From the beginning, the project set out to systematically dissect the relationship between genetic variation and phenotypic diversity using the budding yeast Saccharomyces cerevisiae as a model. This required the coordinated development of comprehensive population genomic resources, high-throughput phenotyping datasets, and new methods for data integration and analysis.
The first phase of the work focused on generating foundational resources. Over 1,000 natural isolates of S. cerevisiae were sequenced and phenotyped, creating one of the most complete population genomic frameworks available for any eukaryote. These resources were complemented with a few telomere-to-telomere genome assemblies, allowing the construction of a detailed pangenome that captures both core and accessory genes as well as large-scale structural variants.
Building on this foundation, the project integrated multi-omics layers - transcriptomes, and proteomes - across hundreds of isolates. This enabled a species-wide analysis of the genetic control of molecular traits and their relationship to organismal phenotypes. Results demonstrated that copy number variants, accessory genes, and rare alleles contribute disproportionately to phenotypic diversity, while transcript and protein abundances are governed by largely distinct genetic architectures. These findings were disseminated through high-profile publications (Nature, Nature Genetics, Nature Communications, PNAS) and made openly available to the scientific community.
The project also extended beyond S. cerevisiae to investigate the role of polyploidization and hybridization in other yeast species, notably Brettanomyces bruxellensis. These studies revealed how genome duplication and hybrid origin shape evolutionary trajectories and adaptive potential.
Exploitation and dissemination were key components of the action.
The genomic, phenotypic, and multi-omics datasets have been deposited in public repositories and linked through dedicated portals, ensuring accessibility for future research. The publications arising from the project have established yeast as a model system to understand genotype-phenotype relationships at population scale, and the methodological advances developed provide a blueprint for similar efforts in other eukaryotic systems.
In summary, the project delivered a comprehensive framework that links natural genomic diversity to molecular and organismal traits. It demonstrated the power of population-scale, multi-layered approaches for resolving complex genotype-phenotype maps and laid the foundation for translating these insights into broader biological and societal contexts.
