Life on Earth is a paradox—to function, all organisms need energy. But to harness that energy, living creatures rely on enzymes that have evolved over billions of years to make possible everything from respiration to photosynthesis to DNA repair. So what came first, the enzyme or the organism? A new study suggests that the iron-and-sulfur clusters at the heart of many life-critical enzymes could have been floating around Earth’s primordial seas some 4 billion years ago, produced by nothing more than primitive biomolecules, iron salts, and a previously unknown ingredient—ultraviolet (UV) light.
“It’s intriguing,” says Robert Hazen, a geophysicist who studies interactions between the mineral and living worlds at the Carnegie Institution for Science’s Geophysical Laboratory in Washington, D.C. “[The development of iron-sulfide clusters] was likely an important step in life’s origins.”
Most research into life’s origins has focused on how organic building blocks, like amino acids and nucleic acids, arose and assembled themselves into proteins and RNA. Less studied is the genesis of iron-sulfur clusters, the active core in enzymes that drive almost every aspect of cellular chemistry. Genetic analysis suggests they’ve been around at least since the time of our last common ancestor. “I’ve never seen an organism that doesn’t depend on them,” says Sheref Mansy, a biochemist at the University of Trento in Italy who led the new work.
But modern metabolic reactions are carefully calibrated inside living cells, in the presence of oxygen. Neither condition would have existed on Earth without life.
To find out whether iron-sulfur clusters were a core ingredient for life from the start—or whether the first organisms got along fine without them—Mansy and his team recreated the conditions of early Earth in their lab. University of Trento biochemist Claudia Bonfio removed oxygen and mixed together a brew of iron and glutathione, a sulfur-containing peptide likely present in the prebiotic chemical soup. When the iron was in an oxidation state that predominated on early Earth, iron (II), nothing happened. But when Bonfio flicked on the lights, a transformation took place.
“After a few minutes you could start to see the formation of iron-sulfur clusters,” she says. In the presence of UV light, the solution went from violet to red, indicating that the iron and sulfur were reacting. “And if you waited longer,” she says, “more complex clusters formed that gave the solution a brown color.” The light was simultaneously freeing sulfur atoms from the peptides and oxidizing the iron—turning it into a form, iron (III), that could readily interact with the sulfur, the team reports this week in Nature Chemistry.
The team then tested more than 30 other potential compounds under different conditions, and found that the reactions also worked with simpler sulfur-containing molecules. Some of them even worked inside fatty acid vesicles, a laboratory stand-in for protocells. In most cases, the process was “strikingly similar” to the way iron-sulfur clusters synthesize in modern living cells, the authors write.
It makes sense, says Mansy, that sunlight would play a role in early iron-sulfur synthesis. That’s because Earth lacked an ozone layer to protect it from UV light—which was far more intense 4 billion years ago than it is now. What’s more, lakes all over young Earth would have hosted mineral-rich stews similar to those in the experiment. That’s particularly true for those inside volcanic craters and impact areas, where water moving through fractured rocks could bring iron to the surface, says Jack Szostak, a Harvard University molecular biologist who also took part in the work. Indeed, a paper by co-author John Sutherland—a chemist at the Medical Research Council Laboratory for Molecular Biology in Cambridge, U.K.—suggests that all the basic chemicals for life can be cooked up in a water-filled impact crater.
But Mansy himself is cautious about the new work’s significance. Showing that something can happen in the lab is different from saying that it did happen, he emphasizes. “This reaction only becomes truly important if we can show that there is some kind of selective advantage to the network of chemicals involved.” If that’s the case, it could begin to explain how nonliving chemistry generated reactions that eventually evolved into living systems. But discovering the exact sequence of events that gave life its spark may be forever lost behind time’s horizon, Hazen warns. “Like so many chemical experiments pitched as ‘origins of life’ contributions, [this] is more suggestive than definitive.”