Altheide Tasha K, Hayakawa Toshiyuki, Mikkelsen Tarjei S, Diaz Sandra, Varki Nissi, Varki Ajit
Glycobiology Research and Training Center, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093-0687, USA.
J Biol Chem. 2006 Sep 1;281(35):25689-702. doi: 10.1074/jbc.M604221200. Epub 2006 Jun 12.
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.
许多脊椎动物基因参与了与糖缀合物相连的寡糖链的生物学过程。在传统的基因本体分类中，这些基因分属于不同的类别。然而，应从功能和进化的角度，采用“生化系统”方法将它们放在一起进行评估，同时考虑每个单糖单元的生物合成、激活、转运、修饰、转移、循环利用、降解和识别。唾液酸（Sia）残基是脊椎动物细胞表面聚糖和分泌分子末端的单糖，介导内在或外在（病原体）受体的识别。多个基因组序列的可得性使得我们能够在灵长类动物和啮齿动物之间，对所有直接参与Sia生物学过程的基因进行全系统比较。采用这种方法，我们进一步证明了CD33相关的Sia识别免疫球蛋白样凝集素的Sia结合结构域存在加速进化。其他基因类别则更为保守，包括那些编码将Sia残基连接到聚糖上的唾液酸转移酶的基因。尽管存在这种保守性，但这些物种之间的组织唾液酸化模式差异很大，推测是由于唾液酸转移酶表达模式的快速进化。对这些以及其他哺乳动物类群的红细胞和血浆糖肽的N-聚糖和O-聚糖的分析证实了这一现象。这些糖肽上的Sia修饰似乎也在经历快速进化。唾液酸组的这种快速进化可能是由于生物体持续需要逃避将Sia残基作为受体的微生物病原体。抑制性CD33相关的Sia识别免疫球蛋白样凝集素的Sia结合结构域的快速进化可能是一个次要结果，因为这些抑制性受体可能需要跟上对快速进化的“自身”唾液酸组的识别。
