Study suggests bacteria and archaea became free-living cells independently

An international team led by biologists at Heinrich Heine University Düsseldorf has reported evidence that bacteria and archaea, the two deepest branches of cellular life, may have become free-living cells through independent evolutionary events. The study, published in Science Advances, analyzed the complete set of 420 chemical reactions that constitute core metabolism across both domains.

The researchers found that while the metabolic reaction network itself is highly conserved, the enzymes catalyzing those reactions are not conserved between bacteria and archaea to the same degree. Their reconstruction indicates that the last universal common ancestor, LUCA, possessed enzymes for only about half of these reactions, relying on metal catalysts from the hydrothermal vent environment for the rest.

By tracing the evolutionary history of these enzymes, the team identified cases where bacteria and archaea independently evolved structurally distinct enzymes to perform the same essential metabolic tasks. This parallel invention of different protein catalysts for identical reactions suggests each lineage developed its own enzymatic toolkit to replace environmental metal catalysts.

The transition from metal-dependent to enzyme-driven metabolism appears to have occurred in stages: first purely metal-catalyzed reactions, then a hybrid phase in LUCA where metals and early enzymes coexisted, followed by divergent paths in which each lineage gradually replaced inorganic catalysts with its own newly evolved enzymes. This process would have reduced dependence on vent chemistry and enabled survival as independent cells.

The study also proposes a plausible pre-ATP energy source for early metabolism. Experiments showed that phosphite, a form of phosphorus found in hydrothermal vents, can drive metabolic phosphorylation reactions in water overnight when combined with palladium, a metal naturally present in vent systems. This phosphite-palladium system could have supplied energy before complex ATP-based machinery evolved.

To analyze the highly interconnected 420-reaction network, mathematicians Mike Steel of the University of Canterbury and Daniel Huson of the University of Tübingen developed an algorithm that orders reactions from simplest to most complex. The resulting sequence may reflect the approximate chronological order in which metabolic pathways emerged during early evolution.

The researchers conclude that while all known life shares a single ancient genetic code, the transition to free-living cellular existence — the defining feature of life — occurred twice. Bacteria and archaea each made the leap from vent-confined chemistry to independent cellular life separately, representing two distinct origins of life as free-living entities.