The Role of transcription in stationary phase mutagenesis in Bacillus subtilis

Stationary phase mutagenesis, also known as stress-induced or adaptive mutagenesis, is defined as the accumulation of mutations during conditions of no net growth or conditions of stress. This process has been implicated in acquiring antibiotic resistance and evasion of host immune responses in microbial pathogens and in the generation of mutations that lead to neoplasia in animal cells. Previous work has shown that defects in DNA synthesis and repair systems contribute to the formation of adaptive mutations; however the role of transcription in the accumulation of mutations is still being examined. It is speculated that transcriptional derepression leads to an increase in the accumulation of mutations. We tested the transcription associated mutagenesis hypothesis by modulating the level of transcription of a point-mutated leuC allele. We modulated transcription by altering growth conditions which physiologically altered transcription and genetically through the use of inducible and repressible promoters. We found that increases in transcription correlated with the accumulation of mutations that confer leucine prototrophy. Since transcription is a ubiquitous biological process, transcription-associated mutagenesis may influence evolutionary processes in all organisms