Molecular evolution of odorant receptor specificities in Drosophila

行为是由大量基因之间的相互作用决定的。为了了解基因 行为变异的基础，其潜在的遗传结构必须被解剖和 必须确定导致行为功能差异的特定遗传多态。 化学感觉行为是解决这些目标的一个很好的系统，因为最近 揭示遗传因素和涉及的神经编码的进展。化学感官 感知是一个重要的人类健康问题。老年人嗅觉丧失可能 营养和生活质量受损以及嗅觉缺陷是几种神经性疾病的诊断 人类对化学感觉的感知是不同的，有一些特定的 嗅觉障碍是由基因决定的。然而，尽管我们对气味编码的理解有所进步，但 初级气味受体水平上嗅觉变异的分子基础 人们对此仍然知之甚少。脊椎动物和昆虫气味编码的相似性表明 类似的原则构成了他们嗅觉系统的组织基础。在这两个系统中，家庭 气味感受器被用来区分大量的气味物质。果蝇 然而，嗅觉系统在数量上不那么复杂，果蝇的使用很容易 用于遗传背景和环境的控制。这个系统为我们提供了一个极好的 阐明气味受体的分子多态如何有助于 嗅觉行为的变异。本申请提出了三个具体目标：(1)测量 野生近交系果蝇嗅觉行为的自然变异 (2)量化气味受体分子变异对天然 以及(3)测试气味受体等位基因变异的功能效应。 将评估一系列气味的行为变异和单核苷酸多态 将通过对气味受体基因家族进行测序来鉴定。多态现象导致 然后将识别嗅觉行为的自然变异，并使用杂交进一步验证 在野生衍生品系中。此外，对潜在机制的功能研究 导致嗅觉行为变异的行为将被进行。这些实验将提供新的 洞察识别特定气味的受体集合如何有助于自然 单核苷酸多态水平上的行为变异。更广泛地说，结果将是 为理解候选基因座的遗传变异如何导致功能性 行为上的差异以及变异产生和维持的机制 自然界中的复杂特征。

Behavior is shaped by interactions among a large number of genes. To understand the genetic underpinnings of variation in behavior, its underlying genetic architecture must be dissected and the specific genetic polymorphisms that cause functional differences in behavior must be identified. Chemosensory behavior is an excellent system for addressing these goals because of recent advances uncovering both the genetic factors and neural coding involved. Chemosensory perception is an important human health issue. Loss of olfactory acuity in the elderly can compromise nutrition and quality of life and olfactory deficits are diagnostic of several neurological disorders, such as Alzheimer's. Human chemosensory perception is variable, with some specific anosmias genetically determined. Yet despite advances in our understanding of odor coding, the molecular basis of variation in olfactory perception at the level of the primary odorant receptors remains poorly understood. The similarity of odor coding in both vertebrates and insects suggests analogous principles underlie the organization of their olfactory systems. In both systems, families of odorant receptors are used to discriminate among a vast repertoire of odorants. The Drosophila olfactory system, however, is quantitatively less complex and the use of Drosophila readily allows for the control of genetic background and environment. This system provides us with an excellent opportunity for elucidating how molecular polymorphisms in odorant receptors contribute to variation in olfactory behavior. This application proposes three specific aims: (1) to measure natural variation in olfactory behavior in a population of wild-derived inbred lines of Drosophila melanogaster; (2) to quantify the contribution of molecular variation in odorant receptors to natural variation in behavior, and (3) to test the functional effects of allelic variation in odorant receptors. Behavioral variation to an array of odorants will be assessed and single nucleotide polymorphisms will be identified by sequencing the odorant receptor gene family. Polymorphisms contributing to natural variation in olfactory behavior will then be identified and further validated using crosses among wild-derived lines. In addition, functional studies of the underlying mechanisms that contribute to variation in olfactory behavior will be conducted. These experiments will provide new insights into how ensembles of receptors that recognize defined odorants contribute to natural variation in behavior at the level of single nucleotide polymorphisms. More broadly, the results will provide a model for understanding how genetic variation in candidate loci results in functional differences in behavior and the mechanisms underlying the origin and maintenance of variation in complex traits in nature.