RoL: Salivary proteome evolution as a framework to elucidate the mechanisms of functional change involving genomic structural variation

进化是生命惊人多样性的基础。了解进化运作的具体机制将有助于我们理解新的特征、能力和形态是如何出现的。唾液可以作为研究这种进化变化的理想候选者，因为它是食物、微生物和其他外来分子进入我们身体的第一个界面。这个项目将探索新的基因是如何进化的，以及它们是如何影响唾液功能的。它将通过比较不同哺乳动物物种的遗传变异、基因表达水平和蛋白质含量来做到这一点，重点是唾液功能。这个项目的结果将揭示一些基本问题，如进化是如何运作的，新基因是如何形成的，它们的功能是如何随时间变化的，以及为什么哺乳动物的唾液特性差异如此之大。将采用最先进的方法，并通过实践讲习班向来自不同机构的不同研究生群体传播。此外，研究小组的工作还包括举办一年一度的五大湖进化基因组学研讨会，接待了100多名对进化基因组学感兴趣的学员和教员。该项目将作为研究团队与公众接触的平台，在国内和国际舞台上促进STEM培训和进化生物学。该团队最近的工作强调了特定类型的基因组结构变异（SVs）在唾液快速进化中的重要性。在这项提议中，研究小组将使用创新的基于长读测序的方法从多种哺乳动物的唾液腺中产生de-novo组装和RNA序列。本文将提出三个假设：1)快速的基因转换是哺乳动物物种特异性唾液蛋白质组的基础。2)基因复制是唾液中蛋白质剂量和功能微调的主要机制。3)分泌的富含脯氨酸的蛋白是通过扩增亚显子重复序列形成新的粘蛋白的天然底物。本研究将提供：1)最完整的哺乳动物唾液腺基因组和转录组变异数据集；2)一种新的方法框架，其中DNA和RNA水平的长读测序数据将被整合；3)对唾液表型（如口腔润滑、膳食淀粉分解和宿主对病原微生物的防御）具有重要进化和生物医学意义的特定遗传变异的综合数据库。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。

Evolution underlies the amazing diversity of life. Understanding the specific mechanisms through which evolution operates will help us to understand how new traits, abilities, and forms emerge. Saliva can serve as an ideal candidate for studying such evolutionary changes because it acts as the first interface for food, microorganisms, and other foreign molecules entering our bodies. This project will explore how new genes evolve and how they affect salivary function. It will do so by comparing the genetic variation, gene expression levels, and protein content of diverse mammalian species, focusing on salivary function. The results of this project will shed light on fundamental questions about how evolution operates, how new genes are formed, how their functions change over time, and why the properties of saliva vary so much among mammals. State-of-the-art approaches will be used and disseminated to a diverse group of graduate students from different institutions through hands-on workshops. Additionally, the research team’s efforts include hosting the annual Great Lakes Evolutionary Genomics Symposium, hosting more than 100 trainees and faculty interested in evolutionary genomics. The project will serve as a platform for the research team to engage with the public, promoting STEM training and evolutionary biology at both the national and international stage.The team’s recent work underlined the importance of particular types of genomic structural variants (SVs) in rapid salivary evolution. In this proposal, the research team will use innovative long-read sequencing-based approaches to generate de-novo assemblies and RNA sequences from the salivary glands of multiple mammalian species. Three hypotheses will be addressed: 1) Rapid gene turnover underlies the species-specific salivary proteome repertoires among mammals. 2) Gene duplications are a major mechanism through which protein dosage and function are fine-tuned in saliva. 3) Secreted proline-rich proteins are natural substrates for novel mucin formation through the expansion of subexonic repeats. This study will provide: 1) the most complete genomic and transcriptomic variation datasets for mammalian salivary glands; 2) a novel methodological framework where long-read sequencing data at the DNA and RNA levels will be integrated; and 3) a comprehensive database of specific genetic variations that will be of considerable evolutionary and biomedical significance for salivary phenotypes, such as lubrication of the oral cavity, breakdown of dietary starch, and host defense against pathogenic microorganisms.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.