Systems Behavior in Phage λ and Evolution of Complex Regulatory Circuitry

John Little, Univeristy of Arizona

Abstract

How do complex regulatory circuits arise during evolution? In one plausible model, a simple circuit arises, and is later refined in ways that improve its behavior, either by fine-tuning parameters or by adding new features ("bells and whistles"). We explore this two-stage model using the regulatory circuit of phage λ, which can exist in either of two alternative states. Of these, the lysogenic state is highly stable, but it can switch to the lytic state in the process of prophage induction. To test the second stage of the evolution model, we removed one of several features of the λ circuitry that might be considered refinements—positive autoregulation of the regulatory gene cI; cooperative DNA binding by CI repressor; or differential affinities of CI for various operators. In each case, a feature was removed by mutation; sometimes suppressors were added. We can isolate variants with qualitatively normal behavior, suggesting that these features are indeed refinements. In the first stage of the evolution model, a simple circuit arises, and is fixed because it offers a selective advantage (lysogeny in the λ case). If a circuit arose by recombination between simpler modules, the circuit might retain a modular organization. To test this we replaced λ Cro repressor with Lac repressor, and found that the λ circuit retains a modular organization. We later replaced CI with Tet repressor as well; variants carrying both TetR and LacR have an altered wiring diagram, possibly reflecting the loss of features conferring positive feedback and non-linearity.

Back to The First q-bio Conference.