INTRODUCTION

Expression of the majority of proteins and other cellular constituents within bacteria such as Escherichia coli appears to be homogeneous within the bacterial population, changing only in response to specific alterations in the environment. Moreover, for most cellular properties, environmental change appears to elicit a uniform response from each cell. However, for a subset of genes, expression is restricted to a fraction of the population. In this more unusual mode of gene regulation, termed phase variation, individual cells switch between expressing (ON) and non-expressing (OFF) states reversibly at frequencies that can be as high as one switch per cell per generation to one switch per 10,000 cells per generation. Thus, at the level of an individual cell, it appears that, in molecular terms, one or more of the steps that are required for phase switching occurs at a low frequency. Furthermore, phase variation appears to be a random or stochastic process. According to this hypothesis, the molecular events leading to phase switching occur with equal probability for each cell in a given phase over the course of the cell cycle. As described in more detail below, phase variation is nevertheless regulated in most (if not all) phase variable systems in E. coli in response to specific environmental signals. Where regulation does occur, it seems likely that switching still occurs at random, even though the regulation results in switching at a different frequency. In the related phenomenon of antigenic variation, different cells express variants of the same protein or other macromolecule.