CAREER: Epigenetic Dynamics Shaping the Early Evolution of Duplicate Genes

基因复制是一个频繁的突变过程，可以帮助产生新的生物功能。虽然基因组中的许多基因都是通过复制产生的，但大多数新的复制基因都是从冗余的基因拷贝开始的。额外的基因拷贝可能会因剂量不平衡而造成潜在危害，导致健康失调，并阻止新的复制基因进化出新的功能。能够成功补偿这种剂量效应的基因调控机制为长期的重复基因保留和功能多样化提供了一条途径。通过研究复制基因在其早期进化生命周期中的调控动态，本研究旨在评估不同表观遗传因素在复制后调节基因表达和影响基因保留和进化中的作用。学生的参与和培训是该项目的核心，其中包括由不同的第一代大学生进行数据分析，以及将编码和分析技能转移给STEM中代表性不足群体的高中生。基于课程的本科生研究经验将有助于生成基因组和计算分析的在线视频教程，这些视频将成为公开可用的资源。这些资料将用于为高中教育工作者编写讲习班材料，以建立基因组学课程，帮助加强基因组数据素养。在拷贝数多态性阶段对新复制基因的调控对于确定其达到固定并随时间保留的可能性至关重要。该项目将使用长读测序和组装来确定自然种群中多态重复基因的转录和表观基因组景观。基因年龄和不同选择制度下的表观遗传抑制程度将用于测试表观遗传机制是否促进重复基因在分化前的保留和进化。建立多态类似物的进化动力学将提供对表观遗传修饰在调节新出现基因中的作用的见解。这个奖项是由分子和细胞生物科学部的遗传机制组和环境生物学部的进化过程组共同资助的。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Gene duplication is a frequent mutational process that can help generate new biological functions. While many genes in a genome have arisen by duplication, most new duplicate genes start off as redundant genetic copies. Extra copies of genes can be potentially harmful via dosage imbalances, causing health disorders and preventing new duplicate genes from evolving new functions. Gene regulatory mechanisms that can successfully compensate for such dosage effects offer a pathway for long term duplicate gene retention and functional diversification. By studying the regulatory dynamics of duplicate genes across their early evolutionary lifespan, this research aims to evaluate the role of different epigenetic factors in modulating expression and impacting gene retention and evolution after duplication. Student participation and training is central to this project, which includes data analysis by a diverse base of first-generation college students, and the transfer of coding and analytical skills to high school students from underrepresented groups in STEM. Course-based undergraduate research experiences will help generate online video tutorials on genomic and computational analysis that will become publicly available resources. These will be used in the development of workshop materials for high school educators to establish genomics curricula to help strengthen genome data literacy.The regulation of a newly duplicated gene during its copy-number polymorphic phase is critical in establishing its likelihood to reach fixation and be retained over time. This project will use long-read sequencing and assembly to determine the transcriptional and epigenomic landscape of polymorphic duplicate genes among natural populations. The extent of epigenetic repression by gene age and under different selection regimes will be used to test whether epigenetic mechanisms facilitate the retention and evolution of duplicate genes before they diverge. Establishing the evolutionary dynamics of polymorphic paralogs will provide insights into the role of epigenetic modifications in regulating newly emerged genes. This award was co-funded by the Genetic Mechanisms cluster of the Division of Molecular and Cellular Biosciences and the Evolutionary Processes cluster of the Division of Environmental Biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.