Reacción a "A Spanish study published in Nature reimagines the origin of our cells as a story of microbial alliances"

My overall assessment of the article is very positive. It is a technically sound piece of work, based on a large-scale phylogenomic analysis, which represents a significant contribution to the debate on the origin of eukaryotes.

One of its main merits is that it challenges the overly simplified view of eukaryogenesis as a single event resulting from a binary interaction between an archaeon and the future mitochondrion. Furthermore, it stands out for the enormous number of genomes analysed. In this respect, the work fits well with previous proposals suggesting the involvement of multiple microbial partners during the transition to eukaryotes, including possible contributions from groups such as Myxococcales or Planctomycetes.

However, I believe that some of the article’s more ambitious conclusions should be interpreted with caution.

The study detects phylogenetic signals consistent with gene contributions from various bacterial groups, in addition to the alpha-proteobacteria associated with the origin of mitochondria. This reinforces and expands on previous observations. What is novel about the work is the scale of the analyses and the integration of these results into a broader framework that also incorporates a possible role for viruses.

However, these results do not necessarily imply that we can precisely identify which specific ecological partners were involved in eukaryogenesis. The main reason is that horizontal gene transfer is extremely common in bacteria. Added to this are gene loss, gene duplication, the extinction of entire lineages, and the dynamics of pan-genomes. Consequently, the evolutionary history of a gene may differ considerably from the evolutionary history of the cell that carries it.

Therefore, when a eukaryotic gene shows affinity with extant bacterial groups such as Planctomycetota or Myxococcota, we must be cautious. What we are likely observing is a relationship with a gene reservoir associated with those groups, not necessarily direct evidence that these lineages represent the original donors or that there was a specific biological interaction with them. In other words, these genes could, despite their descent from Myxococcales, have been part of the alpha-proteobacterial cell population that gave rise to mitochondria. The combination of fluid chromosomes, open pangenomes and massive horizontal gene transfer can explain much of the observed patterns without the need to invoke specific ecological associations. Put another way, the same signals could emerge from complex networks of gene exchange within microbial communities where genes circulated amongst numerous organisms over long periods of time.

This raises another conceptual question: what exactly do we mean by LECA?

Traditionally, there has been a tendency to imagine LECA [Last Common Eukaryotic Ancestor] as a well-defined individual cell, and I believe the authors view it in this way. However, an alternative view is to consider LECA as a diverse population, possibly with a pan-genomic structure, in which different individuals shared a common core of genes but maintained variable accessory repertoires.

If this view is correct, reconstructing the history of LECA gene by gene may prove problematic. Perhaps the most relevant question is not ‘from which bacterium does this gene originate?’, but rather ‘what gene pool was available in the ancestral populations that gave rise to eukaryotes?’. The focus would thus shift from a specific ancestral cell to a dynamic ancestral population.

From this perspective, the results of the article would not so much be a demonstration of exclusive associations with certain bacterial groups as a confirmation that eukaryogenesis took place within a context of intense genetic connectivity within complex microbial communities.

In summary, I consider the article to be an important contribution because it reinforces an increasingly accepted view of eukaryogenesis as a gradual, population-based and ecologically complex process. However, we must be cautious when interpreting the bacterial groups identified as specific actors in that process. Horizontal gene transfer, the dynamics of pan-genomes and the gene loss accumulated over billions of years limit our ability to accurately reconstruct who interacted with whom at the origins of eukaryotes.