New theory on the origins of life on Earth
Active vents on the ocean floor, such as this approximately 30-meter-tall vent located in the Lost City hydrothermal field in the Atlantic Ocean, rapidly produce simple organic molecules that may have played a key role in the appearance of life on Earth.
According to some scientists, metabolism could have arisen spontaneously: a controversial theory that could change the very definition of life on our planet.
Markus Ralser never intended to study the origin of life. His research focused on how cells feed themselves, and how these processes can malfunction in stressed or diseased organisms. But about ten years ago, by pure chance, Ralser and his team made a surprising discovery.
The group, then based at the University of Cambridge, were studying glycolysis, a process by which sugar is broken down through a series of chemical reactions, releasing energy which can then be used by cells. When they used sensitive techniques to track the many steps in this process, they were surprised to find that some reactions seemed to "happen spontaneously", says Ralser, who is now based at the Francis Crick Institute in London . In control experiments in which some of the molecules needed for chemical reactions were not present, parts of the process of glycolysis still occurred.
"That can't be true," other scientists then replied to Ralser.
Every living cell has some sort of chemical engine within it. This is just as true for a neuron in a human brain as it is for the simplest of bacteria. These chemical motors power metabolism, that is, all the processes that transform a source of energy such as food into useful elements and thus build cells. Obviously, metabolic processes, including glycolysis, require a sophisticated microscopic system to function. But Ralser's team found that one of these motors was able to function on its own, in the absence of many of the complex molecules the scientists thought were necessary.
Since this fortuitous discovery, a wave of enthusiasm has taken hold of researchers who study the origins of life. After all, if it could have happened in a test tube, maybe it also happened billions of years ago in a volcanic vent on the high seas, in hot springs on Earth, or in any other place with a lot of chemical activity and organic matter. It could even be that metabolic reactions initiated the chain of events that led to the birth of life on our planet.
Some teams are now working to make these chemical engines from scratch. In addition to glycolysis, the scientists recreated parts of other fundamental cellular processes, including the reverse citric acid cycle, or reverse Krebs cycle , which is believed to have first appeared in very ancient cells.
This fascinating new area of research is causing scientists to rethink the steps that could have led to the creation of the first living organism, and forcing them to confront once again a long-standing question: how do we define life?
ENIGMATIC ORIGINS
The origin of life is one of science's greatest mysteries . We know that this phenomenon occurred early in the history of our planet, because fossils of microorganisms have been discovered in rocks dating back 3.5 billion years , only a billion years later. the formation of the Earth. What remains unclear, however, is how and where this happened.
One of the main problems is that living organisms are incredibly complicated. Even the simplest bacterial cell has hundreds of genes and thousands of different molecules. All of these elements work with each other in a kind of complex dance: they bring food into the cell and evacuate waste, repair damage, copy genes, and much more.
A study published in 2021, which compares the DNAs of 1,089 bacteria , which are the simplest living organisms, illustrates the extent of this complexity. The researchers, led by bioengineer Joana C. Xavier , who was then at the Heinrich Heine University of Düsseldorf in Germany, searched for families of proteins common to all species of bacteria, likely to be very old, dating back over three billion years to the last common ancestor of all bacteria. They found 146 families of such proteins, which revealed that the first bacteria were already extremely complex, and the product of a long period of evolution.
Lakes rich in carbonates and phosphorus, such as Mono Lake in California, would have been common on early Earth, possibly providing an environment for the formation of life.
All hypotheses about the origin of life try to put all this complexity aside and imagine something much simpler, which could have happened spontaneously. The difficulty is determining what this proto-life would have looked like. What parts of the living cells we know today were the first to form?
Many ideas have been put forward to answer this question, including that of a molecule capable of copying itself, such as a strand of RNA, or even that of a "bubble" or a "droplet". » fat which could have played a role of structure within which a cell could have formed. However, more and more scientists believe that, even before the existence of genes or cell walls, the very first thing that life needed to exist was an engine.
THE FIRST METABOLISM
Life is, in essence, active. Even in seemingly constant organisms like trees, there is intense activity taking place at the microscopic level.
Xavier, who is now based at University College London, compares a living cell to a cup of water with a hole in the bottom and placed under an open tap. If the two flows are equal, the volume of water contained in the cup always remains the same, “but a transformation takes place permanently. »
In the same way, all living beings absorb nutrients which they use to build and repair their bodies. For humans, this involves ingesting food and then using our digestive system to break it down and turn it into simple chemicals, which can then be used by our bodies.
Other organisms get their energy from sunlight or chemicals like methane, but the principle is the same. Thousands of reactions are constantly transforming one substance into another, and bringing what is needed, where it is needed. All these processes make up the metabolism of an organism. If a metabolism stops working, the organism dies.
The chemistry of metabolism is so fundamental to life that many researchers believe it was arguably central to the very first living cells. According to them, once a metabolic engine was launched, it could have created other substances necessary for life and, little by little, the cells would have assembled themselves, explains Joseph Moran of the University of Strasbourg.
However, all theories that believe metabolism is what created life have a common problem: metabolism, like life, is extremely complex. In Xavier's study of the oldest common ancestor of bacteria, the scientist estimated that the genes of this ancient organism could produce 243 chemicals through metabolic processes, but also transform them into each other.
