Chemists Have Replicated a Critical Moment in The Creation of Life

The laboratory may finally have captured the spontaneous coming-together of molecules that ultimately gave rise to life on primordial Earth around 4 billion years ago.

By recreating conditions thought to resemble those on our young planet, chemists have managed to connect RNA and amino acids - a foundational early step on the path to the abundance of living organisms now found across Earth.

This experimental result could shed fresh light on one of biology’s most fundamental partnerships: the relationship between nucleic acids and proteins.

RNA, amino acids, and the origin of protein synthesis

"Life today uses an immensely complex molecular machine, the ribosome, to synthesize proteins. This machine requires chemical instructions written in messenger RNA, which carries a gene's sequence from a cell's DNA to the ribosome. The ribosome then, like a factory assembly line, reads this RNA and links together amino acids, one by one, to create a protein," explains chemist Matthew Powner of University College London.

"We have achieved the first part of that complex process, using very simple chemistry in water at neutral pH to link amino acids to RNA. The chemistry is spontaneous, selective, and could have occurred on the early Earth."

It is clear that life emerged from Earth’s early chemical mix - we exist as proof - yet researchers remain far less certain about how that transition happened. One increasingly supported idea is the RNA world hypothesis, which proposes that RNA acted as a self-replicating nucleic acid and, because it can also carry out mechanical work, could catalyse additional chemical reactions.

Proteins, by contrast, cannot replicate themselves; the precise order of their amino acids is specified by sequences of nucleic acid such as RNA.

That means that although proteins are essential across biology, nucleic acids provide the indispensable template that enables proteins to be produced. Even so, for life to get going, these two molecular players still had to find a way to connect under the wet, hot conditions of early Earth.

"Life relies on the ability to synthesize proteins – they are life's key functional molecules. Understanding the origin of protein synthesis is fundamental to understanding where life came from," Powner says.

"Our study is a big step towards this goal, showing how RNA might have first come to control protein synthesis."

Why earlier RNA–amino acid experiments struggled

Scientists have repeatedly tried to mimic the natural merging of amino acids and RNA. Doing so typically demands a high-energy mediator, and earlier work has shown that certain highly reactive compounds are ill-suited because they tend to degrade in water. When that happens, amino acids are more likely to react with one another instead of attaching to RNA.

Thioester chemistry in a simulated primordial organic soup

Under the leadership of chemist Jyoti Singh of University College London, the team instead looked to biology for inspiration. They tested a thioester as the mediator - a high-energy, highly reactive compound made of carbon, oxygen, hydrogen and sulfur, four of the six elements believed to be crucial for life.

Thioesters are already known to serve as important intermediates in some biological processes, and they are thought to have been common in the “primordial organic soup”. Some researchers argue that widespread thioesters may have come before the RNA world, an idea referred to as the thioester world hypothesis.

In their laboratory version of an organic soup, the scientists found that the thioester supplied the external energy required for an amino acid to bond to RNA - a notable advance that also links the two competing frameworks.

"Our study unites two prominent origin of life theories – the 'RNA world', where self-replicating RNA is proposed to be fundamental, and the 'thioester world', in which thioesters are seen as the energy source for the earliest forms of life," Powner says.

What still needs to be shown

Even with this progress, a full, detailed account of how life began remains a long way off. The new findings indicate that these components can indeed be brought together when a high-energy mediator is present; the next question is whether RNA will preferentially attach to particular amino acids in a way that could have helped genetic code emerge.

"Imagine the day that chemists might take simple, small molecules, consisting of carbon, nitrogen, hydrogen, oxygen, and sulphur atoms, and from these Lego pieces form molecules capable of self-replication. This would be a monumental step towards solving the question of life's origin," Singh says.

"Our study brings us closer to that goal by demonstrating how two primordial chemical Lego pieces (activated amino acids and RNA) could have built peptides, short chains of amino acids that are essential to life."

The research has been published in Nature.