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

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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.