Cloning and comparative analyses of the zebrafish Ugt repertoire reveal its evolutionary diversity.
Cloning and comparative analyses of the zebrafish Ugt repertoire reveal its evolutionary diversity.
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斑马鱼 Ugt 库的克隆和比较分析揭示了其进化多样性
DOI：
10.1371/journal.pone.0009144
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发表时间：
2010-02-10
期刊：
影响因子：
3.7
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Huang H;Wu Q
UDP-葡萄糖醛酸转移酶（Ugts）是II相药物代谢酶的超基因家族，其催化许多疏水性小分子与UDP-葡萄糖醛酸的缀合，将其转化为亲水性分子。在这里，我们报告的鉴定和克隆的完整斑马鱼Ugt基因剧目。我们发现斑马鱼基因组包含45个Ugt基因，可分为三个家族：Ugt 1，Ugt 2和Ugt 5。Ugt 1和Ugt 2都有两个不相连的簇：a和B。Ugt 1a、Ugt 1b、Ugt 2a和Ugt 2b簇均含有可变区和恒定区，与原钙粘蛋白（Pcdh）、免疫球蛋白（IG）和T细胞受体（Tcr）簇相似。克隆全长编码序列证实，每个可变外显子分别剪接到每个斑马鱼Ugt簇内的恒定外显子组。比较分析表明，斑马鱼Ugt 1和Ugt 2基因的a簇和B簇在其他硬骨鱼中均具有同源性，表明它们可能是由“鱼类特异性”的全基因组复制事件引起的。Ugt 5基因是存在于硬骨鱼和两栖类中的一个新的Ugt基因家族。它们的整个开放阅读框架由单个大外显子编码。斑马鱼Ugt 1、Ugt 2和Ugt 5基因可以通过选择性剪接产生额外的转录本多样性。系统发育分析的基础上，我们提出，祖先的四足动物和硬骨鱼Ugt 1集群包含多个Ugt 1旁系同源。物种形成后，这些祖先Ugt 1集群经历了谱系特异性基因丢失和复制。祖先脊椎动物Ugt 2簇也经历了谱系特异性复制。无内含子的Ugt 5开放阅读框可能来源于反转录转座，随后是基因复制。它们在硬骨鱼类中急剧扩大，并已成为这些谱系中最丰富的Ugt家族。这些发现对于脊椎动物中具有多样化可变外显子的基因的分子进化具有有趣的意义。
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.
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