# Eukaryogenesis: Did an Oxidative Crucible Result in Misleading Bioinformatic Analyses?

**Authors:** Dave Speijer

PMC · DOI: 10.1002/bies.70115 · Bioessays · 2026-02-17

## TL;DR

This paper challenges a recent study's conclusion about eukaryote evolution by suggesting that high mutation rates from oxidative stress may have skewed the results.

## Contribution

The paper introduces a novel critique of phylogenetic timing methods in eukaryogenesis studies, highlighting oxidative stress effects on mutation rates.

## Key findings

- High ROS levels from endosymbiont entry could cause inflated mutation rates and misleading phylogenetic timescales.
- Phylogenetic analyses may misinterpret host mutation rates as evidence for gradual eukaryote evolution rather than symbiogenesis.
- Current models may underestimate the impact of oxidative stress on early eukaryotic gene duplication timing.

## Abstract

Recently, Nature published a large‐scale analysis (“Dated gene duplications elucidate the evolutionary assembly of eukaryotes” by Christopher Kay and co‐workers) that seems to put an end to symbiogenic models for eukaryogenesis. They state that the pre‐mitochondrion arrives late, after practically all of the signature eukaryotic characteristics have evolved independently. However, this conclusion is based on reconstructed timescales for the gene duplications allowing these crucial eukaryotic cell functions. The reconstruction might be fundamentally flawed, because enhanced internal ROS formation upon endosymbiont entry would lead to both high mutation rates and strong selection for antioxidant as well as repair functions. As the endosymbiont had co‐evolved with molecular oxygen, while the archaeal host had not, a phylogenetic analysis might misconstrue the higher rate of change in the host as indicative of much longer timescales for host gene duplications.

Recently, Nature published a timed gene duplication analysis favoring gradual models for eukaryogenesis. However, high initial mutation rates due to endogenous ROS formation by the OXPHOS system of the future mitochondrion and ensuing positive selection for countermeasures might strongly inflate branch lengths in such analyses. Ruling out symbiogenesis seems premature.

## Full-text entities

- **Genes:** METTL4 (methyltransferase 4, N6-adenosine) [NCBI Gene 64863] {aka HsT661}
- **Chemicals:** ROS (MESH:D017382), ATP (MESH:D000255), carbon (MESH:D002244), O2 (MESH:D010100), ROS (-)

## Full text

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## Figures

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## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12910325/full.md

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Source: https://tomesphere.com/paper/PMC12910325