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 w hich two regulatory elements negatively regulate one another. For example, two repressor proteins might control one another's synthesis. Qualitative r easoning suggests that such a system will have two stable states, one in wh ich the first element is "on" and the second "off", and another in which th ese 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 ele ment on the other must meet certain criteria in order for two steady states to exist. Many biologically reasonable functions do not meet these criteri a. In particular, repression that is well described by a Michaelis-Menten-t ype equation cannot lead to a working switch. However, functions describing positive cooperativity of binding, nonadditive effects of multiple operato r sites, or depletion of free repressor can lead to working switches. (C) 2 000 Academic Press.