The Emergence of Cellular Complexity at the Dawn of the Eukaryotes: Reconstructing the Endomembrane System with In Silico and Functional Analyses

Eukaryotic cells depend on a complex network of intracellular organelles to perform endocytosis and exocytosis. These trafficking routes underlie many vital cellular processes, including nutrition, responses to environmental cues, defense from pathogens, and differentiation. Multiple disease mechanisms arise from defects in these pathways. How this complex system arose, especially when compared to the simpler trafficking systems of prokaryotes, remains largely unanswered. However, the availability of fully sequenced genomes from many diverse eukaryotic taxa and representing distinct lineages, increasingly facilitates the reconstruction of very early events in eukaryotic evolution. Studies based on comparative genomics and phylogenetics point to great complexity being already present in the last common ancestor of all eukaryotes and enriched with lineage-specific variability/flexibility. Here we describe the methodology and limitations behind such studies, how conclusions can be enhanced by functional analysis, as well as recent results relating to evolution of Rab small GTPases and the retromer complex.