Structural, functional genomics olfactory receptor genes

结构、功能基因组学嗅觉受体基因

• 批准号: 7380059
• 负责人: BARBARA J. TRASK
• 金额: $ 84.32万
• 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 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380059
• 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

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，是外部环境的精致传感器。对于大多数动物来说，嗅觉对于寻找食物，避免伤害，导航和个体之间的交流至关重要。负责气味分子识别的嗅觉受体（ORs）家族以其大小、多样性、基因组分布、进化动力学和不寻常的调节控制而引人注目。拥有超过1000个基因并占据约1%的核DNA，OR“亚基因组”为研究形成基因组的进化过程提供了独特且具有挑战性的机会。该项目的总体目标是了解这些过程如何参与OR基因家族的进化，最终使动物适应不断变化的嗅觉景观。为了实现这一目标，我们结合联合收割机的计算和实验方法，以全球性的特点或基因的进化，变异和调节。在目标1中，我们研究了影响多个物种OR进化的选择压力。气味识别和神经元布线的互补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性如何转化为嗅觉感知的理解。在目标2中，我们研究了重复和基因转换如何导致OR家族的扩张和多样化，并有助于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ORs的表达谱，鉴定ORs表达的其他组织，以及在发育、衰老以及不同环境和生理条件下表达模式如何变化。最后，在目标4中，我们结合联合收割机小鼠遗传学和基因组分析，以获得新的见解的监管机制，决定嗅觉感觉神经元如何选择一个单一的基因从整个或剧目的表达。总之，这些相互关联和互补的研究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。

项目成果

Degeneration of the olfactory guanylyl cyclase D gene during primate evolution.

• DOI: 10.1371/journal.pone.0000884
• 发表时间: 2007-09-12
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Young JM;Waters H;Dong C;Fülle HJ;Liman ER
• 通讯作者: Liman ER

Rigorous and thorough bioinformatic analyses of olfactory receptor promoters confirm enrichment of O/E and homeodomain binding sites but reveal no new common motifs.

对嗅觉受体启动子的严格而彻底的生物信息学分析证实了 O/E 和同源域结合位点的富集，但没有揭示新的共同基序。

• DOI: 10.1186/1471-2164-12-561
• 发表时间: 2011
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Young,JanetM;Luche,RalfM;Trask,BarbaraJ
• 通讯作者: Trask,BarbaraJ

Odorant receptor expressed sequence tags demonstrate olfactory expression of over 400 genes, extensive alternate splicing and unequal expression levels.

• DOI: 10.1186/gb-2003-4-11-r71
• 发表时间: 2003
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Young JM;Shykind BM;Lane RP;Tonnes-Priddy L;Ross JA;Walker M;Williams EM;Trask BJ
• 通讯作者: Trask BJ

Crystal structure of an ephrin ectodomain.

肝配蛋白胞外域的晶体结构。

• DOI: 10.1016/s1534-5807(01)00002-8
• 发表时间: 2001
• 期刊: Developmental cell.
• 作者: Toth,J;Cutforth,T;Gelinas,AD;Bethoney,KA;Bard,J;Harrison,CJ
• 通讯作者: Harrison,CJ

Extensive copy-number variation of the human olfactory receptor gene family.

• DOI: 10.1016/j.ajhg.2008.07.005
• 发表时间: 2008-08
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: Janet M. Young;Raelynn M Endicott;Sean S. Parghi;M. Walker;J. Kidd;B. Trask