Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast
Open accessAbstract
Aneuploidy, referring here to genome contents characterized by abnormal numbers of chromosomes, has been associated with developmental defects, cancer and adaptive evolution in experimental organisms. 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
C. albicans, like S. cerevisiae, generates large scale genetic variation as a means of adaptation.
“Thus, C. albicans like S. cerevisiae (Gresham et al., 2008; Pavelka et al., 2010; Yona et al., 2012; Chang et al., 2013) generates large scale genetic variation as a means of adaptation.”
From The evolution of drug resistance in clinical isolates of Candida albicans. (2015) · cites this paper as Pavelka et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gentleman R: R: A language for data analysis and graphics
Ihaka, R., & Gentleman, R. (1996) · Journal of Computational and Graphical Statistics · doi:10.1080/10618600.1996.10474713 · Cited by 11,747 · see citing works
Eng, J. K., McCormack, A. L., & Yates, J. R. (1994) · Journal of the American Society for Mass Spectrometry · doi:10.1016/1044-0305(94)80016-2 · Cited by 6,484 · see citing works
Genomic Expression Programs in the Response of Yeast Cells to Environmental Changes
Gasch, A. P., Spellman, P. T., Kao, C. M., Carmel-Harel, O., Eisen, M. B., Storz, G., Botstein, D., & Brown, P. O. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.12.4241 · Cited by 4,815 · see citing works
Large-scale analysis of the yeast proteome by multidimensional protein identification technology
Washburn, M. P., Wolters, D. A., & Yates, J. R. (2001) · Nature Biotechnology · doi:10.1038/85686 · Cited by 4,759 · see citing works
Proteome survey reveals modularity of the yeast cell machinery
Gavin, A., Aloy, P., Grandi, P., Krause, R., Böesche, M., Marzioch, M., Rau, C., Jensen, L. J., Bastuck, S., Dümpelfeld, B., et al. (2006) · Nature · doi:10.1038/nature04532 · Cited by 2,544 · see citing works
Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast
Torres, E. M., Sokolsky, T., Tucker, C. M., Chan, L. Y., Boselli, M., Dunham, M. J., & Amon, A. (2007) · Science · doi:10.1126/science.1142210 · Cited by 935 · see citing works
Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast
de Godoy, L. M. F., Olsen, J. V., Cox, J., Nielsen, M. L., Hubner, N. C., Fröhlich, F., Walther, T. C., & Mann, M. (2008) · Nature · doi:10.1038/nature07341 · Cited by 873 · see citing works
Aneuploidy and Isochromosome Formation in Drug-Resistant <i>Candida albicans</i>
Selmecki, A., Forche, A., & Berman, J. (2006) · Science · doi:10.1126/science.1128242 · Cited by 733 · see citing works
Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells
Williams, B. R., Prabhu, V. R., Hunter, K. E., Glazier, C. M., Whittaker, C. A., Housman, D. E., & Amon, A. (2008) · Science · doi:10.1126/science.1160058 · Cited by 665 · see citing works
Dunham, M. J., Badrane, H., Ferea, T., Adams, J., Brown, P. O., Rosenzweig, F., & Botstein, D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242624799 · Cited by 564 · see citing works
Weaver, B. A. A., & Cleveland, D. W. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.10.002 · Cited by 560 · see citing works
Widespread aneuploidy revealed by DNA microarray expression profiling
Hughes, T. R., Roberts, C. J., Dai, H. A., Jones, A. R., Meyer, M. R., Slade, D., Burchard, J., Dow, S., Ward, T. R., Kidd, M. J., et al. (2000) · Nature Genetics · doi:10.1038/77116 · Cited by 482 · see citing works
