The power of the AC-DC circuit: Operating principles of a simple multi-functional transcriptional network motif

TL;DR

This paper analyzes the simple AC-DC genetic circuit, revealing its ability to exhibit oscillations, bistability, and multi-functionality, which are useful for synthetic biology and understanding natural regulatory networks.

Contribution

The study provides a dynamical systems analysis of the AC-DC circuit, demonstrating its multi-functionality and potential for synthetic circuit design.

Findings

The AC-DC circuit can exhibit both oscillations and bistability.

Both dynamical regimes can coexist in the same parameter space.

The circuit can switch rapidly between different behaviors and control oscillation coherence.

Abstract

Genetically encoded regulatory circuits control biological function. A major focus of systems biology is to understand these circuits by establishing the relationship between specific structures and functions. Of special interest are multifunctional circuits that are capable of performing distinct behaviors without changing their topology. A particularly simple example of such a system is the AC-DC circuit. Found in multiple regulatory processes, this circuit consists of three genes connected in a combination of a toggle switch and a repressilator. Using dynamical system theory we analyze the available dynamical regimes to show that the AC-DC can exhibit both oscillations and bistability. We found that both dynamical regimes can coexist robustly in the same region of parameter space, generating novel emergent behaviors not available to the individual subnetwork components. We demonstrate that the AC-DC circuit provides a mechanism to rapidly switch between oscillations and steady expression and, in the presence of noise, the multi-functionality of the circuit offers the possibility to control the coherence of oscillations. Additionally, we provide evidence that the availability of a bistable oscillatory regime allows the AC-DC circuit to behave as an excitable system capable of stochastic pulses and spatial signal propagation. Taken together these results reveal how a system as simple as the AC-DC circuit can produce multiple complex dynamical behaviors in the same parameter region and is well suited for the construction of multifunctional synthetic genetic circuits. Likewise, the analysis reveals the potential of this circuit to facilitate the evolution of distinct patterning mechanisms.