How RNA got started

Scientists may have figured out the chemistry that sparked the beginning of life on Earth.

The new findings map out a series of simple, efficient chemical reactions that could have formed molecules of RNA, a close cousin of DNA, from the basic materials available more than 3.85 billion years ago, researchers report online May 13 in Nature. 

“This is a very impressive piece of work — a really excellent analysis,” comments chemist James Ferris of the Rensselaer Polytechnic Institute in Troy, N.Y.

The new research lends support to the idea that RNA-based life-forms were the first step toward the evolution of modern life. Called the RNA world hypothesis, the idea was first proposed some 40 years ago. But until now, scientists couldn’t figure out the chemical reactions that created the earliest RNA molecules.

Today, DNA encodes the genetic blueprint for life — excluding some viruses, for those who consider viruses living — and RNA acts as an intermediary in the process, making protein from DNA. But most scientists think it’s unlikely that DNA was the basis of the origin of life, says study coauthor John Sutherland of the University of Manchester in England.

Information-bearing DNA holds the code needed to put proteins together, but at the same time, proteins catalyze the reactions that produce DNA. It’s a chicken-or-egg problem. Scientists don’t think that DNA and proteins could have come about independently — regardless of which came first — and yet still work together in this way.

It’s more plausible that the first life-forms were based on a single molecule that could replicate itself and store genetic information — a molecule such as RNA (SN: 4/7/01, p. 212). RNA world proponents speculate modern DNA and proteins evolved from this RNA-dominated early life, and RNA in cells today is left over from this early time.

While reactions to make RNA from ancient precursors worked on paper, the chemistry didn’t work in the lab. And some scientists thought even RNA molecules were too complex to have spontaneously formed in the primordial soup. Sutherland and his colleagues have shown the reactions are possible.

RNA molecules are formed from three components: a sugar, a base and a phosphate group. In past research, chemists developed each of the components and then tried to put them together to make the complete molecule. “But the components are quite stable, and so they wouldn’t stick together,” Sutherland says. “After 40 years of trying, we decided there had to be a better way of doing this reaction.”

The team took a different approach, starting with a common precursor molecule that had a bit of the sugar and the base. “Basically, we took half a base, added that to half a sugar, added the other piece of base, and so on,” Sutherland says. “The key turned out to be the order that the ingredients are added and the way you put them together — like making a soufflé.”

Another difference is that Sutherland and his team added the phosphate to the mix earlier than in past experiments. Having the phosphate around so early helped the later stages of the reaction happen more quickly and efficiently, the scientists say.

The starting materials and the conditions of the reaction are consistent with models of the geochemistry of an early Earth, the team says.

“But while this is a step forward, it’s not the whole picture,” Ferris points out. “It’s not as simple as putting compounds in a beaker and mixing it up. It’s a series of steps. You still have to stop and purify and then do the next step, and that probably didn’t happen in the ancient world.”

Sutherland and his team can so far make RNA molecules with two different bases, and there are still another two bases to figure out. “It’s related chemistry,” Sutherland says. “That’s how it must have been in the very beginning — a series of fundamental reactions that could make all four types of RNA molecule.”

Once those RNA molecules formed, they would have had to string together to make multiple letters of the code, which could then make proteins. Proteins could then make all the components that make up a cell, and the process would continue from there.