Chemists may be zeroing in on chemical reactions that sparked the first life

DNA is better known, but many researchers today believe that life on Earth got started with its cousin RNA, because that nucleic acid can act as both a repository of genetic information and a catalyst to speed up biochemical reactions. But those favoring this “RNA world” hypothesis have struggled for decades to explain how the molecule’s four building blocks could have arisen from the simpler compounds present during our planet’s early days. Now, chemists have identified simple reactions that, using the raw materials on early Earth, can synthesize close cousins of all four building blocks. The resemblance isn’t perfect, but it suggests scientists may be closing in on a plausible scenario for how life on Earth began.

RNA’s four building blocks are called nucleotides. Each is composed of ribose, a ring-shaped sugar molecule, connected to one of four different ring-shaped “bases,” adenine (A), guanine (G), cytosine (C), and uracil (U). C and U are structurally similar to each other and collectively known as pyrimidines, whereas A and G resemble each other and are known as purines. In 2009, researchers led by Matthew Powner and John Sutherland at the Medical Research Council in Cambridge, U.K., came up with the first plausible chemical reactions that could have synthesized pyrimidines on early Earth. But very different reactions, in different conditions, seemed necessary to make purines. That begged the question of how all four nucleotides could have wound up in the same place to give rise to the first “living” RNA molecules.

Powner, who moved to University College London in 2012, and colleagues have now found a way to extend their earlier pyrimidinemaking chemistry to create purine cousins. As before, they start with a simple sugar called an aldehyde, thought to have been present on early Earth. A handful of simple steps transformed the aldehyde into two compounds resembling adenine- and guanine-containing nucleotides, they report today in Nature Communications . The resemblance wasn’t perfect: In the base of each, a carbon atom was bound to an oxygen atom instead of a hydrogen atom as in the familiar purines.

“It’s nice chemistry,” says Nicholas Hud, an RNA chemist at Georgia Institute of Technology in Atlanta. However, he says, that wayward oxygen atom is a key stumbling block. There’s no simple way to exchange it for hydrogen. And the unconventional purines might have been unable to form RNA analogs with the properties needed to spark life. Powner says he and his colleagues are now looking for solutions. If they succeed, the path from simple chemicals to life will be a whole lot clearer.