Evolution of Canalizing Mechanisms in Gene Expression

描述（由申请人提供）：果蝇胚胎发生的特点是一系列高度协调的事件，这些事件由一个调控基因级联引导，沿着胚胎的前后轴和背腹轴创建一个坐标系统。这一过程必须被高度控制，以抑制由环境和突变变异引入的发育噪声。但在细胞化之前，形成形态发生里程碑的步骤是扩散介导的，预计对初始形态因子浓度、卵子形态和环境条件（如温度）敏感。这些因素在物种内部和物种之间差别很大。本研究的主要目的是研究果蝇发育过程中遗传和环境变化在多大程度上和机制上受到抑制，以及这些调节机制如何响应物种间坐标系统的进化变化。实验将用于：验证ds-调控元件是管道构建模块的假设测量前后模式通路对其组成基因表达水平和定位调节的敏感性研究不同卵大小和发育速度的等基因菌株之间模式形成的遗传变异。比较近缘种果蝇的相同性状，以研究前后模式管道化的进化。类似的抑制环境和遗传变异的机制有望在人类发展中发挥作用。拟议的研究可能有助于更好地了解人类中隐藏的基因多态性，这种多态性在表达时可能导致疾病易感性或耐药性、药物反应和副作用以及其他医学相关特征的个体差异。

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.