title: Stability and instability in the lysogenic state of phage lambda.
abstract: Complex gene regulatory circuits exhibit emergent properties that are difficult to predict from the behavior of the components. One such property is the stability of regulatory states. Here we analyze the stability of the lysogenic state of phage λ. In this state, the virus maintains a stable association with the host, and the lytic functions of the virus are repressed by the viral CI repressor. This state readily switches to the lytic pathway when the host SOS system is induced. A low level of SOS-dependent switching occurs without an overt stimulus. We found that the intrinsic rate of switching to the lytic pathway, measured in a host lacking the SOS response, was almost undetectably low, probably less than 10(-8)/generation. We surmise that this low rate has not been selected directly during evolution but results from optimizing the rate of switching in a wild-type host over the natural range of SOS-inducing conditions. We also analyzed a mutant, λprm240, in which the promoter controlling CI expression was weakened, rendering lysogens unstable. Strikingly, the intrinsic stability of λprm240 lysogens depended markedly on the growth conditions; lysogens grown in minimal medium were nearly stable but switched at high rates when grown in rich medium. These effects on stability likely reflect corresponding effects on the strength of the prm240 promoter, measured in an uncoupled assay system. Several derivatives of λprm240 with altered stabilities were characterized. This mutant and its derivatives afford a model system for further analysis of stability.
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA. jlittle@u.arizona.edu
authors.forename: John W
authors.initials: JW
authors.lastname: Little
authors.forename: Christine B
authors.initials: CB
authors.lastname: Michalowski
mesh_terms: D001433:Bacteriolysis; D010582:Bacteriophage lambda / Q000254:growth & development / Q000502:physiology*; D003470:Culture Media / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D008242:Lysogeny; D009154:Mutation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism
chemical_list: D003470:Culture Media; D012097:Repressor Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins