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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Autogenous and nonautogenous control of response in a genetic network
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Autogenous and nonautogenous control of response in a genetic network

机译：遗传网络中响应的自主和非自主控制

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Feedback-based control methods determine the behavior of cellular systems, an example being autogenous control, the regulation of production of a protein by itself. This control strategy was theoretically shown to be superior to an equivalent but nonautogenously regulated system when based on a repressor. Although some of its advantages were later confirmed with isolated synthetic circuits, the superiority of autogenous control in natural networks remains untested. Here, we use the SOS DNA repair system of Escherichia coli, where autogenous control is part of a single-input module, as a valid model to evaluate the functional advantages and biological implications of this mechanism. We redesign the control of its master regulator, the protein LexA, so that it becomes nonautogenously controlled. We compare both systems by combining high-resolution expression measurements with mathematical modeling. We show that the stronger stability associated with the autogenous regulation prevents false triggering of the response due to transient fluctuations in the inducing signal and that this control also reduces the system recovery time at low DNA damage. Likewise, autoregulation produces responses proportional to the damage signal level. In contrast, bacteria with LexA constitutively expressed induce maximal action even for very low damage levels. This excess in response comes at a cost, because it reduces comparatively the growth rate of these cells. Our results suggest that autogenous control evolved as a strategy to optimally respond to multiple levels of input signal minimizing the costs of the response and highlights reasons why master regulators of single-input modules are mostly autorepressed.
机译：基于反馈的控制方法决定了细胞系统的行为，例如自体控制，自身蛋白质生产的调控。从理论上讲，这种控制策略在基于阻遏器时优于同等但非自调节的系统。尽管其某些优势后来被隔离的合成电路所证实，但自然网络中自发控制的优越性仍未得到检验。在这里，我们使用大肠杆菌的SOS DNA修复系统（其中自体控制是单输入模块的一部分）作为评估此机制的功能优势和生物学含义的有效模型。我们重新设计了其主调节剂LexA蛋白的控制，从而使其成为非自发控制的。我们通过将高分辨率表达测量与数学建模相结合来比较两种系统。我们表明，与自体调节相关的更强稳定性可防止由于诱导信号中的瞬时波动而引起的错误触发响应，并且这种控制还减少了低DNA损伤时的系统恢复时间。同样，自动调节会产生与损伤信号水平成比例的响应。相反，具有LexA组成型表达的细菌即使在非常低的伤害水平下也能发挥最大作用。这种过量的响应是有代价的，因为它相对地降低了这些细胞的生长速率。我们的结果表明，自发控制已发展成为一种对多级输入信号进行最佳响应的策略，可将响应成本降至最低，并突出说明了单输入模块的主调节器大多会被自动抑制的原因。

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