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，但随着时间的推移，它们可以获得必要的作用，但它们是如何做到这一点目前尚不清楚。这个项目将使用易驯服的果蝇模型系统来研究三个年轻的基因是如何进化出新的能力的，包括物理结合伙伴和复杂的表达模式。最终，这些发现将阐明新基因获得功能所需的基因变化类型。该项目还将增强一个纯本科生机构的研究能力，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身临其境的付费暑期研究项目，以及一个针对一年级学生的基于队列的指导计划，旨在支持来自STEM领域历史上代表性不足的一年级学生的坚持不懈。主办系的生物信息学课程将通过开发一门以实验室为基础的基因组学课程来扩展，该课程将为原本可能不参与原创研究的本科生提供基于课程的研究体验。该项目将探索可能来自非蛋白质编码DNA序列的新进化基因如何获得基本功能。它将使用之前显示的对果蝇精子发生至关重要的三个基因作为案例研究。首先，将使用一种进化方法来估计每个基因何时成为生殖所必需的，并确定对编码蛋白质的功能至关重要的关键氨基酸延伸。具体地说，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基因拷贝的黑腹果蝇的能力。这些实验将产生可检验的假说，即这些蛋白质在现存的黑腹果蝇中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，将结合生物化学和遗传学方法来确定每个焦点蛋白质的相互作用伙伴。第三，这个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，从而进化出表达的时空模式。这些实验将比较转录本和蛋白质的定位模式，并从遗传学上调查不同上下游调节区对新基因表达的作用。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.