Superstability of the yeast cell cycle dynamics: Ensuring causality in the presence of biochemical stochasticity

Abstract

Gene regulatory dynamics is governed by molecular processes and therefore exhibits an inherent stochasticity. However, for the survival of an organism it is a strict necessity that this intrinsic noise does not prevent robust functioning of the system. It is still an open question how dynamical stability is achieved in biological systems despite the omnipresent fluctuations. In this paper we investigate the cell-cycle of the budding yeast Saccharomyces cerevisiae as an example of a well-studied organism. We study a genetic network model of eleven genes that coordinate the cell-cycle dynamics using a modeling framework which generalizes the concept of discrete threshold dynamics. By allowing for fluctuations in the transcription/translation times, we introduce noise in the model, accounting for the effects of biochemical stochasticity. We study the dynamical attractor of the cell cycle and find a remarkable robustness against fluctuations of this kind. We identify mechanisms that ensure reliability in spite of fluctuations: 'Catcher' states and persistence of activity levels contribute significantly to the stability of the yeast cell cycle despite the inherent stochasticity.