Christopher T. Hittinger, Ph.D. - US grants

Brewing yeasts are an attractive living system for studying rapid genetic change because they have adapted to an environment recently created by humans. Saccharomyces cerevisiae, a same warm-adapted species, is traditionally used for wine-making, bread-leavening, and in the bioethanol industry. In contrast, a hybrid of the Saccharomyces cerevisiae strain and a recently discovered species, Saccharomyces eubayanus, are cold-adapted and are used in other applications. The objectives of this study are to determine 1) which traits were contributed to lager yeast by each parent, 2) which genetic changes occurred in the brewing environment, 3) and whether variation in the parental species contributed to lager yeast traits. Hundreds of genome sequences of yeasts isolated from natural and brewing environments will be generated and analyzed to identify candidate differences, which will be tested through genetic manipulation.
Understanding how wild yeast adapt to industrial environments will provide a framework and candidate genes for improving biofuel strains. This project will also help train the next generation of scientists and educators, from high school students and teachers to postdoctoral researchers, including individuals from underrepresented minority backgrounds. In particular, the Yeast Exploration and Analysis Science Team ("Wild YEAST Program") directly involves high school and early-stage undergraduate students in using modern isolation and genetic identification techniques to study natural variation and genetic diversity in Saccharomyces and other yeasts. Visiting high school teachers will develop classroom lab modules that address the Next-Generation Science Standards while engaging students in real biodiversity and genetics research.

The yeasts are model organisms for understanding and integrating the genetic and ecological factors that drive species diversification and generate biodiversity. Yeasts show remarkably different types of metabolism, allowing them to successfully inhabit every continent and every major aquatic and terrestrial habitat, however little is known about the distribution of these traits among the diversity of yeast species. By creating and analyzing the first comprehensive genomic dataset and catalog of metabolic diversity for a high-level taxonomic rank (subphylum), this project will provide insight into how key changes in metabolism shape eukaryotic microbial ecology and diversity. Inclusive large-scale analysis of the genome data will be fostered by creating an interactive web-based interface for researchers, clinicians, teachers, and students to explore the subphylum as a model for understanding the making of biodiversity. These data will be of potential value for practitioners using yeast to improve industrial and medical processes.

The goals of this project are to determine the metabolic and ecological diversity of the Saccharomycotina subphylum at the genetic and phenotypic (e.g. metabolism, morphology) levels, and then to infer the tempo and mode of change across its history. To determine the genetic basis of metabolic diversity, the project will generate functionally annotated genome sequences for all ~1,000 known species and compare genome content with ecological and metabolic data from the entire subphylum. The project will accurately reconstruct the phylogenetic relationships of all known species and will use these relationships to develop a stable taxonomy of medically and biotechnologically important yeasts. The project will provide new insights into the manner in which biodiversity arises and the key changes that drive and shape it by tracing the history of yeast metabolism, ecology, and pathogenicity.

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.