Protein domain patterns reveal a functional diversity of the archaeal Cdv system and give insights into the origin of the eukaryotic ESCRT system

The archaeal cell division machinery Cdv is closely related to the eukaryotic ESCRT system and it is often suggested that Cdv may represent a simplified functional model of ESCRT. However, experimental data suggests that even amongst archaea Cdv-based mechanisms differ, questioning the idea of a common basic principle. Furthermore, both Cdv and ESCRT have had the same time to evolve since their deviation from a putative common ancestor, a fact which is often ignored when archaea are treated as 9simpler versions9 of eukaryotes. Here, we use a range of computational methods to elucidate these functional differences and to provide a guide on which Cdv-based mechanisms may or may not be compared to ESCRT. We infer a comprehensive mechanistic theory of Cdv-based cell division based on protein domains that correctly predicts the functional differences found between organisms in experiments and describes the protein evolution that underlies this functional diversity. From these results we infer that there are at least three evolutionary and functionally different Cdv-based systems in archaea, complicating the idea of comparative approaches to ESCRT. However, we describe that the Cdv machinery found in the archaeal super-phylum Asgard probably is functionally highly comparable to the eukaryotic ESCRT system, making it a promising candidate for comparative studies. Taken together, via a novel mechanistic theory of archaeal Cdv-based systems we explain experimental findings of the past and provide a guide for various hypothesis-driven experiments in the future that may lead to a functional model of the highly researched eukaryotic ESCRT system.