Transcription increases multiple spontaneous point mutations in Salmonella enterica

Abstract

The spontaneous rate of G·C→A·T mutations and a hotspot T·A→G·C transversion are known to increase with the frequency of transcription - increases that have been ascribed primarily to processes that affect only these specific mutations. To investigate how transcription induces other spontaneous point mutations, we tested for its effects in repair-proficient Salmonella enterica using reversion assays of chromosomally inserted alleles. Our results indicate that transcription increases rates of all tested point mutations in the induced gene: induction significantly increased the individual rates of an A·T→T·A transversion, an A·T→G·C transition and the pooled rates of the three other point mutations assayed. Although the S.enterica genome is thought to have a mutational bias towards G·C base pairs, transitions creating A·T pairs were approximately 10 times more frequent than the reverse mutation, resulting in an overall mutation pressure to lower G+C contents. Transitions occurred at roughly twice the rate of transversions, similar to results from sequence comparisons; however, several individual transversions are more frequent than the least common transition.