Evolution of vertebrate sensory genes

描述（由申请人提供）：我的实验室的长期目标是了解遗传变化如何有助于生物体的生存，适应和进化。所有生物都生活在随时间变化的生物和非生物环境中。感觉基因负责检测这些环境变化，因此在包括人类在内的生物体的日常生活中发挥着关键作用。化学感受是特别感兴趣的，因为生物体识别和响应的化学物质的巨大多样性。在这里，我们专注于进化的脊椎动物基因和遗传途径负责两个化学感觉，有显着的进化分支和机制的相似性：犁鼻信息素检测和味剂检测。这两个系统使脊椎动物能够找到有营养的食物和合适的配偶，并避免捕食者和有毒物质。两个不相关的大的超家族，V1 Rs和V2 Rs，作为信息素受体在犁鼻感觉神经元，和离子通道TRPC 2是不可缺少的犁鼻转导。苦味促味剂在味蕾中由与V1 R进化相关的T2 R受体家族识别，而甜味和鲜味促味剂由与V2 R相关的T1 R受体检测。信息素和味觉感受的微观和宏观进化将使用遗传/基因组方法进行研究。我们的具体目标是：（1）利用两个密切相关的小鼠物种来检验V1 R和V2 R基因的种内变异和种间分歧的预测;（2）通过基因组分析来检查脊椎动物V1 R和V2 R的宏观进化模式，包括检验关于陆地脊椎动物出现时V1 R/V2 R谱系转移的假设，（3）通过对早期分化的脊椎动物和脊索动物的系统特异性基因的追踪，研究犁鼻系统的起源;（4）通过群体遗传学和进化分析，评估V1 R基因在缺乏功能性犁鼻器的人类和相关猿类中的功能;（5）通过比较基因组分析研究脊椎动物T1受体和T2受体的宏观进化;（6）通过对人类和相关猿类中T2受体的群体遗传分析来检验人类苦味受体的功能限制放松的假说。这些研究还将有助于了解人类嗅觉和味觉的变化和紊乱。

DESCRIPTION (provided by applicant): The long-term objective of my laboratory is to understand how genetic changes contribute to the survival, adaptation, and evolution of organisms. All organisms live in biotic and abiotic environments that change over time. Sensory genes are responsible for detecting these environmental changes and thus play a pivotal role in the daily life of organisms, including humans. Chemoreception is of particular interest because of the tremendous diversity of chemicals that organisms recognize and respond to. Here we focus on the evolution of vertebrate genes and genetic pathways responsible for two chemosensations that have significant evolutionary ramifications and mechanistic similarities: vomeronasal pheromone detection and tastant detection. These two systems enable vertebrates to find nutritious food and suitable mates, and to avoid predators and toxic substances. Two unrelated large superfamilies, V1 Rs and V2Rs, serve as pheromone receptors in vomeronasal sensory neurons, and the ion channel TRPC2 is indispensable in vomeronasal transduction. Bitter tastants are recognized in taste buds by a family of T2R receptors that are evolutionary related to V1 Rs, whereas sweet and umami tastants are detected by T1R receptors that are related to V2Rs. Micro- and macro-evolution of pheromone and taste receptions will be examined using genetic/genomic approaches. Our specific aims are (1) to test predictions of intra-specific variation and inter-specific divergence of V1R and V2R genes using two closely related mouse species; (2) to examine the macro- evolutionary patterns of vertebrate V1 Rs and V2Rs by genomic analysis, including tests of hypotheses on a shift of V1R/V2R repertoires in the emergence of land vertebrates, on coevolution of V1R/V2R genes with other genes, and on the losses of V2R genes in various vertebrates; (3) to study the origin of the vomeronasal system by tracing the system-specific genes in early diverging vertebrates and chordates; (4) to assess the functionality of V1R genes in humans and related apes that lack a functional vomeronasal organ by population genetic and evolutionary analyses; (5) to study the macro-evolution of vertebrate T1 Rs and T2Rs by comparative genomic analysis; and (6) to test the hypothesis of relaxation of functional constraints on human bitter taste receptors by population genetic analysis of T2Rs in humans and related apes. These studies will also help understand human smell and taste variations and disorders.