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Module-Based Analysis of Robustness Tradeoffs in the Heat Shock Response System

机译:基于模块的热冲击响应系统鲁棒性折衷分析

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摘要

Biological systems have evolved complex regulatory mechanisms, even in situations where much simpler designs seem to be sufficient for generating nominal functionality. Using module-based analysis coupled with rigorous mathematical comparisons, we propose that in analogy to control engineering architectures, the complexity of cellular systems and the presence of hierarchical modular structures can be attributed to the necessity of achieving robustness. We employ the Escherichia coli heat shock response system, a strongly conserved cellular mechanism, as an example to explore the design principles of such modular architectures. In the heat shock response system, the sigma-factor σ32 is a central regulator that integrates multiple feedforward and feedback modules. Each of these modules provides a different type of robustness with its inherent tradeoffs in terms of transient response and efficiency. We demonstrate how the overall architecture of the system balances such tradeoffs. An extensive mathematical exploration nevertheless points to the existence of an array of alternative strategies for the existing heat shock response that could exhibit similar behavior. We therefore deduce that the evolutionary constraints facing the system might have steered its architecture toward one of many robustly functional solutions.
机译:即使在简单得多的设计似乎足以产生标称功能的情况下,生物系统也已发展出复杂的调节机制。结合基于模块的分析和严格的数学比较,我们提出,类似于控制工程架构,蜂窝系统的复杂性和分层模块化结构的存在可以归因于实现鲁棒性的必要性。我们以大肠杆菌热休克反应系统(一种高度保守的细胞机制)为例,来探索这种模块化体系结构的设计原理。在热冲击响应系统中,西格玛因子σ32是一个中央调节器,它集成了多个前馈和反馈模块。这些模块中的每一个都在瞬态响应和效率方面以其固有的折衷提供了不同类型的鲁棒性。我们演示了系统的整体架构如何平衡这种折衷。然而,广泛的数学探索指出,对于现有的热冲击响应,可能存在表现出相似行为的一系列替代策略。因此,我们推断出系统所面临的进化限制可能已将其体系结构引向许多功能强大的解决方案之一。

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