1932

Abstract

Fungal species have dynamic genomes and often exhibit genomic plasticity in response to stress. This genome plasticity often comes with phenotypic consequences that affect fitness and resistance to stress. Fungal pathogens exhibit genome plasticity in both clinical and agricultural settings and often during adaptation to antifungal drugs, posing significant challenges to human health. Therefore, it is important to understand the rates, mechanisms, and impact of large genomic changes. This review addresses the prevalence of polyploidy, aneuploidy, and copy number variation across diverse fungal species, with special attention to prominent fungal pathogens and model species. We also explore the relationship between environmental stress and rates of genomic changes and highlight the mechanisms underlying genotypic and phenotypic changes. A comprehensive understanding of these dynamic fungal genomes is needed to identify novel solutions for the increase in antifungal drug resistance.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-micro-041320-112443
2023-09-15
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/micro/77/1/annurev-micro-041320-112443.html?itemId=/content/journals/10.1146/annurev-micro-041320-112443&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Albertin W, Marullo P. 2012. Polyploidy in fungi: evolution after whole-genome duplication. Proc. R. Soc. B 279:17382497–509
    [Google Scholar]
  2. 2.
    Albert FW, Bloom JS, Siegel J, Day L, Kruglyak L. 2018. Genetics of trans-regulatory variation in gene expression. eLife 7:e35471
    [Google Scholar]
  3. 3.
    Anderson MZ, Thomson GJ, Hirakawa MP, Bennett RJ. 2019. A “parameiosis” drives depolyploidization and homologous recombination in Candida albicans. Nat. Commun. 10:4388
    [Google Scholar]
  4. 4.
    Araya CL, Payen C, Dunham MJ, Fields S. 2010. Whole-genome sequencing of a laboratory-evolved yeast strain. BMC Genom. 11:88
    [Google Scholar]
  5. 5.
    Avecilla G, Chuong JN, Li F, Sherlock G, Gresham D, Ram Y. 2022. Neural networks enable efficient and accurate simulation-based inference of evolutionary parameters from adaptation dynamics. PLOS Biol. 20:5e3001633
    [Google Scholar]
  6. 6.
    Bennett RJ, Forche A, Berman J. 2014. Rapid mechanisms for generating genome diversity: whole ploidy shifts, aneuploidy, and loss of heterozygosity. Cold Spring Harb. Perspect. Med. 4:10a019604
    [Google Scholar]
  7. 7.
    Bennett RJ, Johnson AD. 2003. Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains. EMBO J. 22:102505–15
    [Google Scholar]
  8. 8.
    Berkow EL, Lockhart SR. 2017. Fluconazole resistance in Candida species: a current perspective. Infect. Drug Resist. 10:237–45
    [Google Scholar]
  9. 9.
    Bing J, Hu T, Zheng Q, Muñoz JF, Cuomo CA, Huang G. 2020. Experimental evolution identifies adaptive aneuploidy as a mechanism of fluconazole resistance in Candida auris. Antimicrob. Agents Chemother. 65:e01466
    [Google Scholar]
  10. 10.
    Birchler JA, Veitia RA. 2010. The gene balance hypothesis: implications for gene regulation, quantitative traits and evolution. New Phytol. 186:154–62
    [Google Scholar]
  11. 11.
    Bouchonville K, Forche A, Tang KES, Selmecki A, Berman J. 2009. Aneuploid chromosomes are highly unstable during DNA transformation of Candida albicans. Eukaryot. Cell 8:101554–66
    [Google Scholar]
  12. 12.
    Bravo Ruiz G, Ross ZK, Holmes E, Schelenz S, Gow NAR, Lorenz A. 2019. Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates. Curr. Genet. 65:51217–28
    [Google Scholar]
  13. 13.
    Brewer BJ, Payen C, Di Rienzi SC, Higgins MM, Ong G et al. 2015. Origin-dependent inverted-repeat amplification: tests of a model for inverted DNA amplification. PLOS Genet. 11:12e1005699
    [Google Scholar]
  14. 14.
    Brimacombe CA, Burke JE, Parsa J-Y, Catania S, O'Meara TR et al. 2019. A natural histone H2A variant lacking the Bub1 phosphorylation site and regulated depletion of centromeric histone CENP-A foster evolvability in Candida albicans. PLOS Biol. 17:6e3000331
    [Google Scholar]
  15. 15.
