Evolutionary origins of the N-glycosylation from the perspective of Homo sapiens genome

Glycosylation is present in all living organisms, ranging from bacteria and archaea all the way to humans. Glycan structures attached to lipids and proteins are not coded into the genome but are precisely added by enzymes involved in the glycosylation process. The observed increase in glycan structure complexity through evolution suggests that the glycosylation processes are under continuous evolutionary change. To reconstruct the evolutionary origin of the genes involved in N-glycosylation and their target proteins in H. sapiens we applied the phylostratigraphic approach. Results showed that homologs of most human genes involved in N- glycosylation could be traced back to the last universal common ancestor (LUCA) suggesting that the protein glycosylation is essential to all cellular life. Apart from that, we observed significant enrichment in the last eukaryotic common ancestor (LECA), probably linked to the emergence of the endomembrane system which plays important role in eukaryotic N-glycosylation. Focusing on the enzymes of the N-glycosylation biosynthetic pathway localized on the cytosolic and luminal side of the membrane of the endoplasmic reticulum, it has been observed that these enzymes are grouped into blocks and that evolutionarily older enzymes, originated in LUCA, are oriented toward the cytosolic side, while evolutionarily newer enzymes, originated in LECA, are oriented towards the lumen of the endoplasmic reticulum. Such rearrangement supports suggested theories of eukaryogenesis which theorize the development of the endomembrane system from the cell membrane of the host cell.