Genetic and molecular analysis of multiple functions of the Drosophila melanogaster foraging gene

我们感兴趣的是了解基因如何与环境相互作用，在复杂特征中产生个体差异。我们的研究重点是食物相关的特征，包括食物搜索、食物摄入量和食物充足和食物匮乏环境中的甘油三酯水平。我们使用果蝇黑腹果蝇模型及其无与伦比的遗传工具包，将重点放在果蝇觅食基因上。觅食基因产生了两个自然变异，我们称之为漫游者和Sitter。与保姆苍蝇相比，路虎苍蝇活动更多，摄食更少，甘油三酯水平更低。觅食编码cGMP依赖的蛋白激酶(PKG)，目前尚不清楚觅食是如何完成其多种功能来影响食物相关性状的个体差异的。 我们最近发现，觅食是一个35kb的复杂基因，由12个外显子、4个转录起始点(最小启动子)和1个转录终止点组成。它产生了许多基因产物，包括代表9个开放阅读框架的21个转录本。在整个发育和成年期，觅食存在于多种组织和细胞类型中。 我们假设该基因的结构和复杂性促进了它的许多功能。此外，我们推测，一个特定的觅食基因产物可能被用于多种方式(在相同或不同的组织中)，以影响觅食的多种功能。 我们的具体研究问题是： 1)觅食的最小启动子、多个转录本和蛋白质亚型在食物相关性状中扮演什么角色？ 2)哪些DNA序列调节觅食的基因产物(指导它们在生物体中何时何地表达)，以及这种表达如何调节觅食的食物相关特征？ 3)觅食的组织特异性功能的潜在分子机制是什么？ 4)哪些漫游者和Sitter的DNA序列变异与每个与食物相关的性状分离？ 对涉及基因、表型和环境的关系的分子解剖对于我们理解个体差异以及它们是如何产生的至关重要。由于觅食在食物相关特征中的作用在无脊椎动物和脊椎动物中都是保守的，我们将有能力将我们的结果推广到其他物种。从应用的角度来看，这种对基因和表型之间关系的新理解对于有针对性的遗传或化学操作是至关重要的。这些技术通常用于害虫管理和保护。利用这些应用努力将被认为是这些操作的“副作用”降至最低，了解受相关主要基因和过程影响的多种表型的作用是打开大门的关键。

We are interested in understanding how genes interact with the environment to generate individual differences in complex traits. Our research focuses on food-related traits including food search, food intake and triglyceride levels in well-fed and food-deprived environments. We use the fruit fly Drosophila melanogaster model with its unsurpassed genetic tool kit, focussing our efforts on the Drosophila foraging gene. The foraging gene gives rise to two natural variants that we call rover and sitter. Rover flies move more, feed less and have lower triglyceride levels than do sitter flies. It is not known how foraging, which encodes a cGMP dependent protein kinase (PKG) accomplishes its multiple functions to affect individual differences in food-related traits. We recently discovered that foraging is a complex 35 kb gene with 12 exons, 4 transcription start sites (minimal promoters) and 1 transcription termination site. It produces many gene products including 21 transcripts representing 9 open reading frames. foraging is found in multiple tissue and cell types throughout development and adulthood. We hypothesize that the gene's structure and complexity facilitates its many functions. Additionally, we speculate that a given foraging gene product might be used in multiple ways (within the same or different tissues) to affect foraging's multiple functions. Our specific research questions are: 1) What roles do foraging's minimal promoters, multiple transcripts and protein isoforms play in food-related traits? 2) Which DNA sequences regulate foraging's gene products (guiding them regarding when and where to be expressed in the organism) and how does this expression regulate foraging's food-related traits? 3) What are the underlying molecular mechanisms for the tissue-specific functions of foraging? 4) Which rover and sitter DNA sequence variations segregate with each of the food-related traits? The molecular dissection of the relationships involving genotype, phenotype and the environment is critical for our understanding of individual differences and how they arise. Because foraging's role in food-related traits is conserved in both invertebrates and vertebrates, we will have the ability to generalise our results to other species. From an applied perspective, this new understanding of the relationship between genotype and phenotype is critical for targeted genetic or chemical manipulations. These techniques are commonly used for insect pest management and conservation. Utilizing these applied endeavours will minimize what are thought to be the "side-effects" of these manipulations and understanding the role of the multiple phenotypes affected by relevant major genes and processes holds the key to unlocking the door.