Binder Sebastian C, Eckweiler Denitsa, Schulz Sebastian, Bielecka Agata, Nicolai Tanja, Franke Raimo, Häussler Susanne, Meyer-Hermann Michael
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30265 Hannover, Germany.
Sci Rep. 2016 Feb 26;6:22212. doi: 10.1038/srep22212.
The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability.
现代分子生物学的重点已从赋予单个基因功能转向理解复杂分子组的表达和调控。在此，我们提供证据表明，病原体铜绿假单胞菌中的替代西格玛因子调控子在很大程度上代表了绝缘的功能模块，这些模块为参与一般适应和生存过程的关键生物组织水平提供了支持。对西格玛因子网络运行状态的分析表明，转录因子在功能上连接了西格玛因子调控子，并在面对具有挑战性的环境时显著调节转录水平。当考虑到西格玛因子网络的结构组织时，新进化的转录因子在计算机模拟测试中更快、更稳健地达到了阈值质量。这些结果表明，替代西格玛因子调控子的模块化结构为铜绿假单胞菌提供了一个强大的框架，使其能够在其环境中充分发挥功能，同时促进进化变化。我们的数据支持这样一种观点，即广泛存在的模块化保证了生物网络的稳健性，并且是可进化性的关键驱动因素。
