Equipment Supplement: Genomic and Systemic Approaches of Evolutionary Mechanisms

项目摘要 国际和平研究所研究计划的长期目标是发现和理解 分子遗传机制和驱动力方面的进化。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，基因组的快速积累 序列和功能基因组数据，最重要的是，在不同领域的概念发展 生物学。基因组和系统进化的方法特别有价值，因为基因组 方法允许评估已发现的单个机制的一般性和相对贡献，并 系统的方法有助于将研究的重点从个体的角色转移到进化过程。 基因/突变与基因/突变(和环境)之间的相互作用，这是 揭示生物系统的内部运作和进化。少年派的实验室研究进化 从基因组和系统的角度使用多种模型系统(主要是酵母菌和 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，以及分子和基因组实验。这项提议主要围绕两个方面 对进化具有根本重要性的相关主题：上位性和多效性。关于……的话题 上位性，PI和他的团队将通过作图来表征基因内和基因间的上位性模式 代表基因的适应度景观和相互作用的基因对的联合适应度景观，研究 基因组水平上基因重要性的遗传背景依赖性，实验检验假说 RNA编辑的存在和持久性是通过进化根据地来解释的，并试图 从适应性进化和突变中解决上位性模式的明显矛盾推论 积累。关于多效性的主题，Pi和他的团队将绘制出 具有代表性的基因，研究环境多效性突变的一般模式，确定共同的基因座 环境适应，量化多效性对变化中分子适应的影响 环境，并评估多效性对表型进化和人类衰老的影响 疾病。总之，这些项目有望加深对遗传机制和驱动因素的理解 并阐明了疾病的机制和流行情况。

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.