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The origin of life on Earth explored at MRC LMB in Cambridge using a flask and a lamp

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It’s not every week that our understanding of how life began on planet Earth is changed.

But armed with some flasks and a UV lamp, scientists at the MRC Laboratory of Molecular Biology in Cambridge have wound the clock back billions of years to give us fresh insight into one of the most fundamental questions facing humankind.

How did life begin on Earth?
How did life begin on Earth?

Their work suggests that DNA could have been around with RNA from the beginning, helping to carry the genetic code essential for the emergence of life.

“The best models show that the Earth is about 4.5 billion years old and there is evidence for life about four billion years ago,” says Dr Nicholas Green, who was part of the team delving into the primordial soup for answers.

In this early, somewhat inhospitable environment, surface temperatures are believed to have ranged from zero to 100 degrees or more, and the atmosphere featured much less oxygen and much more carbon dioxide than today.

A lack of ozone meant far higher levels of UV radiation reached the surface of the planet, which was also struck by a barrage of meteorites.

“We are getting better and better models of what the Earth was like,” Nick tells the Cambridge Independent. “That’s part of the reason why origins research is really interesting at the moment. We use information from planetary scientists and geochemists in our research. They tell us what kind of conditions were probably around in the early Earth.

“This information is gathered by looking not only at the Earth but other planets in the solar system or the other systems that we are learning about now.

“We can also deduce something about what conditions would have been like by looking at biology as well. If biology did originate on Earth, then that imposes some conditions on the chemical reactions that would have happened, and therefore we can make some inferences about what the Earth must have been like.”

The first complex organisms emerged in the oceans in a burst of activity called the Cambrian explosion – provoked by changing environmental conditions – some 540 million years or so ago. Dinosaurs didn’t turn up until about 230 million years ago.

This is the recent past compared to the period that Nick – along with Jianfeng Xu, Václav Chmela and David Russell, all from John Sutherland’s group at the LMB, and others, including theoreticians led by Rafal Szabla at Edinburgh University – have been attempting to illuminate.

Prof John Sutherland's group at the MRC LMB. Picture: MRC Laboratory or Molecular Biology
Prof John Sutherland's group at the MRC LMB. Picture: MRC Laboratory or Molecular Biology

Their interest lies in how the first building blocks of life emerged – the primitive genetic code, or alphabet, that was essential for the evolution and development of all future life.

“Francis Crick was the first to postulate the central dogma, which basically explains biology. The central dogma says DNA is transcribed into RNA, which is then translated into protein,” says Nick.

“Origin of life studies have to focus on the synthesis of those three key classes of molecules, as well as membrane-type molecules, which encapsulate what is happening in the central dogma.”

Significant debate surrounds the origin of life question, and the nature of the first genetic polymer.

“In the 1950s, Stanley Miller was famously able to show that many simple biological molecules could be made by planetary-type processes.

“But the nucleic acids RNA and DNA are a lot more difficult to make than, for example, the amino acids that he was able to make,” explains Nick. “Since they are so difficult, people assumed it would be much simpler to make just one.

“In the 1980s, a lot of evidence started to emerge that RNA could do what DNA does and more, meaning it could fulfil the role in the central dogma that DNA now plays – that is, it could provide genetic information storage as well as performing catalysis, and other functions.”

And so the ‘RNA world theory’, suggesting RNA was the sole genetic polymer at the dawn of life, became the prevailing view for the last 40 years or more.

“The term was coined in the 1980s, and there has been a lot of study into RNA and all the amazing things it can do by itself since then,” says Nick.

The idea that DNA was around from the beginning has also been postulated, but it has remained in the shadow of the RNA world theory.

“But if you look at the structures of RNA and DNA, they are very similar, so in some ways it makes sense that if you have one, you would also have the other,” Nick notes. “There is certainly an attractiveness to the theory that the way biology works now is probably the way it started. We can’t take away DNA from biology now, so in some ways it is compelling that it was around from the very beginning, as well as RNA.”

RNA and DNA synthesising in sunlight on the early Earth. Illustration: MRC Laboratory of Molecular Biology
RNA and DNA synthesising in sunlight on the early Earth. Illustration: MRC Laboratory of Molecular Biology

How, though, can researchers recreate the conditions of primordial Earth in the lab to explore these theories?

