The First Complex Cells Weren’t a Simple Union — They Were a Crowd
The origin of complex cells — eukaryotes, the domain that includes every animal, plant, and fungus — has long been taught as a story of two: an archaeon swallowed a bacterium, and the bacterium became the mitochondrion. This binary partnership, formalized decades ago, is one of the most celebrated narratives in evolutionary biology.
A new study published June 10 in Nature by researchers at the Barcelona Supercomputing Center and the Institute for Research in Biomedicine (IRB Barcelona) suggests the story has been missing most of its cast. The last eukaryotic common ancestor (LECA) — the hypothetical ancestor from which all eukaryotes descend — appears to have drawn its genome from at least four distinct microbial groups, not just two.
“The narrative is incomplete,” said Dr. Toni Gabaldón, ICREA researcher and senior author of the study. “There were more actors on the stage.”
The team, led by co-first authors Moisès Bernabeu, Saioa Manzano-Morales, and Marina Marcet-Houben, built three independent datasets of 100 eukaryotic proteomes each, drawn from 185 unique species spanning nine eukaryotic supergroups. They clustered proteins into orthologous groups — genes that share a common ancestral sequence — and filtered for families that could be traced back to LECA.
For each of these ancestral gene families, they searched a database of 65,703 prokaryotic genomes (62,291 bacteria and 3,412 archaea from the Genome Taxonomy Database) and 1.32 million viral protein clusters (from RVDB v.25.0) to identify the phylogenetic sister group — the lineage whose genes most closely resemble the eukaryotic ancestor’s.
The result was a consensus LECA proteome of 5,317 KEGG Orthology terms. Of these, roughly 53% had identifiable non-eukaryotic origins, 33% appeared to be eukaryotic innovations (no recognizable prokaryotic relative), and 13% could not be confidently assigned.
The Cast of Contributors
The dominant signal from Asgard archaea was expected — these organisms are widely considered the closest prokaryotic relatives of eukaryotes. What surprised the researchers was the strength and diversity of bacterial contributions.
The alphaproteobacterial lineage (the group that gave rise to mitochondria) contributed roughly 3.99% of the LECA proteome. But two other bacterial groups contributed nearly as much:
- Myxococcota — a group of soil bacteria known for complex multicellular behavior and predatory swarming — contributed approximately 3.92% of LECA proteins, including steroid biosynthesis enzymes essential for building eukaryotic cell membranes.
- Planctomycetota — bacteria with unusual internal compartmentalization — contributed roughly 2.24%. Timing analysis suggests Planctomycetota were the earliest bacterial contributors, predating even mitochondrial acquisition.
- Asgard archaea contributed about 3.28%.
The total bacterial contributions, when all lineages are included, significantly exceed the archaeal contribution — overturning the assumption that the archaeal host was the dominant genetic scaffold.
The Viral Vector Hypothesis
Perhaps the most striking finding involves giant viruses. Approximately 4.5% of LECA gene families had a viral sister group, with 74% of those belonging to Nucleocytoviricota — a group of giant viruses known to infect unicellular eukaryotes and carry large genomes that include genes acquired from their hosts.
Gabaldón’s team proposes that these viruses acted as gene-transfer vehicles, shuttling DNA between coexisting microbes in the ancient microbial mats where early eukaryotes likely evolved. The proposal is consistent with the known ecology: Asgard archaea, Planctomycetota, Myxococcota, and Alphaproteobacteria all coexist in layered microbial mat communities, and the inferred timing of gene acquisition — Planctomycetota first, then Myxococcota, then Alphaproteobacteria — matches the stratified structure of these mats.
A Paradigm in Transition
The paper is not uncontested. In January 2026, a group led by Eugene Koonin at the NIH published a study in Nature arguing for a dominant contribution of Asgard archaea to eukaryotic gene systems, with bacterial contributions appearing scattered and inconsistent. Gabaldón’s team attributes the difference to database size — their database of 65,703 prokaryotic genomes is substantially larger than the one used in Koonin’s analysis. When they re-analyzed the earlier study’s data with their own pipeline, the difference disappeared.
The debate underscores a fundamental challenge in molecular archaeology: the events happened roughly two billion years ago, and there are no fossils to consult. Everything is inferred from the genomes of modern organisms.
“We are trying to reconstruct a story that took place billions of years ago and for which we have no direct fossils,” the authors wrote. “That is why we have been very conservative: we only kept the most robust evolutionary signals.”
What This Means
The traditional binary narrative — an archaeon plus a bacterium — captured the essential insight that endosymbiosis created the mitochondrion. The new study does not dispute that. It adds a layer of complexity: before and during that pivotal event, genetic material was flowing freely across microbial boundaries, possibly mediated by viruses, in a gradual multi-partner process.
LECA emerges from this analysis as an aerobic heterotroph with a complex cytoplasm — endocytosis machinery, phagosomes, peroxisomes, motor proteins, and mitochondria capable of aerobic respiration. It was already a sophisticated cell before any of its descendants diverged.
“All genomes preserve traces of their history,” Gabaldón said. “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.”
Source: Bernabeu, M., Manzano-Morales, S., Marcet-Houben, M. & Gabaldón, T. (2026). “Gene ancestries reveal diverse microbial associations during eukaryogenesis.” Nature. DOI: 10.1038/s41586-026-10639-9.