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A New Study Points to Two Origins of Life on Earth by Tracing Early Chemical Reactions in Single-Celled Organisms
The work challenges the assumption that all life descended from one free-living cell. Instead, it suggests that two microbial lineages, the bacteria and archaea, evolved independently from a primordial, nonliving ancestor
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Among biologists, few questions have been debated as fiercely as the origin of life. How did self-sustaining organisms, capable of transforming molecules to capture energy, arise on the primitive Earth?
Before any cells existed, scientists suspect chemical reactions occurred around deep-sea hydrothermal vents, where heat and high pressures led to spontaneous chemistry that was sped up, or catalyzed, by metals in Earth’s crust. One possibility for the origin of life is that, over time, these relatively simple geochemical reactions evolved into the reactions that create the building blocks of life.
Living creatures rely on a core network of about 400 metabolic reactions that are catalyzed by proteins known as enzymes. This “core metabolism” creates energy and makes key materials for cells, like nucleic acids, amino acids and vitamins.
Now, a team of researchers has retraced the steps for how this essential metabolic network was assembled, in a paper published today in Science Advances. One of their most striking findings: Life on Earth likely evolved not once, but twice.
“This just opens up a whole lot of questions, in terms of what is alive, what is life, what is possible, and what we might find elsewhere,” says senior author William Martin, an evolutionary biologist at the University of Düsseldorf in Germany.
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All organisms alive today descend from the last universal common ancestor (LUCA) that likely dwelled in the early oceans. This mysterious ancestor, the new study suggests, was still reliant on its environment to conduct metabolism. Rather than fueling its energy-producing reactions on its own with enzymes, LUCA depended on small organic molecules and metals in the environment to conduct about half of the core metabolic reactions, the researchers found. Then, over time, some of these metals were replaced with more specific and efficient enzymes as the proteins evolved to do the same jobs.
“What’s so cool about this is we’re probing a phase of evolution where new enzyme activities are still arising, replacing geochemical reactions, and giving rise to coalescence of metabolism in the ancestors of archaea and bacteria,” Martin says.
Archaea and bacteria are two of the three domains of life, and these microbes arose early in Earth’s history. The third domain, eukaryotes—the one that animals, plants and all organisms with nucleus-containing cells belong to—evolved later, from a hybrid of the first two groups.
For many years, scientists contemplated three possible scenarios for the origin of life: Either bacteria evolved from archaea, archaea evolved from bacteria, or both independently evolved from LUCA. The new study makes the argument that the last possibility is the most likely one.
Quick fact: Archaea and bacteria
While bacteria live in diverse environments, archaea thrive under extreme conditions, like high heat and acidity.
Scientists can illuminate how bacteria and archaea emerged by comparing when their ancestors evolved certain traits and pinning down which of those traits might have been inherited from LUCA. Earlier work did this with ribosomes, the parts of a cell that produce proteins. It showed that LUCA had primitive ribosomes that were composed of 33 proteins. Then, from LUCA, the bacterial lineage evolved 21 unique ribosomal proteins, while the archaeal lineage evolved 29 unique ribosomal proteins. Each lineage, in essence, independently continued tweaking and enhancing how its ribosomes worked.
For their latest investigation focused on reconstructing metabolism, Martin’s team took a similar approach. This time, they examined the genes for metabolic enzymes in modern bacteria and archaea to reconstruct their evolutionary history. Just as some elements of the ribosome were universal across the two groups, while each lineage also evolved its own ribosomal proteins, “we realized, looking at our metabolic genes, that this is a similar pattern,” says lead author Natalia Mrnjavac, a graduate student in Martin’s lab.
They first worked to narrow down which enzymes LUCA was using and which of its metabolic reactions required metals from the hydrothermal vents. The team reasoned that each reaction in this primitive metabolism either used elements available in the environment or elements generated by other reactions in the system. Over time, these reactions could build on the previous ones, leading to new biochemical possibilities and an increasingly complex metabolic network. The key was to identify which metabolic reactions had to come first and which subsequent ones depended on which others.
