Pheromone Receptor Genomic Evolution and Gene Regulation

信息素受体基因组进化和基因调控

• 批准号: 6885760
• 负责人: Robert P. Lane
• 金额: $ 36.78万
• 依托单位: WESLEYAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885760
• 关键词: biochemical evolution; comparative genomic hybridization; genetic promoter element; genetic regulation; genetic regulatory element; genetic transcription; genetically modified animals; in situ hybridization; laboratory mouse; pheromone; receptor expression; transcription factor; vomeronasal systems

DESCRIPTION (provided by applicant): Pheromonal communication is a critical mediator of reproductive and social behaviors. The ability to respond to pheromonal cues from individuals within the species, and to avoid being confused by pheromonal signals from other species, is clearly important. This raises interesting questions regarding the evolution of distinct pheromonal systems during speciation. This project utilizes a combination of molecular, genetic, and genomic approaches to investigate how rodent pheromonal systems have evolved in species-specific ways and how pheromone receptor genes are regulated to recognize and distinguish pheromones. In Aim 1, we will investigate our hypothesis that repeat-mediated V1R duplication led to punctuate divergence in routine pheromone systems. These studies will indicate subsets of pheromone receptor genes that likely underlie the ability of species to communicate exclusively. More broadly, these studies should provide insights into the general role of repeat structures in the punctuated evolution of genomes. In Aim 2, we will use bioinformatic approaches to identify putative regulatory sequences in V1R promoter regions. These studies will build on j previous work in which locus-specific and cross-locus putative regulatory features were identified. The specific hypothesis we are investigating is that V1R gene choice is hierarchical, involving selection of a genomic locus followed by selection of a single gene within the cluster. In Aim 3, we will identify transcription factors that interact with putative regulatory sequences identified previously. Specifically, we will investigate the function of a locus-specific promoter motif identified near all V1R promoters in one cluster, as well as a motif within this cluster that is homologous to the globin Locus Control Region. In Aim 4, we will test the hypothesis that VIR genes regulate by locus-based mechanisms, a hypothesis that is born from several genomic observations and is consistent with the punctuated expansion of specific loci during evolution. We will knock-in a V1R transgene to a non-native (and native) genomic position to investigate whether V1R genes regulate autonomously. More broadly, these studies may provide insights into how the genome is partitioned into regulatory compartments. The partnership between the Chess group, with considerable expertise in transgenics and olfactory biology, and the Lane group, with broad experience in bioinformatics and molecular evolution, represents an important niche that unites genomics and functional biology.

描述（由申请人提供）：信息素通讯是生殖和社会行为的关键中介。对物种内个体的信息素信号做出反应并避免被其他物种的信息素信号混淆的能力显然很重要。这提出了关于物种形成过程中不同信息素系统进化的有趣问题。该项目综合利用分子、遗传和基因组方法来研究啮齿动物信息素系统如何以物种特异性方式进化，以及如何调节信息素受体基因来识别和区分信息素。在目标 1 中，我们将研究我们的假设，即重复介导的 V1R 复制导致常规信息素系统出现间断分歧。这些研究将表明信息素受体基因的子集可能是物种排他性交流能力的基础。更广泛地说，这些研究应该提供对重复结构在基因组间断进化中的一般作用的见解。在目标 2 中，我们将使用生物信息学方法来识别 V1R 启动子区域中推定的调控序列。这些研究将建立在先前工作的基础上，其中确定了基因座特异性和跨基因座的假定调控特征。我们正在研究的具体假设是，V1R 基因选择是分层的，包括选择基因组位点，然后选择簇内的单个基因。在目标 3 中，我们将鉴定与先前鉴定的假定调控序列相互作用的转录因子。具体来说，我们将研究在一个簇中所有 V1R 启动子附近鉴定的基因座特异性启动子基序的功能，以及该簇内与球蛋白基因座控制区同源的基序。在目标 4 中，我们将检验 VIR 基因通过基于基因座的机制进行调节的假设，该假设源自多次基因组观察，并且与进化过程中特定基因座的间断扩展一致。我们将把 V1R 转基因敲入非天然（和天然）基因组位置，以研究 V1R 基因是否自主调节。更广泛地说，这些研究可能提供关于基因组如何划分为调控区室的见解。 Chess 团队在转基因和嗅觉生物学方面拥有丰富的专业知识，而 Lane 团队在生物信息学和分子进化方面拥有丰富的经验，两者之间的合作代表了将基因组学和功能生物学结合起来的重要利基市场。