NSF Postdoctoral Fellowship in Biology FY 2021: The role of dosage balance in duplicate gene retention

该行动资助2021财年NSF生物学博士后研究奖学金，研究基因组，环境和表型之间相互作用的生命规则的综合研究。该奖学金支持将以创新方式为《生活规则》领域作出贡献的研究员的研究和培训。生物表现出巨大的生活方式和形态的多样性，这种多样性是基于进化过程中新基因的起源。新基因的主要来源是旧基因的复制。但一个核心问题是，新复制的基因如何在持续突变的情况下持续存在并获得新的功能。虽然一些重复的基因很快就消失了，但其他的基因会持续数百万年。解释基因保留的中心假设是需要维持适当数量的蛋白质产物（剂量平衡）。这种剂量平衡假说（DBH）已被发现在植物、酵母和人类的基因保留和丢失中起主要作用。然而，它还没有在任何昆虫中进行过测试，而昆虫代表了大多数动物的多样性。这个项目将通过测试蚜虫的胸径来解决为什么一些重复基因会随着时间的推移而保留。该项目还将阐明基因复制的作用，并提高对基因组如何进化的理解。除了指导和培训来自不同背景的本科研究人员外，生物信息学和基因组学的推广将在本科生物学课程中进行。该项目旨在整合蚜虫的基因组学、蛋白质组学和表型信息，以测试DBH作为控制基因命运的潜在生命规则。蚜虫是一种独特的测试DBH的系统，因为它们具有高比例的重复基因，并且没有经历过整个基因组的重复。本研究将使用染色体水平基因组组装的比较基因组学方法来揭示蚜虫基因复制的速度和模式。本研究还将使用共分馏质谱法建立一个蛋白质相互作用网络，利用监督机器学习来确定蚜虫中数千种蛋白质的相互作用。DBH的预测将在一个统计框架下通过整合基因复制历史和蛋白质相互作用网络的结果进行测试。该项目还将通过整合基因复制历史、蛋白质相互作用以及与共生、氧化应激和着色等生态作用相关的基因家族的表型信息，来测试DBH是否可以影响生态上重要的表型。该研究员将在德克萨斯大学奥斯汀分校接受基因组学和蛋白质组学的技术培训。在这个项目中产生的所有数据和计算资源将通过公共存储库免费提供给更广泛的研究社区。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。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the Fellow that will contribute to the area of Rules of Life in innovative ways. Organisms show immense diversity of lifestyles and forms, and this diversity is based on the origins of new genes during evolution. The main source of new genes is the duplication of older genes. But a central problem is how newly duplicated genes can persist and acquire new functions despite ongoing mutations. Although some duplicate genes are lost quickly, others persist for millions of years. The central hypothesis to explain gene retention is the need to maintain the proper amount of protein products (dosage balance). This dosage balance hypothesis (DBH) has been found to play a major role in gene retention and loss in plants, yeast, and humans. However, it has not been tested in any insects, which represent the majority of animal diversity. This project will address why some duplicate genes are retained over time by testing the DBH in aphids. This project will also shed light on the role of gene duplication, and improve understanding of how genomes evolve. Outreach in bioinformatics and genomics will be conducted in undergraduate biology courses, in addition to the mentoring and training of undergraduate researchers from diverse backgrounds.This project aims to integrate genomics, proteomics, and phenotypic information in aphids to test the DBH as a potential Rule of Life that governs the fate of genes. Aphids are a unique system to test the DBH because they have high fractions of duplicate genes and have not experienced a whole genome duplication. This research will use a comparative genomics approach on chromosome level genome assemblies to reveal the tempo and mode of gene duplications in aphids. This study will also build a protein interaction network using co-fractionation mass spectrometry to determine the interactions of thousands of proteins in aphids, using supervised machine learning. Predictions from the DBH will be tested under a statistical framework by integrating results from gene duplication history and protein interaction networks. This project will also test to determine if DBH can affect ecologically important phenotypes by integrating gene duplication history, with protein interactions, and phenotypic information for gene families with ecological roles involving symbiosis, oxidative stress, and coloration. The Fellow will receive technical training in genomics and proteomics at the University of Texas at Austin. All data and computational resources generated during this project will be freely available to the broader research community through public repositories.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.