Comparative genomics revealed the origin and evolution of autophagy pathway

Abstract

Autophagy is prevalent in eukaryotic organisms. Massive research efforts have focused on the mechanism and functionality of autophagy in eukaryotes, for example, their role in human diseases. However, little is known about how this fundamental pathway evolved; in particular, there is an absence of research in prokaryotes.Here, we carried out a comparative genomics analysis among 84 species ranging from eukaryotes to eubacteria and archaebacteria. We found that most of the core proteins in the autophagy pathway were ubiquitous in eukaryotes, whereas the distribution of proteins involved in selective autophagy were limited. In prokaryotes, distant homologs of autophagy-related proteins were also found. Species in Cyanobacteria and Euryarchaeota possess relatively more of these homologs compared to other prokaryotes, which indicated the prokaryotic origin of some autophagyrelated proteins. Phylogenic tree analysis and the distribution of homologs suggested that the presence of proteins involved in autophagosome formation should be an important sign of autophagy. Furthermore, we found that distribution of mitochondrial protein importing-related proteins was quite similar to that of autophagy-related proteins in eukaryotes and that their phylogenic profile was closer to that of several core autophagy proteins compared with 16S/18S ribosomal RNAs, suggesting the engulfment of mitochondria may be the driving force for the evolution of autophagy. Autophagy may have evolved as a quality control system for mitochondria at the very beginning of evolution of eukaryotes. This research shed light on the prokaryotic origin of autophagy and provided a new perspective that mitochondria and autophagy may interplay during the course of eukaryotic evolution.

Autophagy: An evolutionarily conserved process in the maintenance of stem cells and aging

“…Therefore, it is an appropriate approach to track the traces of autophagy through evolution beginning with prokaryotes. Evidences suggests the presence of some distant homologues of Atg s in cyanobacteria and euryarchaeota . Atg1/ULK1 is the first protein complex involved in the induction of autophagy.…”

“…A comparative genomic study on the presence of the Atg genes in parasites such as Entamoeba histolytica , Plasmodium yoelii , Trypanosoma brucei , and Encephalitozoon cuniculi showed relatively less Atg s . In the protist, E. histolytica , the activity of autophagy in proliferation and differentiation has been reported .…”

“…Evidences suggests the presence of some distant homologues of Atgs in cyanobacteria and euryarchaeota. 21 Atg1/ULK1 is the first protein complex involved in the induction of autophagy. When looking for similar orthologs in prokaryotes, proteins resembling the serine/threonine kinases have been observed (Table 1).…”

“…A comparative genomic study on the presence of the Atg genes in parasites such as Entamoeba histolytica, Plasmodium yoelii, Trypanosoma brucei, and Encephalitozoon cuniculi showed relatively less Atgs. 21 In the protist, E. histolytica, the activity of autophagy in proliferation and differentiation has been reported. 25 Orthologs of Atg proteins involved in the expansion and completion of vesicles were found in Plasmodium falciparum, whereas genes involved in either of the two ubiquitin-like conjugations required for the induction of autophagy and cargo delivery to lysosomes seem completely absent.…”

Endosymbiosis before eukaryotes: mitochondrial establishment in protoeukaryotes

“…While intracellular digestion is only known in eukaryotes, an (auto)phagocytic host to mitochondria is not ruled out yet [54,104,142,159]. Modern mitochondria are subject to autophagy and this mechanism might have evolved in eukaryotes to control defective or corrupted symbionts, as was hypothesized by [160] based on the similarity of mitochondrial protein importing and eukaryotic autophagy-related proteins.…”