Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
PLoS One. 2010 Feb 10;5(2):e9144. doi: 10.1371/journal.pone.0009144.
UDP-glucuronosyltransferases (Ugts) are a supergene family of phase II drug-metabolizing enzymes that catalyze the conjugation of numerous hydrophobic small molecules with the UDP-glucuronic acid, converting them into hydrophilic molecules. Here, we report the identification and cloning of the complete zebrafish Ugt gene repertoire. We found that the zebrafish genome contains 45 Ugt genes that can be divided into three families: Ugt1, Ugt2, and Ugt5. Both Ugt1 and Ugt2 have two unlinked clusters: a and b. The Ugt1a, Ugt1b, Ugt2a, and Ugt2b clusters each contain variable and constant regions, similar to that of the protocadherin (Pcdh), immunoglobulin (Ig), and T-cell receptor (Tcr) clusters. Cloning the full-length coding sequences confirmed that each of the variable exons is separately spliced to the set of constant exons within each zebrafish Ugt cluster. Comparative analyses showed that both a and b clusters of the zebrafish Ugt1 and Ugt2 genes have orthologs in other teleosts, suggesting that they may be resulted from the "fish-specific" whole-genome duplication event. The Ugt5 genes are a novel family of Ugt genes that exist in teleosts and amphibians. Their entire open reading frames are encoded by single large exons. The zebrafish Ugt1, Ugt2, and Ugt5 genes can generate additional transcript diversity through alternative splicing. Based on phylogenetic analyses, we propose that the ancestral tetrapod and teleost Ugt1 clusters contained multiple Ugt1 paralogs. After speciation, these ancestral Ugt1 clusters underwent lineage-specific gene loss and duplication. The ancestral vertebrate Ugt2 cluster also underwent lineage-specific duplication. The intronless Ugt5 open reading frames may be derived from retrotransposition followed by gene duplication. They have been expanded dramatically in teleosts and have become the most abundant Ugt family in these lineages. These findings have interesting implications regarding the molecular evolution of genes with diversified variable exons in vertebrates.
UDP-葡糖醛酸基转移酶 (UGTs) 是一种 II 相药物代谢酶的超基因家族，可催化许多疏水性小分子与 UDP-葡糖醛酸的缀合，将它们转化为亲水性分子。在这里，我们报告了斑马鱼 Ugt 基因全谱的鉴定和克隆。我们发现，斑马鱼基因组包含 45 个 Ugt 基因，可分为三个家族：Ugt1、Ugt2 和 Ugt5。Ugt1 和 Ugt2 都有两个不相连的簇：a 和 b。Ugt1a、Ugt1b、Ugt2a 和 Ugt2b 簇都包含可变区和恒定区，类似于原钙黏蛋白 (Pcdh)、免疫球蛋白 (Ig) 和 T 细胞受体 (Tcr) 簇。克隆全长编码序列证实，每个可变外显子都分别与每个斑马鱼 Ugt 簇中的一组恒定外显子拼接。比较分析表明，斑马鱼 Ugt1 和 Ugt2 基因的 a 和 b 簇在其他硬骨鱼中都有同源基因，这表明它们可能是由“鱼类特异性”全基因组复制事件产生的。Ugt5 基因是硬骨鱼和两栖动物中一个新的 Ugt 基因家族。它们的整个开放阅读框由单个大外显子编码。斑马鱼 Ugt1、Ugt2 和 Ugt5 基因可以通过选择性剪接产生额外的转录多样性。基于系统发育分析，我们提出，祖先后肢动物和硬骨鱼 Ugt1 簇包含多个 Ugt1 旁系同源基因。在物种形成后，这些祖先 Ugt1 簇经历了谱系特异性基因丢失和复制。祖先后肢动物 Ugt2 簇也经历了谱系特异性复制。无内含子的 Ugt5 开放阅读框可能来自逆转录转座后基因复制。它们在硬骨鱼中得到了极大的扩展，并成为这些谱系中最丰富的 Ugt 家族。这些发现对具有多样化可变外显子的脊椎动物基因的分子进化具有有趣的意义。