    Burrack LS, Todd RT, Soisangwan N, Wiederhold NP, Selmecki A. 2022. Genomic diversity across Candida auris clinical isolates shapes rapid development of antifungal resistance in vitro and in vivo. mBio 13:4e00842
    [Google Scholar]
  16. 16.
    Carreté L, Ksiezopolska E, Gómez-Molero E, Angoulvant A, Bader O et al. 2019. Genome comparisons of Candida glabrata serial clinical isolates reveal patterns of genetic variation in infecting clonal populations. Front. Microbiol. 10:112
    [Google Scholar]
  17. 17.
    Carreté L, Ksiezopolska E, Pegueroles C, Gómez-Molero E, Saus E et al. 2018. Patterns of genomic variation in the opportunistic pathogen Candida glabrata suggest the existence of mating and a secondary association with humans. Curr. Biol. 28:115–27.e7
    [Google Scholar]
  18. 18.
    Chauvel M, Nesseir A, Cabral V, Znaidi S, Goyard S et al. 2012. A versatile overexpression strategy in the pathogenic yeast Candida albicans: identification of regulators of morphogenesis and fitness. PLOS ONE 7:9e45912
    [Google Scholar]
  19. 19.
    Chen G, Bradford WD, Seidel CW, Li R. 2012. Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy. Nature 482:7384246–50
    [Google Scholar]
  20. 20.
    Chen G, Mulla WA, Kucharavy A, Tsai H-J, Rubinstein B et al. 2015. Targeting the adaptability of heterogeneous aneuploids. Cell 160:4771–84
    [Google Scholar]
  21. 21.
    Chen L, Zhou W, Zhang L, Zhang F. 2014. Genome architecture and its roles in human copy number variation. Genom. Inform. 12:4136–44
    [Google Scholar]
  22. 22.
    Chen Y, Chen S, Li K, Zhang Y, Huang X et al. 2019. Overdosage of balanced protein complexes reduces proliferation rate in aneuploid cells. Cell Syst. 9:2129–42.e5
    [Google Scholar]
  23. 23.
    Cowen LE. 2008. The evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype. Nat. Rev. Microbiol. 6:3187–98
    [Google Scholar]
  24. 24.
    Dambuza IM, Drake T, Chapuis A, Zhou X, Correia J et al. 2018. The Cryptococcus neoformans titan cell is an inducible and regulated morphotype underlying pathogenesis. PLOS Pathog. 14:5e1006978
    [Google Scholar]
  25. 25.
    Douglas AC, Smith AM, Sharifpoor S, Yan Z, Durbic T et al. 2012. Functional analysis with a barcoder yeast gene overexpression system. G3 2:101279–89
    [Google Scholar]
  26. 26.
    D'Souza CA, Kronstad JW, Taylor G, Warren R, Yuen M et al. 2011. Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts. mBio 2:1e00342
    [Google Scholar]
  27. 27.
    Dumeaux V, Massahi S, Bettauer V, Khurdia S, Costa A et al. 2022. Candida albicans exhibits heterogeneous and adaptive cytoprotective responses to anti-fungal compounds. bioRxiv 2022.07.20.500774. https://doi.org/10.1101/2022.07.20.500774
  28. 28.
    Dunham MJ, Badrane H, Ferea T, Adams J, Brown PO et al. 2002. Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. PNAS 99:2516144–49
    [Google Scholar]
  29. 29.
    Dutta A, Dutreux F, Schacherer J. 2021. Loss of heterozygosity results in rapid but variable genome homogenization across yeast genetic backgrounds. eLife 10:e70339
    [Google Scholar]
  30. 30.
    Dutta A, Dutreux F, Schacherer J. 2022. Loss of heterozygosity spectrum depends on ploidy level in natural yeast populations. Mol. Biol. Evol. 39:msac214
    [Google Scholar]
  31. 31.
    Elde NC, Child SJ, Eickbush MT, Kitzman JO, Rogers KS et al. 2012. Poxviruses deploy genomic accordions to adapt rapidly against host antiviral defenses. Cell 150:4831–41
    [Google Scholar]
  32. 32.
    Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM et al. 2022. Tackling the emerging threat of antifungal resistance to human health. Nat. Rev. Microbiol. 20:9557–71
    [Google Scholar]
  33. 33.
    Forche A. 2014. Large-scale chromosomal changes and associated fitness consequences in pathogenic fungi. Curr. Fungal Infect. Rep. 8:2163–70
    [Google Scholar]
  34. 34.
    Forche A, Abbey D, Pisithkul T, Weinzierl MA, Ringstrom T et al. 2011. Stress alters rates and types of loss of heterozygosity in Candida albicans. mBio 2:400129
    [Google Scholar]
  35. 35.
    Forche A, Alby K, Schaefer D, Johnson AD, Berman J, Bennett RJ. 2008. The parasexual cycle in Candida albicans provides an alternative pathway to meiosis for the formation of recombinant strains. PLOS Biol. 6:5e110
    [Google Scholar]
  36. 36.
    Forche A, Cromie G, Gerstein AC, Solis NV, Pisithkul T et al. 2018. Rapid phenotypic and genotypic diversification after exposure to the oral host niche in Candida albicans. Genetics 209:3725–41
    [Google Scholar]
  37. 37.
    Forche A, Magee PT, Selmecki A, Berman J, May G 2009. Evolution in Candida albicans populations during a single passage through a mouse host. Genetics 182:3799–811
    [Google Scholar]
  38. 38.
    Forche A, Solis NV, Swidergall M, Thomas R, Guyer A et al. 2019. Selection of Candida albicans trisomy during oropharyngeal infection results in a commensal-like phenotype. PLOS Genet. 15:5e1008137
    [Google Scholar]
  39. 39.
    Ford CB, Funt JM, Abbey D, Issi L, Guiducci C et al. 2015. The evolution of drug resistance in clinical isolates of Candida albicans. eLife 4:e00662
    [Google Scholar]
  40. 40.
    Fouché S, Badet T, Oggenfuss U, Plissonneau C, Francisco CS, Croll D. 2020. Stress-driven transposable element de-repression dynamics and virulence evolution in a fungal pathogen. Mol. Biol. Evol. 37:1221–39
    [Google Scholar]
  41. 41.
    Fouché S, Plissonneau C, Croll D. 2018. The birth and death of effectors in rapidly evolving filamentous pathogen genomes. Curr. Opin. Microbiol. 46:34–42
    [Google Scholar]
  42. 42.
    Gasch AP, Hose J, Newton MA, Sardi M, Yong M, Wang Z. 2016. Further support for aneuploidy tolerance in wild yeast and effects of dosage compensation on gene copy-number evolution. eLife 5:e14409
    [Google Scholar]
  43. 43.
    Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB et al. 2000. Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell 11:124241–57
    [Google Scholar]
  44. 44.
    Gasch AP, Werner-Washburne M. 2002. The genomics of yeast responses to environmental stress and starvation. Funct. Integr. Genom. 2:4/5181–92
    [Google Scholar]
  45. 45.
    Gerstein AC, Fu MS, Mukaremera L, Li Z, Ormerod KL et al. 2015. Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation. mBio 6:5e01340Finds that polyploid C. neoformans titan cells, under antifungal drug stress, produce multiple aneuploid and diploid daughters which show fitness advantages over the typical haploid progeny.
    [Google Scholar]
  46. 46.
    Gilchrist C, Stelkens R. 2019. Aneuploidy in yeast: segregation error or adaptation mechanism?. Yeast 36:9525–39
    [Google Scholar]
  47. 47.
    Gresham D, Desai MM, Tucker CM, Jenq HT, Pai DA et al. 2008. The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. PLOS Genet. 4:12e1000303
    [Google Scholar]
  48. 48.
    Gresham D, Usaite R, Germann SM, Lisby M, Botstein D, Regenberg B. 2010. Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus. PNAS 107:4318551–56
    [Google Scholar]
  49. 49.
    Harari Y, Ram Y, Rappoport N, Hadany L, Kupiec M. 2018. Spontaneous changes in ploidy are common in yeast. Curr. Biol. 28:6825–35.e4Finds a high frequency of diploidization in haploid S. cerevisiae caused by endoreduplication or mating.
    [Google Scholar]
  50. 50.
