RUI: Understanding how de novo evolved genes evolve protein interactions and regulatory mechanisms in Drosophila reproduction

新进化的基因，一开始不是必需的，随着时间的推移，可以获得重要的作用，但它们是如何做到的，目前还不清楚。该项目将使用可驯化的果蝇模型系统来研究三种年轻基因是如何进化出新的能力的，包括生理结合伴侣和复杂的表达模式。最终，这些发现将揭示新基因获得功能所需的基因变化类型。这个项目也将提高本科院校的研究能力，从而为学生提供进行原创研究的机会。PI的实验室将参与一个面向二年级和三年级学生的沉浸式暑期有偿研究项目，以及一个面向一年级学生的基于队列的指导项目，该项目旨在支持来自STEM领域历史上代表性不足背景的一年级学生的坚持。主办部门的生物信息学课程将通过开发以实验室为基础的基因组学课程来扩展，这将为本科生提供基于课程的研究经验，否则他们可能不会参与原始研究。该项目将探索新进化的基因是如何从非蛋白质编码DNA序列中获得基本功能的。它将使用三个基因作为案例研究，这些基因先前被证明是果蝇精子发生所必需的。首先，将使用进化方法来估计每个基因何时成为繁殖所必需的，并确定对编码蛋白质功能重要的关键氨基酸延伸。具体来说，将测量现有的同源蛋白序列和推断的祖先序列拯救缺乏内源性基因拷贝的黑腹果蝇的能力。这些实验将产生可测试的假设，即在现存的黑腹果蝇中，这些蛋白质的基本功能需要哪些序列特征。其次，为了研究新进化的蛋白质如何在现有的细胞网络中进化功能并获得与其他分子的相互作用，将使用生化和遗传方法相结合的方法来确定每个焦点蛋白质的相互作用伙伴。第三，本项目将研究新进化的基因如何获得基因调控的转录后机制，从而进化出时空表达模式。这些实验将比较转录和蛋白质定位模式，并研究不同的上游和下游调控区域在新基因表达中的遗传学作用。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。

Newly evolved genes, which are non-essential at first, can acquire essential roles over time, but how they do so is currently unclear. This project will use the tractable fruit fly model system to investigate how three young genes, which have gained essential functions in male fertility, evolved novel capabilities, including physical binding partners and complex expression patterns. Ultimately, these findings will shed light on the kinds of genetic changes a new gene requires to gain functionality. This project will also enhance the research capacity of an exclusively undergraduate institution, thus providing opportunities for students to conduct original research. The PI’s lab will participate in an immersive, paid summer research program for second- and third-year students and a cohort-based mentoring program for first-year students designed to bolster the persistence of first-year students from backgrounds historically underrepresented in STEM fields. The host department’s bioinformatic curriculum will be expanded through the development of a lab-based genomics course that will provide a course-based research experience to undergraduates who may not otherwise participate in original research.This project will explore how newly evolved genes that likely arose from non-protein-coding DNA sequences acquire essential functions. It will use as case studies of three genes shown previously to be essential for spermatogenesis in Drosophila melanogaster. First, an evolutionary approach will be used to estimate when each gene became essential for reproduction and to identify key amino acids stretches important for the function of the encoded protein. Specifically, the ability of both extant orthologous protein sequences and inferred ancestral sequences to rescue D. melanogaster flies lacking an endogenous copy of the gene will be measured. These experiments will generate testable hypotheses about which sequence features are required for these proteins’ essential functions in extant D. melanogaster flies. Second, to investigate how newly evolved proteins evolve functions in existing cellular networks and gain interactions with other molecules, a combination of biochemical and genetic approaches will be used to identify interacting partners of each focal protein. Third, this project will investigate how newly evolved genes gain post-transcriptional mechanisms of gene regulation and thus evolve spatiotemporal patterns of expression. These experiments will compare transcript and protein localization patterns and investigate genetically the role of different upstream and downstream regulatory regions on new gene expression.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.