Gresham, D., Desai, M. M., Tucker, C. M., Jenq, H. T., Pai, D. A., Ward, A., DeSevo, C. G., Botstein, D., & Dunham, M. J. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000303 · Cited by 482 · see citing works
Aneuploidy: Cells Losing Their Balance
Torres, E. M., Williams, B. R., & Amon, A. (2008) · Genetics · doi:10.1534/genetics.108.090878 · Cited by 409 · see citing works
Zhang, Y., Wen, Z., Washburn, M. P., & Florens, L. A. (2010) · Analytical Chemistry · doi:10.1021/ac9023999 · Cited by 386 · see citing works
Self-citationRancati, G. I., Pavelka, N., Fleharty, B., Noll, A. C., Trimble, R., Walton, K., Perera, A. G., Staehling‐Hampton, K., Seidel, C. W., & Li, R. (2008) · Cell · doi:10.1016/j.cell.2008.09.039 · Cited by 335 · see citing works
Self-citationSelmecki, A., Gerami‐Nejad, M., Paulson, C., Forche, A., & Berman, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06176.x · Cited by 325 · see citing works
Selmecki, A. M., Dulmage, K., Cowen, L. E., Anderson, J. B., & Berman, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000705 · Cited by 319 · see citing works
Proteomic Analysis by Multidimensional Protein Identification Technology
Florens, L. A., & Washburn, M. P. (2006) · Humana Press eBooks · doi:10.1385/1-59745-026-x:159 · Cited by 242 · see citing works
Self-citationFormation of new chromosomes as a virulence mechanism in yeast <i>Candida glabrata</i>
Poláková, S., Blume, C., Zárate, J. Á., Mentel, M., Jørck-Ramberg, D., Stenderup, J., & Piškur, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809793106 · Cited by 206 · see citing works
A general lack of compensation for gene dosage in yeast
Springer, M., Weissman, J. S., & Kirschner, M. W. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.19 · Cited by 122 · see citing works
Dr Jekyll and Mr Hyde: role of aneuploidy in cellular adaptation and cancer
Pavelka, N., Rancati, G. I., & Li, R. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.06.003 · Cited by 110 · see citing works
Self-citationThe tolerance of aneuploidy in yeast
Parry, E. M., & Cox, B. S. (1970) · Genetics Research · doi:10.1017/s0016672300002597 · Cited by 75 · see citing works
Meiotic Chromosome Segregation in Triploid Strains of Saccharomyces cerevisiae
Charles, J. S., Hamilton, M. L., & Petes, T. D. (2010) · Genetics · doi:10.1534/genetics.110.121533 · Cited by 54 · see citing works
Mack, M., Gömpel-Klein, P., Haase, E., et al. (1988) · Molecular and General Genetics MGG · doi:10.1007/bf00330602 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Domestication and Divergence of Saccharomyces cerevisiae Beer Yeasts
Gallone, B., Steensels, J., Prahl, T., Soriaga, L., Saels, V., Herrera-Malaver, B., Merlevede, A., Roncoroni, M., Voordeckers, K., Miraglia, L., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.020 · Cited by 679 · see citing works
Chromosomal duplication is a transient evolutionary solution to stress
Yona, A. H., Manor, Y. S., Herbst, R. H., Romano, G. H., Mitchell, A., Kupiec, M., Pilpel, Y., & Dahan, O. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211150109 · Cited by 376 · see citing works
Genetic and phenotypic intra-species variation in <i>Candida albicans</i>
Hirakawa, M. P., Martinez, D. A., Sakthikumar, S., Anderson, M. Z., Berlin, A., Gujja, S., Zeng, Q., Zisson, E., Wang, J. M., Greenberg, J. M., et al. (2015) · Genome Research · doi:10.1101/gr.174623.114 · Cited by 320 · see citing works
The evolution of drug resistance in clinical isolates of Candida albicans.
