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Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast


Aneuploidy, referring here to genome contents characterized by abnormal numbers of chromosomes, has been associated with developmental defects, cancer and adaptive evolution in experimental organisms1,2,3,4,5,6,7,8,9. However, it remains unresolved how aneuploidy impacts gene expression and whether aneuploidy could directly bring about phenotypic variation and improved fitness over that of euploid counterparts. Here we show, using quantitative mass spectrometry-based proteomics and phenotypic profiling, that levels of protein expression in aneuploid yeast strains largely scale with chromosome copy numbers, following the same trend as that observed for the transcriptome, and that aneuploidy confers diverse phenotypes. We designed a novel scheme to generate, through random meiotic segregation, 38 stable and fully isogenic aneuploid yeast strains with distinct karyotypes and genome contents between 1N and 3N without involving any genetic selection. Through quantitative growth assays under various conditions or in the presence of a panel of chemotherapeutic or antifungal drugs, we found that some aneuploid strains grew significantly better than euploid control strains under conditions suboptimal for the latter. These results provide strong evidence that aneuploidy directly affects gene expression at both the transcriptome and proteome levels and can generate significant phenotypic variation that could bring about fitness gains under diverse conditions. Our findings suggest that the fitness ranking between euploid and aneuploid cells is dependent on context and karyotype, providing the basis for the notion that aneuploidy can directly underlie phenotypic evolution and cellular adaptation.

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Figure 1: Generation of aneuploid yeast strains.
Figure 2: Phenotypic profiling of aneuploid strains.
Figure 3: Effects of aneuploidy on the proteome.

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Data deposits

Microarray data are deposited in ArrayExpress under accession numbers E-MTAB-318 and E-MTAB-325. Sequencing data are deposited in the NCBI SRA database under accession number SRP003582.


  1. Torres, E. M., Williams, B. R. & Amon, A. Aneuploidy: cells losing their balance. Genetics 179, 737–746 (2008)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Weaver, B. A. & Cleveland, D. W. Does aneuploidy cause cancer? Curr. Opin. Cell Biol. 18, 658–667 (2006)

    CAS  Article  PubMed  Google Scholar 

  3. Selmecki, A., Forche, A. & Berman, J. Aneuploidy and isochromosome formation in drug-resistant Candida albicans . Science 313, 367–370 (2006)

    CAS  ADS  Article  PubMed  PubMed Central  Google Scholar 

  4. Polakova, S. et al. Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata . Proc. Natl Acad. Sci. USA 106, 2688–2693 (2009)

    CAS  ADS  Article  PubMed  PubMed Central  Google Scholar 

  5. Dunham, M. J. et al. Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae . Proc. Natl Acad. Sci. USA 99, 16144–16149 (2002)

    CAS  ADS  Article  PubMed  PubMed Central  Google Scholar 

  6. Gresham, D. et al. The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. PLoS Genet. 4, e1000303 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

  7. Rancati, G. et al. Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor. Cell 135, 879–893 (2008)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Selmecki, A., Gerami-Nejad, M., Paulson, C., Forche, A. & Berman, J. An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1 . Mol. Microbiol. 68, 624–641 (2008)

    CAS  Article  PubMed  Google Scholar 

  9. Selmecki, A. M., Dulmage, K., Cowen, L. E., Anderson, J. B. & Berman, J. Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance. PLoS Genet. 5, e1000705 (2009)

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hughes, T. R. et al. Widespread aneuploidy revealed by DNA microarray expression profiling. Nature Genet. 25, 333–337 (2000)

    CAS  Article  PubMed  Google Scholar 

  11. Torres, E. M. et al. Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317, 916–924 (2007)

    CAS  ADS  Article  PubMed  Google Scholar 

  12. Williams, B. R. et al. Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. Science 322, 703–709 (2008)

    CAS  ADS  Article  PubMed  PubMed Central  Google Scholar 

  13. Pavelka, N., Rancati, G. & Li, R. Dr Jekyll and Mr Hyde: role of aneuploidy in cellular adaptation and cancer. Curr. Opin. Cell Biol. advance online publication 10.1016/ (23 July 2010)

