Parasexual Ploidy Reduction Drives Population Heterogeneity Through Random and Transient Aneuploidy in Candida albicans
Open accessAbstract
The opportunistic pathogen Candida albicans has a large repertoire of mechanisms to generate genetic and phenotypic diversity despite the lack of meiosis in its life cycle. Its parasexual cycle enables shifts in ploidy, which in turn facilitate recombination, aneuploidy, and homozygosis of whole chromosomes to fuel rapid adaptation. Here we show that the tetraploid state potentiates ploidy variation and drives population heterogeneity. In tetraploids, the rate of losing a single heterozygous marker [loss of heterozygosity (LOH)] is elevated ∼30-fold higher than the rate in diploid cells. Furthermore, isolates recovered after selection for LOH of one, two, or three markers were highly aneuploid, with a broad range of karyotypes including strains with a combination of di-, tri-, and tetrasomic chromosomes. We followed the ploidy trajectories for these tetraploid- and aneuploid-derived isolates, using a combination of flow cytometry and double-digestion restriction-site-associated DNA analyzed with next-generation sequencing. Isolates derived from either tetraploid or aneuploid isolates predominately resolved to a stable euploid state. The majority of isolates reduced to the conventional diploid state; however, stable triploid and tetraploid states were observed in ∼30% of the isolates. Notably, aneuploid isolates were more transient than tetraploid isolates, resolving to a euploid state within a few passages. Furthermore, the likelihood that a particular isolate will resolve to the same ploidy state in replicate evolution experiments is only ∼50%, supporting the idea that the chromosome loss process of the parasexual cycle is random and does not follow trajectories involving specific combinations of chromosomes. Together, our results indicate that tetraploid progenitors can produce populations of progeny cells with a high degree of genomic diversity, from altered ploidy to homozygosis, providing an excellent source of genetic variation upon which selection can act.
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Chr6 and ChrR were previously found to be the 2 most common aneuploidies remaining in otherwise euploid strains after 28 days of daily passaging of initially tetraploid and initially aneuploid strains in standard lab YPD.
“Interestingly, Chr6 and ChrR were previously found to be the 2 most common aneuploidies remaining in otherwise euploid strains after 28 days of daily passaging of initially tetraploid and initially aneuploid strains in standard lab YPD (Hickman et al. 2015).”
From Acquisition of cross-azole tolerance and aneuploidy in <i>Candida albicans</i> strains evolved to posaconazole (2022) · cites this paper as Hickman et al. 2015
Tetraploid C. albicans cells can generate diverse fitness and heterogeneity through increased rates of heterozygosity loss.
“The discovery of tetraploid cells of C. albicans, containing four homologous sets of chromosomes, and their ability to generate a diverse range of fitness and heterogeneity through increased rates of heterozygosity loss”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus<i>Candida albicans</i> (2020) · cites this paper as [158]
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- Authors
- Hickman, M. A., Paulson, C., Dudley, A., & Berman, J.
- Affiliations
- University of Minnesota (US)
- Pacific Northwest Diabetes Research Institute, Seattle, Washington 98122
- Corresponding author
- Berman, Judith
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05-18
- Volume
- 200
- Issue
- 3
- Pages
- 781-794
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC4512543
- OpenAlex
- W2152997141
- Cited by
- 113
- References
- 85
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 15 · 2019: 25 · 2018: 10 · 2017: 13 · 2016: 7 · 2015: 4
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Université du Luxembourg
- European Commission (303635)
- National Institutes of Health (1f32gm096536-01a1)
- National Cancer Institute (P30CA077598)
- National Institute of General Medical Sciences (F32GM096536-02, F32 GM096536)
- National Institute of Allergy and Infectious Diseases (AI0624273)
- FP7 Ideas: European Research Council (340087)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- Candida albicans, parasexual cycle, ploidy reduction, tetraploidy, aneuploidy, loss of heterozygosity, karyotype stability, triploidy, genomic diversity, population heterogeneity, recombination
- MeSH terms
- Adaptation, Biological, Aneuploidy, Candida albicans, Genetic Variation, Chromosomes, Fungal, Loss of Heterozygosity, Tetraploidy
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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.
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