It sounds like it would be hard, with hundreds of reactions, to work out the sequence in which they developed, says Mike Steel, a mathematician at the University of Canterbury in New Zealand and a co-author of the study. “But it turns out there’s a fast algorithm for doing this.”
The team then found that bacteria and archaea shared some enzymes with LUCA—but each lineage also had some that were not present in the ancestor. Essentially, bacteria and archaea independently evolved different enzymes to replace the same metal-catalyzed reactions. “This shows the reaction is older than the enzymes that catalyze it,” says University of Ottawa chemist Joseph Moran, a co-author of the study.
These distinct solutions to the same metabolic problems are evidence to Martin that bacteria could not have been derived from archaea, or the reverse. “The simplest interpretation,” he says, “is that there were two independent transitions” from LUCA to free-living cells.
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Not all researchers agree on this description of LUCA. Some have proposed that LUCA was a more complex cell with simple membranes that were perhaps made of a mix of archaeal and bacterial fats, or lipids. Then, this blended ancestor would have eventually diverged into the archaeal and bacterial lineages in only one origin of free-living cellular life, explains protein crystallographer and origin of life researcher Juan Fontecilla-Camps of the Institute of Structural Biology in France, who was not involved with the new study.
But Martin argues that this complexity is unlikely: Bacteria and archaea use distinct methods for making the lipids in their cell membranes, he says, so they probably didn’t both inherit those mechanisms from LUCA. “They really are totally different,” adds Sonja-Verena Albers, who studies the biology of archaea at the University of Freiburg in Germany and was not involved in this work. “You need a totally different setup of genes or enzymes to make the different lipids.”
Based on its metabolism, too, Martin argues that LUCA was a simpler ancestor—something not completely alive. “There can be no question that free-living cells are alive,” says Martin, referring to cells that are capable of growing, dividing and surviving on their own. “We can all agree on that.” But LUCA was still reliant on small organic molecules and metals in the Earth’s crust to carry out metabolism. When it comes to being classified as truly alive, “that’s not going to cut the mustard,” he says.
Martin has long argued that metals were the original catalysts for metabolic reactions, and that over time, those metals were replaced by enzymes. “There’s strong support for the idea that geochemistry would have led to life’s biochemistry,” says Donato Giovannelli, a microbiologist at the University of Naples Federico II in Italy who studies the origin of life.
For instance, many enzymes have metals in their catalytic sites, where the chemical reactions occur. And in the last several years, Martin, Moran, biochemist Martina Preiner and their colleagues have shown experimentally that many of the reactions used in core metabolism today can indeed proceed when they swap enzymes out for metals, suggesting that they could have been catalyzed by metals before those enzymes evolved.
One of the most important metabolic reactions creates the energy-carrying molecule of cells, essentially a tiny battery that powers them. Today, this molecule is primarily ATP, but the primitive oceans did not have ATP for LUCA to use. Martin’s team revealed how, in this ancestor’s primordial metabolism, this key reaction could have been catalyzed by metals: They found that phosphite, a form of phosphorous, could react with organic molecules with the help of palladium, a metal in the platinum group of metals. This reaction allowed LUCA to store energy as ADP, a precursor to ATP.
The ability to transiently store energy was game-changing, because it could power many other metabolic reactions that need an input of energy, such as the formation of peptide bonds between amino acids, or the activity of ribosomes during translation of RNAs into proteins. This reaction paved the way for the shift from geochemical to metabolic reactions and explains how phosphorus became such a central player in our own biochemistry.
“That’s one of the key discoveries in this paper,” says Giovannelli, who was not involved in the new study.
Reconstructing early metabolic networks as the team did in the new paper “is a valid thing to do,” Fontecilla-Camps says. “The question is whether that’s the way it really happened or not. And that’s very difficult to know.”
Giovannelli says that the team has produced “a strong paper that puts forth a different line of thought and brings together things that had not been connected before.” But he suggests thinking about their conclusion as a possible scenario for the origin of life, rather than a definitive answer: “We can reconstruct how plausible things might be, but it’s going to be almost impossible to know exactly how things happened.”