Let there be multifunctionality: Uncovering the criticality zoo of the AC-DCgenetic circuit
Smitha MaretvadakethopeiD, Içvara AoriD, Matthias M. FischeriD, Àngela Pantebre Pedrosa, Yolanda SchaerliiD, Rubén Perez‐CarrascoiD
Abstract
Gene regulatory networks (GRNs) govern processes such as cell fate, patterning, and adaptation. While multistability and oscillations are both common GRN dynamics in cell biology, they are typically studied and engineered in isolation. Here, we challenge this separation using the AC-DC circuit, a minimal three- gene network that merges the classical toggle switch and repressilator. Using a thermodynamic formalism and Bayesian inference, we show that even a single-inducer version of the circuit can display diverse mul-tifunctional dynamics, including the coexistence of oscillations and multistability. In addition we explore robustness, classify emergent behaviours, and analyse critical slowing down and regime transitions. Re-markably, the AC-DC circuit can produce more than 30 topologically distinct bifurcation diagrams, chal-lenging the classical view that network topology rigidly constrains dynamical outcomes. This flexibility enables synthetic capabilities that couple hysteresis with oscillations, critical slowing down, and reversibility. By uncovering the hidden potential of minimal genetic circuits and outlining design principles for their implementation, this work opens new directions for harnessing emergent complexity using the basic building blocks of life.
02 /Specification & Classification
Click any tag to browse matching papers- Citations
- 2
- Approach
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Canalization and competition: the cornerstone of genetic network's dynamic stability and evolution
Yuxiang Yao, Zi‐Gang Huang, Duanqing Pei·bioRxiv·May 13, 2024
- Functional resilience of mutually repressing motifs embedded in larger regulatory networks
Pradyumna Harlapur, Atchuta Srinivas Duddu, … Mohit Kumar Jolly·BiomoleculesPeer-reviewed·Dec 9, 2022
- A geometric and structural approach to the analysis and design of biological circuit dynamics: a theory tailored for synthetic biology
John P. Marken, Fangzhou Xiao, Richard M. Murray·bioRxiv·Feb 18, 2020
- Mixed positive and negative feedback loops drive diverse single-cell gene expression dynamics
Torkel E. Loman, Christian Schwall, … James C W Locke·Nature CommunicationsPeer-reviewed·Aug 17, 2026
- UNFOLDing Robustness, Plasticity, Evolvability and Canalisation of Biological Function
Debomita Chakraborty, Raghunathan Rengaswamy, Karthik Raman·PLoS Computational BiologyPeer-reviewed·May 28, 2026
- Mapping Synthetic Circuit Design Space through Massively Parallel Measurement of Single-Cell Dynamics
Noah Olsman, Jacob Quinn Shenker, … Johan Paulsson·bioRxiv·Oct 13, 2026