Comprehensive analysis of small GTPases in Microsporidia reveals new extremes in eukaryotic cell biology

Microsporidia are a fungi-related rapidly evolving lineage of obligate intracellular parasites with poorly known cell biology. Cellular processes in eukaryotes heavily rely on a group of proteins known as the Ras GTPase superfamily, so a comprehensive analysis of these proteins in Microsporidia is expected to provide fundamental insights into the microsporidian cell biology. Adopting a complex bioinformatic approach to cope with the high divergence of microsporidian genes, we reconstructed the evolutionary history of the Ras superfamily of GTPases in Microsporidia and their closest relatives.

Our results demonstrate that gene loss along the whole microsporidian phylogeny has been a vastly dominating factor shaping the Ras superfamily gene complements in extant Microsporidia. This trend has most massively affected Hepatospora eriocheir with a mere 12 Ras superfamily genes, the smallest number recorded so far for an autonomously reproducing eukaryote. Also notable is the loss of the virtually ubiquitous Rab GTPase Rab5 and its dedicated regulators in two different microsporidian lineages, or the Rho family GTPases of most Microsporidia having lost C-terminal prenylation. Most unexpectedly, two different microsporidian species lack detectable orthologs of the beta subunit of the signal recognition particle (SRP) receptor, a loss unknown from any other eukaryote. Strikingly, the loss of SRβ is apparently compensated for by the SRP receptor alpha subunit of these species uniquely possessing a predicted transmembrane domain, potentially anchoring the protein in the ER membrane.

Our findings thus define new extremes in the impact of reductive evolution on core processes of the eukaryotic cell.