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。对物种内个体的信息素信号作出反应的能力，以及避免被其他物种的信息素信号所混淆的能力，显然是很重要的。这就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。本项目利用分子、遗传和基因组方法的结合来研究啮齿动物信息素系统是如何以物种特异性的方式进化的，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。在目的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的间断分化。这些研究将表明，信息素受体基因的亚群可能是物种间排他性交流能力的基础。更广泛地说，这些研究应该为重复结构在基因组间断进化中的一般作用提供见解。在目标2中，我们将使用生物信息学方法来鉴定V1R启动子区域的推定调控序列。这些研究将建立在先前的工作基础上，其中确定了基因座特异性和交叉基因座推定的调节特征。我们正在研究的具体假设是，V1R基因的选择是分层的，包括选择一个基因组位点，然后选择集群中的单个基因。在目标3中，我们将确定与先前确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启动子附近发现的位点特异性启动子基序的功能，以及该簇中与珠蛋白位点控制区同源的基序。在Aim 4中，我们将验证VIR基因通过基于位点的机制进行调控的假设，这一假设来自于几项基因组观察，与进化过程中特定位点的间断扩展相一致。我们将把V1R转基因敲入到非原生（和原生）基因组位置，以研究V1R基因是否自主调节。更广泛地说，这些研究可能提供了关于基因组如何划分为调控区室的见解。在转基因和嗅觉生物学方面拥有丰富专业知识的Chess小组与在生物信息学和分子进化方面拥有丰富经验的Lane小组之间的合作，代表了将基因组学和功能生物学结合起来的重要利基。

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.