arXiv subjects

William F. Martin

Publications and source records attributed to William F. Martin.

3 recordsLinked to original sources

arXiv2025

GTP before ATP: The energy currency at the origin of genes

Life is an exergonic chemical reaction. Many individual reactions in metabolism entail slightly endergonic steps that are coupled to free energy release, typically as ATP hydrolysis, in order to go forward. ATP is almost always supplied by the rotor-stator ATP synthase, which harnesses chemiosmotic ion gradients. Because the ATP synthase is a protein, it arose after the ribosome did. What was the energy currency of metabolism before the origin of the ATP synthase and how (and why) did ATP come to be the universal energy currency? About 27% of a cell's energy budget is consumed as GTP during translation. The universality of GTP-dependence in ribosome function indicates that GTP was the ancestral energy currency of protein synthesis. The use of GTP in translation and ATP in small molecule synthesis are conserved across all lineages, representing energetic compartments that arose in the last universal common ancestor, LUCA. And what came before GTP? Recent findings indicate that the energy supporting the origin of LUCA's metabolism stemmed from H2-dependent CO2 reduction along routes that strongly resemble the reactions and transition metal catalysts of the acetyl-CoA pathway.

physics.bio-ph↗

arXiv2025

Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent

The origin of life required the emergence of metabolism, an autocatalytic network of enzymatic reactions that synthesize amino acids, nucleotides and cofactors. At the origin of metabolism there were no enzymes--how did it start? Empirical studies addressing early metabolic evolution are lacking. Harnessing protein structures for metabolic enzymes, we identify intermediate states in primordial metabolic assembly. We show that enzymatic metabolism in the universal common ancestor was incomplete, undergoing final assembly independently in the lineages leading to Bacteria and Archaea. Native transition metals--Fe0, Co0, Ni0, Pd0--served as the catalytic forerunners of both enzymes and cofactors at metabolic origin while phosphite supplied energy, as it phosphorylates AMP to ADP and serine to phosphoserine using native metal catalysts in water. Phosphite and native metals occur in serpentinizing hydrothermal systems, identifying an energy-supplying, catalytic site of metabolic origin. Cofactors liberated nascent metabolism from native metal catalysts, engendering its autocatalytic state.

q-bio.PE↗

arXiv2025

ATP requirements for growth reveal the bioenergetic impact of mitochondrial symbiosis

Studies by microbiologists from the 1970s provided robust estimates for the energy supply and demand of a prokaryotic cell. The amount of ATP needed to support growth was calculated from the chemical composition of the cell and known enzymatic pathways that synthesize its constituents from known substrates in culture. Starting in 2015, geneticists and evolutionary biologists began investigating the bioenergetic role of mitochondria at eukaryote origin and energy in metazoan evolution using their own, widely trusted but hitherto unvetted model for the costs of growth in terms of ATP per cell. The more recent model contains, however, a severe and previously unrecognized error that systematically overestimates the ATP cost of amino acid synthesis up to 200 fold. The error applies to all organisms studied by such models and leads to conspicuously false inferences, for example that the synthesis of an average amino acid in humans requires 30 ATP, which no biochemistry textbook will confirm. Their ATP cost calculations would require that Escherichia coli obtains roughly 100 ATP per glucose and that mammals obtain roughly 240 ATP per glucose, propositions that invalidate evolutionary inferences so based. By contrast, established methods for estimating the ATP cost of microbial growth show that the first mitochondrial endosymbionts could have easily doubled the hosts available ATP pool, provided that genes for growth on environmental amino acids were transferred from the mitochondrial symbiont to the archaeal host and that the host for mitochondrial origin was an autotroph using the acetyl-CoA pathway.

q-bio.MN↗