Kingdon, E. M. | bioRxiv Science

bioRxiv2025

Comparative genomics of the lipid droplet-associated protein Seipin across eukaryotic diversity illuminates an ancient origin and conserved structural diversity.

Lipid droplets (LDs) are ubiquitous across living organisms. Characterised in eukaryotes by their lipid monolayer and essential for lipid storage and metabolism in animals, plants, and yeast, little is known about the evolutionary diversity of extant LDs across the eukaryotic tree of life. LDs facilitate an impressive variety of cellular functions outside of just lipid storage; in Metazoa, these include stress responses, cellular signaling, and membrane remodeling. Likewise, the distribution of these functions across eukaryotic diversity is unknown. We have examined the evolutionary trajectory of seipin, a protein associated with LD biogenesis, across eukaryotic diversity. We have identified a pan-eukaryotic distribution of seipin, with an evolutionary pattern that indicates presence in the Last Eukaryotic Common Ancestor. Ancient conservation of multiple variants of seipin suggests that seipin may multiple conserved functional roles within the cell. Finally, we identify a lack of sequence homology between BSCL2/seipin in Homo sapiens and the sei-1 gene previously identified as a functional homologue of BSCL2 in Saccharomyces cerevisiae. Though our results suggest that sei-1 may be a highly divergent homologue of BSCL2 / seipin rather than an unrelated protein, the divergence suggests that researchers may need to be cautious applying results obtained in Saccharomyces spp.. Visual abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/683490v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1d380c5org.highwire.dtl.DTLVardef@ab2432org.highwire.dtl.DTLVardef@1d56cb5org.highwire.dtl.DTLVardef@d3fcbc_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

The ARF regulatory GTPase in Giardia intestinalis is associated with vesicle formation and membrane fusion machinery at non-canonical endosomal compartments

The intestinal parasite Giardia intestinalis, the causative agent of the globally distributed diarrheal disease Giardiasis, is one of the few genetically tractable members of the phylum Fornicata, which includes both parasitic and free-living species. The diversity of membrane traffic machinery in this lineage is of special interest in relation to the evolution of parasitism and the emergence of specialized organelles as possible adaptations to parasitism. Here, we performed a functional characterization of the ARF family of regulatory GTPases and their regulators in Giardia traffic, including three ARF paralogues, one ARF GAP and one ARF GEF. Using a combination of bioinformatic tools, protein network discovery and validation, and confocal light microscopy, we show that the Giardia ARF complement studied here is robustly associated with peripheral endocytic compartments (PECs), essential feeding organelles that are unique to Giardia parasites. Intersection of the interactomes of this ARF complement with previously published data for PECs-proteins (including membrane adaptors, predicted retromer subunits and SNAREs), revealed a complex crosstalk between the ARF complement and several membrane traffic processes.

cell biology↗