Scientists have reconstructed a possible sequence of events linking the chemistry of hydrothermal vents to the emergence of the first free-living cells—and their findings suggest that life may have crossed a crucial threshold twice. An international team led by researchers at Heinrich Heine University Düsseldorf has mapped how early metabolism could have developed from reactions driven by metals in Earth’s crust into the enzyme-controlled networks found in modern organisms. The study, published in Science Advances, proposes that bacteria and archaea independently evolved the biochemical machinery needed to survive outside the protective chemical environments of hydrothermal vents.
The research focuses on a central question in biology: how did nonliving chemistry become the organized metabolism of the first cells? Rather than examining individual reactions, the scientists analyzed metabolism as an interconnected system. They studied approximately 420 reactions that convert simple compounds thought to have been available on the early Earth—including hydrogen, ammonia and carbon dioxide—into amino acids, RNA bases, vitamins and other molecular building blocks. These reactions form a complex network in which metabolites are shared between multiple pathways, allowing the researchers to investigate not only what reactions existed, but also how the entire system may have developed.
The team compared the enzymes used by modern bacteria and archaea with the chemical reactions those enzymes perform. Enzymes are sophisticated proteins that accelerate biochemical reactions, but the study found that the enzymes carrying out corresponding reactions in bacteria and archaea are often evolutionarily unrelated. This lack of shared ancestry is significant. It indicates that the last universal common ancestor, or LUCA—the ancestral population from which all modern cellular life descended—may not have possessed the complete enzyme-based metabolism seen today. Instead, LUCA appears to have relied on a combination of enzymes and inorganic catalysts.
According to the reconstruction, LUCA had enzymes for only about half of the reactions in the metabolic network. The remaining reactions may have been catalyzed by metals naturally present in the environments where early metabolism arose. Minerals associated with hydrothermal systems can promote chemical transformations by stabilizing reactive molecules or facilitating the transfer of electrons between compounds. In this scenario, the first metabolic networks were not purely biological. They were hybrid systems in which geological catalysts performed some of the work later taken over by genetically encoded proteins.
This proposed transition from metal catalysis to enzyme catalysis unfolded in several stages. The researchers describe an initial phase dominated by inorganic chemistry, followed by a metal-enzyme hybrid stage associated with LUCA. Later, the bacterial and archaeal lineages developed independently, each adding and refining enzymes that replaced reactions once supported by the surrounding minerals. In some cases, the two groups appear to have evolved structurally different enzymes for the same essential reaction. These examples of parallel biochemical evolution provide evidence that bacteria and archaea may have acquired the capacity for free-living existence separately rather than inheriting it from a single fully independent cellular ancestor.
The study also addresses how early metabolism could have been powered. Modern cells rely heavily on ATP, or adenosine triphosphate, to drive energetically unfavorable reactions. ATP is produced through complex enzyme-dependent systems, making it unlikely that it was readily available in the earliest hydrothermal environments. The researchers propose that phosphite, a reduced form of phosphorus that can occur in hydrothermal settings, may have provided an alternative source of chemical energy. In laboratory experiments, phosphite reacted with organic compounds in water in the presence of palladium, producing phosphorylation reactions overnight.
Phosphorylation attaches phosphate groups to organic molecules and is one of the most important forms of chemical energy transfer in biology. In contemporary cells, enzymes and ATP control this process with extraordinary precision. The experiments suggest that palladium and phosphite could have performed a simpler version of the same chemistry before ATP-based energy metabolism evolved. Palladium is a powerful catalyst, and metals with related chemical properties occur in geological environments. Although the experiments do not demonstrate that palladium powered the first cells, they show how environmental chemistry might have supplied both catalysts and energy-transfer reactions before sophisticated molecular biology existed.
To determine whether the metabolic network could be arranged into a plausible sequence, researchers used mathematical methods developed for complex networks. The 420 reactions are highly interconnected, and many compounds participate in several pathways, making a simple chronological reconstruction difficult. Network specialists from the University of Canterbury and the University of Tübingen developed an approach for ordering reactions from relatively simple to more complex. The method first tests whether the network permits a unique ordering and then uses that structure to identify a possible progression for the emergence of metabolism.
The findings reshape the question of life’s origin by separating two events that are often treated as one. The genetic code may have had a single origin, and all modern cellular organisms may ultimately share ancestry through LUCA. But the emergence of free-living cells—organisms capable of maintaining metabolism outside a mineral-rich vent environment—could have occurred independently in the bacterial and archaeal lineages. The researchers therefore describe a model involving one origin of the genetic code but two origins of life in the ecological and cellular sense. The conclusion remains a scientific hypothesis, but it is supported by comparisons of genomes, protein structures, chemical reactions and laboratory catalysis.
Together, the results present early evolution as a gradual handoff between geology and biology rather than a sudden appearance of fully formed cellular machinery. Metals may have initiated and sustained key reactions, while natural selection later favored organisms that encoded more reliable catalysts in proteins. As bacterial and archaeal ancestors became increasingly independent from their mineral surroundings, they followed separate biochemical paths. The study offers a detailed framework for understanding how chemistry at ancient hydrothermal vents could have developed into the first durable forms of cellular life.
Subject of Research: Origins of life, early metabolism, hydrothermal vent chemistry, and the evolution of bacterial and archaeal cells
Article Title: Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent
Web References: https://doi.org/10.1126/sciadv.aef3128
References: Natalia Mrnjavac, Nadja K. Hoffmann, Manon L. Schlikker, Maximilian Burmeister, Loraine Schwander, Carolina García García, Max Brabender, Mike Steel, Daniel H. Huson, Sabine Metzger, Quentin Dherbassy, Bernhard Schink, Mirko Basen, Joseph Moran, Harun Tüysüz, Martina Preiner and William F. Martin. “Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent.” Science Advances 12, eaef3128 (2026).
Image Credits: HHU/Nadja Hoffmann
Keywords: Origins of life, metabolism, hydrothermal vents, LUCA, bacteria, archaea, enzyme evolution, metal catalysis, palladium, phosphite, phosphorylation, astrobiology
