Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Non-classic effects in stochastic gene expression
Tatiana T. Marquez-Lago

Last modified: 2014-03-31


Gene expression processes can be broken down to sets of chemical reactions. By consequence, any accurate representation necessarily accounts for discreteness and stochasticity. However, subtle assumptions can still yield erroneous results, masking key discrete effects. For instance, transcription and translation are delayed processes, but this is often ignored. Thus, effects such as delay-induced stochastic oscillations at the single-cell level have remained relatively unexplored.

We have explored and systematically analysed several minimal models of gene regulation, where a transcriptional repressor negatively regulates its own expression [1,2]. By means of modelling and exact stochastic simulations, we studied the influence of negative feedback strength and transcriptional/translational rates and delays on expression dynamics.

Negative feedbacks do not necessarily lead to noise reduction, and qualitatively distinct expression profiles can be generated from structurally identical network topologies [1]. Also, once explicit delays are incorporated to both transcription and translation processes [2], new types of non-classic effects can be observed. For instance, an oscillatory regime emerges through a Hopf bifurcation in both deterministic and stochastic frameworks. Additionally, delays increase the number of accessible states in a multimodal regime, introducing features typical of excitable systems. These techniques and findings have never been described in gene expression analysis before.

Our work provides deeper insight into the mathematical subtleties that should be considered for proper design of single gene/single cell experiments with oscillatory, multimodal, and burst-like expression profiles.


[1] Marquez-Lago T, Stelling J. Counter-intuitive stochastic behavior of simple gene circuits with negative feedbacks. Biophysical J. 2010 Vol. 98(9):1742-1750.

[2] Zavala E, Marquez-Lago T. Delays Induce Novel Stochastic Effects in Negative Feedback Gene Circuits. Biophysical J. 2014 Vol. 106(2): 467-478


Gene expression; Stochastic bifurcation; Excitable system