Rethinking The Origin Of Our Cells As A Story Of Microbial Alliances

All cells in animals, plants, fungi, and protists share a fundamental characteristic: they are eukaryotic cells—complex cells with specialized internal compartments. The cells that make up our bodies are no exception.

How this type of cell emerged is one of the great questions in biology. For decades, the dominant explanation has placed the acquisition of the mitochondrion as the ultimate turning point: an archaeon was thought to have established a symbiotic relationship with a bacterium, which eventually became the mitochondrion, and this alliance opened the door to cellular complexity.

Now, a study led by Dr. Toni Gabaldón—an ICREA researcher at IRB Barcelona and the Barcelona Supercomputing Center-Centro Nacional de Supercomputación (BSC-CNS)—published in Nature, rethinks this view. The work does not deny the central role of the mitochondrion, but suggests that the origin of complex cells was a longer, more gradual, and more collaborative process than previously thought. According to the results, other bacterial groups—in addition to the ancestor of the mitochondrion—left a significant imprint on the common ancestor of all eukaryotes.

“For a long time, we have explained the origin of complex cells as a story with two main protagonists: an archaeon and the bacterium that gave rise to the mitochondrion. Our study suggests that this narrative is incomplete and that there were more actors on stage, including other bacterial groups and giant viruses that may have facilitated gene exchange,” explains Dr. Gabaldón.

Fossils written in genes

Unlike what happens with dinosaurs, the origin of eukaryotes cannot be reconstructed from visible bones or fossils. It occurred about 2 billion years ago in microscopic organisms, of which barely any direct traces remain. However, their footprints are still present in today’s genomes.

To trace them, the team approached the problem as a form of computational molecular archaeology, using the computing power of the MareNostrum series of supercomputers to analyse public genomic data spanning biodiversity as a whole.

First, they reconstructed the repertoire of gene and protein families of the last common ancestor of all eukaryotes, known as LECA (Last Eukaryotic Common Ancestor). They then analyzed its evolutionary origin by comparing these families against databases containing tens of thousands of bacterial, archaeal, and viral genomes.

Thus, after more than five years of work using complex mathematical models and processing large volumes of genomic sequences, the team was able to detect signals that would otherwise have remained invisible.

“We are trying to reconstruct a story that took place billions of years ago and for which we have no direct fossils. That is why we have been very conservative: we only kept the most robust evolutionary signals—those with a strength comparable to the signals already accepted for the ancestral archaeon and for the bacterium that gave rise to the mitochondrion,” explain Moisès Bernabeu, Saioa Manzano-Morales, and Marina Marcet-Houben, authors of the study and researchers in the Comparative Genomics group led by Dr. Gabaldón at IRB Barcelona and the BSC.

More actors than just the mitochondrion

Beyond the mitochondrion, the study identifies two particularly relevant bacterial signals: Myxococcota and Planctomycetota. The former are related to metabolic functions, including processes linked to lipids and membranes. The latter are bacteria known for their structural complexity, featuring internal compartments that are unusual for bacterial organisms.

The analyses suggest that these contributions did not happen all at once. Planctomycetota appear as an older signal, whereas Myxococcota and the bacterium that gave rise to the mitochondrion show signals that are closer in time.

This vision fits with the idea that the ancestors of eukaryotic cells lived in environments rich in microbial communities, such as microbial mats, where different microorganisms coexist in layers under varying chemical conditions. In this context, genetic exchanges would have allowed them to acquire new biological capabilities over time.

Giant viruses as vehicles for genetic exchange

One of the most unexpected findings of the study is the involvement of giant viruses, specifically Nucleocytoviricota. These viruses have genomes that are much larger than those of most known viruses, and they infect single-celled eukaryotic organisms.

The study shows that some genes integrated during the early evolution of eukaryotes appear to come from giant viruses. The authors propose that these viruses could have acted as vehicles for genetic transfer between microorganisms coexisting in the same ecosystem, facilitating exchanges that helped shape the ancestral genome of eukaryotic cells.

A fundamental question about the history of life

The study addresses one of the major questions in biology: how the complexity of the cells that form our bodies came to be. By reconstructing the genetic traces of that process, the work provides a new perspective on a key episode in the history of life: the origin of the cellular lineage to which animals, plants, fungi, and protists belong.

The paper expands on a line of research initiated by Dr. Gabaldón himself in 2016, when he published a study in Nature that already suggested the mitochondrion might have been acquired relatively late in the process of eukaryotic origins. Now, with much more genomic data available and more powerful computational tools, the team has been able to analyze in greater detail which other organisms left their mark on that common ancestor.

“All genomes preserve traces of their history. In the case of eukaryotes, those traces tell us of ancient alliances between microorganisms. Understanding them helps us answer a very profound question: what we are and where we come from,” concludes Dr. Gabaldón.

The project was funded mainly by the Gordon and Betty Moore Foundation, utilized computational resources from the Spanish Supercomputing Network (RES) provided by the B

Gene ancestries reveal diverse microbial associations during eukaryogenesis, Nature (open access)

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