Origins of spontaneous mutants: cellular strategies for controlling their formation in response to changing environments.

Spontaneous and induced mutational events may not be as readily distinguishable as has been generally assumed. It is suggested that the later stages of the processes leading to the establishment of fixation of mutations may consist of a 'mutational pathway', with many features in common with the better-known metabolic pathways of organisms like Escherichia coli. If so, the mutational pathway may be controlled by catabolite repression, a cellular mechanism which switches metabolic pathways on and off (or more probably up and down) in response to intracellular levels of a molecular messenger known as cyclic adenosine monophosphate (cAMP). Mutation rates could then be regulated by an intracellular messenger in precisely the way which we would predict they ought to be regulated, if they are to cope with evolutionary pressures for increased variability.