Pheromone Receptor Genomic Evolution and Gene Regulation

描述（由申请人提供）：信息素通信是生殖和社会行为的关键调解人。对来自物种内个体的信息素线索做出反应的能力，以及避免被来自其他物种的信息素信号所迷惑的能力，显然是重要的。这提出了有趣的问题，不同的信息素系统在物种形成过程中的演变。该项目利用分子，遗传和基因组的方法相结合，调查啮齿动物信息素系统如何在物种特异性的方式和信息素受体基因是如何调节识别和区分信息素进化。在目的1中，我们将探讨我们的假设，重复介导的V1R重复导致标点分歧在常规信息素系统。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排他性交流能力的基础。更广泛地说，这些研究应该提供洞察重复结构在间断进化的基因组中的一般作用。在目标2中，我们将使用生物信息学的方法来确定在V1R启动子区域的推定的调控序列。这些研究将建立在J以前的工作中，位点特异性和跨位点推定的监管功能进行了鉴定。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，然后选择簇内的单个基因。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，我们将调查一个位点特异性启动子基序的功能，确定在一个集群中的所有V1R启动子附近，以及在这个集群内的一个基序是同源的珠蛋白基因座控制区。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，这一假设来自于几个基因组观察，并与进化过程中特定基因座的间断扩张一致。我们将敲入V1R转基因到非天然（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，这些研究可以提供关于基因组如何被划分为调控区室的见解。在转基因和嗅觉生物学方面具有丰富专业知识的Chess小组与在生物信息学和分子进化方面具有广泛经验的Lane小组之间的伙伴关系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.