Evolution of Canalizing Mechanisms in Gene Expression

基因表达中渠道机制的演变

• 批准号: 7659592
• 负责人: Martin E KREITMAN
• 金额: $ 34.82万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7659592
• 关键词: Adverse effects; Affect; Anterior; Buffers; Cells; Cephalic; Development; Diffusion; Disease susceptibility; Dorsal; Drosophila genus; Drug resistance; Embryo; Embryonic Development; Enhancers; Event; Evolution; Financial compensation; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Head; Human; Human Development; Individual; Knock-out; Knowledge; Lead; Length; Location; Measures; Mediating; Molecular; Morphology; Noise; Pathway interactions; Pattern; Pattern Formation; Positioning Attribute; Principal Investigator; Process; Regulator Genes; Regulatory Element; Research; Shapes; Site; Site-Directed Mutagenesis; System; Temperature; Testing; Variant; base; egg; morphogens; pressure; research study; response; trait

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.

描述（由申请人提供）：果蝇胚胎发生的特征是由由调节基因级联导演的一组高度精心策划的事件，该事件沿着胚胎的前后和背腹轴形成坐标系统。该过程必须高度携带，以抑制环境和突变变化引入的发育噪声。但是，在细胞化之前，创建形态学地标的步骤是介导的扩散，预计将对初始形态浓度，卵形形态和环境条件（例如温度）敏感。这些因素在物种之间和物种之间差异很大。该提案的总体目的是研究果蝇发育中前后轴模式期间抑制遗传和环境变异的程度和机制，以及这些引导机制如何响应物种之间坐标系统的进化变化。实验将进行：测试以下假设：DS调节元件是载口的基础，衡量了前后形式的图案途径的灵敏度，以调节表达水平的调节和其组成基因的定位研究其组成基因的位置，研究了卵子大小和发育速率不同的模式形成的遗传变异。比较果蝇的密切相关物种的相同特征，以研究前后型模式的载量的演变。预计抑制环境变异和遗传变异的类似机制将在人类发展中起作用。拟议的研究可能导致对人类隐藏的基因多态性有更好的理解，当表达时，这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。