How to make a Biological Switch

Some biological regulatory systems must remember a state for long periods of time. A simple type of system that can accomplish this task is one in which two regulatory elements negatively regulate one another. For example, two repressor proteins might control one another's synthesis. Qualitative reasoning suggests that such a system will have two stable states, one in which the first element is on and the second off, and another in which these states are reversed. Quantitative analysis shows that the existence of two stable steady states depends on the details of the system. Among other things, the shapes of functions describing the effect of one regulatory element on the other must meet certain criteria in order for two steady states to exist. Many biologically reasonable functions do not meet these criteria. In particular, repression that is well described by a Michaelis-Menten-type equation cannot lead to a working switch. However, functions describing positive cooperativity of binding, nonadditive effects of multiple operator sites, or depletion of free repressor can lead to working switches. (C) 2000 Academic Press.