Ford, C. B., Funt, J. M., Abbey, D., Issi, L., Guiducci, C., Martinez, D. A., Delorey, T., Li, B. Y., White, T. C., Cuomo, C., et al. (2015) · eLife · doi:10.7554/elife.00662 · Cited by 348 · see citing works
Gene Copy-Number Alterations: A Cost-Benefit Analysis
Tang, Y.-C., & Amon, A. (2013) · Cell · doi:10.1016/j.cell.2012.11.043 · Cited by 348 · see citing works
Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy
Chen, G., Bradford, W. D., Seidel, C. W., & Li, R. (2012) · Nature · doi:10.1038/nature10795 · Cited by 274 · see citing works
Self-citationStress Alters Rates and Types of Loss of Heterozygosity in Candida albicans
Forche, A., Abbey, D., Pisithkul, T., Weinzierl, M. A., Ringstrom, T., Bruck, D., Petersen, K., & Berman, J. (2011) · mBio · doi:10.1128/mbio.00129-11 · Cited by 234 · see citing works
A Tetraploid Intermediate Precedes Aneuploid Formation in Yeasts Exposed to Fluconazole
Harrison, B. D., Hashemi, J., Bibi, M., Pulver, R., Bavli, D., Nahmias, Y., Wellington, M., Sapiro, G., & Berman, J. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001815 · Cited by 174 · see citing works
Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation
Gerstein, A. C., Fu, M. S., Mukaremera, L., Li, Z., Ormerod, K. L., Fraser, J. A., Berman, J., & Nielsen, K. (2015) · mBio · doi:10.1128/mbio.01340-15 · Cited by 167 · see citing works
Schvartzman, J.-M., Duijf, P. H. G., Sotillo, R., Coker, C., & Benezra, R. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.017 · Cited by 181 · see citing works
Expandable and reversible copy number amplification drives rapid adaptation to antifungal drugs
Todd, R. T., & Selmecki, A. (2020) · eLife · doi:10.7554/elife.58349 · Cited by 138 · see citing works
Bennett, R. J., Forche, A., & Berman, J. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019604 · Cited by 118 · see citing works
Mutational landscape of yeast mutator strains
Serero, A., Jubin, C., Loeillet, S., Legoix-Né, P., & Nicolas, A. G. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314423111 · Cited by 126 · see citing works
Genome plasticity in Candida albicans is driven by long repeat sequences
Todd, R. T., Wikoff, T. D., Forche, A., & Selmecki, A. (2019) · eLife · doi:10.7554/elife.45954 · Cited by 118 · see citing works
The functional basis of adaptive evolution in chemostats
Gresham, D., & Hong, J. (2014) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12082 · Cited by 122 · see citing works
Hickman, M. A., Paulson, C., Dudley, A., & Berman, J. (2015) · Genetics · doi:10.1534/genetics.115.178020 · Cited by 113 · see citing works
Aneuploidy Enables Cross-Adaptation to Unrelated Drugs
Yang, F., Teoh, F., Tan, A. S. M., Cao, Y., Pavelka, N., & Berman, J. (2019) · Molecular Biology and Evolution · doi:10.1093/molbev/msz104 · Cited by 101 · see citing works
Self-citationProtein aggregation mediates stoichiometry of protein complexes in aneuploid cells
Brennan, C. M., Vaites, L. P., Wells, J. N., Santaguida, S., Paulo, J. A., Storchova, Z., Harper, J. W., Marsh, J. A., & Amon, A. (2019) · Genes & Development · doi:10.1101/gad.327494.119 · Cited by 109 · see citing works
Forche, A., Cromie, G., Gerstein, A. C., Solis, N. V., Pisithkul, T., Srifa, W., Jeffery, E., Abbey, D., Filler, S. G., Dudley, A. M., et al. (2018) · Genetics · doi:10.1534/genetics.118.301019 · Cited by 94 · see citing works
Fitness Trade-Offs Associated with the Evolution of Resistance to Antifungal Drug Combinations
Hill, J. A., O’Meara, T. R., & Cowen, L. E. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.009 · Cited by 80 · see citing works
The fitness costs and benefits of trisomy of each <i>Candida albicans</i> chromosome
Yang, F., Todd, R. T., Selmecki, A., Jiang, Y.-Y., Cao, Y.-B., & Berman, J. (2021) · Genetics · doi:10.1093/genetics/iyab056 · Cited by 72 · see citing works
