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酵母细胞周期动力学的超稳定性:在生化随机性存在的情况下确保因果关系。

Superstability of the yeast cell-cycle dynamics: ensuring causality in the presence of biochemical stochasticity.

作者信息

Braunewell Stefan, Bornholdt Stefan

机构信息

Institute for Theoretical Physics, University of Bremen, D-28359 Bremen, Germany.

出版信息

J Theor Biol. 2007 Apr 21;245(4):638-43. doi: 10.1016/j.jtbi.2006.11.012. Epub 2006 Nov 21.

Abstract

Gene regulatory dynamics are 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 11 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 process times, we introduce noise into 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.

摘要

基因调控动力学受分子过程支配,因此具有内在的随机性。然而,对于生物体的生存来说,至关重要的是这种内在噪声不会妨碍系统的稳健运行。尽管存在无处不在的波动,但生物系统如何实现动态稳定性仍是一个悬而未决的问题。在本文中,我们以研究充分的芽殖酵母酿酒酵母的细胞周期为例进行研究。我们使用一个推广了离散阈值动力学概念的建模框架,研究了一个由11个基因组成的遗传网络模型,这些基因协调细胞周期动力学。通过允许过程时间的波动,我们将噪声引入模型,以考虑生化随机性的影响。我们研究了细胞周期的动态吸引子,发现其对这类波动具有显著的稳健性。我们确定了尽管存在波动仍能确保可靠性的机制:“捕获状态”和活性水平的持续性对酵母细胞周期的稳定性有显著贡献,尽管存在内在的随机性。

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