Researchers have discovered genes that duplicated before the last universal common ancestor of all life, offering insights into evolution's earliest stages. These universal paralogs, present in nearly every organism, suggest protein production and membrane transport were among the first biological functions. The findings, published in Cell Genomics, highlight how ancient genetic patterns can reveal pre-LUCA history.
Every organism on Earth descends from the last universal common ancestor (LUCA), which existed around four billion years ago. This ancient entity already possessed key features like cell membranes and DNA-based genetic storage. To probe even earlier evolution, scientists Aaron Goldman of Oberlin College, Greg Fournier of MIT, and Betül Kaçar of the University of Wisconsin-Madison analyzed universal paralogs—gene families duplicated before LUCA and appearing in at least two copies across nearly all modern genomes.
"While the last universal common ancestor is the most ancient organism we can study with evolutionary methods," Goldman explained, "some of the genes in its genome were much older." Universal paralogs differ from typical paralogs, like the human hemoglobin genes that arose from a single ancestral globin around 800 million years ago through copying errors and specialization.
The team's review of known universal paralogs revealed they all function in protein synthesis or molecule transport across membranes, indicating these processes evolved early. In Goldman's lab, researchers reconstructed an ancestral protein from a paralog family involved in embedding proteins into membranes. This ancient form retained the ability to bind membranes and engage with protein-production machinery, providing clues to primitive cellular operations.
"While there are precious few universal paralogs that we know," Goldman noted, "they can give us a lot of information about what life was like before the time of the last universal common ancestor." Fournier emphasized their value: "The history of these universal paralogs is the only information we will ever have about these earliest cellular lineages, and so we need to carefully extract as much knowledge as we can from them."
Advances in AI-based tools are facilitating deeper analysis of these genes. Kaçar added, "By following universal paralogs, we can connect the earliest steps of life on Earth to the tools of modern science. They provide us a chance to transform the deepest unknowns of evolution and biology into discoveries we can actually test."
The study appears in Cell Genomics (2026; DOI: 10.1016/j.xgen.2026.101140).