All life on Earth shares a common ancestor that lived roughly four billion years ago. This so-called "last universal common ancestor" represents the most ancient organism that researchers can study.
Previous research on the last universal common ancestor has found that all the characteristics we see in organisms today, like having a cell membrane and a DNA genome, were already present by the time of this ancestor. So, if we want to understand how these foundational characteristics of life first emerged, then we need to be able to study evolutionary history prior to the last universal common ancestor.
In a new article published in the journal Cell Genomics, scientists Aaron Goldman (Oberlin College), Greg Fournier (MIT), and Betül Kaçar (University of Wisconsin-Madison) describe a method to do just that. "While the last universal common ancestor is the most ancient organism we can study with evolutionary methods," said Goldman, "some of the genes in its genome were much older." The authors describe a type of gene family known as a "universal paralog," which provides evidence of evolutionary events that occurred before the last universal common ancestor.
A paralog is a gene family that has multiple members in the same genome. For example, in our own genome, we have eight versions of hemoglobin genes, which encode proteins that bind to oxygen and carry it through the blood. All of these paralog genes descended from an ancient globin gene that existed as a single copy about 800 million years ago. The paralogs were created by repeated duplications of that gene through DNA copying errors, with each copy then evolving its own distinct features over millions of years.
Universal paralogs are a rare, special type of paralog that have at least two copies in the genomes of all or nearly all organisms alive today. This broad presence indicates that the duplication of an original gene must have taken place before the last universal common ancestor, with multiple copies inherited by its descendants, all the way to the present day.
For this reason, the authors argue that universal paralogs provide an indispensable, but underutilized, target for understanding the earliest history of life on Earth, especially as tools for such research improve with the arrival of new AI-based techniques and AI-optimized hardware.
"While there are precious few universal paralogs that we know," says Goldman, "they can give us a lot of information about what life was like before the time of the last universal common ancestor." Fournier adds, "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."
In their article, Goldman, Fournier, and Kaçar, survey all known universal paralogs. These universal paralogs are all associated with the production of proteins or the movement of different molecules across cell membranes. These two features of the cell were therefore among the earliest characteristics of life to have evolved.
The authors also recommend deeper descriptions of the ancient ancestral genes themselves. For example, Goldman's own lab at Oberlin studied a universal paralog family that is responsible for embedding enzymes and other proteins into cell membranes. Using common techniques of evolutionary biology and computational biology, they reconstructed the protein encoded by the original ancestor of this protein. They found that the simpler, ancient version of this protein was still able to perform functions like binding to the membrane and binding to the protein synthesis machinery, and could have assisted simple proteins in implanting themselves into an early cell membrane.
Ultimately, the authors hope that increasingly sophisticated computational tools will allow researchers to discover new universal paralog families and describe their ancient ancestors in greater detail. "By following universal paralogs," says Kaçar, "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". They envision painting a more detailed picture of evolution prior to the last universal common ancestor, when life as we know it first emerged.