The Dynamic Fungal Genome: Polyploidy, Aneuploidy and Copy Number Variation in Response to Stress
Vande Zande, P., Zhou, X., & Selmecki, A. (2023) · Annual Review of Microbiology · doi:10.1146/annurev-micro-041320-112443 · Cited by 70 · see citing works
Carolus, H., Sofras, D., Boccarella, G., Sephton-Clark, P., Biriukov, V., Cauldron, N. C., Lobo Romero, C., Vergauwen, R., Yazdani, S., Pierson, S., et al. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01854-z · Cited by 72 · see citing works
A Double-Edged Sword: Aneuploidy is a Prevalent Strategy in Fungal Adaptation
Tsai, H.-J., & Nelliat, A. (2019) · Genes · doi:10.3390/genes10100787 · Cited by 60 · see citing works
Anderson, M. Z., Saha, A., Haseeb, A., & Bennett, R. J. (2017) · Microbiology · doi:10.1099/mic.0.000478 · Cited by 53 · see citing works
Tunicamycin Potentiates Antifungal Drug Tolerance via Aneuploidy in Candida albicans
Yang, F., Gritsenko, V., Slor Futterman, Y., Gao, L., Zhen, C., Lu, H., Jiang, Y.-Y., & Berman, J. (2021) · mBio · doi:10.1128/mbio.02272-21 · Cited by 59 · see citing works
Ngamskulrungroj, P., Chang, Y., Hansen, B., Bugge, C., Fischer, E., & Kwon-Chung, K. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033022 · Cited by 56 · see citing works
Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in <i>Candida albicans</i>
Todd, R. T., Soisangwan, N., Peters, S., Kemp, B., Crooks, T., Gerstein, A., & Selmecki, A. (2023) · Molecular Biology and Evolution · doi:10.1093/molbev/msad009 · Cited by 53 · see citing works
Mba, I. E., Nweze, E. I., Eze, E. A., & Anyaegbunam, Z. K. G. (2022) · Infection, Genetics and Evolution · doi:10.1016/j.meegid.2022.105256 · Cited by 46 · see citing works
Karyotypic Aberrations in Oncogenesis and Cancer Therapy
Vitale, I., Manic, G., Senovilla, L., Kroemer, G., & Galluzzi, L. (2015) · Trends in Cancer · doi:10.1016/j.trecan.2015.08.001 · Cited by 34 · see citing works
The dynamics of adaptation to stress from standing genetic variation and de novo mutations
Ament-Velásquez, S. L., Gilchrist, C., Rêgo, A., Bendixsen, D. P., Brice, C., Grosse-Sommer, J. M., Rafati, N., & Stelkens, R. (2022) · Molecular Biology and Evolution · doi:10.1093/molbev/msac242 · Cited by 31 · see citing works
Aneuploidy Underlies Brefeldin A‐Induced Antifungal Drug Resistance in Cryptococcus Neoformans
Zhang, Z.-H., Sun, L.-L., Fu, B.-Q., Deng, J., Jia, C.-L., Miao, M.-X., Yang, F., Cao, Y.-B., & Yan, T.-H. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1397724 · Cited by 14 · see citing works
- Authors
- Pavelka, N., Rancati, G., Zhu, J., Bradford, W. D., Saraf, A., Florens, L., Sanderson, B. W., Hattem, G. L., & Li, R.
- Affiliations
- Stowers Institute for Medical Research (US)
- Corresponding author
- Li, Rong
- ORCID
- Venue
- Nature
- Published
- 2010-10-20
- Volume
- 468
- Issue
- 7321
- Pages
- 321-325
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2978756
- OpenAlex
- W1971013077
- Cited by
- 577
- References
- 25
- Citations by year
- 2026: 15 · 2025: 30 · 2024: 31 · 2023: 36 · 2022: 23 · 2021: 39 · 2020: 29 · 2019: 35 · 2018: 37 · 2017: 35 · 2016: 40 · 2015: 64 · 2014: 41 · 2013: 45 · 2012: 44
- FWCI
- 16.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM059964)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- aneuploidy, Saccharomyces cerevisiae, proteome, transcriptome, phenotypic variability, fitness, chromosome copy number, karyotype, drug resistance, antifungal susceptibility, phenotypic evolution, cellular adaptation
- MeSH terms
- Aneuploidy, Antifungal Agents, Cell Division, Karyotyping, Meiosis, Phenotype, Polyploidy, Saccharomyces cerevisiae, Stress, Physiological, Transcription, Genetic, Chromosomes, Fungal, Gene Expression Regulation, Fungal, Proteome, Gene Expression Profiling, Proteomics, Genetic Fitness
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
