Originally published as Genetics Published Articles Ahead of Print on September 30, 2004.

Genetics, Vol. 169, 1187-1202, March 2005, Copyright © 2005
doi:10.1534/genetics.104.031955

The Bacillus subtilis sin Operon

An Evolvable Network Motif

{dagger} Lawrence Berkeley National Laboratory, Berkeley, California 94720
* Department of Bioengineering, University of California, Berkeley, California 94720

1 Corresponding author: Department of Pharmaceutical Chemistry, Box 2280, 600 16th St., University of California, San Francisco, CA 94107.
E-mail: cavoigt{at}picasso.ucsf.edu

The strategy of combining genes from a regulatory protein and its antagonist within the same operon, but controlling their activities differentially, can lead to diverse regulatory functions. This protein-antagonist motif is ubiquitous and present in evolutionarily unrelated regulatory pathways. Using the sin operon from the Bacillus subtilis sporulation pathway as a model system, we built a theoretical model, parameterized it using data from the literature, and used bifurcation analyses to determine the circuit functions it could encode. The model demonstrated that this motif can generate a bistable switch with tunable control over the switching threshold and the degree of population heterogeneity. Further, the model predicted that a small perturbation of a single critical parameter can bias this architecture into functioning like a graded response, a bistable switch, an oscillator, or a pulse generator. By mapping the parameters of the model to specific DNA regions and comparing the genomic sequences of Bacillus species, we showed that phylogenetic variation tends to occur in those regions that tune the switch threshold without disturbing the circuit function. The dynamical plasticity of the protein-antagonist operon motif suggests that it is an evolutionarily convergent design selected not only for particular immediate function but also for its evolvability.




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