Chemists at UCL have shown how two of biology's most fundamental ingredients, RNA (ribonucleic acid) and amino acids, could have spontaneously joined together at the origin of life four billion years ago.
Amino acids are the building blocks of proteins, the "workhorses" of life essential to nearly every living process. But proteins cannot replicate or produce themselves – they require instructions. These instructions are provided by RNA, a close chemical cousin of DNA (deoxyribonucleic acid).
In a new study, published in Nature, researchers chemically linked life's amino acids to RNA in conditions that could have occurred on the early Earth – an achievement that has eluded scientists since the early 1970s.
Senior author Professor Matthew Powner, based at UCL's Department of Chemistry, said: "Life relies on the ability to synthesise 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.
"Life today uses an immensely complex molecular machine, the ribosome, to synthesise 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."
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 theorised to play a role at the start of life*.
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."
In order to form these thioesters, the amino acids react with a sulphur-bearing compound called pantetheine. Last year, the same team published a paper demonstrating pantetheine can be synthesised under early Earth-like conditions, suggesting it was likely to play a role in starting life.
The next step, the researchers said, was to establish how RNA sequences could bind preferentially to specific amino acids, so that RNA could begin to code 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 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.
"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.
"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).
The work was funded by the Engineering and Physical Sciences Research Council (EPSRC), the Simons Foundation and the Royal Society.
*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.
** 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 on to the RNA, they could synthesise with other amino acids to form peptides.
