Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Institute for Systems Biology, Seattle, WA, USA.
Nat Commun. 2021 May 26;12(1):3178. doi: 10.1038/s41467-021-23214-9.
Living systems formed and evolved under constraints that govern their interactions with the inorganic world. These interactions are definable using basic physico-chemical principles. Here, we formulate a comprehensive set of ten governing abiotic constraints that define possible quantitative metabolomes. We apply these constraints to a metabolic network of Escherichia coli that represents 90% of its metabolome. We show that the quantitative metabolomes allowed by the abiotic constraints are consistent with metabolomic and isotope-labeling data. We find that: (i) abiotic constraints drive the evolution of high-affinity phosphate transporters; (ii) Charge-, hydrogen- and magnesium-related constraints underlie transcriptional regulatory responses to osmotic stress; and (iii) hydrogen-ion and charge imbalance underlie transcriptional regulatory responses to acid stress. Thus, quantifying the constraints that the inorganic world imposes on living systems provides insights into their key characteristics, helps understand the outcomes of evolutionary adaptation, and should be considered as a fundamental part of theoretical biology and for understanding the constraints on evolution.
生命系统是在与无机世界相互作用的约束条件下形成和进化的。这些相互作用可以用基本的物理化学原理来定义。在这里，我们制定了一套全面的 10 条非生物约束条件，这些条件定义了可能的定量代谢组。我们将这些约束条件应用于代表大肠杆菌 90%代谢组的代谢网络。我们表明，非生物约束条件允许的定量代谢组与代谢组学和同位素标记数据是一致的。我们发现：（i）非生物约束条件驱动高亲和力磷酸盐转运体的进化；（ii）电荷、氢和镁相关约束条件是对渗透压胁迫的转录调控反应的基础；（iii）氢离子和电荷失衡是对酸胁迫的转录调控反应的基础。因此，量化无机世界对生命系统施加的约束条件可以深入了解它们的关键特征，有助于理解进化适应的结果，并且应该被视为理论生物学和理解进化约束的一个基本部分。
