Hlavacek W S, Savageau M A
Department of Chemical Engineering, University of Michigan, Ann Arbor 48109-0620, USA.
J Mol Biol. 1996 Jan 12;255(1):121-39. doi: 10.1006/jmbi.1996.0011.
The induction of effector genes that encode enzymes is often controlled by the protein product of a regulator gene that is directly involved in the control of its own expression. This coupling of elementary gene circuits can lead to three patterns of regulator and effector gene expression. As effector gene expression increases, regulator gene expression can increase, remain the same, or decrease, and these are referred to as directly coupled, uncoupled, or inversely coupled patterns. To determine the relative merits of each pattern, we have constructed appropriate mathematical models for the alternative gene circuits and made well-controlled comparisons using a priori criteria to evaluate their functional effectiveness. We have considered both negatively and positively controlled systems that are induced by an intermediate of the regulated pathway. Different results are obtained in the two cases. Our results indicate that direct coupling is better than inverse coupling or uncoupling for negatively controlled systems, while inverse coupling is better than the other two patterns for positively controlled systems. These optimal forms of coupling promote a fast response to inducer. Our results also indicate that realization of the optimal forms of coupling is influenced by the subunit structure of regulator proteins and requires a low capacity for induction, i.e. the ratio of maximal to minimal level of effector gene expression is small. These results lead to testable predictions, which we have compared with experimental data from over 30 systems.
编码酶的效应基因的诱导通常受调节基因的蛋白质产物控制，该调节基因直接参与自身表达的调控。这种基本基因回路的耦合可导致调节基因和效应基因表达的三种模式。随着效应基因表达增加，调节基因表达可增加、保持不变或减少，这些分别被称为直接耦合、非耦合或反向耦合模式。为了确定每种模式的相对优点，我们为替代基因回路构建了适当的数学模型，并使用先验标准进行了严格控制的比较，以评估它们的功能有效性。我们考虑了由被调节途径的中间产物诱导的负调控和正调控系统。在这两种情况下得到了不同的结果。我们的结果表明，对于负调控系统，直接耦合优于反向耦合或非耦合，而对于正调控系统，反向耦合优于其他两种模式。这些最佳耦合形式促进了对诱导剂的快速反应。我们的结果还表明，最佳耦合形式的实现受调节蛋白亚基结构的影响，并且需要低诱导能力，即效应基因表达的最大水平与最小水平之比很小。这些结果导致了可检验的预测，我们已将其与来自30多个系统的实验数据进行了比较。
