origin of life

tiny,-45-base-long-rna-can-make-copies-of-itself

Tiny, 45 base long RNA can make copies of itself

biochemistry, Biology, evolution, origin of life, ribozymes, RNA, Science / /

Self-copying RNAs may have been a key stop along the pathway to life.

By base pairing with themselves, RNAs can form complex structures with enzymatic activity. Credit: Laguna Design

There are plenty of unanswered questions about the origin of life on Earth. But the research community has largely reached consensus that one of the key steps was the emergence of an RNA molecule that could replicate itself. RNA, like its more famous relative DNA, can carry genetic information. But it can also fold up into three-dimensional structures that act as catalysts. These two features have led to the suggestion that early life was protein-free, with RNA handling both heredity and catalyzing a simple metabolism.

For this to work, one of the reactions that the early RNAs would need to catalyze is the copying of RNA molecules, without which any sort of heritability would be impossible. While we’ve found a number of catalytic RNAs that can copy other molecules, none have been able to perform a key reaction: making a copy of themselves. Now, however, a team has found an incredibly short piece of RNA—just 45 bases long—that can make a copy of itself.

Finding an RNA polymerase

We have identified a large number of catalytic RNAs (generically called ribozymes, for RNA-based enzymes), and some of them can catalyze reactions involving other RNAs. A handful of these are ligases, which link together two RNA molecules. In some cases, they need these molecules to be held together by a third RNA molecule that base pairs with both of them. We’ve only identified a few that can act as polymerases, which add RNA bases to a growing molecule, one at a time, with each new addition base pairing with a template molecule.

Black on white image showing 3 different enzymatic activities. One links any two nucleic acid strands, the other only links base paired strands, and the third links one base at a time.

Some ligases can link two nucleic acid strands (left), while others can link the strands only if they’re held together by base pairing with a template (center). A polymerase can be thought of as a template-dependent ligase that adds one base at a time. The newly discovered ribozyme sits somewhere between a template-directed ligase and a polymerase.

Credit: John Timmer

Some ligases can link two nucleic acid strands (left), while others can link the strands only if they’re held together by base pairing with a template (center). A polymerase can be thought of as a template-dependent ligase that adds one base at a time. The newly discovered ribozyme sits somewhere between a template-directed ligase and a polymerase. Credit: John Timmer

Obviously, there is some functional overlap between them, as you can think of a polymerase as ligating on one base at a time. And in fact, at the ribozyme level, there’s some real-world overlap, as some ribozymes that were first identified as ligases were converted into polymerases by selecting for this new function.

While this is fascinating, there are a few problems with these known examples of polymerase ribozymes. One is that they’re long. So long, in fact, that they’re beyond the length of the sort of molecules that we’ve observed forming spontaneously from a mix of individual RNA bases. This length also means they’re largely incapable of making copies of themselves—the reactions are slow and inefficient enough that they simply stop before copying the entire molecule.

Another factor related to their length is that they tend to form very complex structures, with many different areas of the molecule base-paired to one another. That leaves very little of the molecule in a single-stranded form, which is needed to make a copy.

Based on past successes, a French-UK team decided to start a search for a polymerase by looking for a ligase. And they limited that search in an important way: They only tested short molecules. They started with pools of RNA molecules, each with a different random sequence, ranging from 40 to 80 bases. Overall, they estimated that they made a population of 1013 molecules out of the total possible population of 1024 sequences of this type.

These random molecules were fed a collection of three-base-long RNAs, each linked to a chemical tag. The idea was that if a molecule is capable of ligating one of these short RNA fragments to itself, it could be pulled out using the tag. The mixtures were then placed in a salty mixture of water and ice, as this can promote reactions involving RNAs.

After 11 rounds of reactions and tag-based purification, the researchers ended up with three different RNA molecules that could each ligate three-base-long RNAs to existing molecules. Each of these molecules was subjected to mutagenesis and further rounds of selection. This ultimately left the researchers with a single, 51-base-long molecule that could add clusters of three bases to a growing RNA strand, depending on their ability to base-pair with an RNA template. They called this “polymerase QT-51,” with QT standing for “quite tiny.” They later found that they could shorten this to QT-45 without losing significant enzyme activity.

Checking its function

The basic characterization of QT-45 showed that it has some very impressive properties for a molecule that, by nucleic acid standards, is indeed quite tiny. While it was selected for linking collections of molecules that were three bases long, it could also link longer RNAs, work on shorter two-base molecules, or even add a single base at a time, though this was less efficient. While it worked slowly, the molecule’s active half-life was well over 100 days, so it had plenty of time to get things done before it degraded.

