Department of Bioengineering, University of California-San Diego, La Jolla, CA, 92093, USA.
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Lyngby, Denmark.
Nat Commun. 2018 Sep 18;9(1):3796. doi: 10.1038/s41467-018-06219-9.
Biological regulatory network architectures are multi-scale in their function and can adaptively acquire new functions. Gene knockout (KO) experiments provide an established experimental approach not just for studying gene function, but also for unraveling regulatory networks in which a gene and its gene product are involved. Here we study the regulatory architecture of Escherichia coli K-12 MG1655 by applying adaptive laboratory evolution (ALE) to metabolic gene KO strains. Multi-omic analysis reveal a common overall schema describing the process of adaptation whereby perturbations in metabolite concentrations lead regulatory networks to produce suboptimal states, whose function is subsequently altered and re-optimized through acquisition of mutations during ALE. These results indicate that metabolite levels, through metabolite-transcription factor interactions, have a dominant role in determining the function of a multi-scale regulatory architecture that has been molded by evolution.
生物调控网络架构在功能上具有多尺度性，可以自适应地获得新功能。基因敲除 (KO) 实验不仅为研究基因功能提供了一种既定的实验方法，也为揭示涉及基因及其基因产物的调控网络提供了一种方法。在这里，我们通过对代谢基因 KO 菌株进行适应性实验室进化 (ALE) 来研究大肠杆菌 K-12 MG1655 的调控架构。多组学分析揭示了一种通用的整体模式，描述了适应的过程，其中代谢物浓度的干扰导致调控网络产生次优状态，其功能随后通过 ALE 期间的突变获得而改变和重新优化。这些结果表明，代谢物水平通过代谢物-转录因子相互作用，在决定由进化塑造的多尺度调控架构的功能方面起着主导作用。
