL as demonstrated here. So the conversion could be regarded as spontaneous and MMR-negative cells should start accumulating genetic changes swiftly, with those that acquired the ‘right’ genetic traits becoming more fit and thus selected for. Mutation rate variation in relation to fitness differences has been reported (Saunders et al., 2003), and here we provide experimental evidence showing that levels of mutability, or variation of mutation rates, could be modulated by allele conversion of an MMR gene. Tandem repeats in bacterial genomes have been widely studied in relation to pathogenicity or escape from the host immunity (Hollingshead et al., 1987; Stem Cell Compound Library Madoff et al., 1996; Tonjum et al., 1998; Jordan et al., 2003), but to our knowledge we are the first to report tandem repeats in MMR genes, and playing important roles in modulating

bacterial mutability. The repetitive structure within the sequence of mutL enables it to function as a genetic switch modulating bacterial mutability, to be turned on or off at the population level nearly spontaneously. Fluctuations in the frequency of 6bpΔmutL cells SPTBN5 in the bacterial populations would provide the bacteria with exceptional adaptation potential. One point that we need to emphasize is that the genetic ‘switch’ is turned on or off at the population level by selection of existing cells possessing

the favorable traits, rather than at a single-cell level by any induced adaptive mechanisms. In conclusion, the 6bpΔmutL genotype will facilitate genetic variation and gradual divergence of the bacteria. It is important to note, however, that the scenario presumed to be occurring in the sealed agar stabs is a slow-played version of what might occur in nature, because, in the natural environment, where competition constantly works to renew survivors, cells will quickly become predominant in the populations if selected, or quickly disappear if counter-selected, leading to reasonably low frequencies of 6bpΔmutL cells most of the time. The basic idea of a spontaneous genetic switch model may be generalized to other bacteria, because all bacteria evolve and, when doing so, need a genetic switch to transiently allow the genome to accept foreign DNA or to accumulate mutations. Eventually, variants of the bacteria with beneficial genetic changes will be selected.