When Dr. Jyoti Singh, a post‑doctoral researcher in the chemistry department at University College London, and her colleagues demonstrated that RNA strands can copy themselves without enzymes, the impact rippled through the origins‑of‑life community.
The breakthrough was unveiled on at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, and the full findings appeared in Nature ChemistryLondon the following day.
By using three‑letter “triplet” RNA building blocks—known as trinucleotides—and cycling the solution through acid, heat, neutralisation, and freeze‑thaw steps, the team coaxed the molecules into a repeatable, exponential replication loop. The result? RNA replication that proceeds in conditions plausibly found on the Hadean Earth, roughly 4.4 billion years ago.
Why This Matters: The RNA‑World Puzzle
For decades, the RNA‑world hypothesis has been the leading narrative for the first genetic system, but it hit a snag: RNA loves to form double helices that act like molecular Velcro, making strand separation extremely hard. Earlier attempts—like the 2015 enzyme‑free system from the Sutherland lab—required chemically exotic reagents and could only produce short oligonucleotides (< 30 bases). Singh’s approach sidesteps the Velcro problem by letting the triplet units coat the strands during the fleeting liquid gaps that form between ice crystals, preventing them from snapping back together.
“In those liquid gaps the triplet building blocks act like tiny spacers, keeping the strands apart just long enough for a new copy to form,” Singh explained. “It’s a bit like using a piece of foam to keep two Lego bricks from sticking permanently.”
How the Experiment Worked
- Prepare a solution of RNA strands and synthetic trinucleotides.
- Drop the pH to ~3 and heat to 70 °C for five minutes—this “unzips” the double helix.
- Neutralise to pH 7 and immediately place the tube in a –20 °C freezer.
- As ice crystals form, thin liquid channels remain; the triplets bind to the single‑stranded RNA.
- Warm the sample back to 25 °C, allowing a ribozyme polymerase to extend the primers.
- Repeat the cycle. Each round roughly doubles the amount of RNA.
After 20 cycles, the researchers measured strands up to 150 nucleotides—long enough to fold into catalytic ribozymes. That length is comparable to the smallest known natural ribozymes that can accelerate chemical reactions.
Quotes from the Team and External Experts
“The elegance is that we’re using nothing more exotic than pH swings and freeze‑thaw—processes that would have been common near volcanic vents or tidal pools,” said Prof. Matthew Powner, a senior chemist at UCL who helped design the ribozyme used in the study.
Professor John Sutherland of the University of Cambridge, a pioneer of prebiotic chemistry, called the work “a decisive step toward a self‑sustaining RNA world” in a commentary published later that month.
Broader Implications for the Origin‑of‑Life Field
The methodology aligns with geological evidence that Hadean Earth experienced rapid temperature shifts due to geothermal heating and night‑day cycles. Cyclers could have occurred in shallow ponds, volcanic steam vents, or even in impact‑generated melt pools.
Statistically, the paper reports that the replication efficiency peaked at 92 % after the sixth cycle, a figure that dwarfs the 15 % yields of earlier non‑enzymatic systems. If similar efficiencies persisted in natural settings, RNA could have reached functional concentrations within a few thousand years—a blink of an eye in geological terms.
Beyond pure replication, the same laboratory has shown that activated amino acids (thioesters derived from Coenzyme A) can link to RNA under comparable conditions, hinting at a bridge between the genetic and metabolic worlds.
What Comes Next?
The team plans to test whether the replicated RNA can catalyse peptide bond formation, a step that would directly address Prof. Powner’s “most challenging and exciting” question: how the first proteins emerged from an RNA‑only system.
Field trials are also in the works: sealed basaltic rock chambers will mimic early Earth pores, allowing scientists to watch replication in a semi‑natural mineral matrix.
Key Facts
- Date of breakthrough: 27 May 2025.
- Primary researchers: Dr. Jyoti Singh (UCL) and Prof. Matthew Powner (UCL).
- Method: pH‑freeze‑thaw cycles with trinucleotide substrates.
- Result: RNA strands up to 150 nt, replication efficiency ≈ 92 %.
- Implication: Supports a plausible, enzyme‑free RNA‑world scenario for Hadean Earth.
Frequently Asked Questions
How does this experiment affect the plausibility of the RNA‑world hypothesis?
By showing that RNA can replicate exponentially using only simple pH and temperature swings—conditions likely on early Earth—the study removes a major mechanistic hurdle. It demonstrates that long, potentially catalytic RNA strands could arise without proteins or sophisticated catalysts, strengthening the hypothesis that RNA was the first hereditary molecule.
What specific environmental conditions were mimicked in the lab?
The researchers reproduced cycles of acidification (pH ≈ 3), heating to about 70 °C, rapid neutralisation, and freezing to –20 °C. Such swings could have occurred in geothermal hot springs, volcanic pools, or tidal zones on the Hadean Earth, where day‑night temperature changes were extreme.
Why were trinucleotides chosen instead of single nucleotides?
Trinucleotides act like three‑letter “LEGO” bricks, allowing the nascent RNA strand to grow in larger, more stable steps. This reduces the chance of premature termination and helps overcome the kinetic barrier that single‑nucleotide additions face under prebiotic conditions.
What are the next experimental milestones?
The team aims to demonstrate that the replicated RNA can catalyse peptide bond formation, linking genetic replication to primitive metabolism. Parallelly, they will test replication inside mineral pores to see if rocks can further stabilise the process.
Could this mechanism have operated in the oceans?
The researchers argue that dilution in open oceans would have hampered the concentration of trinucleotides. Shallow pools or evaporative basins concentrate reactants, making the pH‑freeze‑thaw cycles far more effective than in the vast marine environment.
