Genomic analysis of feeding behavior and fitness in Drosophila

描述（由申请人提供）：虽然能量稳态是进食行为的核心，但进食的决定不仅仅是饥饿的问题。在食物通常稀缺的自然环境中，评估获得食物的好处超过寻找和获得食物的能量成本或风险，以及决定是寻找食物还是原地不动并保存能量对于生存至关重要。然而，觅食决策行为的遗传和分子基础，以及它们在适应性中的功能意义却知之甚少。我们提出了一个自下而上的方法：从定义明确的行为是必不可少的食物寻求决策的果蝇，利用其丰富的遗传工具和基因组资源。此外，苍蝇是可行性研究的理想选择，以检查遗传变异、决策差异和不同环境条件下适应性差异之间的关系。我们已经迈出了关键的一步，设计了新的检测方法。我们将优化以下检测方法，用于本应用中的定量分析。在以下几种情况下做出选择的决策：1）小的免费奖励或需要工作的大奖励; 2）小的奖励或大的奖励，其可用性相对较低; 3）小的奖励或大的奖励，与获得有毒食物的潜在风险配对; 4）立即的小奖励或延迟的大奖励。我们将利用不同的D.生活在非洲的黑腹果蝇种群。我们将建立200个重组近交系，这些近交系来源于原始的非洲品系，具有针对每种决策行为的极端行为表型。我们将进行QTL定位，并确定QTL，有助于在食物寻求决策和健身的变化。然后，我们将使用RNAi转基因株系来鉴定负责上述行为变异的特定基因和变体。虽然我们的研究最有可能直接的临床相关性是肥胖，但它将对神经经济学、一般行为的遗传基础、进化和生态学产生更广泛的影响。

DESCRIPTION (provided by applicant): Although energy homeostasis is central in feeding behavior, the decision to eat is not merely a question of hunger. In a natural environment in which food is often scarce, evaluating the benefit of gaining food over the energy cost or risk in seeking and acquiring food, and the decision to either seek food or stay put and conserve energy is essential for survival. However, the genetic and molecular basis of food-seeking decision-making behaviors, and their functional significance in fitness are poorly understood. We propose a bottom-up approach: starting from well-defined behaviors that are essential for food-seeking decision-making in Drosophila, taking advantage of its rich genetic tools and genomic resources. Moreover, flies are ideal for viability studies to examine the relations between genetic variations, differences in decision- making and differences in fitness under different environmental conditions. We have already taken the critical step and designed novel assays. We will optimize the following assays for quantitative analysis in this application. Decision-making in choosing between 1) small free reward or large reward that requires work; 2) small reward or large reward with a relatively low probability in its availability; 3) small reward or large reward that is paired with potential risks of getting noxious food; and 4) immediate small reward or delayed large reward. We will take advantage of natural variation in genetics and behaviors between different D. melanogaster populations living in African. We will establish 200 recombinant inbred strains derived from original African strains with extreme behavioral phenotypes for each decision-making behavior. We will perform QTL mapping and identify QTLs that contribute to the variations in food-seeking decision-making and fitness. We will then use RNAi transgenic lines to identify specific genes and variants responsible for the above behavioral variations. Although the most likely immediate clinical relevance of our study is obesity, it will have a much broader impact on neuroeconomics, the genetic basis of behavior in general, evolution and ecology.