New Insights into the Origins of Life
Scientists reveal how ancient RNA may have survived Earth's harsh beginnings
The emergence of life remains one of science's greatest unsolved mysteries. How could complex molecules form and persist over time without breaking down? A team from Munich's ORIGINS Cluster of Excellence has now demonstrated a mechanism that may have stabilized the first RNA molecules in the primordial soup: when two RNA strands pair up, their stability and longevity increase significantly.
Life on Earth most likely began in water—perhaps in a tidal pool, cut off from the ocean at low tide but flooded by waves at high tide. Over billions of years, complex molecules like DNA, RNA, and proteins, and eventually the first cells, emerged there. But exactly how this happened remains unexplained.
"We know which molecules existed on the early Earth," says Job Boekhoven, Professor of Supramolecular Chemistry at the Technical University of Munich (TUM). "The question is: Can we recreate the origins of life from them in the lab?" His team at the ORIGINS Cluster of Excellence is particularly interested in RNA. "RNA is a fascinating molecule," Boekhoven explains. "It can store information and catalyze biochemical reactions." Many scientists therefore believe that among all complex molecules, RNA was the first to form.
The challenge is that functional RNA molecules consist of hundreds or thousands of bases and are highly unstable. In water, RNA strands quickly degrade into their components—a process known as hydrolysis. So how could RNA have survived in the primordial soup?
How Did Double Strands Form in the Primordial Soup?
In the lab, researchers from TUM and Ludwig Maximilian University (LMU) used a simplified RNA base model that forms bonds more easily than the naturally occurring bases in modern cells. "We didn't have millions of years to wait—we wanted answers quickly," Boekhoven notes. The team added these fast-binding RNA bases to an aqueous solution, introduced an energy source, and checked how long the resulting RNA molecules lasted. The sobering result: strands of up to five base pairs survived only a few minutes.
The picture changed when the researchers added short, preformed RNA strands at the start. Free complementary bases quickly attached to these, a process called hybridization, forming double strands of three to five base pairs that remained stable for hours. "What's exciting is that double strands enable RNA to fold, which can make it catalytically active," Boekhoven explains. Double-stranded RNA thus has two advantages: it extends the molecule's lifespan in the primordial soup and provides the foundation for catalytically active RNA.
But how could a double strand have formed in the first place? "We're currently testing whether RNA could have generated its own complementary strand," the chemist says. It's possible that a three-base molecule paired with another containing three complementary bases, producing a stable double strand. Thanks to its longer lifespan, additional bases could then attach, allowing the strand to grow.
An Evolutionary Advantage for Protocells
Another property of double-stranded RNA may have further aided the emergence of life. RNA molecules can form protocells—tiny droplets with an interior separated from the outside world. However, these protocells lack stable membranes and can easily fuse, mixing their contents. This is problematic for evolution, as it prevents individual protocells from developing distinct identities. But if a protocell's boundary is made of double-stranded RNA, it becomes more stable, making fusion less likely.
Implications for Medicine
The findings may also hold significance for medical research.
In the future, Job Boekhoven plans to continue his work on understanding the formation and stabilization of the first RNA molecules. "Some people think this research is just a kind of hobby," he says, "but during the COVID-19 pandemic, everyone saw how crucial RNA molecules can be—for vaccines, for example. Our work isn't just about answering one of science's oldest questions. We're also generating knowledge about RNA that could benefit many people."
