Adenine DNA methylation associated to transcription is widespread across eukaryotes
Posted on: 13 January 2025 , updated on: 14 January 2025
Preprint posted on 28 October 2024
Categories: bioinformatics, evolutionary biology, genomics
Background
Chemical modifications on DNA are a common occurrence in most organisms. These modifications can have various impacts on both gene regulation and genome organization. While the methylation of the 5-carbon position of the cytosine nucleotide (5mC) is probably the most studied modification in eukaryotes, the presence of other modifications has always been a topic for debate and speculation.
In this preprint from Romero-Charria and colleagues, the authors make use of recent advancements of the Oxford Nanopore sequencing platform to answer—in a very comprehensive manner—whether 6mA (N6 methyladenine), a DNA modification common in bacteria, is present in eukaryotes.
Since 6mA is not well-studied in eukaryotes, the authors looked to find the source of this DNA modification, its genomic distribution, and possible roles that it could have in gene regulation.
Key findings
- The authors first identified the gene AMT1 as the potential source of 6mA DNA methylation in eukaryotes by describing the evolution of MTA-70 methyltransferases.
- By sequencing different species under conditions that excluded other sources of DNA contamination, the authors linked the presence of AMT1 to the presence of 6mA in various organisms representing different eukaryotic groups (Figure 2a).

- The authors described that 5mC and 6mA are not linked functionally, and that transcriptionally active genes tend to have higher levels of 6mA.
- Nucleosomes containing the H3K3me3 tended to also have 6mA modifications and provide a hypothesis on how the epigenome of the last eukaryotic common ancestor was regulated through different DNA modifications (Figure 5).
Figure 5 from the preprint – Reconstruction of the epigenome of the last eukaryotic common ancestor, as well as the current epigenome of different extant taxa in terms of DNA modifications.
Why is this paper important?
In this study the authors make good use of an emerging technology to address the long-standing question of whether 6mA is widespread throughout the tree of life. This work also offers insights into the evolution of gene regulation, as it seems that this modification was lost in eukaryotes.
Personally, I relate to this preprint as we work often with Nanopore sequencing, and it is quite exciting to see the possibilities this technology brings not just in terms of genome assembly, but also to study nucleic acid modifications in such elegant and reliable manner. Another aspect I am quite fond of is the effort the authors took to uncover the ancestral state of the eukaryotic common ancestor, something I am working on in my day to day, although in a smaller evolutionary scale.
doi: https://doi.org/10.1242/prelights.39131
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