DYNAMICAL BEHAVIOR OF BIOLOGICAL REGULATORY NETWORKS .2. IMMUNITY CONTROL IN BACTERIOPHAGE-LAMBDA

A number of bacterial and viral genes take part in the decision betwee n lysis and lysogenization in temperate bacteriophages. In the lambda case, at least five viral genes (cI, cro, cII, N and cIII) and several bacterial genes are involved. Several attempts have been made to mode l this complex regulatory network. Our approach is based on a logical method described in the first paper of the series which formalizes the interactions between the elements of a regulatory network in terms of discrete variables, functions and parameters. In this paper two model s are described and discussed, the first (two-variable model) focused on cI and cro interactions, the second (four-variable model) consideri ng, in addition, genes cII and N. The treatment presented emphasizes t he roles of positive and negative feedback loops and their interaction s in the development of the phage. The role of the loops between cI an d cro, and of cl on itself (which both have to be positive loops) was discovered earlier; this group's contribution to this aspect mainly de als with the possibility of treating these loops as parts of a more ex tended network. In contrast, the role of the negative loop of cro on i tself had apparently remained unexplained. We realized that this loop buffers the expression of genes cro itself, cII, O and P against the i nflation due to the rapid replication of the phage. More generally, ne gative auto-control of a gene appears an efficient way to render its e xpression insensitive (or less sensitive) to gene dosage, whereas a si mple negative control would not provide this result.