Tuning a genetic switch: experimental evolution and natural variation of prophage induction.

Genetic switches allow organisms to modulate their phenotype in response to environmental changes. Understanding the evolutionary processes by which switches are tuned is central to understanding how phenotypic variation is realized. Prophage induction by phage lambda is the classic example of a genetic switch and allows lambda to move between two different modes of transmission: as a lysogen it reproduces vertically as a component of the host genome; as a free phage it reproduces horizontally by infectious epidemic spread. We show that the lambda switch can respond rapidly to selection for alteration in sensitivity and threshold. Sequencing of candidate genes in the genetic circuitry underlying the switch revealed mutations of likely adaptive significance in some, but not all candidates, suggesting that the core genetic circuitry plays a limited role in the fine-tuning of the switch in vivo. The relative ease with which the switch could be tuned by selection was further indicated by extensive variation in sensitivity and threshold of its response function among wild lambdoid phages. Together, our findings emphasize the adaptive significance of a finely tuned switch and draw attention to the selective factors shaping prophage induction in natural phage populations.