    Harrison BD, Hashemi J, Bibi M, Pulver R, Bavli D et al. 2014. A tetraploid intermediate precedes aneuploid formation in yeasts exposed to fluconazole. PLOS Biol. 12:3e1001815
    [Google Scholar]
  51. 51.
    Hartmann FE, Sánchez-Vallet A, McDonald BA, Croll D. 2017. A fungal wheat pathogen evolved host specialization by extensive chromosomal rearrangements. ISME J. 11:51189–204
    [Google Scholar]
  52. 52.
    Hastings PJ, Lupski JR, Rosenberg SM, Ira G. 2009. Mechanisms of change in gene copy number. Nat. Rev. Genet. 10:8551–64
    [Google Scholar]
  53. 53.
    Hickman MA, Paulson C, Dudley A, Berman J. 2015. Parasexual ploidy reduction drives population heterogeneity through random and transient aneuploidy in Candida albicans. Genetics 200:3781–94
    [Google Scholar]
  54. 54.
    Hirakawa MP, Chyou DE, Huang D, Slan AR, Bennett RJ. 2017. Parasex generates phenotypic diversity de novo and impacts drug resistance and virulence in Candida albicans. Genetics 207:31195–211
    [Google Scholar]
  55. 55.
    Hirakawa MP, Martinez DA, Sakthikumar S, Anderson MZ, Berlin A et al. 2015. Genetic and phenotypic intra-species variation in Candida albicans. Genome Res. 25:3413–25
    [Google Scholar]
  56. 56.
    Hommel B, Mukaremera L, Cordero RJB, Coelho C, Desjardins CA et al. 2018. Identification of environmental and genetic factors important for Cryptococcus neoformans titan cell formation using new in vitro inducing conditions. PLOS Pathog. 14:5e1006982
    [Google Scholar]
  57. 57.
    Hose J, Escalante LE, Clowers KJ, Dutcher HA, Robinson D et al. 2020. The genetic basis of aneuploidy tolerance in wild yeast. eLife 9:e52063Identifies the translational regulator SSD1 as a major driver of the fitness cost of aneuploidy, which varies across different genetic backgrounds of S. cerevisiae.
    [Google Scholar]
  58. 58.
    Hose J, Yong CM, Sardi M, Wang Z, Newton MA, Gasch AP. 2015. Dosage compensation can buffer copy-number variation in wild yeast. eLife 4:e05462
    [Google Scholar]
  59. 59.
    Hughes TR, Roberts CJ, Dai H, Jones AR, Meyer MR et al. 2000. Widespread aneuploidy revealed by DNA microarray expression profiling. Nat. Genet. 25:3333–37
    [Google Scholar]
  60. 60.
    Hull RM, Cruz C, Jack CV, Houseley J. 2017. Environmental change drives accelerated adaptation through stimulated copy number variation. PLOS Biol. 15:6e2001333
    [Google Scholar]
  61. 61.
    Ippolito MR, Martis V, Martin S, Tijhuis AE, Hong C et al. 2021. Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy. Dev. Cell 56:172440–54.e6
    [Google Scholar]
  62. 62.
    Jackson CA, Castro DM, Saldi G-A, Bonneau R, Gresham D. 2020. Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments. eLife 9:e51254
    [Google Scholar]
  63. 63.
    Janbon G, Sherman F, Rustchenko E. 1999. Appearance and properties of l-sorbose-utilizing mutants of Candida albicans obtained on a selective plate. Genetics 153:2653–64
    [Google Scholar]
  64. 64.
    Kaizu K, Moriya H, Kitano H. 2010. Fragilities caused by dosage imbalance in regulation of the budding yeast cell cycle. PLOS Genet. 6:4e1000919
    [Google Scholar]
  65. 65.
    Ksiezopolska E, Schikora-Tamarit , Beyer R, Nunez-Rodriguez JC, Schüller C, Gabaldón T. 2021. Narrow mutational signatures drive acquisition of multidrug resistance in the fungal pathogen Candida glabrata. Curr. Biol. 31:235314–26.e10
    [Google Scholar]
  66. 66.
    Kumaran R, Yang S-Y, Leu J-Y. 2013. Characterization of chromosome stability in diploid, polyploid and hybrid yeast cells. PLOS ONE 8:7e68094
    [Google Scholar]
  67. 67.
