In a laboratory in Barcelona, scientists have discovered something remarkable about what makes a cell come alive. The signals that tell genes to switch on — to produce the proteins that build bones, digest food, or capture light — have remained almost unchanged for 2 billion years, surviving every twist and turn of evolution that led from the first complex cells to humans, trees, and mushrooms today.
But the signals that silence genes? Those are a different story entirely.
Researchers at the Center for Genomic Regulation (CRG) found that the molecular instructions for turning genes off have drifted and diverged over billions of years, with different branches of life inventing their own solutions to the same problem. The team, led by Dr. Arnau Sebé-Pedrós, published their findings in the journal Nature Genetics.
"The cell's instructions for activating genes are essentially the same in a human, a sea anemone and a soil amoeba," Dr. Sebé-Pedrós said. "But the instructions for silencing genes have been continuously evolving since our last common eukaryotic ancestor. Different branches of life have developed different molecular toolkits to do the same thing."
The study represents the broadest comparison ever attempted of how different life forms regulate their genetic instruction manuals. DNA in every cell is wrapped around proteins called histones, and small chemical tags on these proteins act like signposts, telling the cell which genes to read and which to ignore. These tags date back roughly 2 billion years to a single-celled organism known as LECA — the Last Eukaryotic Common Ancestor — the shared ancestor of every plant, animal, fungus, and single-celled organism on Earth.
What made this research possible was a new laboratory technique called iChIP2, developed at the CRG. Previous methods worked well for a handful of well-studied species like humans, mice, fruit flies, and yeast, but the vast majority of life had never had its chromatin — the protein scaffold that controls how DNA is read — mapped at this level. The Barcelona team wanted to change that.
The project began in 2017, when Dr. Sebé-Pedrós and Dr. David Lara-Astiaso, now at the Arc Institute in California, began adapting an existing technique to work across the entire tree of life. "We wanted to map epigenetic states in scarce cell types in mice and humans," Dr. Lara-Astiaso recalled. "Eventually, we managed to transform that precursor into a general method for mapping genome regulation across the tree of life."
Using iChIP2, the team profiled 12 different chemical tags across 12 diverse species, including soil amoebae, freshwater amoebae, fungi, algae, moss, and single-celled predators. Many of these organisms had never been studied this way before. Some species, like the chytrid fungus Spizellomyces punctatus and the ciliate Tetrahymena thermophila, had their chromatin mapped for the very first time.
The findings could eventually help scientists understand diseases that arise when gene regulation goes wrong. Faults in chromatin regulation are linked to cancers and other serious conditions. By revealing how gene-silencing mechanisms evolved, the research opens new avenues for understanding — and perhaps someday treating — these illnesses. The new method also offers a tool for broader efforts to catalogue the molecular diversity of life on Earth.