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

我们有兴趣了解基因如何与环境相互作用，以产生复杂性状的个体差异。我们的研究重点是食物相关的性状，包括食物搜索，食物摄入量和甘油三酯水平在良好的喂养和食物匮乏的环境。我们使用果蝇黑腹果蝇模型及其无与伦比的遗传工具包，专注于我们的努力果蝇觅食基因。觅食基因产生了两种自然变异，我们称之为“漫游者”和“栖息者”。漫游蝇比坐蝇移动更多，进食更少，甘油三酯水平更低。目前尚不清楚编码cGMP依赖性蛋白激酶（PKG）的觅食如何实现其多种功能，以影响食物相关性状的个体差异。 我们最近发现觅食是一个复杂的35 kb基因，有12个外显子，4个转录起始位点（最小启动子）和1个转录终止位点。它产生许多基因产物，包括代表9个开放阅读框的21个转录物。觅食在整个发育和成年期的多种组织和细胞类型中被发现。 我们假设基因的结构和复杂性促进了它的许多功能。此外，我们推测，一个给定的觅食基因产物可能会以多种方式（在相同或不同的组织）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异构体在食物相关性状中起什么作用？ 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性状？ 3)觅食的组织特异性功能的潜在分子机制是什么？ 4)哪种漫游者和定居者的DNA序列变异与每种食物相关的性状分离？ 基因型、表型和环境之间关系的分子解剖对于我们理解个体差异及其产生的机制至关重要。由于觅食在食物相关性状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，这种对基因型和表型之间关系的新理解对于靶向遗传或化学操作至关重要。这些技术通常用于害虫管理和保护。利用这些应用的努力将最大限度地减少被认为是这些操作的“副作用”，并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钥匙。

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.