Turcot-Dubois Anne-Laure, Le Moullac-Vaidye Béatrice, Despiau Stéphanie, Roubinet Francis, Bovin Nicolai, Le Pendu Jacques, Blancher Antoine
INSERM U601, Université de Nantes, Institut de Biologie, 9 Quai Moncousu, 44093 Nantes Cedex, and Laboratoire d'Immunologie, Hôpital Rangueil, Toulouse, France.
Glycobiology. 2007 May;17(5):516-28. doi: 10.1093/glycob/cwm016. Epub 2007 Feb 13.
Functional glycosyltransferase 6 (GT6) family members catalyze the transfer of galactose or N-acetylgalactosamine in alpha1,3 linkage to various substrates and synthesize structures related to the A and B histo-blood group antigens, the Forssman antigen, alphaGal epitope, and iGb3 glycolipid. In rat, mouse, dog, and cow genomes, we have identified three new mammalian genes (GT6m5, GT6m6, and GT6m7) encoding putative proteins belonging to the GT6 family. Among these, GT6m6 protein does not display major alterations of the GT6 motifs involved in binding of the divalent cation and the substrate. Based on protein sequence comparison, gene structure, and synteny, GT6 homologous sequences were also identified in bird, fish, and amphibian genomes. Strikingly, the number and type of GT6 genes varied widely from species to species, even within phylogenetically related groups. In human, except ABO functional alleles, all other GT6 genes are either absent or nonfunctional. Human, mouse, and cow have only one ABO gene, whereas rat and dog have several. In the chicken, the Forssman synthase-like is the single GT6 family member. Five Forssman synthase-like genes were found in zebrafish, but are absent from three other fishes (fugu, puffer fish, and medaka). Two iGb3 synthase-like genes were found in medaka, which are absent from zebrafish. Fugu, puffer fish, and medaka have an additional GT6 gene that we termed GT6m8, which is absent from all other species analyzed here. These observations indicate that individual GT6 genes have expanded and contracted by recurrent duplications and deletions during vertebrate evolution, following a birth-and-death evolution type.
功能性糖基转移酶6(GT6)家族成员催化将α1,3连接的半乳糖或N-乙酰半乳糖胺转移至各种底物,并合成与A和B组织血型抗原、福斯曼抗原、αGal表位及iGb3糖脂相关的结构。在大鼠、小鼠、狗和牛的基因组中,我们鉴定出三个新的哺乳动物基因(GT6m5、GT6m6和GT6m7),它们编码属于GT6家族的推定蛋白。其中,GT6m6蛋白在参与二价阳离子和底物结合的GT6基序方面未显示出重大改变。基于蛋白质序列比较、基因结构和同线性分析,在鸟类、鱼类和两栖动物基因组中也鉴定出了GT6同源序列。引人注目的是,GT6基因的数量和类型在不同物种间差异很大,即使在系统发育相关的类群中也是如此。在人类中,除ABO功能等位基因外,所有其他GT6基因要么缺失,要么无功能。人类、小鼠和牛只有一个ABO基因,而大鼠和狗有多个。在鸡中,福斯曼合酶样蛋白是唯一的GT6家族成员。在斑马鱼中发现了五个福斯曼合酶样基因,但在其他三种鱼类(河豚、河鲀和青鳉)中不存在。在青鳉中发现了两个iGb3合酶样基因,斑马鱼中没有。河豚、河鲀和青鳉有一个额外的GT6基因,我们将其命名为GT6m8,本文分析的所有其他物种中均不存在。这些观察结果表明,在脊椎动物进化过程中,单个GT6基因通过反复的复制和缺失经历了扩增和收缩,遵循一种生死进化类型。