Genomic analysis of feeding behavior and fitness in Drosophila

描述（由申请人提供）：虽然能量平衡是进食行为的核心，但进食的决定并不仅仅是饥饿的问题。在食物往往稀缺的自然环境中，评估获得食物的好处超过寻找和获取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，对生存至关重要。然而，人们对觅食决策行为的遗传和分子基础及其在适合度中的功能意义知之甚少。我们提出了一种自下而上的方法：从果蝇寻找食物决策所必需的明确行为开始，利用其丰富的遗传工具和基因组资源。此外，苍蝇是研究不同环境条件下遗传变异、决策差异和适应度差异之间关系的理想动物。我们已经迈出了关键的一步，设计了新的检测方法。我们将在本应用程序中优化以下定量分析方法。在1)免费的小奖励或需要付出劳动的大奖励之间做出选择；2)小奖励或大奖励的可得性概率相对较低；3)小奖励或大奖励，伴随着获得有毒食物的潜在风险；4)即时小奖励或延迟大奖励。我们将利用生活在非洲的不同黑腹龙种群之间遗传和行为的自然差异。我们将建立200个来自非洲原始菌株的重组近交系，每个决策行为具有极端的行为表型。我们将进行QTL定位，并确定有助于寻找食物决策和适应性变化的QTL。然后，我们将使用RNAi转基因系来识别导致上述行为变化的特定基因和变体。虽然我们的研究最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.