The origins of phagocytosis and eukaryogenesis

Abstract

Background: Phagocytosis, that is, engulfment of large particles by eukaryotic cells, is found in diverse organisms and is often thought to be central to the very origin of the eukaryotic cell, in particular, for the acquisition of bacterial endosymbionts including the ancestor of the mitochondrion.

Results: Comparisons of the sets of proteins implicated in phagocytosis in different eukaryotes reveal extreme diversity, with very few highly conserved components that typically do not possess readily identifiable prokaryotic homologs. Nevertheless, phylogenetic analysis of those proteins for which such homologs do exist yields clues to the possible origin of phagocytosis. The central finding is that a subset of archaea encode actins that are not only monophyletic with eukaryotic actins but also share unique structural features with actin-related proteins (Arp) 2 and 3. All phagocytic processes are strictly dependent on remodeling of the actin cytoskeleton and the formation of branched filaments for which Arp2/3 are responsible. The presence of common structural features in Arp2/3 and the archaeal actins suggests that the common ancestors of the archaeal and eukaryotic actins were capable of forming branched filaments, like modern Arp2/3. The Rho family GTPases that are ubiquitous regulators of phagocytosis in eukaryotes appear to be of bacterial origin, so assuming that the host of the mitochondrial endosymbiont was an archaeon, the genes for these GTPases come via horizontal gene transfer from the endosymbiont or in an earlier event.

Conclusion: The present findings suggest a hypothetical scenario of eukaryogenesis under which the archaeal ancestor of eukaryotes had no cell wall (like modern Thermoplasma) but had an actin-based cytoskeleton including branched actin filaments that allowed this organism to produce actin-supported membrane protrusions. These protrusions would facilitate accidental, occasional engulfment of bacteria, one of which eventually became the mitochondrion. The acquisition of the endosymbiont triggered eukaryogenesis, in particular, the emergence of the endomembrane system that eventually led to the evolution of modern-type phagocytosis, independently in several eukaryotic lineages.

Figure 1

A maximum likelihood tree of actin-related proteins. The root position was forced between the HSP70 superfamily and the actin superfamily. The tree was constructed by analysis of 295 aligned amino acid residues (Additional File 8). Support values are indicated only for major internal branches (not within smaller monophyletic groups). The protein sequences whose structure alignment was used to correct the multiple protein alignment of actin-related proteins are denoted in red. For the complete legend, see Additional File 5.

Figure 2

Selected prokaryotic actin homologs aligned with eukaryotic actins and actin-related proteins 2 and 3. Green boxes 1 and 2 highlight the major inserts in Arp 2, 3 distinguishing them from actins [118]: a loop in subdomain 4 of Arp3 (green box 1) and elongated loops in subdomain 3 in both Arp 2 and Arp 3 (green box 2). ALP, actin-like protein. Red boxes indicate homologous inserts shared between crenarchaeal and eukaryotic proteins. For the complete legend, see Additional File 5.

Figure 3

A Maximum Likelihood tree of the Ras superfamily of GTPases. The tree was constructed using 120 aligned positions (additional File 7). The tree is unrooted but shown in a pseudo-rooted form solely for convenience. Bacterial and archaeal clusters are shown in green and red, respectively. Support values are shown only for major internal branches. For the complete legend, see Additional File 5.

Figure 4

The proposed endosymbiotic scenario of eukaryogenesis and subsequent origin of phagocytosis. The evolutionary tree of archaea is shown as a multifurcation of 5 major branches: Crenarchaeota, Euryarchaeota, Korarchaeota, Thaumarchaeota, and the hypothetical Archaeal Ancestor of Eukaryotes which is depicted as an irregular shape to emphasize the likely absence of a rigid cell wall. LECA, Last Universal Eukaryotic Ancestor. HGT, Horizontal Gene Transfer. The primary radiation of eukaryotes is shown as a multifurcation of 5 supergroups: Unikonts, Chromalveolata, Excavates, Rhizaria, and Planta. At least, three of the supergroups evolved full-fledged phagocytosis (Ph).