In pursuit of a molecular mechanism for adaptive gene amplification.

"Adaptive" or "stationary-phase" mutation is a collection of apparent stress responses in which cells exposed to a growth-limiting environment generate genetic changes, some of which can allow resumption of rapid growth. In the well-characterized Lac system of Escherichia coli, reversions of a lac frameshift allele give rise to adaptive point mutations. Also in this system, adaptive gene amplification has been documented as a separate and parallel response that allows growth on lactose medium without acquisition of a compensatory frameshift mutation. In amplification, the DNA region containing the weakly functional lac allele becomes amplified to multiple copies, which produce sufficient enzyme activity to allow growth on the otherwise growth-limiting lactose medium. The amplifications are "adaptive" in that they occur after cells encounter the growth-limiting environment. Adaptive amplification is a reversible genetic change that allows adaptation and growth. It may be similar to chromosomal instability observed in the origins and progression of many cancers. We explore possible molecular mechanisms of adaptive amplification in the bacterial system and note parallels to chromosomal instability in other systems.