Oswal Nupur, Sahni Narinder Singh, Bhattacharya Alok, Komath Sneha Sudha, Muthuswami Rohini
School of Life Sciences, Jawaharlal Nehru University, New Delhi - 110 067, India.
BMC Evol Biol. 2008 Jun 4;8:168. doi: 10.1186/1471-2148-8-168.
The first step of GPI anchor biosynthesis is catalyzed by PIG-A, an enzyme that transfers N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol. This protein is present in all eukaryotic organisms ranging from protozoa to higher mammals, as part of a larger complex of five to six 'accessory' proteins whose individual roles in the glycosyltransferase reaction are as yet unclear. The PIG-A gene has been shown to be an essential gene in various eukaryotes. In humans, mutations in the protein have been associated with paroxysomal noctural hemoglobuinuria. The corresponding PIG-A gene has also been recently identified in the genome of many archaeabacteria although genes of the accessory proteins have not been discovered in them. The present study explores the evolution of PIG-A and the phylogenetic relationship between this protein and other glycosyltransferases.
In this paper we show that out of the twelve conserved motifs identified by us eleven are exclusively present in PIG-A and, therefore, can be used as markers to identify PIG-A from newly sequenced genomes. Three of these motifs are absent in the primitive eukaryote, G. lamblia. Sequence analyses show that seven of these conserved motifs are present in prokaryote and archaeal counterparts in rudimentary forms and can be used to differentiate PIG-A proteins from glycosyltransferases. Using partial least square regression analysis and data involving presence or absence of motifs in a range of PIG-A and glycosyltransferases we show that (i) PIG-A may have evolved from prokaryotic glycosyltransferases and lipopolysaccharide synthases, members of the GT4 family of glycosyltransferases and (ii) it is possible to uniquely classify PIG-A proteins versus glycosyltransferases.
Besides identifying unique motifs and showing that PIG-A protein from G. lamblia and some putative PIG-A proteins from archaebacteria are evolutionarily closer to glycosyltransferases, these studies provide a new method for identification and classification of PIG-A proteins.
糖基磷脂酰肌醇（GPI）锚生物合成的第一步由PIG - A催化，该酶将N - 乙酰葡糖胺从UDP - N - 乙酰葡糖胺转移至磷脂酰肌醇。这种蛋白质存在于从原生动物到高等哺乳动物的所有真核生物中，是一个由五到六个“辅助”蛋白质组成的更大复合物的一部分，其在糖基转移酶反应中的各自作用尚不清楚。PIG - A基因已被证明是各种真核生物中的必需基因。在人类中，该蛋白质的突变与阵发性夜间血红蛋白尿有关。最近在许多古细菌的基因组中也发现了相应的PIG - A基因，尽管尚未在其中发现辅助蛋白质的基因。本研究探讨了PIG - A的进化以及该蛋白质与其他糖基转移酶之间的系统发育关系。
在本文中我们表明，在我们鉴定出的12个保守基序中，有11个仅存在于PIG - A中，因此可作为从新测序基因组中鉴定PIG - A的标记。这些基序中的三个在原始真核生物蓝氏贾第鞭毛虫中不存在。序列分析表明，这些保守基序中的七个以基本形式存在于原核生物和古细菌对应物中，可用于将PIG - A蛋白与糖基转移酶区分开来。使用偏最小二乘回归分析以及涉及一系列PIG - A和糖基转移酶中基序存在与否的数据，我们表明：（i）PIG - A可能从原核糖基转移酶和脂多糖合酶进化而来，它们是糖基转移酶GT4家族的成员；（ii）有可能将PIG - A蛋白与糖基转移酶进行独特分类。
除了鉴定独特的基序并表明蓝氏贾第鞭毛虫的PIG - A蛋白和一些来自古细菌的假定PIG - A蛋白在进化上更接近糖基转移酶外，这些研究还提供了一种鉴定和分类PIG - A蛋白的新方法。