It also didn’t need to interact with any specific RNA sequences to work, suggesting it had a general affinity for RNA molecules. As a result, it wasn’t especially picky about the sequences it could copy.

As you might expect from such a small molecule, QT-45 didn’t tolerate changes to its own sequence very well—nearly the entire molecule was important in one way or another. Tests that involved changing every single individual base one at a time showed that almost all the changes reduced the ribozyme’s activity. There were, however, a handful of changes that improved things, suggesting that further selection could potentially yield additional improvements. And the impact of mutations near the center of the sequence was far more severe, suggesting that region is critical for QT-45’s enzymatic activity.

The team then started testing its ability to synthesize copies of other RNA molecules when given a mixture of all possible three-base sequences. One of the tests included a large stretch in which one end of the sequence base-paired with the other. To copy that, those base pairs need to somehow be pried apart. But QT-45 was able to make a copy, meaning it synthesized a strand that was able to base pair with the original.

It was also able to make a copy of a template strand that would base pair with a small ribozyme. That copying produced an active ribozyme.

But the key finding was that it could synthesize a sequence that base-pairs with itself, and then synthesize itself by copying that sequence. This was horribly inefficient and took months, but it happened.

Throughout these experiments, the fidelity averaged about 95 percent, meaning that, in copying itself, it would make an average of two to three errors. While this means a fair number of its copies wouldn’t be functional, it also means the raw materials for an evolutionary selection for improved function—random mutations—would be present.

What this means

It’s worth taking a moment to consider the use of three-base RNA fragments by this enzyme. On the surface, this may seem a bit like cheating, since current RNA polymerases add sequence one base at a time. But in reality, any chemical environment that could spontaneously assemble an RNA molecule 45 bases long will produce many fragments shorter than that. So in many ways, this might be a more realistic model of the conditions in which life emerged.

The authors note that these shorter fragments may be essential for QT-45’s activity. The short ribozyme probably doesn’t have the ability to enzymatically pry base-paired strands of RNA apart to copy them. But in a mixture of lots of small fragments, there’s likely to be an equilibrium, with some base-paired sequences spontaneously popping open and temporarily base pairing with a shorter fragment. Working with these base-paired fragments is probably essential to the ribozyme’s overall activity.

Right now, QT-45 isn’t an impressive enzyme. But the researchers point out that it has only been through 18 rounds of selection, which isn’t much. The most efficient ribozyme polymerases we have at present have been worked on by multiple labs for years. I expect QT-45 to receive similar attention and improve significantly over time.

Also notable is that the team came up with three different ligases in a test of just a small subset of the possible total RNA population of this size. If that frequency holds, there are on the order of 1011 ligating ribozymes among the sequences of this size. Which raises the possibility that we could find far more if we do an exhaustive search. That suggests the first self-copying RNA might not be as improbable as it seems at first.

Science, 2026. DOI: 10.1126/science.adt2760  (About DOIs).

Photo of John Timmer

John is Ars Technica’s science editor. He has a Bachelor of Arts in Biochemistry from Columbia University, and a Ph.D. in Molecular and Cell Biology from the University of California, Berkeley. When physically separated from his keyboard, he tends to seek out a bicycle, or a scenic location for communing with his hiking boots.

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How old is the earliest trace of life on Earth?

Biology, Earth science, Features, geology, origin of life, radioisotope dating, Science / /

A recent conference sees doubts raised about the age of the oldest signs of life.

Where the microbe bodies are buried: metamorphosed sediments in Labrador, Canada containing microscopic traces of carbon. Credit: Martin Whitehouse

Where the microbe bodies are buried: metamorphosed sediments in Labrador, Canada containing microscopic traces of carbon. Credit: Martin Whitehouse

The question of when life began on Earth is as old as human culture.

“It’s one of these fundamental human questions: When did life appear on Earth?” said Professor Martin Whitehouse of the Swedish Museum of Natural History.

So when some apparently biological carbon was dated to at least 3.95 billion years ago—making it the oldest remains of life on Earth—the claim sparked interest and skepticism in equal measure, as Ars Technica reported in 2017.

Whitehouse was among those skeptics. This July, he presented new evidence to the Goldschmidt Conference in Prague that the carbon in question is only between 2.7–2.8 billion years old, making it younger than other traces of life found elsewhere.

Organic carbon?

The carbon in question is in rock in Labrador, Canada. The rock was originally silt on the seafloor that, it’s argued, hosted early microbial life that was buried by more silt, leaving the carbon as their remains. The pressure and heat of deep burial and tectonic events over eons have transformed the silt into a hard metamorphic rock, and the microbial carbon in it has metamorphosed into graphite.

