Evolutionary Behavioral Genomics of Drosophila Courtship

描述（申请人提供）：全基因组关联研究有望全面系统地鉴定自然性状变异的遗传基础。通过量化遗传多态性如何对性状产生大的、小的、精确的、一般的或条件性的影响，我们可以解开一个巨大的自然变异库，这将有助于我们理解生物系统如何运作和进化。然而，识别具有低群体频率或适度效应的变异的良好统计功效需要通常令人望而却步的样本量。在这里，我们开发了一种新的方法，“进化和重新排序”（E&R），克服了这一障碍，使用遗传模型系统果蝇。我们重新利用D的实验进化。melanogaster，它已被用于解决人口遗传学的基本问题超过100年，并将其用于全基因组作图。结合高通量行为量化和各种统计方法，我们的技术将用于建立基于基因型的行为模型。这些模型的预测能力将告诉我们很多关于遗传信息的本质以及将这些信息转化为行为输出的分子系统的信息。 这项研究的长期目标是描述遗传和环境的影响，导致求偶行为的变化，男性和女性，在多个果蝇物种。这项工作开始于描述雄性求偶歌曲的产生：在求偶过程中，果蝇雄性伸出一只翅膀，反复地“twangs”这只翅膀，产生一系列脉冲组成的翅膀振动歌曲。这些特征是果蝇行为的最佳特征之一，无论是在D。黑腹鱼和整个属，他们是目前的重点，在神经生物学和分子遗传学密集的努力。因此，这些特征可以作为研究动物行为遗传基础的模型系统。具体而言，本研究的目的是：1）定位和表征影响D. melanogaster，2）对近缘种D. simulans，比较和对比多个物种的结果，以及3）开始对目标1和2中发现的基因和基因系统进行分子遗传学研究。 公共卫生相关性：包括人类在内的几乎所有物种的种群都存在巨大的遗传多样性。在模型系统中，我们可以使用遗传变异作为工具来了解遗传信息是如何编码和部署的，但这需要开发新的实验和统计工具。我们的建议开发了新的创新，以利用果蝇的这种资源来了解行为的遗传基础。

DESCRIPTION (provided by applicant): Genome-wide association studies hold the promise of comprehensive and systematic identification of the genetic basis of natural trait variation. By quantifying how genetic polymorphisms induce large, small, precise, general, or conditional effects on traits, we can unlock a vast reservoir of natural variation that will help us understand how biological systems function and evolve. However, good statistical power to identify variants with low population frequencies or modest effects requires sample sizes that are generally prohibitive. Here, we develop a new approach, "Evolve and Resequence" (E&R), that overcomes this barrier using the genetic model system Drosophila. We have re-purposed experimental evolution of D. melanogaster, which has been used for over 100 years to address fundamental questions in population genetics, and adapted it for use in genome-wide mapping. Together with high-throughput behavioral quantification and various statistical approaches, our technique will be used to build models of behavior based on genotype. The predictive power of these models will tell us a great deal about the nature of genetic information and the molecular systems that translate this information into behavioral output. The long-term goal of this research is to characterize the genetic and environmental influences that result in variation in courtship behavior, for both males and females, in multiple Drosophila species. This work begins with characterization of male courtship song production: during courtship, a Drosophila male extends a single wing and "twangs" this wing repeatedly to produce a wing vibration song consisting of a series of pulses. These traits are among the best characterized of Drosophila behaviors, both in D. melanogaster and across the genus, and they are currently the focus of intensive efforts in neurobiology and molecular genetics. As such, these traits serve as a model system for studying the genetic basis of behavior in animals. Specifically, this proposal aims to 1) locate and characterize the genetic variants affecting courtship song in D. melanogaster, 2) do the same for the closely related D. simulans, to compare and contrast results from multiple species, and 3) begin molecular genetic investigation of the genes and gene systems discovered in aims 1 and 2. PUBLIC HEALTH RELEVANCE: There is tremendous genetic diversity in populations of nearly all species, including humans. In model systems, we can use genetic variation as a tool to understand how heritable information is encoded and deployed, but this requires the development of new experimental and statistical tools. Our proposal develops new innovations in order to tap into this resource in Drosophila to understand the genetic basis of behavior.