The quantitative metabolome is shaped by abiotic constraints

Abstract

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.

Origin of electroneutrality in living system

“…It is also regarded as a fundamental constraint that biological systems are subject to [25,11]. As such, it is believed to underlie regulatory responses to several stress conditions [24,11]. However, as discussed in the main text, violation of electroneutrality is essential for the mechanism that we proposed to promote the evolution of early metabolic cycles in primitive cells that lack lipid membranes and enzymes.…”

“…In modern cells, there are two main constraints that govern the flow of ions into and out of the cell, namely species mass balance and electroneutrality [10,11]. Thanks to several specialized ion channels in their ion-impermeable lipid membranes, modern cells can generate local ion gradients in their membranes and a nonzero membrane potential while maintaining electroneutrality on both sides of the membrane [12].…”

“…So far, we focused our discussion on the role that the membrane potential could have played as a barrier, preventing organic molecules, synthesized by earliest metabolic reactions, from dissipating into the ocean. In modern cells, this role has been taken over by lipid bilayer membranes, while the membrane potential together with membrane proteins are involved in membrane bioenergetics [21], pH and metal-ion homeostasis [11], controlling material flow into and out of the cell [22,12], and stress regulation [23,10]. As previously stated, a nonzero membrane potential in protocells with ionpermeable membranes would have necessitated the violation of electroneutrality.…”

“…Electroneutrality is often treated as a fundamental law governing the state of electrolyte systems [29]. It is also regarded as a fundamental constraint that biological systems are subject to [25,11]. As such, it is believed to underlie regulatory responses to several stress conditions [24,11].…”

“…where ∆Π := Π in − Π out is the osmotic pressure differential, Π in pressure in the cell, Π out pressure in the ocean, andρ w reduced water density (see the work of Akbari et al [11] for definition and detailed discussion). We assume that the thermodynamic state of the ocean is specified, so that the last term in Eq.…”