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Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean

Fig 5

Nonlatching positive feedback substantially dampens the Poissonian noise-mean inverse relationship, allowing stochastic extinction despite increasing mean-expression levels.

(A) In the classical Poisson or super-Poissonian transcriptional burst models [50], the expression mean scales with variance (σ2 ∝ μ) such that the noise magnitude (CV2 = σ2 / μ2) decreases proportionally to the inverse of the mean. Nonlatching positive feedback breaks the Poissonian relationship such that σ2 ∝ μN with 1 < N < 2 [44]. In the extreme case where N = 2, CV2 becomes independent of the mean. (B) Monte-Carlo (Gillespie) simulations for three different population mean values in absence (left) and presence (right) of positive feedback showing that stochastic extinction can be decoupled from the mean (when N = 2). (C) Analysis of the data in Fig 3 shows that the Tat circuit displays partial decoupling of noise and mean (N ≈ 1.5).

Fig 5

doi: https://doi.org/10.1371/journal.pbio.2000841.g005