“They are very tiny, little graphite bits,” said Whitehouse.

The key to showing that this graphite was originally biological versus geological is its carbon isotope ratio. From life’s earliest days, its enzymes have preferred the slightly lighter isotope carbon-12 over the marginally heavier carbon-13. Organic carbon is therefore much richer in carbon-12 than geological carbon, and the Labrador graphite does indeed have this “light” biological isotope signature.

The key question, however, is its true age.

Mixed-up, muddled-up, shook-up rocks

Sorting out the age of the carbon-containing Labrador rock is a geological can of worms.

These are some of the oldest rocks on the planet—they’ve been heated, squished, melted, and faulted multiple times as Earth went through the growth, collision, and breakup of continents before being worn down by ice and exposed today.

“That rock itself is unbelievably complicated,” said Whitehouse. “It’s been through multiple phases of deformation.”

In general, the only ways to date sediments are if there’s a layer of volcanic ash in them, or by distinctive fossils in the sediments. Neither is available in these Labrador rocks.

“The rock itself is not directly dateable,” said Whitehouse, “so then you fall onto the next best thing, which is you want to look for a classic field geology cross-cutting relationship of something that is younger and something that you can date.”

The idea, which is as old as the science of geology itself, is to bracket the age of the sediment by finding a rock formation that cuts across it. Logically, the cross-cutting rock is younger than the sediment it cuts across.

In this case, the carbon-containing metamorphosed siltstone is surrounded by swirly, gray banded gneiss rock, but the boundary between the siltstone and the gray gneiss is parallel, so there’s no cross-cutting to use.

Professor Tsuyoshi Komiya of The University of Tokyo was a coauthor on the 3.95 billion-year age paper. His team used a cross-cutting rock they found at a different location and extrapolated that to the carbon-bearing siltstone to constrain its age. “It was discovered that the gneiss was intruded into supracrustal rocks (mafic and sedimentary rocks),” said Komiya in an email to Ars Technica.

But Whitehouse disputes that inference between the different outcrops.

“You’re reliant upon making these very long-distance assumptions and correlations to try to date something that might actually not have anything to do with what you think you’re dating,” he said.

Professor Jonathan O’Neil of the University of Ottawa, who was not involved in either Whitehouse’s or Komiya’s studies but who has visited the outcrops in question, agrees with Whitehouse. “I remember I was not convinced either by these cross-cutting relationships,” he told Ars. “It’s not clear to me that one is necessarily older than the other.”

With the field geology evidence disputed, the other pillar holding up the 3.95-billion-year-old date is its radiometric date, measured in zircon crystals extracted from the rocks surrounding the metamorphosed siltstone.

The zircon keeps the score

Geologists use the mineral zircon to date rocks because when it crystallizes, it incorporates uranium but not lead. So as radioactive uranium slowly decays into lead, the ratio of uranium to lead provides the age of the crystal.

But the trouble with any date obtained from rocks as complicated as these is knowing exactly what geological event it dates—the number alone means little without the context of all the other geological evidence for the events that affected the area.

Both Whitehouse and O’Neil have independently sampled and dated the same rocks as Komiya’s team, and where Komiya’s team got a date of 3.95, Whitehouse’s and O’Neil’s new dates are both around 3.87 billion years. Importantly, O’Neil’s and Whitehouse’s dates are far more precise, with errors around plus-or-minus 5 or 6 million years, which is remarkably precise for dates in rocks this old. The 3.95 date had an error around 10 times bigger. “It’s a large error,” said O’Neil.

But there’s a more important question: How is that date related to the age of the organic carbon? The rocks have been through many events that could each have “set” the dates in the zircons. That’s because zircons can survive multiple re-heatings and even partial remelting, with each new event adding a new layer, or “zone,” on the outer surface of the crystal, recording the age of that event.

“This rock has seen all the events, and the zircon in it has responded to all of these events in a way that, when you go in with a very small-scale ion beam to do the sampling on these different zones, you can pick apart the geological history,” Whitehouse said.

Whitehouse’s team zapped tiny spots on the zircons with a beam of negatively charged oxygen ions to dislodge ions from the crystals, then sucked away these ions into a mass spectrometer to measure the uranium-lead ratio, and thus the dates. The tiny beam and relatively small error have allowed Whitehouse to document the events that these rocks have been through.

