title: System-wide genomic and biochemical comparisons of sialic acid biology among primates and rodents: Evidence for two modes of rapid evolution.
abstract: Numerous vertebrate genes are involved in the biology of the oligosaccharide chains attached to glycoconjugates. These genes fall into diverse groups within the conventional Gene Ontology classification. However, they should be evaluated together from functional and evolutionary perspectives in a "biochemical systems" approach, considering each monosaccharide unit's biosynthesis, activation, transport, modification, transfer, recycling, degradation, and recognition. Sialic acid (Sia) residues are monosaccharides at the outer end of glycans on the cell-surface and secreted molecules of vertebrates, mediating recognition by intrinsic or extrinsic (pathogen) receptors. The availability of multiple genome sequences allows a system-wide comparison among primates and rodents of all genes directly involved in Sia biology. Taking this approach, we present further evidence for accelerated evolution in Sia-binding domains of CD33-related Sia-recognizing Ig-like lectins. Other gene classes are more conserved, including those encoding the sialyltransferases that attach Sia residues to glycans. Despite this conservation, tissue sialylation patterns are shown to differ widely among these species, presumably because of rapid evolution of sialyltransferase expression patterns. Analyses of N- and O-glycans of erythrocyte and plasma glycopeptides from these and other mammalian taxa confirmed this phenomenon. Sia modifications on these glycopeptides also appear to be undergoing rapid evolution. This rapid evolution of the sialome presumably results from the ongoing need of organisms to evade microbial pathogens that use Sia residues as receptors. The rapid evolution of Sia-binding domains of the inhibitory CD33-related Sia-recognizing Ig-like lectins is likely to be a secondary consequence, as these inhibitory receptors presumably need to keep up with recognition of the rapidly evolving "self"-sialome.
authors.affiliation: Glycobiology Research and Training Center, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093-0687, USA.
authors.forename: Tasha K
authors.initials: TK
authors.lastname: Altheide
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Tarjei S
authors.initials: TS
authors.lastname: Mikkelsen
authors.forename: Sandra
authors.initials: S
authors.lastname: Diaz
authors.forename: Nissi
authors.initials: N
authors.lastname: Varki
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D005075:Biological Evolution; D016678:Genome; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry; D002679:Pan troglodytes; D017433:Protein Structure, Secondary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D063268:Sialic Acid Binding Ig-like Lectin 3; D013045:Species Specificity
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C571165:Cd33 protein, mouse; D009844:Oligosaccharides; D063268:Sialic Acid Binding Ig-like Lectin 3; D019158:N-Acetylneuraminic Acid