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The B. subtilis SIN Operon: An Evolvable Network Motif. Export

Genetics (30 September 2004)

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dynamics motifs networks

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The strategy of combining a regulatory protein and its antagonist onto 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 B. subtilis sporulation pathway as a model system, we build a theoretical model, parameterize it using data from the literature, and use bifurcation analyses to determine the circuit functions it could encode. The model demonstrates that this motif can generate a bistable switch with tunable control over the switching threshold and the degree of population heterogeneity. Further, we show 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 show that phylogenetic variation tends to occur in those regions that tune the switch threshold without disturbing the circuit function. Due to the dynamical plasticity of the protein-antagonist operon motif, we propose that it is an evolutionarily convergent design selected not only for particular immediate function but also for its evolvability.


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