Loss of ancestral N-glycosylation sites in conserved proteins during human evolution

Abstract

N-linked protein glycosylation is involved in various biological processes, such as protein quality control and adhesion or signaling among cells. The loss of ancestrally conserved N-glycosylation sites may result in the evolution of protein structure and function. In the present study, a mouse glycoproteome dataset and mammalian proteome data were assessed to identify 40 ancestral N-glycosylation sites in 37 proteins that disappeared during human evolution since the last common ancestor of the Euarchonta (primates and treeshrews). The results showed that each of the human proteins, CELSR1, ST3GAL5 and VSIG10, lost an ancestrally conserved N-glycosylation site following human-chimpanzee divergence. Notably, CELSR1 and ST3GAL5 are crucial for normal development and function of the mammalian nervous system, suggesting an association with the evolution of human cognitive function. Thus, the lost ancestrally conserved N-glycosylation sites identified in the present study may be useful targets for functional analyses to identify molecular changes linked with the evolution of human phenotypes.