Amplification-mutagenesis--how growth under selection contributes to the origin of genetic diversity and explains the phenomenon of adaptive mutation.

The behavior of a particular bacterial genetic system has been interpreted as evidence that selective stress induces general mutagenesis or even preferentially directs mutations to sites that improve growth (adaptive mutation). It has been proposed that changes in mutability are a programmed response to stress in non-growing cells. In contrast, the amplification-mutagenesis model suggests that stress has no direct effect on the mutation rate and that mutations arise in cells growing under strong selection. In this model, stress serves only as a selective pressure that favors cells with multiple copies of a growth-limiting gene. Mutations are made more probable because more target copies are added to the selection plate-more cells with more mutational targets per cell. The amplification-mutagenesis process involves standard genetic events and therefore should apply to all biological systems. Idiosyncrasies of the particular system described here accelerate this process, allowing an evolutionary series of events to be completed in only a few days.