Uncovering the design principles analysis of flexibility of circadian clocks: Mathematical and evolutionary goals
Uncovering the design principles analysis of flexibility of circadian clocks: Mathematical and evolutionary goals
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DOI：
10.1016/j.jtbi.2005.06.026
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发表时间：
2006-02-07
影响因子：
2
通讯作者：
Millar, AJ
中科院分区：
文献类型：
--
作者：
Rand, DA;Shulgin, BV;Millar, AJ
在本文中，我们提出了数学细节基础的方法来调节网络的灵活性和昼夜节律钟网络的进化目标的分析表征。细胞调控的一个基本问题是理解调控网络的形式与其功能之间的关系。生物钟就是一个特别有趣的例子。最近的研究表明，它们具有复杂的结构，包括多个相互关联的反馈回路，既有正反馈，也有负反馈。我们解决了为什么它们具有如此复杂的结构的问题，并认为这是为了提供同时获得生物钟的多个关键特性（如强大的夹带和温度补偿）所需的灵活性。要做到这一点，我们要解决两个基本问题：(A)了解时钟的主要进化目标之间的关系；(B)确定时钟结构的灵活性。为了解决第一个问题，我们使用了无穷小响应曲线（IRCs），我们认为这是一种在监管网络分析中具有普遍效用的工具。为了理解第二个问题，我们引入了灵活性维度d，展示了如何计算它，然后用它来分析一系列模型。我们相信我们的结果将推广到广泛的监管网络。(C) 2005 Elsevier Ltd版权所有。
In this paper, we present the mathematical details underlying both an approach to the flexibility of regulatory networks and an analytical characterization of evolutionary goals of circadian clock networks. A fundamental problem in cellular regulation is to understand the relation between the form of regulatory networks and their function. Circadian clocks present a particularly interesting instance of this. Recent work has shown that they have complex structures involving multiple interconnected feedback loops with both positive and negative feedback. We address the question of why they have such a complex structure and argue that it is to provide the flexibility necessary to simultaneously attain multiple key properties of circadian clocks such as robust entrainment and temperature compensation. To do this we address two fundamental problems: (A) to understand the relationships between the key evolutionary aims of the clock and (B) to ascertain how flexible the clock's structure is. To address the first problem we use infinitesimal response curves (IRCs), a tool that we believe will be of general utility in the analysis of regulatory networks. To understand the second problem we introduce the flexibility dimension d, show how to calculate it and then use it to analyse a range of models. We believe our results will generalize to a broad range of regulatory networks. (C) 2005 Elsevier Ltd. All rights reserved.