Phylogenetic Development of a Regulatory Gene for the Core 2 GlcNAc Transferase in Mus musculus
作者:M. Sekine、Y. Kikkawa、S. Takahama、K. Tsuda、H. Yonekawa、A. Suzuki
DOI:10.1093/oxfordjournals.jbchem.a003234
日期:2002.9.1
In our previous study, we identified a mouse gene, Gsl5, that controls the expression of a glycolipid, GL-Y [Galβl–4(Fucαl–3)GlcNAcβ1–6(Ga1β1–3)GalNAcβ1–3Galα1–4Ga1β1–4Glcβ1-Cer], and the core 2 structure of O-linked glycans of glycoproteins, GlcNAcβ1-6(Ga1β1–3)GalNAcα-Ser/Thr, in a kidney tubular cell-specific manner through the regulation of UDP-GlcNAc β-l,6-GlcNAc transferase (GNT). Regulation by the G8l5 gene occurs at the level of GNT mRNA and the recessive allele of G8l5 is rare and carried by DBA/2 and its related strains. Here, we report a sequence comparison of the 5' flanking region of the GNT gene among 5 laboratory strains and 10 wild-derived strains, demonstrating that the DBA/2 allele sequence is similar to the sequence carried by Asian Mus m. musculus and differs substantially from the East European M. m. musculus. These results suggest that the DBA/2 allele of G8l5 was introduced into laboratory mouse strains by Asian wild-derived mice. Phylogenetic comparison of the 5' flanking region sequences between the recessive and dominant G8l5 alleles indicates that mutations to create a functional G8l5 gene occurred approximately one million years ago during the subspeciation of M. musculus, and provides a case for studies on the creation of functional genes involved in tissue-specific transcriptional regulation.
在我们之前的研究中,我们鉴定出一种小鼠基因Gsl5,该基因通过调控UDP-GlcNAc β-l,6-GlcNAc转移酶(GNT),在肾小管细胞特异性地控制糖脂GL-Y和糖蛋白O-连接糖链的核心2结构的表达。该基因的调控发生在GNT mRNA水平,而G8l5的隐性等位基因则很少,只由DBA/2及其相关品系携带。在这里,我们报告了5个实验室品系和10个野生衍生品系GNT基因5'侧翼区域的序列比较,显示DBA/2等位基因序列与亚洲Mus m. musculus携带的序列相似,而与东欧M. m. musculus存在显著差异。这些结果表明G8l5的DBA/2等位基因是通过亚洲野生衍生小鼠引入实验室小鼠品系的。对隐性和显性G8l5等位基因5'侧翼区域序列的系统发育比较表明,构建功能性G8l5基因的突变大约发生在一百万年前,即M. musculus的亚物种分化期间,并为研究涉及组织特异性转录调控的功能基因的形成提供了一个案例。