Dissemin is shutting down on January 1st, 2025

Published in

Elsevier, Biophysical Journal, 2(106), p. 467-478, 2014

DOI: 10.1016/j.bpj.2013.12.010

Links

Tools

Export citation

Search in Google Scholar

Delays Induce Novel Stochastic Effects in Negative Feedback Gene Circuits

Journal article published in 2014 by Eder Zavala ORCID, Tatiana T. Marquez-Lago
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Orange circle
Postprint: archiving restricted
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

Stochastic models of reaction networks are widely used to depict gene expression dynamics. However, stochastic does not necessarily imply accurate, as subtle assumptions can yield erroneous results, masking key discrete effects. For instance, transcription and translation are not instantaneous processes—explicit delays separate their initiation from the appearance of their functional products. However, delays are often ignored in stochastic, single-gene expression models. By consequence, effects such as delay-induced stochastic oscillations at the single-cell level have remained relatively unexplored. Here, we present a systematic study of periodicity and multimodality in a simple gene circuit with negative feedback, analyzing the influence of negative feedback strength and transcriptional/translational delays on expression dynamics. We demonstrate that an oscillatory regime emerges through a Hopf bifurcation in both deterministic and stochastic frameworks. Of importance, a shift in the stochastic Hopf bifurcation evidences inaccuracies of the deterministic bifurcation analysis. Furthermore, noise fluctuations within stochastic oscillations decrease alongside increasing values of transcriptional delays and within a specific range of negative feedback strengths, whereas a strong feedback is associated with oscillations triggered by bursts. Finally, we demonstrate that explicitly accounting for delays increases the number of accessible states in the multimodal regime, and also introduces features typical of excitable systems.