Summary:
How life itself is arguably our biggest clue as to how life began, particularly if we focus on the three pivotal processes of energy production, metabolism and genetic information. Nick discussed what these processes may have looked like at the origins of life and the integral role of the proton-motive force.
Abstract:
Life is a surprisingly good guide to its own origins, in terms of membrane energetics, metabolism, and the genetic code1. Specifically, the use of the proton-motive force to drive work is conserved across all life on earth. The most basal form of work was likely CO2 fixation, which could in principle drive flux through an autotrophic protometabolism resembling the conserved core of metabolism 2–4V.
Patterns in the genetic code suggest genes emerged from this protometabolism via direct physical interactions between amino acids and the bases encoding them5. These factors suggest that life arose in structured, continuous flow environments such as alkaline hydrothermal vents6–8. I focus here on our own studies, which show that pH differences across freshly precipitated semi-conducting Fe(Ni)S barriers in microfluidic reactors9 can drive CO2 fixation to produce formate and acetate. Hydrothermal Fischer-Tropsch-type synthesis can generate mixtures of long-chain fatty acids and fatty alcohols 10, and we show these mixtures will form bilayer membranes under alkaline hydrothermal conditions 11.
Under similar conditions, the amino acid cysteine forms [4Fe-4S] clusters12, with a midpoint redox potential of -450 mV, in the same range as ferredoxin. Metal ions can catalyse the synthesis of aspartate from oxaloacetate in the presence of the organic cofactor pyridoxamine13, and we replicate earlier work showing that aspartate is a precursor for a one-pot synthesis of orotate and uracil via the conserved metabolic pathway14. Ferric iron can catalyse phosphoryl transfer from acetyl phosphate to ADP to form ATP, generating the universal energy currency15,16.
I touch on the possible introduction of chirality into gluconeogenesis through chiral-induced spin selectivity on magnetic [4Fe-4S]2+ clusters. Finally, I discuss our work explicating patterns in the genetic code through direct physical interactions5. Molecular dynamics simulations and NMR show the predicted physical interactions are real, albeit weak and statistical17. We correctly predict codon allocation for 50% of anticodon middle bases17. Based on weak physical interactions, we develop an autotrophic protocell model18 to show that the physical templating of peptides by random RNA sequences enables selection for optimal RNA sequences, promoting the growth of evolvable protocells.
References
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