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Unanticipated diversity, undiscovered ancient paralogs, and Asgard origins of the ARF GTPase protein family

By Romana Vargova, Jeremy G. Wideman, Romain Derelle, Richard A. Kahn, Vladimir Klimes, Joel B. Dacks, Marek Elias

Posted 01 Nov 2020
bioRxiv DOI: 10.1101/2020.10.31.363457

ARF family GTPases act in diverse cellular processes, critical for organellar function today and understanding eukaryotic origins. However, our understanding of ARF family evolution is limited. Our phylogenetically comprehensive in silico analyses of ARF family members here doubles the set of ancestral eukaryotic paralogs and challenges existing norms for small GTPases, with examples of non-standard modes of membrane association and novel protein architectures. Evidence for the pan-eukaryotic and ancestral origin of Arf6, Arl13 and Arl16 is presented for the first time, while three newly described ancient sub-families are absent from well-studied model organisms, leaving their functions completely unexplored. Evolutionary analysis of metazoa-specific ARF family GTPases also uncovered several new proteins in animals. Delving back to eukaryogenesis, the relationship within the ARF GTPases sets boundaries for scenarios of vesicle coat origins. Finally, we report the discovery of the archaeal proteins from which the entire eukaryotic ARF family is derived. ### Competing Interest Statement The authors have declared no competing interest.

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