Adaptive Mutations: A Consequence of Prokaryotic Differentiation

University Of Texas At Dallas, Richardson TX

Investigators

Abstract

In 1988, John Cairns and his collaborators discovered so-called "adaptive mutations" These observations, later enhanced by a series of investigators, suggested that some mutants arose in response to specific environmental challenges or situations. The nature of the mechanism that generates these "adaptive mutants" has been hotly debated. It now appears that these mutations are the result of a sub-population of cells that differentiate into a hypermutable state. The genetic control for this differentiation has not yet been elucidated. Preliminary investigations with the bacterial Bacillus subtilis model system indicate that in this organism the genetic mechanism(s) that regulate the development of the hypermutable state overlap with the mechanisms that regulate the processes of sporulation and competence (uptake of extracellular DNA). This project will utilize the knowledge of the genetic control of the processes of sporulation and competence development to delineate the molecular mechanisms responsible for the generation of "adaptive mutations." Using the information that is currently available, a working hypothesis for the generation of "adaptive" mutations would be that under stress, a small subset of cells differentiate into a hypermutable state, and these cells lack a functional DNA mismatch repair system. The research in this project is aimed at testing this hypothesis by utilizing the genetic and molecular biological techniques that have been developed for analyzing differentiation in the Gram-positive, spore forming bacterium Bacillus subtilis. Delineating this system is critical to our understanding of the role played by stress-induced genetic diversity mechanisms in species