Equipment Supplement: Genomic and Systemic Approaches of Evolutionary Mechanisms

设备补充：进化机制的基因组和系统方法

• 批准号: 10793042
• 负责人: JIANZHI ZHANG
• 金额: $ 4.24万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10793042
• 关键词: Aging; Area; Biological Models; Biology; Computer Simulation; Data Analyses; Dependence; Development; Disease; Environment; Equipment; Evolution; Genes; Genetic; Genetic Epistasis; Genetic study; Genome; Genomic approach; Genomics; Human; Individual; Joints; Light; Mammals; Maps; Molecular; Molecular Biology; Molecular Genetics; Mutation; Pattern; Phenotype; Prevalence; Process; RNA Editing; Research; Role; Technology; Testing; Theoretical model; Yeasts; biological systems; disease-causing mutation; driving force; environmental adaptation; fitness; functional genomics; gene interaction; genomic data; human disease; laboratory experiment; pleiotropism; programs

Project Summary The long-term objective of the PI's research program is to discover and understand general principles of evolution in terms of molecular genetic mechanisms and driving forces. This is a rapidly progressing area, thanks to the technological revolution in molecular biology and genomics, rapid accumulation of genome sequences and functional genomic data, and most importantly, conceptual developments in various fields of biology. Genomic and systemic approaches to evolution are especially valuable, because the genomic approach allows assessing the generalities and relative contributions of individual mechanisms discovered and the systemic approach helps refocus the study of evolutionary processes from roles of individual genes/mutations to those of interactions among genes/mutations (and the environment), which are key to uncovering the inner workings and evolution of biological systems. The PI's lab studies evolutionary mechanisms from genomic and systemic perspectives using multiple model systems (mostly yeast and mammals) and a combination of theoretical modeling, computer simulation, integrative data analysis, laboratory experimental evolution, and molecular and genomic experimentation. This proposal centers on two related themes that are of fundamental importance to evolution: epistasis and pleiotropy. On the topic of epistasis, the PI and his team will characterize patterns of intragenic and intergenic epistasis by mapping fitness landscapes of representative genes and joint fitness landscapes of pairs of interacting genes, study the genetic background dependency of gene essentiality at the genomic scale, experimentally test the hypothesis that the existence and persistence of RNA editing is explained by evolutionary entrenchment, and attempt to resolve the apparently contradictory inferences of epistasis patterns from adaptive evolution and mutation accumulation. On the topic of pleiotropy, the PI and his team will map multi-environment fitness landscapes of representative genes to study general patterns of environmental pleiotropy of mutations, identify common loci of environmental adaptations, quantify the influence of pleiotropy on molecular adaptations in changing environments, and assess the impact of pleiotropy on the rate of phenotypic evolution and human aging and disease. Together, these projects promise to deepen the understanding of the genetic mechanisms and driving forces of evolution and shed light on disease mechanisms and prevalence.

项目摘要 PI研究计划的长期目标是发现和理解 进化的分子遗传机制和驱动力。这是一个快速发展的领域， 由于分子生物学和基因组学的技术革命， 序列和功能基因组数据，最重要的是，在各个领域的概念发展， 生物学研究进化的基因组学和系统学方法尤其有价值，因为基因组 这种方法允许评估所发现的各个机制的普遍性和相对贡献， 系统方法有助于重新关注从个人角色到进化过程的研究 基因/突变之间的相互作用（和环境），这是关键， 揭示生物系统的内部运作和进化。私家侦探的实验室研究进化 从基因组和系统的角度使用多个模型系统（主要是酵母和 哺乳动物）和理论建模，计算机模拟，综合数据分析， 实验室实验进化，分子和基因组实验。这一建议集中在两个 对进化至关重要的相关主题：上位性和多效性。先就 上位性，PI和他的团队将通过作图来表征基因内和基因间上位性的模式 代表基因的适应度景观和互作基因对的联合适应度景观，研究了 在基因组尺度上基因重要性的遗传背景依赖性，实验检验假设 RNA编辑的存在和持久性可以用进化的防御来解释，并试图 解决了适应性进化和突变的上位性模式的明显矛盾的推论 积累关于多效性的话题，PI和他的团队将绘制多环境适应性景观， 代表性基因，研究环境多效性突变的一般模式，确定共同位点 环境适应性，量化多效性对变化中分子适应性的影响 环境，并评估多效性对表型进化速度和人类衰老的影响， 疾病总之，这些项目有望加深对遗传机制和驱动力的理解。 进化的力量，并阐明疾病的机制和流行。