Avinash Vicholous Dass

Treatment of cystine (the disulfide‐linked dimer of cysteine) with carbonyl sulfide (COS) results in the formation of cyclocystine, which upon reduction yields the Cys–Cys dipeptide. These findings demonstrate a role for the cystine disulfide bond as a molecular scaffold that favors intramolecular peptide bond formation. In contrast, no dipeptide formation was observed when cysteine was subjected to the same reaction conditions, further supporting the importance of the disulfide scaffold in promoting this transformation. The possible relevance of these observations to selective prebiotic polymerization is discussed. The production of cyclocystine was established using LC‐Orbitrap mass spectrometry as well as proton and COSY NMR spectroscopy, while formation of Cys–Cys dipeptide following reduction was confirmed by LC‐Orbitrap mass spectrometry and comparison with a synthetic standard. Further confirmation of the formation of cyclocystine and the dipeptide product was obtained through benzoylation‐based derivatization.

Templated ligation offers an efficient approach to replicate long strands in an RNA world. The 2',3'-cyclic phosphate (>P) is a prebiotically available activation that also forms during RNA hydrolysis. Using gel electrophoresis and high-performance liquid chromatography, we found that the templated ligation of RNA with >P proceeds in simple low-salt aqueous solutions with 1 mM MgCl₂ under alkaline pH ranging from 9 to 11 and temperatures from -20 to 25 °C. No additional catalysts were required. In contrast to previous reports, we found an increase in the number of canonical linkages to 50%. The reaction proceeds in a sequence-specific manner, with an experimentally determined ligation fidelity of 82% at the 3' end and 91% at the 5' end of the ligation site. With splinted oligomers, five ligations created a 96-mer strand, demonstrating a pathway for the ribozyme assembly. Due to the low salt requirements, the ligation conditions will be compatible with strand separation. Templated ligation mediated by 2',3'-cyclic phosphate in alkaline conditions therefore offers a performant replication and elongation reaction for RNA on early Earth.

For the emergence of life, the abiotic synthesis of RNA from its monomers is a central step. We found that in alkaline, drying conditions in bulk and at heated air‐water interfaces, 2′,3′‐cyclic nucleotides oligomerised without additional catalyst, forming up to 10‐mers within a day. The oligomerisation proceeded at a pH range of 7–12, at temperatures between 40–80 °C and was marginally enhanced by K ⁺ ions. Among the canonical ribonucleotides, cGMP oligomerised most efficiently. Quantification was performed using HPLC coupled to ESI‐TOF by fitting the isotope distribution to the mass spectra. Our study suggests a oligomerisation mechanism where cGMP aids the incorporation of the relatively unreactive nucleotides C, A and U. The 2′,3′‐cyclic ribonucleotides are byproducts of prebiotic phosphorylation, nucleotide syntheses and RNA hydrolysis, indicating direct recycling pathways. The simple reaction condition offers a plausible entry point for RNA to the evolution of life on early Earth.

For the emergence of life, the abiotic synthesis of RNA from its monomers is a central step. We found alkaline, uncatalysed drying conditions in bulk and at heated air-water interfaces where 2´,3´-cyclic nucleotides polymerised, forming up to 10-mers within a day. The polymerisation proceeded at a pH range of 7-12 at temperatures between 40-80 °C and was marginally enhanced by K+ ions. Among the canonical ribonucleotides, cGMP polymerised most efficiently. Quantification was performed using HPLC coupled to ESI-TOF by fitting the isotope distribution to the mass spectra. Our study suggests a polymerisation mechanism where cGMP aids the incorporation of the relatively unreactive nucleotides C, A and U. The 2´,3´-cyclic nucleotides are byproducts of prebiotic phosphorylation, nucleotide syntheses and RNA hydrolysis, indicating direct recycling pathways. The simple reaction condition offers a plausible entry point for RNA to the evolution of life on early Earth.

The exclusive presence of β-D-ribofuranose in nucleic acids is still a conundrum in prebiotic chemistry, given that pyranose species are substantially more stable at equilibrium. However, a precise characterisation of the relative furanose/pyranose fraction at temperatures higher than about 50 °C is still lacking. Here, we employ a combination of NMR measurements and statistical mechanics modelling to predict a population inversion between furanose and pyranose at equilibrium at high temperatures. More importantly, we show that a steady temperature gradient may steer an open isomerisation network into a non-equilibrium steady state where furanose is boosted beyond the limits set by equilibrium thermodynamics. Moreover, we demonstrate that nonequilibrium selection of furanose is maximum at optimal dissipation, as gauged by the temperature gradient and energy barriers for isomerisation. The predicted optimum is compatible with temperature drops found in hydrothermal vents associated with extremely fresh lava flows on the seafloor.

A concise outlook on the potential role of confinement in phosphorylation and phosphate condensation pertaining to prebiotic chemistry is presented. Inorganic confinement is a relatively uncharted domain in studies concerning prebiotic chemistry, and even more so in terms of experimentation. However, molecular crowding within confined dimensions is central to the functioning of contemporary biology. There are numerous advantages to confined environments and an attempt to highlight this fact, within this article, has been undertaken, keeping in context the limitations of aqueous phase chemistry in phosphorylation and, to a certain extent, traditional approaches in prebiotic chemistry.

Critical to the origin of life are the ingredients of life, of course, but also the physical and chemical conditions in which prebiotic chemical reactions can take place. These factors place constraints on the types of Hadean environment in which life could have emerged. Many locations, ranging from hydrothermal vents and pumice rafts, through volcanic-hosted splash pools to continental springs and rivers, have been proposed for the emergence of life on Earth, each with respective advantages and certain disadvantages. However, there is another, hitherto unrecognized environment that, on the Hadean Earth (4.5–4.0 Ga), would have been more important than any other in terms of spatial and temporal scale: the sedimentary layer between oceanic crust and seawater. Using as an example sediments from the 3.5–3.33 Ga Barberton Greenstone Belt, South Africa, analogous at least on a local scale to those of the Hadean eon, we document constant permeation of the porous, carbonaceous, and reactive sedimentary layer by hydrothermal fluids emanating from the crust. This partially UV-protected, subaqueous sedimentary environment, characterized by physical and chemical gradients, represented a widespread system of miniature chemical reactors in which the production and complexification of prebiotic molecules could have led to the origin of life. Key Words: Origin of life—Hadean environment—Mineral surface reactions—Hydrothermal fluids—Archean volcanic sediments. Astrobiology 18, 259–293.

This review introduces its readers to a ‘stochastic approach’ to origins of life research, from the viewpoints of both prebiotic chemistry and geology. The idea of a “primordial soup” has been subject to extensive criticism from thermodynamic, biochemical and geochemical perspectives, yet recent advancements have made clearer the plausibility of this theory. Herein, we review the theoretical and experimental approaches which have previously been explored, among these modelling, laboratory‐confined and geologically motivated experimentation. Of these, we consider organo‐mineral interactions, uniting aspects of prebiotic chemistry and geology, to be an especially promising way forward. However, we aim here to advance current approaches by advocating a methodology involving chemical systems and their stochastic reactivity on heterogeneous geological surfaces. This models the origins of life as a continuity of chemical reactions in an analogue to the early Earth (Hadean) environment.