“Having our own zircon means we’ve been able to go in and look in more detail at the internal structure in the zircon,” said Whitehouse. “Where we might have a core that’s 3.87, we’ll have a rim that is 2.7 billion years, and that rim, morphologically, looks like an igneous zircon,” said Whitehouse.

That igneous outer rim of Whitehouse’s zircons shows that it formed in partially molten rock that would have flowed at that time. That flow was probably what brought it next to the carbon-containing sediments. Its date of 2.7 billion years ago means the carbon in the sediments could be any age older than that.

That’s a key difference from Komiya’s work. He argues that the older dates in the cores of the zircons are the true age of the cross-cutting rock. “Even the igneous zircons must have been affected by the tectonothermal event; therefore, the obtained age is the minimum age, and the true age is older,” said Komiya. “The fact that young zircons were found does not negate our research.”

But Whitehouse contends that the old cores of the zircons instead record a time when the original rock formed, long before it became a gneiss and flowed next to the carbon-bearing sediments.

Zombie crystals

Zircon’s resilience means it can survive being eroded from the rock where it formed and then deposited in a new, sedimentary rock as the undead remnants of an older, now-vanished landscape.

The carbon-containing siltstone contains zombie zircons, and Whitehouse presented new data on them to the Goldschmidt Conference, dating them to 2.8 billion years ago. Whitehouse argues that these crystals formed in an igneous rock 2.8 billion years ago and then were eroded, washed into the sea, and settled in the silt. So the siltstone must be no older than 2.8 billion years old, he said.

“You cannot deposit a zircon that is not formed yet,” O’Neil explained.

greyscale image of tiny fragments of mineral, with multiple layers visible in each fragment. A number of sites are circled on each fragment.

Tiny recorders of history – ancient zircon crystals from Labrador. Left shows layers built up as the zircon went through many heating events. Right shows a zircon with a prism-like outer shape showing that it formed in igneous conditions around an earlier zircon. Circles indicate where an ion beam was used to measure dates. Credit: Martin Whitehouse

This 2.8-billion-year age, along with the igneous zircon age of 2.7 billion years, brackets the age of the organic carbon to anywhere between 2.8 and 2.7 billion years old. That’s much younger than Komiya’s date of 3.95 billion years old.

Komiya disagrees: “I think that the estimated age is minimum age because zircons suffered from many thermal events, so that they were rejuvenated,” he said. In other words, the 2.8-billion-year age again reflects later heating, and the true date is given by the oldest-dated zircons in the siltstone.

But Whitehouse presented a third line of evidence to dispute the 3.95-billion-year date: isotopes of hafnium in the same zombie zircon crystals.

The technique relies on radioactive decay of lutetium-176 to hafnium-176. If the 2.8-billion-year age resulted from rejuvenation by later heating, it would have had to have formed from material with a hafnium isotope ratio incompatible with the isotope composition of the early Earth.

“They go to impossible numbers,” said Whitehouse.

The only way that the uranium-lead ratio can be compatible with the hafnium in the zircons, Whitehouse argued, is if the zircons that settled in the silt had crystallized around 2.8 billion years ago, constraining the organic carbon to being no older than that.

The new oldest remains of life on Earth, for now

If the Labrador carbon is no longer the oldest trace of life on Earth, then where are the oldest remains of life now?

For Whitehouse, it’s in the 3.77-billion-year-old Isua Greenstone Belt in Greenland: “I’m willing to believe that’s a well-documented age… that’s what I think is the best evidence for the oldest biogenicity that we have,” said Whitehouse.

O’Neil recently co-authored a paper on Earth’s oldest surviving crustal rocks, located next to Hudson Bay in Canada. He points there. “I would say it’s in the Nuvvuagittuq Greenstone belt,” said O’Neil, “because I would argue that these rocks are 4.3 billion years old. Again, not everybody agrees!” Intriguingly, the rocks he is referring to contain carbon with a possibly biological origin and are thought to be the remains of the kind of undersea vent where life could well have first emerged.

But the bigger picture is the fact that we have credible traces of life of this vintage—be it 3.8 or 3.9 or 4.3 billion years.

Any of those dates is remarkably early in the planet’s 4.6-billion-year life. It’s long before there was an oxygenated atmosphere, before continents emerged above sea level, and before plate tectonics got going. It’s also much older than the oldest microbial “stromatolite” fossils, which have been dated to about 3.48 billion years ago.

O’Neil thinks that once conditions on Earth were habitable, life would have emerged relatively fast: “To me, it’s not shocking, because the conditions were the same,” he said. “The Earth has the luxury of time… but biology is very quick. So if all the conditions were there by 4.3 billion years old, why would biology wait 500 million years to start?”

