Adaptive mutations in Salmonella typhimurium phenotypic of purR super-repression.

Under non-lethal selective conditions, a non-dividing or very slowly dividing microbial population gives rise to mutations that relieve selective pressures. This process is described as adaptive mutation. Salmonella typhimurium strain 5-28 has been used as a system for studying adaptive mutations in the chromosomal regulatory gene purR and its target, the purD operator. When this strain is plated on a minimal lactose medium, no apparent growth of parent lawn is observed, yet the revertant colonies accumulate over a period of time. Analysis of the purR mutational spectra showed that the frequencies of transitions and transversions were not significantly different among the growth-dependent and adaptive mutations. But the frequencies for five kinds of -1 frameshifts were significantly different between the growth-dependent and adaptive types. Among the growth-dependent mutations, most one-base deletions occurred in non-iterated bases and were distributed randomly. Among adaptive mutations, the frequency of one-base deletions in small mononucleotide repeats was higher and mutations were concentrated at three hotspots. One-base deletion in small mononucleotide repeats are generally believed to result from DNA polymerase slippage errors, which are not corrected by DNA repair machinery. We further investigated the role of DNA repair on adaptive mutation. Our results showed that the mismatch repair (MMR) might function less efficiently during adaptive mutation. However, DNA oxidative damage repair seemed no less effective in correcting errors under selective pressures than during non-selective growth.

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