Madrid. All life on Earth shares a common ancestor that lived approximately 4 billion years ago, according to work led by Oberlin College (United States). This so-called last universal common ancestor represents the oldest organism that researchers have been able to study.

The findings are collected in an article published in the journal Cell Genomics by scientists Aaron Goldman (Oberlin College), Greg Fournier (MIT) and Betül Kaçar (University of Wisconsin-Madison).

Previous research on the last universal common ancestor has found that all the features we see in today’s organisms, such as the cell membrane and DNA genome, were already present in his time. Therefore, if we want to understand how these fundamental characteristics of life emerged, it is necessary to study the evolutionary history before the last universal common ancestor.

This new work describes a method to achieve just that. “While the last universal common ancestor is the oldest organism that we can study with evolutionary methods,” says 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 prior to the last universal common ancestor.

Genes parálogos

A paralog is a gene family that has multiple members in the same genome. For example, in our genome, we have eight versions of hemoglobin genes that code for proteins that bind oxygen and transport it through the blood. All of these paralogous genes are descended from an ancient globin gene that existed as a single copy 800 million years ago. The paralogs were created by repeated duplications of that gene through DNA copying errors, with each copy developing its own distinctive characteristics over millions of years.

Universal paralogs are a rare and special type that present at least two copies in the genomes of all or almost all current living organisms. This widespread presence indicates that duplication of an original gene must have occurred before the last universal common ancestor, with multiple copies inherited by its descendants to the present day.

For this reason, the authors argue that universal paralogues provide an indispensable, but underutilized, lens for understanding the earliest history of life on Earth, especially as the tools for such research improve with the advent of new AI-based techniques and hardware optimized for AI.

“While we know very few universal paralogues,” notes Goldman, “they can tell us a lot about what life was like before the last universal common ancestor.” Fournier adds: “The history of these universal paralogs is the only information we will have about these early cell lineages, so we must carefully extract all possible knowledge from them.”

In their article, the researchers analyze all known universal paralogues. All of these are associated with the production of proteins or the movement of different molecules across cell membranes. Therefore, these two features of the cell are among the first features of life to evolve.

The authors also recommend more detailed descriptions of the ancestral genes. For example, Goldman’s lab at Oberlin studied a universal paralogous family responsible for embedding enzymes and other proteins in cell membranes. Using common techniques from evolutionary biology and computational biology, they reconstructed the protein encoded by the original ancestor of this protein.

They found that the simplest, oldest version of this protein could still perform functions such as binding to the membrane and protein synthesis machinery, and could have helped simple proteins implant into a primitive cell membrane.

Ultimately, the authors hope that increasingly sophisticated computational tools will allow researchers to discover new families of universal paralogs and describe their ancient ancestors in greater detail. “By following universal paralogues,” says Kaçar, “we can connect the first steps of life on Earth with the tools of modern science. They give us the opportunity to transform the deepest unknowns of evolution and biology into discoveries we can actually test.” Their vision is to paint a more detailed picture of evolution before the last universal common ancestor, when life as we know it emerged.

By Editor