  14. Parry, E. M. & Cox, B. S. The tolerance of aneuploidy in yeast. Genet. Res. 16, 333–340 (1970)

    CAS  Article  PubMed  Google Scholar 

  15. St Charles, J., Hamilton, M. L. & Petes, T. D. Meiotic chromosome segregation in triploid strains of Saccharomyces cerevisiae . Genetics 10.1534/genetics.110.121533 (10 August 2010)

  16. Mack, M. et al. Genetic characterization of hyperresistance to formaldehyde and 4-nitroquinoline-N-oxide in the yeast Saccharomyces cerevisiae . Mol. Gen. Genet. 211, 260–265 (1988)

    CAS  Article  PubMed  Google Scholar 

  17. Washburn, M. P., Wolters, D. & Yates, J. R., III Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nature Biotechnol. 19, 242–247 (2001)

    CAS  Article  Google Scholar 

  18. Gavin, A. C. et al. Proteome survey reveals modularity of the yeast cell machinery. Nature 440, 631–636 (2006)

    CAS  ADS  Article  PubMed  Google Scholar 

  19. de Godoy, L. M. et al. Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast. Nature 455, 1251–1254 (2008)

    CAS  ADS  Article  PubMed  Google Scholar 

  20. Gasch, A. P. et al. Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell 11, 4241–4257 (2000)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Springer, M., Weissman, J. S. & Kirschner, M. W. A general lack of compensation for gene dosage in yeast. Mol. Syst. Biol. 6, 368 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  22. Florens, L. & Washburn, M. P. Proteomic analysis by multidimensional protein identification technology. Methods Mol. Biol. 328, 159–175 (2006)

    CAS  PubMed  Google Scholar 

  23. Eng, J. K., McCormack, A. L. & Yates, J. R. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J. Am. Soc. Mass Spectrom. 5, 976–989 (1994)

    CAS  Article  PubMed  Google Scholar 

  24. Zhang, Y., Wen, Z., Washburn, M. P. & Florens, L. Refinements to label free proteome quantitation: how to deal with peptides shared by multiple proteins. Anal. Chem. 82, 2272–2281 (2010)

    CAS  Article  PubMed  Google Scholar 

  25. Ihaka, R. & Gentleman, R. R. A language for data analysis and graphics. J. Comput. Graph. Statist. 5, 299–314 (1996)

    Google Scholar 

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We thank C. W. Seidel for assistance with microarray data analysis, B. Fleharty and A. Peak for technical assistance with microarray hybridization, A. Perera and K. Walton for assistance in genome resequencing, W. McDowell for technical assistance with qPCR, J. Haug for technical support with flow cytometry experiments, G. Chen for technical suggestions, and A. Paulson for assistance with the submission of microarray and sequencing data to public repositories. This work was performed to fulfil, in part, requirements for J. Zhu’s PhD thesis research as a student registered with the Open University. This work was supported by NIH grant RO1GM059964 to R.L.

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Authors and Affiliations



N.P., G.R. and R.L. designed the study. N.P., G.R. and J.Z. performed all experiments. N.P. developed all custom R scripts. N.P., G.R., J.Z., W.D.B. and B.W.S. set up the high-throughput qPCR method. W.D.B. performed all qPCR karyotyping assays. A.S. and L.F. performed mass spectrometry experiments. N.P., G.R., A.S. and L.F. analysed proteomics data. N.P., G.R. and G.L.H. analysed sequencing data. R.L. coordinated and supervised the project. N.P., G.R. and R.L. prepared figures and wrote the manuscript. All authors read and agreed the paper content.

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Correspondence to Rong Li.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-12 with legends, Supplementary Methods, Supplementary Tables 1-5 and additional references. (PDF 1093 kb)

Supplementary Data 1

This file contains detailed peptide and spectral counts for proteins detected by MudPIT analysis of whole-cell lysates from Saccharomyces cerevisiae strains with different chromosome copy numbers. (XLS 7911 kb)

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Pavelka, N., Rancati, G., Zhu, J. et al. Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468, 321–325 (2010).

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