Padraic Heneghan

We hypothesized the DNAPs recognize their own plasmid due to the copy number differences between each VLE. DNAPs are encoded and translated as a fusion with a terminal protein, which binds the inverted repeats at the ends of the VLEs. We believe the TPs provide this specificity!

So much good has come from jumping into the unknown and having an open mind for whatever you may find. Funding bodies should encourage blue skies research. Science has always been about funding ideas that are not necessarily ‘profitable’, creating new methods, therapies, and fields of study.

I’m extremely grateful to our funders, the @erc.europa.eu, for allowing us to explore this area. At the risk of sounding preachy, I want to encourage all researchers to set aside time for looking at that ‘weird’ thing you came across. (10/10)

These plasmids have multiple potential antifungal agents with novel mechanisms of action. Additionally, the idea that multiple VLEs can independently replicate with their own DNAPs in the same fungal cell gives a potential avenue for expanding biotechnological applications like OrthoRep (9/10)

With further database mining, we have discovered ‘constellations’ of plasmids in much older fungal groups, specifically, the Zoopagomycota and Mucoromycota. These constellations have illuminated the linear plasmids’ (and zymocin-like toxins’) introduction to the Ascomycota. (8/10)

So, where did all of these come from? Are there more examples of them? Could a really old group of fungi have donated these killer plasmids to the Ascomycetes (budding yeasts and filamentous ascomycetes), or were they simply vertically inherited? They had to have come from somewhere (7/10)

Zymocin-like killer toxin gene clusters in the nuclear genomes of filamentous fungi Zymocin-like killer toxins are anticodon nucleases secreted by some budding yeast species, which kill competitor yeasts by cleaving tRNA molecules. Th…

Here, we found killer plasmids that appear to have ‘crash-landed’ into the nuclear genomes of these fungi. In some cases, these toxins are under positive selection in major plant fungal pathogens, like Fusarium, which have led to severe crop loss:
www.sciencedirect.com/science/arti... (6/10)

Notably, this demonstrated that it was likely the ancestor of all budding yeasts encoded the toxins. We decided to look for killer plasmids in the sister subphylum to the Saccharomycotina (budding yeasts), the Pezizomycotina, which contains well-known fungi, like Aspergillus, Penicillium, etc.(5/10)

A visual of the budding yeast (Saccharomycotina) phylogenetic tree. Two tables with dots beside the tree detail which species were known to have VLEs before and after our database searches. The 'before' table has four dots in the 'On Plasmid' column, showing which budding yeast species were known to contain zymocin-like toxins on plasmids ('killer plasmids'). The right table has an abundance of dots representing where we found zymocin-like toxins, including many chromosomally encoded, rather than plasmid encoded. These dots span nearly the full length of the phylogenetic tree, indicating that it is most-likely the ancestor of all budding yeast species encoded zymocin-like toxins.

My first publication demonstrated these killer plasmids and their toxins were found in far more species than just the 4 previously known (out of ~1500 known species). Through mining reads from the SRA, we discovered 45 novel toxins, many of which were functional: www.pnas.org/doi/10.1073/... (4/10)

My PhD thesis grappled with a virus-like element (VLE) toxin system that some budding yeasts use to compete with other fungi. The VLEs encoding toxins are killer plasmids. The most famous example is in Kluyvermoyces lactis, and its killer plasmid encodes the toxin, zymocin (see killing below) (3/10)

A common question that all daydreamers and scientists (one and the same) have is “where does this come from?” Or “shouldn’t there be more examples of this?” Similar to looking at the stars in the sky and asking, “Is it really just us? That would be incredibly boring…” (2/10)

Zymocin-like killer plasmids were present in the common ancestor of terrestrial fungi Some budding yeasts secrete killer toxins made by linear dsDNA plasmids located in the cytosol. The best-known example is the Kluyveromyces lactis toxin zymocin, which is encoded by a 9-kb killer plas...

Happy to share the final story from my thesis, demonstrating that the common ancestor of all terrestrial fungi had zymocin-like killer plasmids, a toxin system found in some budding yeasts. Come with me on an all-too-familiar, database dumpster-diving journey (1/10)
www.biorxiv.org/content/10.1...

Centromeres in budding yeasts are conserved in chromosomal location but not in structure. The budding yeast Saccharomyces cerevisiae has ‘point’ centromeres, which are much smaller and simpler than centromeres of most other eukaryotes and have a defined DNA sequence. Other yeast taxa have ...

New preprint from lab adding to recent interest in yeast centromeres. There are dramatic changes in structure, but location is conserved www.biorxiv.org/content/10.1...

Thank you!

Hey! Are you at Beijing #SMBE 2025? Looking for something to do at 10:20 on Thursday? Come to my talk in Symposium 35 to hear about toxins in Fungi