Natural variation within species reveals aspects of genome evolution and function. The fission yeast Schizosaccharomyces pombe is an important model for eukaryotic biology, but researchers typically use one standard laboratory strain. To extend the usefulness of this model, we surveyed the genomic and phenotypic variation in 161 natural isolates. We sequenced the genomes of all strains, finding moderate genetic diversity (π = 3 × 10(-3) substitutions/site) and weak global population structure. We estimate that dispersal of S. pombe began during human antiquity (∼340 BCE), and ancestors of these strains reached the Americas at ∼1623 CE. We quantified 74 traits, finding substantial heritable phenotypic diversity. We conducted 223 genome-wide association studies, with 89 traits showing at least one association. The most significant variant for each trait explained 22% of the phenotypic variance on average, with indels having larger effects than SNPs. This analysis represents a rich resource to examine genotype-phenotype relationships in a tractable model.

] Department of Biochemistry University of Cambridge Cambridge UK [2] Cambridge Systems Biology Centre University of Cambridge Cambridge UK [3] Division of Physiology and Metabolism Medical Research Council National Institute for Medical Research London UK

] Department of Genetics Evolution and Environment University College London London UK [2] University College London Genetics Institute University College London London UK

] Department of Genetics University of Cambridge Cambridge UK [2] Gurdon Institute University of Cambridge Cambridge UK

Associated Regional and University Pathologists Inc University of Utah Salt Lake City Utah USA

Cell Cycle Laboratory Cancer Research UK London Research Institute London UK

Centre for Genetics and Genomics University of Nottingham Nottingham UK

Commonwealth Scientific and Industrial Research Organisation Mathematics Informatics and Statistics North Ryde New South Wales Australia

Department of Biochemistry University of Cambridge Cambridge UK

Department of Cell Biology Faculty of Science Charles University Prague Prague Czech Republic

Department of Genetics Evolution and Environment University College London London UK

Genome Analysis Centre Norwich UK

Natural History Museum of Denmark University of Copenhagen Copenhagen Denmark

Wellcome Trust Centre for Human Genetics Oxford UK

Wellcome Trust Sanger Institute Cambridge UK

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Repression of a large number of genes requires interplay between homologous recombination and HIRA

Spotsizer: High-throughput quantitative analysis of microbial growth

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