Abstract

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.

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Acknowledgements

We thank L. Clissold, H. Musk, D. Baker and R. Davey for their contributions to sequencing, H. Levin for discussions about transposons, and J. Mata and S. Marguerat for comments on the manuscript. This work was supported by a Wellcome Trust Senior Investigator Award to J.B. (grant 095598/Z/11/Z), by the Wellcome Trust to S.B., T.K., J.T.S. and R.D., by grant 260801-BIG-IDEA from the European Research Council (ERC) and grant BB/H005854/1 from the Biotechnology and Biological Sciences Research Council (BBSRC) to A.R. and F.B., by UK Medical Research Council grant G0901388 to D.S. and D.J.B., by a Cancer Research UK Postdoctoral Fellowship to T.M.K.C., by an ERC Starting Grant (SYSGRO) to R.E.C.S., a Wellcome Trust PhD studentship to J.L.D.L. and BBSRC grant BB/K006320/1 to R.E.C.S. and A.C., by a Wellcome Trust grant (RG 093735/Z/10/Z) and ERC Starting Grant 260809 to M.R. (M.R. is a Wellcome Trust Research Career Development and Wellcome-Beit Prize Fellow), by Czech Science Foundation grant P305/12/P040 and Charles University grant UNCE 204013 to M.P. and by Cancer Research UK to L.J. and J.H.

Author information

Author notes

    • Jared T Simpson
    •  & David J Balding

    Present addresses: Ontario Institute for Cancer Research, Toronto, Ontario, Canada (J.T.S.) and School of Biosciences and School of Mathematics and Statistics, University of Melbourne, Melbourne, Queensland, Australia (D.J.B.).

Affiliations

  1. Department of Genetics, Evolution and Environment, University College London, London, UK.

    • Daniel C Jeffares
    • , Charalampos Rallis
    • , Adrien Rieux
    • , Doug Speed
    • , Francesc X Marsellach
    • , Winston Lau
    • , Rodrigo Pracana
    • , Garrett Hellenthal
    • , Bartlomiej Tomiczek
    • , Danny A Bitton
    • , Theodora Sideri
    • , Sandra Codlin
    • , Josephine E E U Hellberg
    • , Laurent van Trigt
    • , Sophie Atkinson
    • , Nikolas Maniatis
    • , David J Balding
    • , Francois Balloux
    •  & Jürg Bähler
  2. University College London Genetics Institute, University College London, London, UK.

    • Adrien Rieux
    • , Doug Speed
    • , Garrett Hellenthal
    • , David J Balding
    • , Francois Balloux
    •  & Jürg Bähler
  3. Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.

    • Martin Převorovský
  4. Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.

    • Tobias Mourier
    •  & Malte Thodberg
  5. Wellcome Trust Centre for Human Genetics, Oxford, UK.

    • Zamin Iqbal
  6. Cell Cycle Laboratory, Cancer Research UK London Research Institute, London, UK.

    • Tammy M K Cheng
    • , Linda Jeffery
    • , Juan-Juan Li
    •  & Jacqueline Hayles
  7. Department of Biochemistry, University of Cambridge, Cambridge, UK.

    • Michael Mülleder
    • , Anatole Chessel
    •  & Markus Ralser
  8. Department of Genetics, University of Cambridge, Cambridge, UK.

    • Jonathan L D Lawson
    •  & Rafael E Carazo Salas
  9. Gurdon Institute, University of Cambridge, Cambridge, UK.

    • Jonathan L D Lawson
    •  & Rafael E Carazo Salas
  10. Wellcome Trust Sanger Institute, Cambridge, UK.

    • Sendu Bala
    • , Thomas Keane
    • , Jared T Simpson
    •  & Richard Durbin
  11. Associated Regional and University Pathologists, Inc. University of Utah, Salt Lake City, Utah, USA.

    • Brendan O'Fallon
  12. Commonwealth Scientific and Industrial Research Organisation (CSIRO) Mathematics, Informatics and Statistics, North Ryde, New South Wales, Australia.

    • Leanne Bischof
  13. Genome Analysis Centre, Norwich, UK.

    • Melanie Febrer
    • , Kirsten McLay
    •  & Nizar Drou
  14. Centre for Genetics and Genomics, University of Nottingham, Nottingham, UK.

    • William Brown
  15. Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.

    • Markus Ralser
  16. Division of Physiology and Metabolism, Medical Research Council (MRC) National Institute for Medical Research, London, UK.

    • Markus Ralser

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Contributions

D.C.J. coordinated all analyses, isolated DNA for sequencing, analyzed and filtered SNP calls, conducted diversity analysis and GWAS and drafted the manuscript. C.R. produced phenotype data for growth on various solid media and growth rates in liquid media. A.R. conducted analysis of dating using mitochondrial data. D.S. conducted GWAS. M.P. analyzed all phenotype data. T.M. identified LTR transposon insertions and analyzed transposon insertion data. F.X.M. conducted crosses for the analysis of spore viability. Z.I. produced indel calls with Cortex. W.L. conducted analysis of recombination rate, LD decay and principal-component analysis for distance between strains. T.M.K.C. assisted with phenotype and population analysis. R.P. analyzed Cortex and GATK indel calls. M.M. conducted amino acid profiling. J.L.D.L. and A.C. produced automated measures of cell morphology. S.B. aligned reads and produced GATK SNP calls. G.H. analyzed population structure using fineSTRUCTURE. B.O'F. estimated the time to the most recent common ancestor from the nuclear genome using ACG. T.K. identified LTR transposon insertions. J.T.S. produced de novo assemblies. L.B. developed the custom Workspace workflow Spotsizer. B.T. assisted with sequence analysis. D.A.B. assisted with analysis of new genes. T.S. assisted with strain verification. S.C. produced images of wild strains and assisted with strain verification. J.E.E.U.H. assisted with SNP validation. L.v.T. and M.T. assisted with LTR validation. L.J. and J.-J.L. assisted with manual measures of cell morphology and FACS. S.A. produced gene expression data. M.F., K.M. and N.D. assisted with sequencing. W.B. initiated and assisted with strain collection. J.H. coordinated manual measures of cell morphology and FACS. R.E.C.S. coordinated automated measures of cell morphology. M.R. coordinated amino acid profiling. N.M. conducted analysis of recombination and LD and advised on aspects of diversity and GWAS. D.J.B. advised on GWAS. F.B. advised on population structure and supervised A.R. R.D. facilitated sequencing. J.B. contributed to the initiation and development of the project and financed the Bähler laboratory.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Daniel C Jeffares or Jürg Bähler.

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DOI

https://doi.org/10.1038/ng.3215

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