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、系统地识别自然性状变异的遗传基础。通过量化遗传多态性如何诱导对性状的大的、小的、精确的、一般的或有条件的影响，我们可以打开一个巨大的自然变异库，这将有助于我们理解生物系统是如何运作和进化的。然而，良好的统计能力来识别具有低总体频率或适度影响的变异，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），利用果蝇的遗传模型系统克服了这一障碍。我们重新利用已经使用了100多年来解决群体遗传学基本问题的黑腹龙的实验进化，并将其用于全基因组定位。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。本研究的长期目标是描述导致多种果蝇雄性和雌性求偶行为变化的遗传和环境影响。这项工作从雄性求偶之歌的特征开始：在求偶期间，雄性果蝇伸出一只翅膀，反复“拍打”这只翅膀，发出由一系列脉冲组成的翅膀振动之歌。这些特征是果蝇行为中最具特征的特征之一，无论是在黑腹果蝇中还是在整个属中，它们都是目前神经生物学和分子遗传学研究的重点。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。具体来说，本研究旨在1)定位和描述影响黑尾海蛞螈求偶鸣叫的遗传变异，2)对近亲海蛞螈做同样的研究，比较和对比多个物种的结果，3)开始对目标1和目标2中发现的基因和基因系统进行分子遗传学研究。

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.