Alternative regulatory circuit architectures. (A) Wild type, uncoupled transcription, and no feedback network models. (B) Sample simulation traces of the HipA and HipB ratio for the alternative circuit topologies. (C) Histograms showing distributions of R (ratio) values for the three circuit topologies. (D) Mean value of R. Note that with transcriptionally uncoupled genes, the mean ratio is closer to persistence. With no feedback, the ratio is further from the persistence threshold. Error bars show standard deviation. (E) Comparison of the noise (variance divided by mean, σ2/μ) for the alternative circuit architectures. The transcriptionally uncoupled network shows increased noise; without feedback there is decreased noise. The combination of elevated mean and noise in the uncoupled transcription case increases the likelihood of persistence events, while the opposite is true for the no feedback case.