Comparative evolutionary analysis of the FoxG1 transcription factor from diverse vertebrates identifies conserved recognition sites for microRNA regulation
Comparative evolutionary analysis of the FoxG1 transcription factor from diverse vertebrates identifies conserved recognition sites for microRNA regulation
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DOI：
10.1007/s00427-006-0128-x
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发表时间：
2007-03-01
影响因子：
2.4
通讯作者：
Illing, Nicola
中科院分区：
文献类型：
--
作者：
Bredenkamp, Nicholas;Seoighe, Cathal;Illing, Nicola
来自不同脊椎动物的直系同源物的比较分析可用于鉴定对基因功能重要的分子特征，其可预测新的调控机制或解释形态多样性。叉头框G1（FoxG 1）转录因子是一个潜在的强有力的候选基因，用于确定前脑的大小在脊椎动物中，由于其在端脑的发展中的作用，在那里它促进祖细胞增殖和抑制过早的神经发生。为了研究FoxG 1在前脑进化中的作用，我们克隆并分析了9个新的FoxG 1直系同源物的cDNA序列，包括6种哺乳动物和3种爬行动物，并显示在N-末端结构域中有一个扩展的脯氨酸和谷氨酰胺区域，该区域是哺乳动物特有的。与以前一些关于大脑大小的其他潜在决定因素的研究相反，我们没有发现任何证据表明FoxG 1的编码序列在脊椎动物中的正选择下进化。先前发表的研究表明，FOXG 1在人类中是重复的，FOXG 1A和FOXG 1B两种形式存在于基因数据库中。我们报告说，FOXG 1还没有在人类中复制，FOXG 1A很可能是一个工件。我们对FOXG 1B及其直向同源物的比较分析表明，FOXG 1B的3'非翻译区（UTR）具有很高的保守性。利用现有的计算工具，我们发现了FoxG 1 3' UTR中miR-9和miR-33 microRNA的保守识别位点的证据，并假设这些脑表达的microRNA可能在前脑发育过程中转录后调节FoxG 1。
Comparative analysis of orthologues from diverse vertebrates can be used to identify molecular signatures that are important for gene function and which may predict novel regulatory mechanisms or explain morphological diversity. The forkhead box G1 (FoxG1) transcription factor is potentially a strong candidate gene for determining forebrain size in vertebrates due to its role in the development of the telencephalon, where it promotes progenitor proliferation and suppresses premature neurogenesis. To investigate the role of FoxG1 in forebrain evolution, we cloned and analyzed the cDNA sequences for nine new FoxG1 orthologues, including six mammals and three reptiles, and show that there is an extended proline and glutamine region in the N-terminal domain that is specific to mammals. In contrast to some previous studies of other potential determinants of brain size, we find no evidence that the coding sequence of FoxG1 has evolved under positive selection in vertebrates. Previously published work has indicated that FOXG1 was duplicated in humans, and two forms, FOXG1A and FOXG1B, are present in the Entrez Gene database. We report that FOXG1 has not been duplicated in humans and that FOXG1A is likely to be an artifact. Our comparative analysis of FOXG1B and its orthologues has revealed a very high level of conservation in the 3' untranslated region (UTR). Using available computational tools, we find evidence for conserved recognition sites for the miR-9 and miR-33 microRNAs in the FoxG1 3' UTR and hypothesize that these brain-expressed microRNAs may regulate FoxG1 post-transcriptionally during forebrain development.