Structural, functional genomics olfactory receptor genes

结构、功能基因组学嗅觉受体基因

• 批准号: 7033923
• 负责人: BARBARA J. TRASK
• 金额: $ 84.35万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033923
• 关键词: animal genetic material tag; biochemical evolution; chemoreceptors; computational biology; cytogenetics; fluorescent in situ hybridization; functional /structural genomics; gene dosage; gene duplication; gene expression profiling; gene targeting; genetic regulation; genetically modified animals; genotype; human genetic material tag; human tissue; laboratory mouse; microarray technology; nucleic acid sequence; odors; olfactions; receptor expression; species difference

DESCRIPTION (provided by applicant): The mammalian nose, with its capacity to detect millions of different odors, is an exquisite sensor of the external environment. For most animals, the sense of smell is essential for locating food, avoiding harm, navigating, and communicating between individuals. The family of olfactory receptors (ORs) responsible for the molecular recognition of odors is remarkable for its size, diversity, genomic distribution, evolutionary dynamics, and unusual regulatory control. With well over 1000 genes and occupying approximately 1% of nuclear DNA, the OR 'subgenome' provides a unique and challenging opportunity to study the evolutionary processes that shape genomes. The overall goal of this project is to understand how these processes participate in the evolution of the OR gene family, ultimately allowing animals to adapt to changing olfactory landscapes. Towards that goal, we combine computational and experimental approaches in order to globally characterize OR gene evolution, variation, and regulation. In Aim 1, we examine the selective pressures that have influenced OR evolution in multiple species. Complementary functional studies of odor recognition and neuronal wiring will further our understanding of how conservation and variation in OR gene sequences translate into olfactory perception. In Aim 2, we examine how duplication and gene conversion have led to expansion and diversification of the OR family and contribute to genotypic variation within and between species. In Aim 3, we use microarray technology to characterize the expressed repertoire of ORs, identifying additional tissues in which ORs are expressed, and how expression patterns change during development, aging, and under different environmental and physiological conditions. Finally, in Aim 4, we combine mouse genetics and genome analyses to gain new insights into the regulatory mechanisms that determine how olfactory sensory neurons select a single gene from the entire OR repertoire for expression. Together, these interrelated and complementary studies address fundamental questions in the fields of olfaction and neurobiology, while also contributing significantly to the areas of gene-family evolution, transcriptional regulation, and the origin and consequences of complex genome architectures.

描述（由申请人提供）：哺乳动物的鼻子能够检测数百万种不同的气味，是外部环境的精密传感器。对于大多数动物来说，嗅觉对于寻找食物、避免伤害、导航以及个体之间的交流至关重要。负责气味分子识别的嗅觉受体 (OR) 家族因其大小、多样性、基因组分布、进化动力学和不寻常的调控控制而引人注目。 OR“亚基因组”拥有超过 1000 个基因，约占核 DNA 的 1%，为研究塑造基因组的进化过程提供了独特且富有挑战性的机会。该项目的总体目标是了解这些过程如何参与 OR 基因家族的进化，最终使动物适应不断变化的嗅觉环境。为了实现这一目标，我们结合计算和实验方法来全面描述 OR 基因的进化、变异和调控特征。在目标 1 中，我们研究了影响多个物种 OR 进化的选择压力。气味识别和神经元连接的补充功能研究将进一步加深我们对 OR 基因序列的保守性和变异如何转化为嗅觉感知的理解。在目标 2 中，我们研究了复制和基因转换如何导致 OR 家族的扩展和多样化，以及如何导致物种内和物种间的基因型变异。在目标 3 中，我们使用微阵列技术来表征 OR 的表达谱，识别 OR 表达的其他组织，以及表达模式在发育、衰老以及不同环境和生理条件下如何变化。最后，在目标 4 中，我们将小鼠遗传学和基因组分析结合起来，以获得对决定嗅觉感觉神经元如何从整个 OR 库中选择单个基因进行表达的调节机制的新见解。这些相互关联和互补的研究共同解决了嗅觉和神经生物学领域的基本问题，同时也对基因家族进化、转录调控以及复杂基因组结构的起源和后果等领域做出了重大贡献。