The limits of metabolic heredity in protocells

Abstract

The universal core of metabolism could have emerged from thermodynamically favoured prebiotic pathways at the origin of life. Starting with H2 and CO2, the synthesis of amino acids and mixed fatty acids, which self-assemble into protocells, is favoured under warm anoxic conditions. Here we address whether it is possible for protocells to evolve greater metabolic complexity, through positive feedbacks involving nucleotide catalysis. Using mathematical simulations to model metabolic heredity in protocells, based on branch points in proto-metabolic flux, we show that nucleotide catalysis can indeed promote protocell growth. This outcome only occurs when nucleotides directly catalyse CO2 fixation. Strong nucleotide catalysis of other pathways (e.g. fatty acids, amino acids) generally unbalances metabolism and slows down protocell growth, and when there is competition between catalytic functions cell growth collapses. Autocatalysis of nucleotide synthesis can promote growth but only if nucleotides also catalyse CO2 fixation; autocatalysis alone leads to the accumulation of nucleotides at the expense of CO2 fixation and protocell growth rate. Our findings offer a new framework for the emergence of greater metabolic complexity, in which nucleotides catalyse broad-spectrum processes such as CO2 fixation, hydrogenation and phosphorylation important to the emergence of genetic heredity at the origin of life.

A self-sustaining serpentinization mega-engine feeds the fougerite nanoengines implicated in the emergence of guided metabolism

“…Subject to entrainment in the hydrothermal updrafts, some of this amalgam is likely to spall off in the general direction of flow, eventually crowding and necking to form offspring capable of interacting and sharing the peptide film (Milner- White and Russell, 2005;Larsen et al 2007;Greenwald and Riek, 2010;Greenwald et al, 2018;Römling, 2022). Yet, it is admitted that this speculation falls well short of how prions in membrane or cell-wall microbes could segue to a peptide-nucleotide world governing metabolic pathways and the reverse Krebs cycle (Gallardo and Rodhe, 1997;Schumann and Huntrieser, 2007;Carey et al 2016;Weiss et al 2016;Bromberg et al, 2022;Harrison et al, 2022;Lane, 2022;Palmeira et al, 2022). For this, we are forced to consider the emergence of an albeit imperfect genetic governance to get life into its historical and present role.…”

“…However, just this year some 'cracks' have appeared on the metabolist-cum-chemical side. The Nick Lane-Stuart Harrison group at the Department of Genetics, Evolution and Environment, University College London, look to how randomly synthesized nuclear monomers could become involved in the very basis of metabolism-namely, as nucleotide catalysts in CO 2 hydrogenation and in amination of carboxylates to amino acids (Harrison et al 2022;Palmeira et al, 2022;Pinna et al 2022). This forward-looking approach can explain why ATP is universally conserved across life (Pinna et al, 2022).…”

A prebiotic basis for ATP as the universal energy currency

“…Which catalysts would best promote ATP hydrolysis coupled to phosphorylation in the aqueous prebiotic environments discussed here is a separate question that will be addressed elsewhere; metal ions, amino acids, short peptides, short ribozymes, or nucleotide cofactors all deserve consideration. We suspect that ATP only displaced earlier phosphorylating agents such as AcP or CP when coupled by catalysts to polymerization reactions linked to the hydrolysis of pyrophosphate, as discussed in the Introduction, or potentially as an autocatalytic feedback loop in purine synthesis, which could have amplified purine nucleotide availability in early evolution [ 18 , 129 ]. Nonetheless, the work presented here shows that ATP might have entered protometabolism at an earlier stage than generally supposed and could have contributed to the transition from a monomer to a polymer world.…”

“…For example, alkaline hydrothermal systems sustain steep pH gradients across thin inorganic barriers, as mildly acidic Hadean ocean waters (pH 5 to 6) continually mix with strongly alkaline hydrothermal fluids (pH 9 to 11) in microporous labyrinths that operate as electrochemical flow reactors [20,47,122,123]. Protocells with mixed amphiphile membranes could bind to mineral barriers and potentially use these proton gradients to drive work, including ATP synthesis [124][125][126][127] Mixed amphiphile membranes are highly permeable to protons, because fatty acid flip flop continuously transfers protons from the acid exterior to the alkaline interior of protocells [124,128,129]. A continuous influx of protons across protocell membranes could in principle promote ADP phosphorylation under locally acidic conditions in the immediate vicinity of the membrane within protocells.…”