Mapping metabolism onto the prebiotic organic chemistry of hydrothermal vents.

Deep-sea hydrothermal vents provide a chemical interface between Earth’s reducing core and its oxidizing oceans. Today these environments support diverse chemosynthetic ecosystems (1), and after being discovered, they were soon proposed as the original site for the emergence of life (2). These hypotheses have considerable appeal but have not been universally accepted, partly because many aspects of the proposed scenarios remain experimentally unconstrained. In particular, much remains unknown about what forms of prebiotic organic chemistry could have been possible at vents, and whether they could have produced abundant biological precursors. Addressing these questions is thus a critical challenge for research on the origin of life. In PNAS, Novikov and Copley (3) take a major next step in addressing this challenge, developing a unique experimental instrument to systematically explore simulated hydrothermal vent chemistry. The authors focus on the chemistry of pyruvate, which has both a central role in modern metabolism and was plausibly formed prebiotically at hydrothermal vents (4). A major distinction among origins of life hypotheses is the level of continuity they assume. “Genes/replication-first” hypotheses generally propose that life arose from selfreplicating polymers and/or vesicles made up of organic substrates of interstellar or atmospheric origins and eventually created metabolism to replace those inputs as they became exhausted. By contrast, “metabolism-first” hypotheses propose that life emerged from energetically driven networks of geochemistry that were preserved and optimized, eventually becoming metabolism (Fig. 1). This debate of whether prebiotic chemistry was rewritten (genes-first) or kinetically encapsulated (metabolism-first) (5) also leaves room for a range of intermediate scenarios involving partial rewriting/encapsulation of prebiotic chemistry. Over the years, a range of arguments has been developed to support metabolism-first scenarios at hydrothermal vents. Hydrothermal vents/chimneys are porous structures with substantial surface areas of potentially catalytic minerals, through which vent effluents circulate under high pressure and across large temperature gradients. Several authors have argued (5–8) that on the early Earth, this would have created a global network of geochemical reactors that could have seeded life by generating and trapping organic substrates from simple inorganic inputs. It has further been argued that the accumulation within vents of inorganic electron donor– acceptor pairs, whose reactions are thermodynamically favored but kinetically slow, would have generated substantial redox stress, and that the emergence of metabolism would have created a chemical channel that allowed this stress to relax (9). From the biological side, many phylogenomic studies conclude that clades exclusive to hydrothermal vents are the deepest branches in the tree of life (1). Further, most metabolic enzymes that catalyze anaerobic reactions with small gas molecules depend on transition-metal sulfide clusters that have been noted to resemble minerals common to vents (7, 10). In addition, a recent complete reconstruction of the evolutionary history of carbon fixation (11) identified strategies generally used by hyperthermophiles as the deepest branching forms. That study led to the conclusion that the hierarchical architecture of metabolism can be explained as the outgrowth of kinetic feedback loops that stabilized an autocatalytic network topology first found at the small-molecule substrate level of the root of the tree of carbon fixation (12). While providing an attractive conceptual framework, the strength of such arguments will ultimately depend on experiments that confirm that prebiotic chemistry at hydrothermal vents could have indeed produced analogs of pathways seen in modern metabolism. Some key results have been obtained in this area (4, 13–17), but in general, small molecule organic chemistry under realistic hydrothermal vent conditions is significantly underexplored. The work of Novikov and Copley thus occupies an important niche within origins of life research. Several key results of their work are highlighted next. First, the authors develop an elegant design, including a unique gas-inlet compressor valve system, that allows experimental conditions to be easily adapted and controlled at the high temperatures (T) and pressures (p) reflective of hydrothermal vents. Previous studies have tended to either operate at more moderate (T, p) conditions (13, 14), or for higher (T, p) regimes, relied on in situ generation of reactant gasses within welded gold tubes (4). This increased control over larger regions of relevant experimental parameter space within the same system is important, because local physical-chemical conditions can vary significantly between different locations within the same vent, as well as between vents. The authors use this capacity to {Ni,Fe}S CO2 CO CH4 H2S S0