title: The multiple evolutionary origins of the eukaryotic N-glycosylation pathway.
abstract: The N-glycosylation is an essential protein modification taking place in the membranes of the endoplasmic reticulum (ER) in eukaryotes and the plasma membranes in archaea. It shares mechanistic similarities based on the use of polyisoprenol lipid carriers with other glycosylation pathways involved in the synthesis of bacterial cell wall components (e.g. peptidoglycan and teichoic acids). Here, a phylogenomic analysis was carried out to examine the validity of rival hypotheses suggesting alternative archaeal or bacterial origins to the eukaryotic N-glycosylation pathway.
  
  
  
  The comparison of several polyisoprenol-based glycosylation pathways from the three domains of life shows that most of the implicated proteins belong to a limited number of superfamilies. The N-glycosylation pathway enzymes are ancestral to the eukaryotes, but their origins are mixed: Alg7, Dpm and maybe also one gene of the glycosyltransferase 1 (GT1) superfamily and Stt3 have proteoarchaeal (TACK superphylum) origins; alg2/alg11 may have resulted from the duplication of the original GT1 gene; the lumen glycosyltransferases were probably co-opted and multiplied through several gene duplications during eukaryogenesis; Alg13/Alg14 are more similar to their bacterial homologues; and Alg1, Alg5 and a putative flippase have unknown origins.
  
  
  
  The origin of the eukaryotic N-glycosylation pathway is not unique and less straightforward than previously thought: some basic components likely have proteoarchaeal origins, but the pathway was extensively developed before the eukaryotic diversification through multiple gene duplications, protein co-options, neofunctionalizations and even possible horizontal gene transfers from bacteria. These results may have important implications for our understanding of the ER evolution and eukaryogenesis.
  
  
  
  This article was reviewed by Pr. Patrick Forterre and Dr. Sergei Mekhedov (nominated by Editorial Board member Michael Galperin).
authors: National Evolutionary Synthesis Center, 2024 W. Main Street Suite A200, Durham, NC, 27705, USA. j.lombard@exeter.ac.uk.|Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, EX4 4QD, UK. j.lombard@exeter.ac.uk.
authors: Jonathan
authors: J
authors: Lombard
mesh_terms: D056890:Eukaryota / Q000145:classification* / Q000378:metabolism*; D019143:Evolution, Molecular; D006031:Glycosylation; D053858:Metabolic Networks and Pathways; D010802:Phylogeny
keywords: Archaea; Bacteria; Eukaryogenesis; Eukaryotes; Glycosyltransferase; N-glycosylation; Polyisoprenol; Prokaryotic cell walls