Evolution of Canalizing Mechanisms in Gene Expression

基因表达中渠道机制的演变

• 批准号: 7870689
• 负责人: Martin E KREITMAN
• 金额: $ 29.97万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-16 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7870689
• 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调控基因级联引导的一系列高度精心策划的事件，该级联沿着胚胎的前后轴和背腹轴创建坐标系。这个过程必须高度疏导，以抑制环境和突变变异引入的发育噪音。但在细胞化之前，创建形态发生标志的步骤是扩散介导的，并且预计对初始形态发生素浓度、卵形态和环境条件（例如温度）敏感。这些因素在物种内部和物种之间差异很大。该提案的总体目的是研究果蝇发育过程中前后轴模式中遗传和环境变异受到抑制的程度和机制，以及这些渠道机制如何响应物种间坐标系的进化变化。进行实验的目的是： 检验 ds 调控元件是管道形成的基础这一假设 测量前后图案形成途径对表达水平调节及其组成基因定位的敏感性 研究不同卵大小和发育速率的同基因菌株之间图案形成的遗传变异。比较密切相关的果蝇物种的相同特征，以研究前后图案管道化的进化。类似的抑制环境和遗传变异的机制预计也会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隐藏的基因多态性，这些基因多态性表达后可能会导致疾病易感性或抵抗力、药物反应和副作用以及其他医学相关特征的个体差异。