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Two origins of life: Free-living cells may have emerged twice as bacteria and archaea diverged

How and where did the first forms of life arise? These are the main questions driving research at the Institute of Molecular Evolution at Heinrich Heine University Düsseldorf (HHU). In a new publication ...

origin of life
Credit: Unsplash/CC0 Public Domain

How and where did the first forms of life arise? These are the main questions driving research at the Institute of Molecular Evolution at Heinrich Heine University Düsseldorf (HHU). In a new publication in Science Advances, an international team led by Düsseldorf biologists uncovers pioneering insights into the network of chemical reactions that the very first cells used to make the building blocks of life and the energy sources they used to drive those reactions.

They retraced the origin of enzymes during life's earliest divergence into bacteria and archaea and found evidence for two independent origins of life for free-living cells.

If we could go back 4 billion years in time and watch as the first cells emerged on Earth, what would we see? "We would see two very different kinds of cells emerging, pioneer bacteria and pioneer archaea, making their first attempts at life outside the confines of a hydrothermal vent," says Natalia Mrnjavac, a biologist at the University of Düsseldorf and lead author of the new publication.

There, Mrnjavac and an international team of scientists report investigations of genomes, protein structures and chemical reactions that probe the earliest phases of microbial evolution before there were free-living cells.

"These comparisons are giving us unprecedented insights into the phase of evolution when metabolism catalyzed by enzymes was arising from spontaneous reactions catalyzed by metals in the Earth's crust," says Düsseldorf biologist William Martin, senior author of the study.

Two origins of life
Metabolism of the first cells: Starting compounds are shown at the left, they are converted by metabolism into the building blocks of life. The 420 enzymatic reactions are indicated as circles, chemical metabolites as diamonds, lines connect reactions having common metabolites. Circles shown in magenta shading indicate reactions that could have been catalyzed by inorganic compounds in the environment where metabolism of the first cells arose. Credit: HHU/Nadja Hoffmann

Metabolism before modern enzymes

The team's approach differs from previous investigations of early evolution by examining the entire set of chemical reactions that cells use to make the building blocks of life (amino acids, RNA bases and vitamins) from compounds present on the early Earth: hydrogen gas, ammonia and CO2. This set of 420 chemical reactions is called metabolism. The chemical reactions themselves are as universally conserved as the genetic code.

Martin says, "The surprise is that the enzymes that catalyze those reactions are not conserved across the evolutionary divide that separates bacteria and archaea. We found that the last universal ancestor of all cells, LUCA, possessed enzymes for only about half of the reactions of metabolism. The other half was catalyzed by metals in the environment where LUCA arose."

"Metals that naturally occur in hydrothermal vents can replace a surprisingly large number of enzymes in metabolism," says Harun Tüysüz, an inorganic chemist from the Max-Planck-Institut für Kohlenforschung and the IMDEA Materials Institute in Madrid, and a co-author of the study.

"The closer we look, the more clearly we can see that early biochemical evolution was a hybrid of enzymatic and metal catalysts," says Joseph Moran from the University of Ottawa, Canada, an international leader in using metals to catalyze metabolic reactions, replacing enzymes and cofactors.

Four stages of early catalysis

A major step forward in the study was that the team could reconstruct four phases of the early evolution of catalysis: metal-only, a metal-enzyme hybrid in LUCA, followed by divergent evolution toward the ancestors of the bacterial and archaeal lineages. In those lineages, new enzymes were arising, replacing inorganic catalysts provided by the environment where metabolism arose.

"We can see cases where the ancestors of bacteria and archaea independently evolved structurally distinct enzymes to catalyze the same essential metabolic reaction," says Mrnjavac. "Such parallel inventions could have paved the way to the independent emergence of free-living bacteria and archaea."

An energy source before ATP

And where did the energy come from to drive these reactions forward? Today, energy in metabolism mainly comes in the form of ATP, but ATP is a complicated molecule, made by enzymes, not a compound that was lying around for free in hydrothermal vents.

"We have identified a new source of energy at metabolic origin," says Manon Schlikker from the Düsseldorf team. Among the metals that naturally occur in hydrothermal vents is palladium, an excellent catalyst known and used by chemists for a century.

"When we react phosphite, a form of phosphorus that naturally occurs in hydrothermal vents, with organic compounds, we get metabolic phosphorylation reactions overnight in water. Phosphite and palladium replace ATP and enzymes; it's amazing, and it makes early evolution a lot easier to grasp," says Schlikker.

Ordering life's earliest reactions

The study is the first focused investigation into the reaction set called metabolism. That reaction set is a highly interconnected network of 420 reactions, with many compounds participating in multiple reactions. Such networks can be mathematically challenging to deal with.

But among the authors are Mike Steel from the University of Canterbury in New Zealand and Daniel Huson from the University of Tübingen. Experts in networks, they devised a new method to order metabolic reactions from the simplest to the most complex, possibly recapitulating the order in which metabolic reactions arose at the origin of life.

"The first question," says Steel, "is whether or not a unique order exists for these reactions. Once we could prove that there is one, the algorithm to order them became tractable."

Two paths to free-living cells

It is part of our human condition to want to know about our origins, where we come from, where life started and how the first cells on Earth made a living. And what is the larger significance of the new findings? Martin said, "The new data leave only one conclusion. The bacterial and archaeal lineages made the transition to the free-living state independently. Only free-living cells are alive. Let's call it by name: We are looking at one origin of the genetic code, but two origins of life."

In addition to researchers from HHU, the international team included scientists from the universities of Canterbury (New Zealand), Rostock, Constance, Ottawa (Canada), Strasbourg and Tübingen; the Max Planck Institute for Terrestrial Microbiology in Marburg; the Max-Planck-Institut für Kohlenforschung in Mülheim/Ruhr; and the IMDEA Materials Institute in Madrid (Spain).

Publication details

Natalia Mrnjavac, Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent, Science Advances (2026). DOI: 10.1126/sciadv.aef3128. www.science.org/doi/10.1126/sciadv.aef3128

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Sadie Harley

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Citation: Two origins of life: Free-living cells may have emerged twice as bacteria and archaea diverged (2026, August 5) retrieved 5 August 2026 from https://phys.org/news/2026-08-life-free-cells-emerged-bacteria.html

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