Stability Puzzles in Phage Lambda

The lysogeny maintenance switch in phage lambda is one of the simplest examples on the molecular level of computation, command and control in a living system. If, following infection of the bacterium E. coli, the virus enters the lysogenic pathway, it represses its developmental functions, and integrates its DNA into the host chromosome. In this state the prophage may be passively replicated for many generations of E. coli. In fact, this repressed state is intrinsically more stable than the gene encoding the repressor. We develop a mathematical formalism to predict the stability of such epigenetic states from affinities of the molecular components. We apply the model to the behavior of recently published mutants at the right operator complex of lambda, and find that the reported stability indicates that the current view of the switch is incomplete. The approach described here should be generally applicable to the stability of expressed states