MicroRNA evolution and species divergence in Drosophila

果蝇的 MicroRNA 进化和物种分化

• 批准号: 7883738
• 负责人: CHUNG-I WU
• 金额: $ 22.44万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-20 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7883738
• 关键词: Address; Affect; Animals; Bioinformatics; Biological Assay; Complex; Drosophila genus; Evolution; Fertility; Gene Expression; Gene Targeting; Genes; Goals; Hereditary Disease; Human; Malignant Neoplasms; Measures; Messenger RNA; MicroRNAs; Modeling; Phenotype; Play; Population; Reporter Genes; Repression; Role; Site; Small RNA; Surveys; Testing; Tissues; Transcript; Transgenes; Transgenic Organisms; Translations; Untranslated Regions; Work; base; falls; fitness; interest; plant growth/development; research study; trait

DESCRIPTION (provided by applicant): The goal is to understand the evolution of microRNAs (miRNAs), the coevolution between miRNAs and their targets, and the role miRNA-target interactions play in the expression divergence between closely related species of Drosophila. miRNAs are small regulatory RNAs, which target mRNA transcripts to repress their expression. Aim 1: The evolution of miRNA genes - Emergence of new miRNA genes and changes in either the sequences of mature miRs or their expression will be studied by extensive sequencing of small RNAs from six tissues in five species of Drosophila. Aim 2: The effects of miRNAs on the evolution of gene expression (I. miRNAs) - First, four conservative miRNAs will be used to transform D. melanogaster and D. simulans. Second, four pairs of evolving miRNAs will be used to transform D. melanogaster. The effects of the transgenes on expression will be assayed by microarrays. Aim 3: The effects of miRNAs on the evolution of gene expression (II. targets) - We will verify and calibrate the results of D2 by selecting the 3' UTR of 15 target genes for reporter assay. Aim 4: The fitness effects of the coevolution between miRNAs and targets - If miRNAs and targets are co-adapted, then miRNAs and target transcripts that have been evolving separately would likely show fitness incompatibilities. This hypothesis, in the frame work of Muller-Dobzhansky model, will be tested. Project Narrative: Micro-RNAs are a large class of regulators of the activities of other genes. They are known to function in animal/plant development, cancer, complex traits and genetic diseases. A survey of the scope of microRNA repertoire and their rise and fall through evolution will be useful for understanding their roles in regulating the normal and aberrant phenotypes in human populations.

描述（由申请人提供）：目标是了解 microRNA (miRNA) 的进化、miRNA 与其靶标之间的共同进化，以及 miRNA-靶标相互作用在果蝇密切相关物种之间的表达差异中所起的作用。 miRNA 是小型调节 RNA，其靶向 mRNA 转录物以抑制其表达。 目标 1：miRNA 基因的进化 - 将通过对来自 5 个果蝇物种的 6 个组织的小 RNA 进行广泛测序来研究新 miRNA 基因的出现以及成熟 miR 序列或其表达的变化。 目标 2：miRNA 对基因表达进化的影响（I. miRNA） - 首先，将使用四种保守 miRNA 来转化黑腹果蝇和模拟果蝇。其次，四对不断进化的 miRNA 将用于转化黑腹果蝇。将通过微阵列测定转基因对表达的影响。 目标3：miRNA对基因表达进化的影响（II.靶标） - 我们将通过选择15个靶基因的3'UTR进行报告基因检测来验证和校准D2的结果。 目标 4：miRNA 和靶标之间共同进化的适应性效应 - 如果 miRNA 和靶标共同适应，那么分别进化的 miRNA 和靶标转录本可能会表现出适应性不相容。这一假设将在 Muller-Dobzhansky 模型的框架中得到检验。 项目叙述：Micro-RNA 是一大类其他基因活性的调节因子。已知它们在动物/植物发育、癌症、复杂性状和遗传疾病中发挥作用。对 microRNA 库的范围及其在进化过程中的兴衰的调查将有助于了解它们在调节人类正常和异常表型中的作用。