METABOLIC CONTROL AND MOLECULAR ADAPTATION IN DROSOPHILA

拟议研究的广泛和长期目标是 了解酶的适应性反应在多大程度上 代谢途径与途径位置有关， 在个体基因座上的自然选择的证据 再加上简单的反应，在选择的生活史相关 代谢能量储存池。 以果蝇为模型 系统，我们将确定参与糖酵解的那些途径步骤 和克雷布斯循环，它们是对自然选择的反应， 因此，在理论上，确定那些具有潜力的步骤， 通过糖酵解及其分支点调节流量。 具体 这将涉及收集果蝇的种群数据 melanogaster、黑腹果蝇D. simulans和D.雅库巴， 在八个基因的DNA序列变异中， 糖酵解和克雷布斯循环。 第二个目标将决定 在丙糖活性部位发现的氨基酸多态性 黑腹果蝇磷酸异构酶影响体外 酶的功能。 第三个目标是确定 其中四种酶的氨基酸多态性和差异 将与已知的3D结构和域连接， 建立了功能意义。 第四，在多大程度上 代谢库和氨基酸存在纬度梯度 在途径点的多态性将在北 美国参考 最后，个别途径步骤的潜力，当 抑制活动，调节流量，从而影响代谢 将对合并水平进行评估。

The broad and long range objective of the proposed research is to understand the extent to which adaptive response of enzymes in a metabolic pathway is related to pathway position, and the extent to which evidence for natural selection at individual loci can be coupled to simple responses in selection on life-history associated metabolic energy storage pools. Using Drosophila as a model system we will identify those pathway steps involved in glycolysis and the Krebs cycle which are responding to natural selection and thereby, in theory, identify those steps that possess the potential to modulate flux through glycolysis and its branch points. Specifically this will involve collection of population data on Drosophila melanogaster, D. simulans and a single sequence for D. Yakuba, for DNA sequence variation at eight genes involved in the glycolytic and Krebs cycle. A second aim will determine if the amino acid polymorphism uncovered in the active site of triose phosphate isomerase in Drosophila melanogaster affects the in vitro function of the enzyme. A third aim is to determine the extent to which amino acid polymorphisms and divergence at four enzymes will be connected with known 3D structures and domains of established functional significance. Fourth, the extent to which latitudinal clines exist for metabolic pools and amino acid polymorphisms at pathway points will be examined in North America. Finally, the potential of individual pathway steps, when depressed in activity, to modulate flux and hence affect metabolic pool levels will be assessed.