From genotype to phenotype with 1,086 near telomere-to-telomere yeast genomes

Abstract

Unravelling the genetic basis of the remarkable phenotypic diversity observed in natural populations remains a central challenge in biology^1-4. Despite major advances^5-19, no species has yet been characterized with a truly comprehensive atlas of genetic variation. Here we present an extensive genomic and phenotypic resource for the yeast Saccharomyces cerevisiae based on near telomere-to-telomere assemblies of 1,086 natural isolates. Leveraging these high-contiguity assemblies, we generated a highly complete species-wide structural variant atlas, gene-based pangenome and graph pangenome. By incorporating the full spectrum of genetic variation captured across the species, we conducted genome-wide association studies across 8,391 molecular and organismal traits^19-22. The inclusion of structural variants and small insertion-deletion mutations improved heritability estimates by an average of 14.3% compared with analyses based only on single-nucleotide polymorphisms. Structural variants were more frequently associated with traits and exhibited greater pleiotropy than other variant types. Notably, the genetic architecture of molecular and organismal traits differed markedly. Together, this work provides a unique dataset that illuminates how diverse forms of genetic variation shape phenotypic diversity and lays the groundwork for integrative, genome-scale studies in other eukaryotic systems.