MicroRNA evolution and species divergence in Drosophila

描述（由申请人提供）：目的是了解microRNA（miRNAs）的进化，miRNAs及其靶标之间的共同进化，以及miRNAs-靶标相互作用在密切相关的果蝇物种之间的表达差异中所起的作用。miRNAs是一种小的调控RNA，其靶向mRNA转录物以抑制其表达。 目标1：miRNA基因的进化-新的miRNA基因的出现和成熟的miR序列或其表达的变化将通过对来自5种果蝇的6种组织的小RNA进行广泛测序来研究。 目的2：miRNAs对基因表达进化的影响（I. miRNAs）-首先，将使用四种保守的miRNAs来转化D. melanogaster和D.模拟。第二，四对不断进化的miRNAs将被用于转化D.黑腹菌将通过微阵列测定转基因对表达的影响。 目的3：miRNA对基因表达进化的影响（II.我们将通过选择15个靶基因的3' UTR进行报告基因测定来验证和校准D2的结果。 目标4：miRNAs和靶基因之间协同进化的适应性效应-如果miRNAs和靶基因是协同适应的，那么单独进化的miRNAs和靶基因转录本可能会表现出适应性不相容。本文将在Muller-Dobzhansky模型的框架下对这一假设进行检验。 Micro-RNA是其他基因活动的一大类调节因子。已知它们在动物/植物发育、癌症、复杂性状和遗传疾病中起作用。对microRNA库的范围及其在进化过程中的上升和下降的调查将有助于了解它们在调节人类群体中正常和异常表型中的作用。

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.