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Mukund Thattai @thattai.bsky.social

I set out to review the evolution of eukaryotic intracellular traffic, but along the way a new hypothesis came into focus: maybe the earliest membrane carriers were tubules, not coated vesicles! New preprint: ecoevorxiv.org/repository/v... Here’s the idea. 🧵

A schematic showing two models for the evolution of the eukaryotic cell plan starting from an archaeal ancestor. The
aug 4, 2025, 8:34 pm • 41 15

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Mukund Thattai @thattai.bsky.social

Eukaryotes arose via a merger between archaea and bacteria, with eukaryotic traits emerging gradually on the path from FECA (the archaeal first eukaryotic common ancestor) to LECA (last eukaryotic common ancestor). What if FECA was already an atypical archaeon with rudimentary eukaryote-like traits?

A simplified evolutionary tree showing how eukaryotes arose from a merger between Asgard archaea (green) and α-proteobacteria (brown). Key nodes include LUCA (last universal common ancestor), FECA (archaeal first eukaryotic common ancestor), FMCA (first mitochondrial common ancestor) and LECA (last eukaryotic common ancestor). The mitochondrial endosymbiosis event is highlighted.
aug 4, 2025, 8:34 pm • 2 0 • view
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Mukund Thattai @thattai.bsky.social

Asgard archaeal genomes encode many eukaryotic signature proteins, previously thought to be restricted to eukaryotes. In modern eukaryotes several of these ESPs are involved in membrane traffic. But Asgard archaea lack canonical vesicle coats. So what were these proteins doing in FECA?

AlphaFold-based structural alignments of Asgard archaeal (red) and eukaryotic (blue) homologs of membrane trafficking proteins. Shown are COPII component Sec24, TRAPP subunit TRAPPC3, AP2 μ and σ subunits, ESCRTIII protein CHMP1B, retromer component VPS29, BAR domain protein Arfaptin, and CORVET/HOPS subunit VPS16. Each pair except CORVET/HOPS show strong structural similarity despite the evolutionary distance.
aug 4, 2025, 8:34 pm • 5 0 • view
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Mukund Thattai @thattai.bsky.social

A closer look shows that in present-day eukaryotes these Asgard ESPs are involved in the generation of tubular carriers at the ER, endosomes/TGN, and at the plasma membrane. In the review I discuss several new studies showing that Asgard versions of these proteins can indeed generate tubules!

Diagram showing Asgard ESP homologs involved in the generation of tubular membrane carriers in modern eukaryotes. The left panel lists sequential stages of carrier generation: initiation, cargo loading, tubulation, scission, tethering, and fusion, with associated protein complexes such as Arf GTPases, BAR domain proteins, ESCRTs, and SNAREs. The right panel shows a stylized eukaryotic cell, indicating sites where tubular carriers are found in present-day eukaryotes (ER exit site, endosome/TGN, plasma membrane).
aug 4, 2025, 8:34 pm • 5 0 • view
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Mukund Thattai @thattai.bsky.social

Open questions remain. Intracellular membranes have not so far been confirmed in Asgard archaea. And what of the origin of other eukaryotic organelles? Could they be stabilised versions of ancient tubular carriers? I'd love to hear your thoughts! New preprint: ecoevorxiv.org/repository/v...

aug 4, 2025, 8:34 pm • 6 2 • view
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Mukund Thattai @thattai.bsky.social

It's a great time to be studying eukaryogenesis, with so much new experimental data from diverse species. I want to thank several folks with whom I've been discussing these ideas for many years, especially @buzzbaum.bsky.social, @gautamdey.bsky.social, @ishier.bsky.social, @dackslabecb.bsky.social.

aug 4, 2025, 8:40 pm • 6 0 • view
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blairhoughton.bsky.social @blairhoughton.bsky.social

That is a tragically bad graphic.

aug 5, 2025, 7:17 pm • 0 0 • view
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bill24me.bsky.social @bill24me.bsky.social

That’s what I’ve been thinking!!

aug 5, 2025, 5:45 pm • 0 0 • view
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Troy Kervin @meowmuir.bsky.social

This might interest you: doi.org/10.1186/s129... Michael Overduin and I want to write a paper about the evolution of the PL code at some point. This will be helpful, thanks!

aug 5, 2025, 1:29 pm • 1 0 • view