Mitrophanov Alexander Y, Jewett Mollie W, Hadley Tricia J, Groisman Eduardo A
Howard Hughes Medical Institute, Washington University, St Louis, MO, USA.
PLoS Genet. 2008 Oct;4(10):e1000233. doi: 10.1371/journal.pgen.1000233. Epub 2008 Oct 24.
Complex genetic networks consist of structural modules that determine the levels and timing of a cellular response. While the functional properties of the regulatory architectures that make up these modules have been extensively studied, the evolutionary history of regulatory architectures has remained largely unexplored. Here, we investigate the transition between direct and indirect regulatory pathways governing inducible resistance to the antibiotic polymyxin B in enteric bacteria. We identify a novel regulatory architecture -- designated feedforward connector loop -- that relies on a regulatory protein that connects signal transduction systems post-translationally, allowing one system to respond to a signal activating another system. The feedforward connector loop is characterized by rapid activation, slow deactivation, and elevated mRNA expression levels in comparison with the direct regulation circuit. Our results suggest that, both functionally and evolutionarily, the feedforward connector loop is the transitional stage between direct transcriptional control and indirect regulation.
复杂的遗传网络由决定细胞反应水平和时机的结构模块组成。虽然构成这些模块的调控结构的功能特性已得到广泛研究，但调控结构的进化历史在很大程度上仍未被探索。在这里，我们研究了肠道细菌中控制对抗生素多粘菌素B诱导抗性的直接和间接调控途径之间的转变。我们鉴定出一种新型调控结构——称为前馈连接环——它依赖于一种调控蛋白，该蛋白在翻译后连接信号转导系统，使一个系统能够对激活另一个系统的信号做出反应。与直接调控回路相比，前馈连接环的特点是激活迅速、失活缓慢且mRNA表达水平升高。我们的结果表明，在前馈连接环在功能和进化上都是直接转录控制和间接调控之间的过渡阶段。
