Abstract
Bacteriophage lambda makes lysis/lysogeny decision based on the number of coinfecting phages, namely the multiplicity of infection (MoI): lysis at low MoI; lysogeny at high MoI. Here, by evaluating various rationally designed models on their ability a) to make lytic decision at MoI of 1 and lysogeny decision at MoI of 2, b) to exhibit bistability at the two MoIs, and c) to perform accurately in the presence of noise, it is demonstrated that lambda’s lysis/lysogeny decision is based on three features, namely a) mutual repression, b) cooperative positive autoregulation of cI, and c) cooperative binding of the activator protein, and not basal expression, triggering the positive autoregulatory loop. Cro and CI are sufficient to acquire the first two features. CII is required to acquire the third feature. The quasi-minimal two-protein model for the switch is justified by showing its qualitative equivalence, except for the Cro repression of pRM, to lambda’s gene regulatory network responsible for lysis/lysogeny decision. A three-protein simplified version of lambda’s switch is shown to possess all the three design features. Existence of bistability at MoI of 1 and 2 confer lysogen stability and lytic development’s stability, respectively.