Photo of Howard Lee

Howard Lee is a freelance science writer focusing on the evolution of planet Earth through deep time. He earned a B.Sc. in geology and M.Sc. in remote sensing, both from the University of London, UK.

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Small charges in water spray can trigger the formation of key biochemicals

biochemistry, Biology, chemistry, origin of life, Physics, Science / /

Once his team nailed how droplets become electrically charged and how the micro-lightning phenomenon works, they recreated the Miller-Urey experiment. Only without the spark plugs.

Ingredients of life

After micro-lightnings started jumping between droplets in a mixture of gases similar to that used by Miller and Urey, the team examined their chemical composition with a mass spectrometer. They confirmed glycine, uracil, urea, cyanoethylene, and lots of other chemical compounds were made. “Micro-lightnings made all organic molecules observed previously in the Miller-Urey experiment without any external voltage applied,” Zare claims.

But does it really bring us any closer to explaining the beginnings of life? After all, Miller and Urey already demonstrated those molecules could be produced by electrical discharges in a primordial Earth’s atmosphere—does it matter all that much where those discharges came from?  Zare argues that it does.

“Lightning is intermittent, so it would be hard for these molecules to concentrate. But if you look at waves crashing into rocks, you can think the spray would easily go into the crevices in these rocks,” Zare suggests. He suggests that the water in these crevices would evaporate, new spray would enter and evaporate again and again. The cyclic drying would allow the chemical precursors to build into more complex molecules. “When you go through such a dry cycle, it causes polymerization, which is how you make DNA,” Zare argues. Since sources of spray were likely common on the early Earth, Zare thinks this process could produce far more organic chemicals than potential alternatives like lightning strikes, hydrothermal vents, or impacting comets.

But even if micro-lightning really produced the basic building blocks of life on Earth, we’re still not sure how those combined into living organisms. “We did not make life. We just demonstrated a possible mechanism that gives us some chemical compounds you find in life,” Zare says. “It’s very important to have a lot of humility with this stuff.”

Science Advances, 2025.  DOI: 10.1126/sciadv.adt8979

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Tiny cracks in rocks may have concentrated chemicals needed for life

biochemistry, Biology, chemistry, geology, origin of life, Science / /
Cartoon of a geologically active area, showing sub-surface channels in different colors to represent various temperatures.

Enlarge / Active geology could have helped purify key chemicals needed for life.

Christof B. Mast

In some ways, the origin of life is looking much less mystifying than it was a few decades ago. Researchers have figured out how some of the fundamental molecules needed for life can form via reactions that start with extremely simple chemicals that were likely to have been present on the early Earth. (We’ve covered at least one of many examples of this sort of work.)

But that research has led to somewhat subtler but no less challenging questions. While these reactions will form key components of DNA and protein, those are often just one part of a complicated mix of reaction products. And often, to get something truly biologically relevant, they’ll have to react with some other molecules, each of which is part of its own complicated mix of reaction products. By the time these are all brought together, the key molecules may only represent a tiny fraction of the total list of chemicals present.

So, forming a more life-like chemistry still seems like a challenge. But a group of German chemists is now suggesting that the Earth itself provides a solution. Warm fluids moving through tiny fissures in rocks can potentially separate out mixes of chemicals, enriching some individual chemicals by three orders of magnitude.

Feeling the heat (and the solvent)

Even in the lab, it’s relatively rare for chemical reactions to produce just a single product. But there are lots of ways to purify out exactly what you want. Even closely related chemicals will often differ in their solubility in different solvents and in their tendency to stick to various glasses or ceramics, etc. The temperature can also influence all of those. So, chemists can use these properties as tools to fish a specific chemical out of a reaction mixture.

But, as far as the history of life is concerned, chemists are a relatively recent development—they weren’t available to purify important chemicals back before life had gotten started. Which raises the question of how the chemical building blocks of life ever reached the sorts of concentrations needed to do anything interesting.

The key insight behind this new work is that something similar to lab equipment exists naturally on Earth. Many rocks are laced with cracks, channels, and fissures that allow fluid to flow through them. In geologically active areas, that fluid is often warm, creating temperature gradients as it flows away from the heat source. And, as fluid moves through different rock types, the chemical environment changes. The walls of the fissures will have different chemical properties, and different salts may end up dissolved in the fluid.

All of that can provide conditions where some chemicals move more rapidly through the fluid, while others tend to stay where they started. And that has the potential to separate out key chemicals from the reaction mixes that produce the components of life.

But having the potential is very different from clearly working. So, the researchers decided to put the idea to the test.

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