Phenotypic consequences of epimutation in a transcription time series. Each plot shows the time series of mRNA production events (black lines indicate error-free transcripts, i.e. the transcript is an accurate complement of the template strand, be it wild-type or mutant); adapted from So et al. . Red lines indicate a stochastic error in information transfer (mutation or epimutation). Blue regions indicate the duration in time of the phenotypic consequences produced by the stochastic error event. The top panels show error-free transcription and the phenotypic consequence; the middle panels show transient RNA errors and the phenotypic consequence; the bottom panels show permanent DNA errors and the phenotypic consequence. (a) Constitutive expression of mutant gene. A transient transcription error that corrects the mutation will produce a burst of gene activity that will degrade over time (middle panel). A reversion mutation will produce maximal gene activity in the mutant cell and in all progeny in the mutant lineage (bottom panel). Therefore, RNA and DNA errors have different phenotypic consequences. (b) Lac repressor negatively regulates lacZ expression. Here two independent time series for lacI and lacZ are shown (this depiction does not imply any synchrony in the time series, nor a similar time scale for the two series). Even in the presence of wild-type repressor, the lac operon occasionally will be expressed producing a burst of β-galactosidase activity that will degrade over time (top panel) . Epimutation in the lacI transcript will produce a non-functional repressor and the lac operon will be expressed (i.e., a noisy system will become noisier); in the presence of a maintenance level of inducer, an autocatalytic positive feedback response will initiate and the cell, and all progeny in the lineage, will produce maximal β-galactosidase activity even though error-free lacI transcripts are subsequently produced (middle panel). A lacI forward mutation will produce maximal β-galactosidase activity in the mutant cell and in all progeny in the mutant lineage (bottom panel). Therefore, RNA and DNA errors can have similar phenotypic consequences.
Curr Opin Microbiol. ;24:80-87.