“It’s important to distinguish between the models we are making and the actual chemistry that would have happened in pools, on surfaces, around volcanoes – that chemistry would have happened over tens of thousands of years. Obviously, we can’t do that…” says Nick. “Our reactions are done in flasks in a laboratory.”

Mercury lamps that give off UV light were used for a key photoreduction step of the team’s experiments. This simulated the early Sun’s output reaching Earth’s surface, driving key reactions essential for the origin of life.

They dissolved the reactants in water, then dried them down and heated them. This mixture was dissolved in water before being irradiated with UV light, to simulate conditions on our rocky planet.

“Last year, in Nature Chemistry we reported how we’d discovered there could be a pre-biological link between RNA and DNA,” Nick explains.

“The structures are quite similar and in modern biology RNA is converted into DNA, but of course today you need enzymes to do that.

“What we found is that you can use this UV light to convert a sulphur-containing RNA molecule into a DNA molecule.

“We’ve now shown you can do that very efficiently. What’s critically important is you can do that reaction in the presence of RNA that has already been made by similar processes. If these processes are compatible and are proceeding from the same intermediate, then it’s very likely that if these conditions were prevailing in some parts of the early Earth that in certain environments you’d have not only RNA but also DNA.”

Nick suggests that the most surprising aspect of the work was how selective the reaction was.

“That is probably the most indicative aspect that it might be relevant to the origin of life,” he says. “When we did this reaction, it was completely selective to the type of isomers you see in modern biology. We don’t have any of the ‘junk’ you might expect many synthesis to end up with.”

The research, published in Nature, did not cover the replication of genetic material.

“This is just the beginning of looking at this type of mosaic nucleic acid. We’ve made the monomers in our study, but there’s still a long way to go to show they can combine in a plausible way to form the polymers that we know code information.

“We will be looking at combining our monomers into larger polymers and seeing how their properties might link to properties we see in modern biology.”

Beginning with a mixed RNA-DNA nucleic acid streamlines the eventual ‘genetic takeover’ of homogeneous DNA from RNA as the principal information storage molecule in the central dogma. But what will this genetic material have been carried in?

“That’s another pressing question. People have different opinions but it comes back to the idea that biology probably started in a similar way to the way it works now. That is, in contrast to trying to reduce it to separate elements, you probably had a little bit of everything going on.

The MRC Laboratory of Molecular Biology on the Cambridge Biomedical Campus. Picture: Keith Heppell
The MRC Laboratory of Molecular Biology on the Cambridge Biomedical Campus. Picture: Keith Heppell

“There probably were molecules that served to compartmentalise the active pieces of RNA, DNA and amino acids that were functioning in a biological sense,” says Nick.

At what stage do we consider these molecules alive?

“To answer that question, we need a definition of life. And that’s something that scientists still can’t agree on,” acknowledges Nick.

“Probably the best way is to think about the origins of life, rather than as a yes or no question, is as a spectrum. The earlier you go, the more towards the non-living end of the spectrum you end up. At some stage, you cross over into the living side of the spectrum, but exactly where is hard to say.”

Further questions surround whether the central dogma at the heart of biology could evolve further or differently – a question pertinent to the search for life elsewhere in the universe.

“Is the biology we have now perfect? Can it be improved? Is it a goldilocks scenario whereby only the combination of chemicals and monomers and polymers can work in the way it does? Or is it a chance event? Perhaps on other planets, something else happened. We only have one data point – life on Earth,” notes Nick. “Synthetic biology is working on that problem and there are some exciting things happening in that regard with artificial life.”

Prof Sutherland , who is a group leader in the PNAC Division, adds: “The nucleic acids, RNA and DNA, are clearly related and this work suggests that they both derive from a hybrid ancestor rather than one preceding the other. Guided by Crick’s central dogma, we now need to uncover how the sequential information which can be stored and purveyed by these nucleic acids was first transferred to proteins.”

The research was funded by UKRI MRC, the Simons Foundation, the National Science Centre Poland, the Polish Ministry of Science and Higher Education, and the Wrocław Centre of Networking and Supercomputing.

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