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Escherichia coli and Bacillus subtilis are two of the best-studiedprokaryotic model organisms. Previous analyses of their transcriptionalregulatory networks have shown that they exhibit high plasticity duringevolution and suggested that both converge to scale-free-like structures.Nevertheless, beyond this suggestion, no analyses have been carried out toidentify the common systems-level components and principles governing theseorganisms. Here we show that these two phylogenetically distant organismsfollow a set of common novel biologically consistent systems principlesrevealed by the mathematically and biologically founded natural decompositionapproach. The discovered common functional architecture is a diamond-shaped,matryoshka-like, three-layer (coordination, processing, and integration)hierarchy exhibiting feedback, which is shaped by four systems-levelcomponents: global transcription factors (global TFs), locally autonomousmodules, basal machinery and intermodular genes. The first mathematicalcriterion to identify global TFs, the $\kappa$-value, was reassessed on B.subtilis and confirmed its high predictive power by identifying all thepreviously reported, plus three potential, master regulators and eight sigmafactors. The functional conserved cores of modules, basal cell machinery, and aset of non-orthologous common physiological global responses were identifiedvia both orthologous genes and non-orthologous conserved functions. This studyreveals novel common systems principles maintained between two phylogeneticallydistant organisms and provides a comparison of their lifestyle adaptations. Ourresults shed new light on the systems-level principles and the fundamentalfunctions required by bacteria to sustain life.

journal of biotechnology

Prokaryotic regulatory systems biology: Common principles governing the  functional architectures of Bacillus subtilis and Escherichia coli unveiled  by the natural decomposition approach