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

Abstract: Life is an exergonic chemical reaction. Many individual reactions in metabolism entail slightly endergonic processes 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 synthetase (the ATPase), which harnesses chemiosmotic ion gradients. Because the ATPase is a protein, it arose after the ribosome did. Here we address two questions using comparative physiology: What was the energy currency of metabolism before the origin of the ATPase? How (and why) did ATP come to be the universal energy currency? About 27 percent 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.