CAREER: Investigation Of How Proto-Gene Expression Impacts Growth In Budding Yeast

该奖项全部或部分由2021年美国救援计划法案（公法117- 2）资助。该项目研究物种如何在分子水平上进化独特的特征。基因组由基因和非基因序列组成。基因序列编码构建蛋白质所必需的信息，蛋白质是我们细胞的主力。基因往往在物种之间高度保守，因为改变其序列的突变可能导致疾病或其他不良后果。相比之下，非基因序列不编码蛋白质，并且在物种之间差异很大。令人惊讶的是，PI和其他人发现，以前被认为是非基因的数千个快速进化的序列似乎确实编码小蛋白质。这些序列既不是基因（因为它们在物种间不保守），也不是非基因（因为它们编码蛋白质），被命名为“原基因”。本研究以芽殖酵母为模式生物，探讨原基因对物种特异性生物学的贡献。这项研究将在主要的本科院校的本科生中进行，他们将“采用一个原型基因”并在他们的家乡机构中对其进行表征。一项合作教育倡议将为教育工作者开发新的教学模块、虚拟讲习班和联网工具。该项目将通过为历史上服务不足的本科生提供序列分析的尖端计算技能，在PI实验室进行带薪暑期研究的机会，以及首次发现新的原始基因的授权经验，使STEM劳动力多样化。协同研究和教育活动的发现将提高我们对基因组的理解，并阐明是什么使一个物种独特，以及全新的基因是如何在进化中出现的。该项目的中心假设是，进化上新颖的原基因可以通过以物种特异性方式调节已建立的细胞过程来介导有益的表型。该项目将功能获得和丧失方法与综合系统水平方法相结合，以确定由原基因调节的细胞过程。在这个项目的过程中产生的数据也可能揭示基因组背景是否以及如何影响原基因的功能潜力，因为它们出现在非基因序列中从头开始。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117- 2).This project investigates how species evolve unique characteristics at the molecular level. Genomes consist of genes and non-genic sequences. Gene sequences encode the information necessary to build proteins, which are the workhorses of our cells. Genes tend to be highly conserved across species because mutations that change their sequences can cause disease or other adverse outcomes. In contrast, non-genic sequences do not encode proteins and are very different across species. Surprisingly, the PI and others discovered that thousands of rapidly evolving sequences previously thought to be non-genic instead do seem to encode small proteins. These sequences, which are neither genes (because they are not conserved across species) nor non-genes (because they encode proteins), have been named “proto-genes.” This research aims to understand how proto-genes contribute to species-specific biology using budding yeast as a model organism. The research will be performed with undergraduate students at primarily undergraduate institutions who will “adopt a proto-gene” and characterize it in their home institutions. A collaborative educational initiative will develop novel teaching modules, virtual workshops and networking tools for educators. This project will diversify the STEM workforce by providing historically underserved undergraduates with cutting-edge computational skills for sequence analyses, with paid summer research opportunities in the PI’s laboratory, and with the empowering experience of having made the very first discovery about a novel proto-gene. The findings from the synergistic research and education activities will improve our understanding of the genome and shed light on what makes a species unique and how entirely novel genes arise in evolution. The central hypothesis of this project is that evolutionarily novel proto-genes can mediate beneficial phenotypes by modulating established cellular processes in a species-specific manner. The project combines gain- and loss-of-function approaches with integrative systems-level approaches to identify cellular processes that are modulated by proto-genes. The data generated during the course of this project may also reveal whether and how genomic context influences the functional potential of proto-genes as they emerge de novo in non-genic sequences.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.