The Evolutionary Origins and Ancestral Features of Septins
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Abstract
Septins are a family of membrane-associated cytoskeletal GTPases that play crucial roles in various cellular processes, such as cell division, phagocytosis, and organelle fission. Despite their importance, the evolutionary origins and ancestral function of septins remain unclear. In opisthokonts, septins form five distinct groups of orthologs, with subunits from multiple groups assembling into heteropolymers, thus supporting their diverse molecular functions. Recent studies have revealed that septins are also conserved in algae and protists, indicating an ancient origin from the last eukaryotic common ancestor. However, the phylogenetic relationships among septins across eukaryotes remained unclear. Here, we expanded the list of non-opisthokont septins, including previously unrecognized septins from rhodophyte red algae and glaucophyte algae. Constructing a rooted phylogenetic tree of 254 total septins, we observed a bifurcation between the major non-opisthokont and opisthokont septin clades. Within the non-opisthokont septins, we identified three major subclades: Group 6 representing chlorophyte green algae (6A mostly for species with single septins, 6B for species with multiple septins), Group 7 representing algae in chlorophytes, heterokonts, haptophytes, chrysophytes, and rhodophytes, and Group 8 representing ciliates. Glaucophyte and some ciliate septins formed orphan lineages in-between all other septins and the outgroup. Combining ancestral-sequence reconstruction and AlphaFold predictions, we tracked the structural evolution of septins across eukaryotes. In the GTPase domain, we identified a conserved GAP-like arginine finger within the G-interface of at least one septin in most algal and ciliate species. This residue is required for homodimerization of the single Chlamydomonas septin, and its loss coincided with septin duplication events in various lineages. The loss of the arginine finger is often accompanied by the emergence of the α0 helix, a known NC-interface interaction motif, potentially signifying the diversification of septin-septin interaction mechanisms from homo-dimerization to hetero-oligomerization. Lastly, we found amphipathic helices in all septin groups, suggesting that curvature-sensing is an ancestral trait of septin proteins. Coiled-coil domains were also broadly distributed, while transmembrane domains were found in some septins in Group 6A and 7. In summary, this study advances our understanding of septin distribution and phylogenetic groupings, shedding light on their ancestral features, potential function, and early evolution.
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In summary, this study advances our understanding of septin distribution and phylogenetic groupings, shedding light on their ancestral features, potential function, and early evolution.
I really enjoyed reading this paper about septin evolution! It opens the door to help us understand more about septins by looking outside of Opisthokonta. The paper is also thorough, and in addition to learning about their newly identified septins, I was also able to learn a lot about septin biology in general. I'm excited to see how this data is used in the future!
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It is interesting to speculate that AspE-type Group 5 septins have retained the ancestral trait to form a homomeric G-dimer using their R-fingers.
This is a really cool section! I love the use of structural analysis + phylogeny to uncover something really cool about the function of these proteins.
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except for Gig2 which appears to be variable in Group 8
Do you have any ideas about the functional consequences of this variability? Do you think it could affect the G-interface dimerization?
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septins
I'm curious how/why you selected these specific species and how you decided which septin to use within each species?
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BLASTP
It sounds like your searches were mostly sequence-based. I know septins can be large and can contain regions of disorder, which may make them difficult to work with structurally. However, I'm curious if you think you might identify more septin sequences using a structure-based search (like Foldseek)?
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Excavata, Archeaplastida, Rhizaria, Heterokonta, and Alveolata
Was your search limited to these taxa or did you search more broadly as well?
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