來自上海交通大學(xué)系統(tǒng)生物醫(yī)學(xué)院的吳強(qiáng)教授近期在復(fù)雜基因簇研究方面又取得新的原創(chuàng)性成果，相關(guān)文章發(fā)表在PLoS One上,。
尿苷二磷酸葡醛酸轉(zhuǎn)移酶（UGT）基因簇和原鈣粘蛋白基因簇具有相似的基因組結(jié)構(gòu),，都具有可變區(qū)和恒定區(qū)，類似于生物抗體的基因結(jié)構(gòu),，通過可變剪接可以產(chǎn)生非常多的蛋白質(zhì)分子多樣性,。UGT蛋白家族在生物體化學(xué)防御和藥物代謝系統(tǒng)中具有重要科學(xué)意義。例如,，UGT蛋白家族在直腸癌藥物伊利替康的肝臟代謝中起著舉足輕重的作用,。因此，研究UGT基因家族對(duì)研究藥物在肝臟中的代謝機(jī)制,，以及指導(dǎo)臨床個(gè)性化藥物治療和合理用藥,、預(yù)測(cè)藥物相互作用、減少藥物不良反應(yīng),、預(yù)防人類疾病都具有重要意義,。但是，UGT分子多樣性的產(chǎn)生機(jī)理還不清楚,。
我們的大腦包含超過一千億個(gè)神經(jīng)元細(xì)胞,，這些細(xì)胞形成約一百五十萬億個(gè)特異性的突觸連接。闡明人類腦神經(jīng)復(fù)雜連接的發(fā)育機(jī)理和大腦學(xué)習(xí)記憶的認(rèn)知功能是生命科學(xué)的巨大挑戰(zhàn),。原鈣粘蛋白家族是大腦神經(jīng)元細(xì)胞膜上具有細(xì)胞特異性表達(dá)模式的細(xì)胞粘連分子,。原鈣粘蛋白有非常復(fù)雜的分子多樣性，可能在腦發(fā)育和腦功能方面起到重要作用,。
該研究通過對(duì)基因打靶小鼠的表型分析,，利用綠色熒光蛋白作為報(bào)告基因敲入原鈣粘蛋白位點(diǎn)，發(fā)現(xiàn)一個(gè)原鈣粘蛋白基因在大腦皮層發(fā)育過程中的中間神經(jīng)元切線狀和放射狀遷移中起到重要作用,。（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS ONE 5(2): e9144. doi:10.1371/journal.pone.0009144
Cloning and Comparative Analyses of the Zebrafish Ugt Repertoire Reveal Its Evolutionary Diversity
Haiyan Huang1,2, Qiang Wu1,2*
1 Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China, 2 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China
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.
