Environmental selection of the feed-forward loop circuit in gene-regulation networks
Environmental selection of the feed-forward loop circuit in gene-regulation networks
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DOI：
10.1088/1478-3975/2/2/001
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发表时间：
2005-06-01
期刊：
影响因子：
2
通讯作者：
Alon, U
中科院分区：
文献类型：
--
作者：
Dekel, E;Mangan, S;Alon, U
基因调控网络包含被称为网络基序的反复出现的基本回路。了解在何种环境条件下可能会选择每种基序是很有意义的。为了解决这个问题，我们研究了最重要的网络基序之一，一种名为连贯前馈环（FFL）的三基因回路。理论和实验都已证明，FFL具有一种基本的信息处理功能：在输入诱导物开启步骤之后它会表现出延迟，但在关闭步骤之后则不会。在此，我们基于这一功能询问在何种环境条件下FFL可能会比更简单的基因回路更受青睐。我们采用一种理论上的成本效益分析来研究在给定环境中基因回路的选择。我们发现环境必须满足一些条件，FFL才会比更简单的回路更受选择：在输入脉冲持续时间分布足够宽泛且包含长脉冲和短脉冲的环境中，FFL会被选择。FFL回路生化参数的最优值是根据环境确定的，这样FFL中的延迟就能阻断有害的短诱导脉冲。这种方法通常可用于研究其他网络基序的进化选择。
Gene-regulation networks contain recurring elementary circuits termed network motifs. It is of interest to understand under which environmental conditions each motif might be selected. To address this, we study one of the most significant network motifs, a three-gene circuit called the coherent feed-forward loop (FFL). The FFL has been demonstrated theoretically and experimentally to perform a basic information-processing function: it shows a delay following ON steps of an input inducer, but not after OFF steps. Here, we ask under what environmental conditions might the FFL be selected over simpler gene circuits, based on this function. We employ a theoretical cost-benefit analysis for the selection of gene circuits in a given environment. We find conditions that the environment must satisfy in order for the FFL to be selected over simpler circuits: the FFL is selected in environments where the distribution of the input pulse duration is sufficiently broad and contains both long and short pulses. Optimal values of the biochemical parameters of the FFL circuit are determined as a function of the environment such that the delay in the FFL blocks deleterious short pulses of induction. This approach can be generally used to study the evolutionary selection of other network motifs.