Where and how did life originate on Earth? Researchers at the Institute for Molecular Evolution at Heinrich Heine University Düsseldorf (HHU) are investigating these fundamental questions. In a new study published in Science Advances, an international team led by Düsseldorf biologists reconstructed the chemical reaction network that early cells may have used to produce amino acids, RNA bases, vitamins, and other building blocks of life. The research also identifies possible energy sources that powered early metabolism and suggests that free-living bacteria and archaea may have emerged independently.
Approximately 4 billion years ago, Earth looked very different from the planet we know today. If the first cellular systems could have been observed, they may have included two distinct forms of primitive life developing near hydrothermal vents.
“We may be looking at the emergence of two fundamentally different cell types—early bacteria and early archaea—that were beginning to survive outside the protective environment of a hydrothermal vent,” says Natalia Mrnjavac, a biologist at Heinrich Heine University Düsseldorf and lead author of the study.
Mrnjavac and her international research team examined some of the earliest stages of microbial evolution, including the period before fully free-living cells existed. Their analysis combined genome comparisons, protein structures, and the chemistry of ancient metabolic reactions.
“These comparisons provide unprecedented insight into the stage of evolution when enzyme-driven metabolism began to develop from spontaneous reactions catalyzed by metals in Earth’s crust,” says Düsseldorf biologist William Martin, a lead author of the study.
Reconstructing the chemistry of early life
Instead of analyzing only selected pathways, the researchers examined the complete network of chemical reactions that cells use to produce essential biological compounds. These reactions rely on materials that were likely available on early Earth, including hydrogen gas, ammonia, and carbon dioxide.
Together, the 420 reactions form a metabolic network. This network is extremely ancient and has been conserved across life almost as broadly as the genetic code itself.
However, the researchers were surprised to find that the enzymes responsible for these reactions are not equally conserved between bacteria and archaea.
“The enzymes that catalyze these reactions are not conserved across the evolutionary divide separating bacteria and archaea,” Martin explains. “We found that the last universal common ancestor, or LUCA, had enzymes for only about half of the metabolic reactions. The remaining reactions were likely catalyzed by metals in the environment where LUCA evolved.”
This finding indicates that early metabolism depended much more heavily on the surrounding environment than modern cellular metabolism does.
“Naturally occurring metals at hydrothermal vents can replace a surprisingly large number of enzymes in metabolic pathways,” says Harun Tüysüz, an inorganic chemist at the Max Planck Institute for Coal Research and the IMDEA Materials Institute in Madrid, who co-authored the study.
“The more we investigate, the clearer it becomes that early biochemical evolution was a hybrid process involving both enzymes and metal catalysts,” says Joseph Moran of the University of Ottawa in Canada, an expert in the use of metals to catalyze metabolic reactions.
From metal catalysts to biological enzymes
One of the study’s key advances is the reconstruction of four stages in the early evolution of biological catalysis.
The process may have started with reactions driven entirely by metals. This was followed by the LUCA stage, when metals and enzymes worked together. Later, bacteria and archaea began evolving along separate paths. Within each lineage, newly evolved enzymes gradually replaced the inorganic catalysts supplied by the environment.
The researchers also identified examples in which bacteria and archaea appear to have independently evolved different enzymes capable of performing the same essential metabolic functions.
“We see cases in which the ancestors of bacteria and archaea independently evolved structurally different enzymes to catalyze the same important reactions,” Mrnjavac says. “These parallel innovations may have enabled bacteria and archaea to become free-living cells independently.”
This parallel evolution could have helped both lineages reduce their dependence on the chemistry of hydrothermal vents and eventually survive as independent organisms.
How was early metabolism powered?
Energy is another major question in the origin-of-life debate. Modern cells rely heavily on ATP to power metabolism, but ATP is a complex molecule that is produced with the help of enzymes. It was unlikely to have been freely available in ancient hydrothermal environments.
The researchers therefore investigated what may have powered metabolic reactions before ATP-based energy systems evolved.
“We identified a possible new energy source linked to early metabolism,” says Manon Schlicker, a member of the Düsseldorf research team.
One candidate is palladium, a metal that occurs naturally in some hydrothermal vent environments. Chemists have known for roughly a century that palladium is an effective catalyst.
The team found that phosphite, a form of phosphorus that can occur in hydrothermal systems, reacts with organic compounds in the presence of palladium. The reaction triggers processes related to metabolic phosphorylation.
“When phosphite reacts with an organic compound in water in the presence of palladium, a metabolic phosphorylation reaction can occur overnight,” Schlicker says. “In this process, phosphite and palladium replace ATP and an enzyme. This result offers a surprising way to understand how early metabolism may have been powered.”
These findings provide a possible explanation for how the first metabolic reactions obtained the energy required to proceed before modern biological energy systems evolved.
Mapping 420 reactions at the origin of metabolism
This is the first study to focus specifically on the complete reaction network known as metabolism in the context of early life.
The network contains 420 closely interconnected reactions, with many compounds participating in multiple parts of the system. Reconstructing how this network developed over time creates complex mathematical and computational challenges.
Professor Mike Steel from the University of Canterbury in New Zealand and Professor Daniel Hewson from the University of Tübingen contributed their expertise in complex network analysis.
They developed a method for organizing metabolic reactions from the simplest to the most complex. These sequences may partly reflect the order in which the reactions emerged during the earliest stages of biological evolution.
“The first question is whether these reactions have an inherent order,” Steel says. “If we can demonstrate that an order exists, algorithms can be used to reconstruct the sequence more effectively.”
One genetic code, but two origins of life
Understanding how life began addresses some of humanity’s most important questions: Where did we come from? Where did the first living systems emerge? How did the earliest cells survive on a young and chemically different Earth?
According to the researchers, the study’s broader implication is that bacteria and archaea may not have become independent cells at the same time. Instead, each lineage appears to have reached the free-living state separately.
“The new data point to one conclusion: bacterial and archaeal lineages independently transitioned to a free-living state,” Martin says. “Only free-living cells are alive. There is one origin of the genetic code, but there may have been two origins of life.”
In addition to researchers from HHU, the international collaboration includes scientists from the University of Canterbury in New Zealand, the University of Rostock, the University of Konstanz, the University of Ottawa in Canada, the University of Strasbourg, the University of Tübingen, the Max Planck Institute for Terrestrial Microbiology in Marburg, the Max Planck Institute for Coal Research in Mülheim an der Ruhr, and the IMDEA Materials Institute in Madrid, Spain.
Background: Bacteria and archaea
Biologists classify cellular life into three domains: Bacteria, Archaea, and Eukaryotes. Eukaryotic cells contain a nucleus, while bacteria and archaea are generally described as prokaryotic organisms because they lack a membrane-bound nucleus.
Bacteria and archaea represent two distinct and ancient lineages of cellular life. Many species can survive in extreme environments, including locations with very high temperatures or highly acidic or alkaline conditions.
Numerous bacteria and archaea live near hydrothermal vents on the ocean floor. These environments provide heat, minerals, hydrogen, and other chemical ingredients that some origin-of-life theories identify as conditions that may have supported the emergence of early metabolism and life.
Source: www.sciencedaily.com


