A Simple Spark That May Explain How Life Began

Scientists have recreated a crucial step that may have set life in motion nearly four billion years ago.

By showing how amino acids, the building blocks of proteins, could spontaneously link with RNA under early Earth conditions, researchers have revealed a potential missing link in biology’s origins.

Origins of Life’s Building Blocks

Researchers at UCL have discovered how two essential ingredients of life, RNA (ribonucleic acid) and amino acids, may have naturally combined about four billion years ago at the dawn of life.

Amino acids are the basic components of proteins, which act as the engines of life and drive nearly every biological function. However, proteins cannot copy themselves or generate instructions for their own production. Those instructions come from RNA, a molecule closely related to DNA (deoxyribonucleic acid).

Proteins, RNA, and the Blueprint of Life

In findings published in Nature, the team successfully attached amino acids to RNA under conditions similar to those that might have existed on early Earth. Scientists have been attempting to accomplish this since the early 1970s without success until now.

Professor Matthew Powner, senior author from UCL’s Department of Chemistry, explained: “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.

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

Toward Understanding 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.

“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.”

Simple Chemistry with Big Implications

Previous attempts to attach amino acids to RNA used highly reactive molecules, but these broke down in water and caused the amino acids to react with each other, rather than become linked to RNA.

For the new study, the researchers took inspiration from biology, using a gentler method to convert life’s amino acids into a reactive form. This activation involved a thioester, a high-energy chemical compound important in many of life’s biochemical processes and that has already been theorized to play a role at the start of life.^[1]

Professor Powner said: “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.”

Bridging Competing Origin Theories

To form these thioesters, the amino acids react with a sulfur-bearing compound called pantetheine. Last year, the same team published a paper demonstrating that pantetheine can be synthesized under early Earth-like conditions, suggesting it was likely to play a role in the origin of life.

The next step, the researchers said, was to determine how RNA sequences could bind preferentially to specific amino acids, allowing RNA to begin coding instructions for protein synthesis—the origin of the genetic code.

“There are numerous problems to overcome before we can fully elucidate the origin of life, but the most challenging and exciting remains the origins of protein synthesis,” said Professor Powner.

Lead author Dr. Jyoti Singh, from UCL Chemistry, said: “Imagine the day that chemists might take simple, small molecules, consisting of carbon, nitrogen, hydrogen, oxygen, and sulfur 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.

“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,^[2] short chains of amino acids that are essential to life.

“What is particularly groundbreaking is that the activated amino acid used in this study is a thioester, a type of molecule made from Coenzyme A, a chemical found in all living cells. This discovery could potentially link metabolism, the genetic code, and protein building.”

While the paper focuses solely on the chemistry, the research team said that the reactions they demonstrated could plausibly have taken place in pools or lakes of water on the early Earth (but not likely in the oceans, as the concentrations of the chemicals would likely be too diluted).

The reactions are too small to see with a visible-light microscope and were tracked using a range of techniques that are used to probe the structure of molecules, including several types of magnetic resonance imaging (which shows how the atoms are arranged) and mass spectrometry (which shows the size of molecules).

Notes

1. The Nobel laureate Christian de Duve proposed that life began with a “thioester world” – a metabolism-first theory that envisages life was started by chemical reactions powered by the energy in thioesters.
2. Peptides typically consist of two to 50 amino acids, while proteins are larger, often containing hundreds or even thousands of amino acids, and are folded into a 3D shape. As part of their study, the research team showed how, once the amino acids were loaded onto the RNA, they could be synthesized with other amino acids to form peptides.

Reference: “Thioester-mediated RNA aminoacylation and peptidyl-RNA synthesis in water” by Jyoti Singh, Benjamin Thoma, Daniel Whitaker, Max Satterly Webley, Yuan Yao and Matthew W. Powner, 27 August 2025, Nature.
DOI: 10.1038/s41586-025-09388-y

The work was funded by the Engineering and Physical Sciences Research Council (EPSRC), the Simons Foundation and the Royal Society.

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