title: The diversity of dolichol-linked precursors to Asn-linked glycans likely results from secondary loss of sets of glycosyltransferases.
abstract: The vast majority of eukaryotes (fungi, plants, animals, slime mold, and euglena) synthesize Asn-linked glycans (Alg) by means of a lipid-linked precursor dolichol-PP-GlcNAc2Man9Glc3. Knowledge of this pathway is important because defects in the glycosyltransferases (Alg1-Alg12 and others not yet identified), which make dolichol-PP-glycans, lead to numerous congenital disorders of glycosylation. Here we used bioinformatic and experimental methods to characterize Alg glycosyltransferases and dolichol-PP-glycans of diverse protists, including many human pathogens, with the following major conclusions. First, it is demonstrated that common ancestry is a useful method of predicting the Alg glycosyltransferase inventory of each eukaryote. Second, in the vast majority of cases, this inventory accurately predicts the dolichol-PP-glycans observed. Third, Alg glycosyltransferases are missing in sets from each organism (e.g., all of the glycosyltransferases that add glucose and mannose are absent from Giardia and Plasmodium). Fourth, dolichol-PP-GlcNAc2Man5 (present in Entamoeba and Trichomonas) and dolichol-PP- and N-linked GlcNAc2 (present in Giardia) have not been identified previously in wild-type organisms. Finally, the present diversity of protist and fungal dolichol-PP-linked glycans appears to result from secondary loss of glycosyltransferases from a common ancestor that contained the complete set of Alg glycosyltransferases.
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 715 Albany Street, Boston, MA 02118-2932, USA. jsamuels@bu.edu
authors.forename: John
authors.initials: J
authors.lastname: Samuelson
authors.forename: Sulagna
authors.initials: S
authors.lastname: Banerjee
authors.forename: Paula
authors.initials: P
authors.lastname: Magnelli
authors.forename: Jike
authors.initials: J
authors.lastname: Cui
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelleher
authors.forename: Reid
authors.initials: R
authors.lastname: Gilmore
authors.forename: Phillips W
authors.initials: PW
authors.lastname: Robbins
mesh_terms: D000818:Animals; D001216:Asparagine; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D019295:Computational Biology; D004286:Dolichols / Q000378:metabolism*; D019143:Evolution, Molecular; D014644:Genetic Variation; D006020:Glycopeptides / Q000096:biosynthesis; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011134:Polysaccharides / Q000737:chemistry*; D013045:Species Specificity
chemical_list: D004286:Dolichols; D006020:Glycopeptides; D011134:Polysaccharides; D001216:Asparagine; D016695:Glycosyltransferases