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 self-replicating 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 systematically explore how the branching ratios of mass flux within a given reaction network change in different parts of parameter space, focusing in particular on the role of mineral catalysts. Similar to findings for other organic species (
16), Novikov and Copley show how different classes of iron-sulfur minerals substantially alter the mass flux topology of the pyruvate reaction network. Studies of this sort can thus help improve our understanding of the variability of prebiotic chemistry within and across hydrothermal vents while also making it possible to consider how the parallel activation of different (sub)networks at different vent locations could have allowed access to pathways not possible under single environmental conditions.
Second, although branching ratios within the network of pyruvate chemistry vary widely, the authors surprisingly find that the total number of contributing pathways across all trials is very limited. If these results prove general for other starting mixtures of plausibly prebiotic small organic molecules, it may help explain why metabolism is sparse, using only a small subset of all possible organic molecules of a given size and stoichiometry (
18). Mass concentration within abiotic networks was likely important, because if matter was distributed over too many different pathways it could have significantly decreased the likelihood of more complex structures and functions emerging. For example, carbonaceous meteorites and asteroids generally contain a much larger suite of organics than is used by living systems, with relatively low concentrations of any one compound. Thus, even if total abundances of such organic inputs were high, scenarios depending on them require plausible mechanisms to explain how only small subsets of compounds could have been selected out of highly distributed sets to become part of living systems. If instead metabolism emerged directly from geochemical networks with inorganic inputs, and studies indicate that the number of significantly contributing pathways at hydrothermal vents was likely somewhat limited, then the sparseness of metabolism could in part be a reflection of the sparseness of hydrothermal geochemistry.
Third, and perhaps most strikingly, most of the reactions and bond formations observed by Novikov and Copley feature prominently
within metabolism, albeit with different catalysts. In particular, the reconstructed reaction network included the formation of thiols and disulfides, and hydrogenation, aldol, and reductive amination reactions. Previous experimental simulations of hydrothermal vent chemistry (4, 13⇓⇓⇓–17) had observed those same classes of organic chemistry, as well as others that have central metabolic roles: (de-)hydration reactions, CO insertions and reductions (to activated methyl groups), and the subsequent formation of activated acetic acid and pyruvate. A limited but growing body of evidence thus suggests that metabolism may indeed exploit organic chemistry readily accessible at hydrothermal vents. Highlighting the possibility of scenarios involving partial rewriting of prebiotic chemistry, the authors also observe the formation of fatty acids through a reaction type not used in metabolism. Debates on the merits of metabolism-first hypotheses would benefit greatly from additional studies systematically exploring these questions.
More generally, prebiotic organic chemistry at hydrothermal vents represents one subspace in a larger “possibility space” of naturally occurring organic chemistry. Examples of other subspaces are those occupied by metabolism, photogeochemistry (
19), interstellar, or atmospheric chemistry. A general goal of the study of living systems and their emergence is to distinguish those features arising from historical contingencies of evolution from those arising from natural laws of biology (
20). Systematic studies of classes of natural organic chemistry, such as pursued by Novikov and Copley for hydrothermal vents, may thus help us not just in asking why life selected the forms of organic chemistry that it uses, but also to identify fundamental constraints in biology that result from that choice of chemistry.
(CNN)