Even the individual metabolic pathways are complex. This is for example the case of the citric acid cycle, or Krebs cycle, which is one of the ways in which cells can extract energy from nutrients. As the name suggests, the cycle begins with citric acid, the chemical that gives citrus fruits their pungent taste. This is transformed into a second substance, cis-aconitic acid, then into seven other substances before the last step recreates citric acid. During this process, biochemicals are produced and distributed to the rest of the cell.
It's hard to imagine how such a complex process could have started on its own. To complicate matters further, each step is controlled by a molecule, called an enzyme, which speeds up the chemical reactions in question. For a process like the Krebs cycle to work, enzymes are needed. But enzymes are complicated molecules that can only be made by metabolism, which is controlled by genes.
Scientists therefore face a biochemical version of the chicken-or-egg dilemma. Which came first: the chemical engine that creates the cell, or the cellular mechanisms that create the engine?
Precambrian stromatolites in the Siyeh formation. In 2002, William Schopf claimed that these formations were 3.5 billion years old, so they would be the oldest traces of life on Earth.
RECREATING THE ENGINES OF LIFE
After making their first discovery in the early 2010s, Ralser and his team decided to study more precisely the metabolic reactions that could work on their own. They dissolved in pure water, each on their own, twelve different chemicals that are used during glycolysis. They then heated the samples to 70°C for five hours, mimicking conditions around an underwater volcano. Seventeen chemical reactions, originating from glycolysis or a related metabolic pathway, began to occur during the experiments.
Ralser then contacted Alexandra Turchyn , a geochemist at Cambridge University, who gave him a list of chemicals believed to have been dissolved in the primordial ocean, including metals like iron and sodium. The team added them to their mixes to see if they made reactions work better.
“Only one worked: iron,” says Ralser. By 2014, they had managed to run twenty-eight reactions, including a full metabolic cycle . The team built on their early results , showing in 2017 that they could perform a sulfate-driven version of the citric acid cycle , and could synthesize glucose from simpler chemicals in a process called gluconeogenesis , although the latter had to be carried out in ice.
The idea of enzyme-free metabolic cycles was later taken up by Moran at the University of Strasbourg, together with his former student Kamila Muchowska . They have made similar advances with other metabolic processes such as the acetyl-CoA pathway , which converts carbon dioxide into acetyl-CoA, one of the most important chemicals in metabolism.
But of the many mechanisms of life, scientists have come back again and again to the reverse citric acid cycle. Some bacteria use this process, which works like the citric acid cycle, but in reverse, to make complex carbon compounds from carbon dioxide and water. And some evidence shows that this process is extremely old.
Like Ralser, Moran and Muchowska used metals such as iron to create chemical reactions in their laboratory. In 2017, they were able to trigger six of the eleven reverse citric acid cycle reactions and, two years later, found additional reactions.
“We never replicated the full cycle,” Moran says. But they are getting close.
NOT QUITE BIOLOGY
Despite their enthusiasm, scientists are split on the possibility of whole cell cycles actually occurring, if they don't have the enzymes to facilitate the process. For Ramanarayanan Krishnamurthy , of the Scripps Research Institute in La Jolla, California, reproducing only certain parts of a cycle is not convincing.
“It's like breaking a glass jar, and saying: the pieces came from the jar, so I can completely rebuild the jar,” he says.
Krishnamurthy and his colleagues try different approaches. "We're disconnecting from biology," he says, because what's happening in cells today isn't a perfect guide to what was happening there billions of years ago. “I'm just going to let the chemistry guide me. »
In 2018, Krishnamurthy's team demonstrated a new metabolic engine that works in two cycles and without enzymes . “We bypass some of the most unstable molecules, some of the most difficult steps that biology is able to do brilliantly with very sophisticated evolved enzymes,” says Krishnamurthy. According to him, the process in question could be an ancient precursor of the inverse Krebs cycle.
More recently, his team attempted to add cyanide, which is thought to have been abundant on prime Earth. Previous research has shown that cyanide was able to produce many chemicals of life due to its high reactivity, but it is uncertain whether it actually played a role in the origin of life, as it is toxic to living organisms. Nonetheless, Krishnamurthy's team showed that cyanide could fire up metabolic motors that resemble certain life functions .
Moran is skeptical of this approach because these reciprocating engines don't make some of the chemicals that are fundamental to life. "I don't understand why anyone would want to do that," he said.
It remains to be seen whether complete versions of all current metabolic cycles could function without enzymes, or whether the very first life had to settle for alternative and simplified versions such as those made by Krishnamurthy.
Current stromatolites in Shark Bay (Australia).
?A LIVE ENGINE
The ability to reproduce the processes of life in simplified forms raises a crucial question: to what extent can we call chemical systems “life”? If a metabolic engine works in a glass vial, is it really alive?
Most scientists would say no. For something to be alive, “we need to have a system complex enough for it to metabolize and replicate,” Ralser explains. A metabolic engine can't do it on its own, but it is a step to something that can.
“No one has really defined what life is,” says Krishnamurthy, and there are so many limits. For example, many definitions of life state that an organism must be able to reproduce, but sexual animals cannot reproduce without a partner: therefore, if we follow these definitions to the letter, a rabbit alone n is not alive.
“Everything between the non-living and the living is a gradient,” Muchowska says. Metabolic engines are not totally inanimate like rocks, nor are they totally alive like bacteria.
Life, in a sense, is a sort of chemical accident, a swirling dance that hasn't stopped for over 3.5 billion years. However we define it, this dance continues, slowly perfecting the biological system that has created the myriad and wondrous forms of the Earth.
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