RNA breakthrough sheds light on the beginning of life

RNA may have played a central role in the origin of life, helping early molecules copy and store information. It’s a type of molecule that also plays a central role in how cells function.

Scientists believe that, long before DNA and proteins, RNA strands carried the instructions needed for life to exist. But exactly how these early molecules managed to replicate without the help of enzymes has puzzled researchers for decades.

Now, a new study sheds light on this mystery. Scientists from University College London (UCL) and the MRC Laboratory of Molecular Biology have found a way to get RNA to replicate itself under simple, natural conditions.

The research opens a window into understanding what the very first steps of life might have looked like.

The RNA replication puzzle

For life to emerge, molecules had to store and copy information. RNA, a close cousin to DNA, was likely the first molecule to take on this task. But RNA strands naturally pair up into a stable double helix – much like Velcro that’s hard to pull apart.

Once zipped together, it becomes almost impossible for the strands to separate and copy themselves. This has made it difficult to recreate early life’s processes in the lab.

The researchers tackled this challenge by using “triplet” RNA building blocks, or trinucleotides, in water. They added acid and heat to the solution, which forced the RNA double strands apart. Afterward, they neutralized and froze the solution.

As the water froze, tiny gaps formed between the ice crystals. These gaps provided the perfect space for the triplets to bind to the separated RNA strands, preventing them from snapping back together too quickly.

By thawing and repeating this freeze-thaw cycle, they created changing pH and temperature conditions. These conditions are common in nature, like those caused by day and night shifts or geothermal activity.

Over time, the RNA began to replicate again and again, producing strands long enough to serve biological functions.

Data dilemma for life

“Life is separated from pure chemistry by information, a molecular memory encoded in the genetic material that is transmitted from one generation to the next,” said Dr. Philipp Holliger of the MRC Laboratory of Molecular Biology.

“For this process to occur, the information must be copied, i.e., replicated, to be passed on.”

Dr. James Attwater, lead author from UCL Chemistry and the MRC Laboratory of Molecular Biology, emphasized how essential replication is to biology.

“Replication is fundamental to biology. In one sense, it is why we are here. But there’s no trace in biology of the first replicator,” said Dr. Attwater.

“Even the single-celled organism that is the ancestor of all known life, the Last Universal Common Ancestor (LUCA), is a pretty complex entity, and behind it lies a lot of evolutionary history that is hidden from us.”

“Our best guess is that early life was run by RNA molecules. But a big problem for this hypothesis is that we haven’t been able to get a molecule of RNA to replicate itself in a way that could have occurred before life began several billion years ago.”

Early RNA replication

Instead of relying on complex enzymes like modern cells do, the team used simple environmental changes to spark replication.

“The changing conditions we engineered can occur naturally, for instance with night and day cycles of temperature, or in geothermal environments where hot rocks meet a cold atmosphere,” Dr. Attwater explained.

Interestingly, the team pointed out that the triplet building blocks they used do not exist in modern biology.

“The triplet or three-letter building blocks of RNA we used, called trinucleotides, do not occur in biology today, but they allow for much easier replication,” noted Dr. Attwater. “The earliest forms of life are likely to have been quite different from any life that we know about.”

“The models of biological species we are trying to build need to be simple enough to have emerged from the chemistry of early Earth.”

Life’s freshwater origins

While their study focused on chemistry, the researchers suggested that freshwater ponds or lakes – especially near geothermal sites – could have provided the right conditions.

The team also discovered that freezing and thawing in saltwater would not work. Salt interferes with the freezing process and prevents the RNA building blocks from reaching the concentration needed for replication.

Although evaporation from puddles could also concentrate RNA, high heat would likely destroy the molecules. This makes the freeze-thaw cycles in freshwater a more realistic scenario.

More than just RNA

The study also points out that RNA alone likely wasn’t enough for life to begin. Scientists believe that life emerged from a mix of ingredients: RNA, peptides (short chains of amino acids), enzymes, and lipids that form protective barriers.

Other teams at UCL and the MRC Laboratory of Molecular Biology have been working on this broader picture.

In recent years, researchers led by Dr. John Sutherland at the MRC Laboratory of Molecular Biology and Professor Matthew Powner at UCL Chemistry have shown how early Earth chemistry could create many key ingredients for life.

The experts have demonstrated how nucleotides (the building blocks of RNA and DNA), amino acids, peptides, simple lipids, and vitamin precursors could form from simple, abundant molecules.

Together, these studies bring us closer to understanding how life’s first spark might have come from the most basic materials on Earth.

The full study was published in the journal Nature Chemistry.

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