Pheromone Receptor Genomic Evolution and Gene Regulation

描述(由申请人提供)：信息素交流是生殖和社会行为的重要中介。对物种内部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所迷惑的能力显然是重要的。这提出了一些有趣的问题，涉及物种形成过程中不同信息素系统的进化。该项目利用分子、遗传和基因组学方法相结合的方法来研究啮齿动物信息素系统是如何以物种特有的方式进化的，以及信息素受体基因是如何被调节来识别和区分信息素的。在目标1中，我们将调查我们的假设，即重复介导的V1R复制导致常规信息素系统中的点状发散。这些研究将指出信息素受体基因的子集，这些基因可能是物种唯一交流能力的基础。更广泛地说，这些研究应该提供对重复结构在基因组断断续续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鉴定V1R启动子区域的假定调控序列。这些研究将建立在先前工作的基础上，在这些工作中，确定了特定于基因座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基因的选择是分层次的，包括选择一个基因组位置，然后选择集群中的单个基因。在目标3中，我们将识别与先前确定的假定调控序列相互作用的转录因子。具体地说，我们将研究一个簇中所有V1R启动子附近发现的一个座位特异性启动子基序的功能，以及该簇中与珠蛋白基因位点控制区同源的一个基序的功能。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控的假设，该假设源于几个基因组观察，并与特定基因座在进化过程中的点状扩展相一致。我们将把V1R转基因基因敲入非天然(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，这些研究可能为基因组如何被划分为调节室提供洞察力。在转基因和嗅觉生物学方面拥有相当专业知识的国际象棋集团和在生物信息学和分子进化方面拥有广泛经验的莱恩集团之间的合作伙伴关系代表着联合基因组学和功能生物学的一个重要利基市场。

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.