Structural, functional genomics olfactory receptor genes

结构、功能基因组学嗅觉受体基因

基本信息

批准号：
7192464
负责人：
BARBARA J. TRASK
金额：
$ 83.7万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
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/7192464
关键词：
Address Affect Afferent Neurons Aging Animals Architecture Area Biochemistry Biology Brain Cations Cell Nucleus Collaborations Complex Condition DNA DNA Sequence Rearrangement Data Development Employee Strikes Environment Event Evolution Exhibits Exposure to Family Food Gene Conversion Gene Duplication Gene Expression Gene Family Gene Structure Gene Targeting Genes Genetic Genetic Polymorphism Genome Genomics Goals Hormonal Human Individual Inherited Laboratories Lead Ligands Mammals Microarray Analysis Molecular Molecular Cytogenetics Molecular Profiling Mus Nature Neurobiology Neurons Nose Nuclear Nutritional status Odorant Receptors Odors Oligonucleotide Microarrays Pattern Perception Physiological Process Proteins Receptor Gene Regulation Research Personnel Shapes Signal Transduction Smell Perception Specificity Structure Testing Tissues Transcriptional Regulation Translating Variant Work comparative computerized tools design dosage functional/structural genomics hybrid gene insight interest member molecular recognition novel olfactory receptor pressure programs receptor receptor expression research study sensor size skills

项目摘要

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）：哺乳动物的鼻子具有检测数百万种不同气味的能力，是外部环境的精美传感器。对于大多数动物而言，嗅觉对于找到食物，避免伤害，导航和在个人之间进行交流至关重要。负责气味分子识别的嗅觉受体（OR）的家族因其大小，多样性，基因组分布，进化动力学和异常调节控制而引人注目。 OR“亚基因组”拥有超过1000个基因并占据了约1％的核DNA，为研究塑造基因组的进化过程提供了一个独特而具有挑战性的机会。该项目的总体目标是了解这些过程如何参与或基因家族的演变，最终允许动物适应不断变化的嗅觉景观。为了实现这一目标，我们将计算和实验方法结合起来，以表征全球或基因演化，变异和调节。在AIM 1中，我们检查了影响多种物种的选择性压力。气味识别和神经元接线的互补功能研究将进一步理解我们对如何或基因序列中如何转化为嗅觉感知的方式。在AIM 2中，我们研究了重复和基因转化是如何导致或家庭的扩展和多样化，并为物种之间和物种之间的基因型变异做出了贡献。在AIM 3中，我们使用微阵列技术来表征ORS表达的曲目，确定表达OR的其他组织以及在发育，衰老以及在不同的环境和生理条件下的表达模式如何变化。最后，在AIM 4中，我们结合了小鼠遗传学和基因组分析，以获得对调节机制的新见解，这些机制决定了嗅觉感觉神经元如何从整个或曲目中选择一个单个基因以表达表达。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中的基本问题，同时也为基因 - 家庭进化，转录调控以及复杂基因组结构的起源和后果做出了重大贡献。