By Science Daily (Science) | Created at 2026-08-12 15:19:41 | Updated at 2026-08-12 18:48:00
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Where and how did life first emerge on Earth? Those questions are at the heart of research at the Institute of Molecular Evolution at Heinrich Heine University Düsseldorf (HHU). Now, an international team led by biologists in Düsseldorf has reported new findings in Science Advances that shed light on the chemical reaction network used by the earliest cells to produce the basic ingredients of life, as well as the energy sources that powered those reactions. By tracing the origins of enzymes during the earliest split between bacteria and archaea, the researchers found evidence that free-living cells may have originated independently twice.
About 4 billion years ago, Earth looked very different from the planet we know today. If it were possible to watch the earliest cells take shape, the scene may have involved two distinct forms of primitive cellular life.
"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, biologist at the University of Düsseldorf and lead author on the new publication in Science Advances.
Mrnjavac and an international team examined genomes, protein structures and chemical reactions to investigate some of the earliest stages of microbial evolution, including the period before fully free-living cells existed.
"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.
Reconstructing the Chemistry of Early Life
Rather than focusing on only selected parts of early metabolism, the researchers examined the complete group of chemical reactions that cells use to manufacture key biological components (amino acids, RNA bases and vitamins) from materials that were available on the early Earth, including hydrogen gas, ammonia and CO2.
Together, these 420 chemical reactions form the metabolic network known as metabolism. The reactions themselves are extremely ancient and are conserved across life to a degree comparable with the genetic code.
What surprised the researchers was that the enzymes responsible for carrying out those reactions do not show the same degree of conservation between bacteria and archaea.
Martin: "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."
That finding suggests that the earliest metabolism depended much more heavily on the surrounding environment than modern cellular metabolism does.
"Metals that naturally occur in hydrothermal vents can replace a surprisingly large number of enzymes in metabolism," says Harun Tüysüz, inorganic chemist from the Max-Planck-Institut für Kohlenforschung and the IMDEA Materials Institute in Madrid, and co-author on 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 the use of metals to catalyze metabolic reactions, replacing enzymes and cofactors.
From Metal Catalysts to Enzymes
One of the study's major advances was the reconstruction of four stages in the early evolution of biological catalysis.
The process appears to have begun with reactions driven entirely by metals. That was followed by a stage in LUCA in which metals and enzymes worked together. Afterward, bacteria and archaea began moving along separate evolutionary paths. Within each lineage, newly evolved enzymes gradually replaced the inorganic catalysts supplied by the environment where metabolism had first developed.
Importantly, the researchers identified examples in which bacteria and archaea appear to have independently developed different enzymes capable of performing the same essential metabolic task.
"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."
That parallel evolution may have been crucial because it could have allowed the two lineages to become less dependent on the chemistry of hydrothermal vents and eventually survive as independent cells.
How Early Metabolism May Have Been Powered
Another major question concerns energy. Modern cells rely heavily on ATP to power metabolism, but ATP is itself a complex molecule produced with the help of enzymes. It would not simply have been freely available in ancient hydrothermal environments.
The researchers therefore investigated what could have supplied energy before ATP-based metabolism existed.
"We have identified a new source of energy at metabolic origin," says Manon Schlikker from the Düsseldorf team.
One possible answer involves palladium, a metal that occurs naturally in hydrothermal vents and has been known to chemists as an effective catalyst for roughly a century.
The team found that phosphite, a form of phosphorus naturally found in hydrothermal vents, can react with organic compounds in the presence of palladium and produce reactions associated with metabolic phosphorylation.
"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.
The result provides a possible explanation for how some of the earliest metabolic reactions could have obtained the energy needed to proceed before modern biological energy systems evolved.
Mapping 420 Reactions at the Origin of Metabolism
The research is the first study specifically focused on the full reaction network known as metabolism.
That network contains 420 highly connected reactions, and many of the same compounds participate in multiple parts of the system. Because of those connections, reconstructing how the network may have developed over time presents a difficult mathematical problem.
Prof. Mike Steel, from the University of Canterbury in New Zealand, and Prof. Daniel Huson from the University of Tübingen brought expertise in analyzing complex networks to the project.
They developed a method that allowed the researchers to arrange metabolic reactions from the simplest to the most complex. The resulting sequence may reflect, at least in part, the order in which those reactions appeared during the earliest stages of biological evolution.
"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."
One Genetic Code, but Two Origins of Life
Understanding how life began addresses one of humanity's most fundamental questions: where we came from, where the first living systems appeared, and how Earth's earliest cells were able to survive.
According to the researchers, the broader implication of their findings is that bacteria and archaea did not make the transition to independent cellular life together. Instead, each lineage appears to have reached the free-living state separately.
Martin: "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 and the Max-Planck-Institut für Kohlenforschung in Mülheim/Ruhr plus the IMDEA Materials Institute in Madrid (Spain).
Background: Bacteria and Archaea
Biologists broadly separate cellular life into two categories. Eukaryotes are advanced cells that contain a nucleus, while the more ancient cellular lineages without a nucleus are known as prokaryotes.
Prokaryotes consist of the two primordial branches of life: Bacteria and Archaea. Many of these organisms are capable of surviving under extreme conditions, including very high temperatures and strongly acidic or alkaline environments.
Many also live around hydrothermal vents on the ocean floor, environments that some theories identify as possible locations where life first arose.
