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。理解进化的具体机制将有助于我们理解新的特征、能力和形式是如何出现的。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。该项目将探索新基因如何进化以及它们如何影响唾液功能。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实现这一目标，重点是唾液功能。该项目的结果将揭示有关进化如何运作的基本问题，新基因如何形成，它们的功能如何随时间变化，以及为什么唾液的特性在哺乳动物中变化如此之大。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各类研究生传播。此外，研究团队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100多名对进化基因组学感兴趣的学员和教师。该项目将作为研究团队与公众接触的平台，在国家和国际舞台上促进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（SV）在快速唾液进化中的重要性。在这项提案中，研究小组将使用创新的基于长读段测序的方法，从多种哺乳动物物种的唾液腺中生成从头组装和RNA序列。将讨论三个假设：1）快速的基因更新是哺乳动物物种特异性唾液蛋白质组谱系的基础。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质是通过扩增外显子下重复序列形成新粘蛋白的天然底物。这项研究将提供：1）哺乳动物唾液腺最完整的基因组和转录组变异数据集; 2）一个新的方法框架，其中将整合DNA和RNA水平的长读段测序数据;和3）特定遗传变异的综合数据库，其对于唾液表型，例如口腔的润滑，膳食淀粉的分解，该奖项反映了NSF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.