具有协同表达的缠结的基因调控网络赋予对不可预见的环境变化的强大适应性反应
Entangled gene regulatory networks with cooperative expression endow robust adaptive responses to unforeseen environmental changes
摘要：
生物体必须对环境变化作出反应。一般来说，准确和快速的反应是由简单的单向网络提供的，该网络将输入与输出连接起来。除了准确性和速度，生物反应还应该对环境或细胞内噪音和突变具有鲁棒性。此外，细胞还必须对以前没有经历过的不可预见的环境变化做出反应，以避免在其网络进化重新布线之前灭绝，这需要数代人。我们研究了相互激活或抑制的基因调控网络，并证明了复杂的纠缠网络可以建立适当的输入输出关系，满足不可预见的挑战所需的鲁棒性和适应性反应。这种纠缠网络的功能是对每个基因表达的低希尔系数反应进行草率和不可靠的响应。为了弥补这种马虎，调控网络中存在一些迂回。与简单的单向电路相比，通过利用这种迂回的平均，网络对环境和细胞内噪声以及网络中的突变表现出更高的鲁棒性。此外，实现了对不可预见的挑战的适当响应，允许功能输出，因为许多基因表现出类似的动态表达响应，而与输入无关，如通过应用动态时间规整和动态模式分解所证实的。由于复杂的缠结网络在基因调控网络中很常见，并且在微生物实验中观察到全局基因表达响应，本文的结果为细胞网络的设计提供了一种新的原则。
英文摘要：
Living organisms must respond to environmental changes. Generally, accurate and rapid responses are provided by simple, unidirectional networks that connect inputs with outputs. Besides accuracy and speed, biological responses should also be robust to environmental or intracellular noise and mutations. Furthermore, cells must also respond to unforeseen environmental changes that have not previously been experienced, to avoid extinction prior to the evolutionary rewiring of their networks, which takes numerous generations. We have investigated gene regulatory networks that mutually activate or inhibit, and have demonstrated that complex entangled networks can make appropriate input-output relationships that satisfy the robust and adaptive responses required for unforeseen challenges. Such entangled networks function for sloppy and unreliable responses with low Hill coefficient reactions for the expression of each gene. To compensate for such sloppiness, several detours in the regulatory network exist. By taking advantage of the averaging over such detours, the network shows a higher robustness to environmental and intracellular noise as well as to mutations in the network, when compared to simple unidirectional circuits. Furthermore, the appropriate response to unforeseen challenges, allowing for functional outputs, is achieved as many genes exhibit similar dynamic expression responses, irrespective of inputs, as confirmed by applying dynamic time warping and dynamic mode decomposition. As complex entangled networks are common in gene regulatory networks and global gene expression responses are observed in microbial experiments, the present results provide a novel design principle for cellular networks.
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