Evolution of Canalizing Mechanisms in Gene Expression

描述（由申请人提供）：果蝇胚胎发生的特征在于由调节基因级联指导的一组高度协调的事件，该级联沿着胚胎的前后轴和背腹轴创建坐标系。这一过程必须高度疏导，以抑制环境和突变变异引起的发育噪音。但在细胞化之前，形成形态发生标志的步骤是扩散介导的，并且预计对初始形态原浓度、卵形态和环境条件（如温度）敏感。这些因素在物种内部和物种之间差异很大。该提案的总体目标是研究果蝇发育前后轴模式化过程中遗传和环境变异被抑制的程度和机制，以及这些渠道机制如何响应物种之间坐标系的进化变化。实验将进行：测试的假设，即反式调节元件是渠道的积木测量的灵敏度的前-后图案化途径的表达水平和定位的调制其组成基因调查遗传变异的模式形成的同基因株不同的鸡蛋大小和发育速度。比较近缘种果蝇的相同特征，以研究前-后模式化渠道的进化。抑制环境和遗传变异的类似机制预计将在人类发育中发挥作用。拟议的研究可能会更好地了解人类隐藏的基因多态性，当表达时可能会导致疾病易感性或抗性，药物反应和副作用以及其他医学相关性状的个体差异。

DESCRIPTION (provided by applicant): Drosophila embryogenesis is characterized by a highly orchestrated set of events directed by a regulatory gene cascade that creates a coordinate system along the anterior-posterior and dorsal-ventral axes of the embryo. This process must be highly canalized to suppress developmental noise introduced by environmental and mutational variation. But prior to cellularization, the steps in creating morphogenetic landmarks are diffusion mediated and are expected to be sensitive to initial morphogen concentrations, egg morphology, and environmental conditions (such as temperature). These factors vary extensively within and between species. The general aim of the proposal is to investigate the extent and mechanisms by which genetic and environmental variation is suppressed during patterning of the anterior-posterior axis in Drosophila development, and how these canalizing mechanisms respond to evolutionary changes in the coordinate system between species. Experiments will be carried out to: Test the hypothesis that ds-regulatory elements are building blocks of canalization Measure the sensitivity of the anterior-posterior patterning pathway to modulation of expression levels and positioning of its constituent genes Investigate genetic variation in pattern formation among isogenic strains differing in egg size and in development rate. Compare closely related species of Drosophila for the same traits to investigate the evolution of canalization of anterior-posterior patterning. Similar mechanisms to suppress environmental and genetic variation are expected to be acting in human development. The proposed research may lead to a better understanding of concealed gene polymorphism in humans, which when expressed may contribute to individual variation in disease susceptibility or resistance, drug response and side effects, as well as other medically relevant traits.