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 代谢途径与途径的位置有关，其程度与代谢途径有关。 个别基因座的自然选择的证据可以是 与生活史相关的选择中的简单反应 代谢能量储存池。以果蝇为模型 系统，我们将识别参与糖酵解的途径步骤 以及克雷布斯循环，它们对自然选择和 因此，在理论上，确定那些步骤具有潜在的 通过糖酵解及其分支点调节通量。特指 这将涉及收集果蝇的种群数据。 和D.yakuba的单一序列， 8个基因的DNA序列变异 糖酵解和克雷布斯循环。第二个目标将决定是否 发现三糖活性部位的氨基酸多态 果蝇磷酸异构酶对体外培养的影响 酶的功能。第三个目标是确定 哪种氨基酸在四种酶上的多态性和差异性 将与已知的3D结构和结构域连接 已确立的功能意义。第四，在何种程度上 存在代谢池和氨基酸的纬向倾斜区 将在北方检查路径点的多态 美国。最后，个别途径的潜力，当 抑制活动，调节流量，从而影响新陈代谢 将对泳池级别进行评估。

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.