Collaborative Research: RoL: The Evolution of the Genotype-Phenotype Map across Budding Yeasts

生物体的外部特征或特征是如何在其基因组中编码的，以及它们如何随时间变化，这些都是重要的、在很大程度上没有答案的生物学问题。该项目将通过研究1000多种已知芽殖酵母及其进化的代谢和基因组来解决这些问题。其中一些酵母菌是重要的机会性病原体，而另一些酵母菌作为食品、饮料、药品和生物燃料的生产者具有重要的工业意义。该项目将跨越生物组织的多个尺度（从分子到细胞，物种等）和大约4亿年的进化，以产生对基因组中特征如何编码，新功能如何进化以及特征与基因组本身之间关系如何进化的基本见解。该项目将支持野生酵母和计算基因组学项目，这两个已建立且非常成功的教育和培训项目，使早期本科生，包括那些来自代表性不足背景的学生，沉浸在真实的、发现驱动的研究中。利用几乎所有已知出芽酵母物种的基因组草图和在不同物种中广泛活跃的最先进的基因组编辑工具，该项目将预测每个酵母物种基因组中每个代谢基因与其功能的联系，并检查出芽酵母亚门Saccharomycotina中每个已知代谢基因、途径和性状的进化。通过对芽殖酵母基因组和代谢多样性的关键代表性类群进行基因组尺度的进化分析和针对性的功能实验，本项目将从功能上表征基因型水平的类群间变异如何引起表型水平的变异。特别是，该项目将绘制DNA、RNA、蛋白质和代谢物水平上的变异如何依次将遗传变异转化为生化功能和生理性状的图表，重点是在预测的基因型-表型图谱中对空白进行功能表征和纠正差异。该项目由环境生物学部的进化过程项目和生物科学理事会分子和细胞生物科学部的遗传机制项目共同资助。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。

How organisms’ external characteristics or traits are encoded in their genomes and how they change over time represent important and largely unanswered biological questions. This project will address these questions by studying the metabolisms and genomes of the more than 1,000 known species of budding yeasts and their evolution. Some of these yeast species are important opportunistic pathogens, while others are of great industrial relevance as producers of foods, beverages, medicines, and biofuels. This project will span multiple scales of biological organization (from molecules to cells, species, and beyond) and ~400 million years of evolution to yield fundamental insights into how traits are encoded in genomes, how new functions evolve, and how the relationship between traits and genomes itself evolves. The project will support the Wild YEAST and Computational Genomics Programs, two established and highly successful educational and training programs that immerse early-stage undergraduate students, including those from underrepresented backgrounds, in authentic, discovery-driven research.Using draft genomes for nearly all known budding yeast species and state-of-the-art genome-editing tools that are broadly active in diverse species, this project will predict the connection of every metabolic gene in every yeast species’ genome to its function(s), as well as examine the evolution of every known metabolic gene, pathway, and trait across the budding yeast subphylum Saccharomycotina. Through genome-scale evolutionary analyses and targeted functional experiments on key representative taxa spanning budding yeast genomic and metabolic diversity, this project will functionally characterize how between-taxa variation at the level of genotypes gives rise to variation at the level of phenotypes. In particular, the project will chart how variation at the level of DNA, RNA, proteins, and metabolites sequentially transforms genetic variation into biochemical functions and physiological traits with an emphasis on functionally characterizing gaps and correcting discrepancies in the predicted Genotype-Phenotype Map.This project is jointly funded by the Evolutionary Processes program in the Division of Environmental Biology and the Genetic Mechanisms program in the Division of Molecular and Cellular Biosciences of the Directorate for Biological Sciences.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.