    Kvitek DJ, Will JL, Gasch AP. 2008. Variations in stress sensitivity and genomic expression in diverse S. cerevisiae isolates. PLOS Genet. 4:10e1000223
    [Google Scholar]
  68. 68.
    Larrimore KE, Barattin-Voynova NS, Reid DW, Ng DTW. 2020. Aneuploidy-induced proteotoxic stress can be effectively tolerated without dosage compensation, genetic mutations, or stress responses. BMC Biol. 18:1117
    [Google Scholar]
  69. 69.
    Lauer S, Avecilla G, Spealman P, Sethia G, Brandt N et al. 2018. Single-cell copy number variant detection reveals the dynamics and diversity of adaptation. PLOS Biol. 16:12e3000069Uses a fluorescent reporter to detect and track aneuploidy and CNVs in S. cerevisiae during in vitro evolution and finds that CNVs are possibly generated by errors during DNA replication.
    [Google Scholar]
  70. 70.
    Legras J-L, Galeote V, Bigey F, Camarasa C, Marsit S et al. 2018. Adaptation of S. cerevisiae to fermented food environments reveals remarkable genome plasticity and the footprints of domestication. Mol. Biol. Evol. 35:71712–27
    [Google Scholar]
  71. 71.
    Lengeler KB, Cox GM, Heitman J. 2001. Serotype AD strains of Cryptococcus neoformans are diploid or aneuploid and are heterozygous at the mating-type locus. Infect. Immun. 69:1115–22
    [Google Scholar]
  72. 72.
    Lin X. 2009. Cryptococcus neoformans: morphogenesis, infection, and evolution. Infect. Genet. Evol. 9:4401–16
    [Google Scholar]
  73. 73.
    Litvintseva AP, Thakur R, Reller LB, Mitchell TG. 2005. Prevalence of clinical isolates of Cryptococcus gattii serotype C among patients with AIDS in sub-Saharan Africa. J. Infect. Dis. 192:5888–92
    [Google Scholar]
  74. 74.
    Liu G, Yong MYJ, Yurieva M, Srinivasan KG, Liu J et al. 2015. Gene essentiality is a quantitative property linked to cellular evolvability. Cell 163:61388–99
    [Google Scholar]
  75. 75.
    Liu H, Krizek J, Bretscher A. 1992. Construction of a GAL1-regulated yeast cDNA expression library and its application to the identification of genes whose overexpression causes lethality in yeast. Genetics 132:3665–73
    [Google Scholar]
  76. 76.
    Loll-Krippleber R, Feri A, Nguyen M, Maufrais C, Yansouni J et al. 2015. A FACS-optimized screen identifies regulators of genome stability in Candida albicans. Eukaryot. Cell 14:3311–22Develops a novel LOH reporter system in C. albicans that combines fluorescent markers and flow cytometry and applies this system to identify genes that regulate genome instability.
    [Google Scholar]
  77. 77.
    Lukow DA, Sausville EL, Suri P, Chunduri NK, Wieland A et al. 2021. Chromosomal instability accelerates the evolution of resistance to anti-cancer therapies. Dev. Cell 56:172427–39.e4
    [Google Scholar]
  78. 78.
    Mäe A, Fillinger S, Sooväli P, Heick TM. 2020. Fungicide sensitivity shifting of Zymoseptoria tritici in the Finnish-Baltic region and a novel insertion in the MFS1 promoter. Front. Plant Sci. 11:385
    [Google Scholar]
  79. 79.
    Marton T, d'Enfert C, Legrand M. 2022. Multiple stochastic parameters influence genome dynamics in a heterozygous diploid eukaryotic model. J. Fungi 8:7650
    [Google Scholar]
  80. 80.
    Møller HD, Mohiyuddin M, Prada-Luengo I, Sailani MR, Halling JF et al. 2018. Circular DNA elements of chromosomal origin are common in healthy human somatic tissue. Nat. Commun. 9:1069
    [Google Scholar]
  81. 81.
    Møller HD, Parsons L, Jørgensen TS, Botstein D, Regenberg B. 2015. Extrachromosomal circular DNA is common in yeast. PNAS 112:24E3114–22
    [Google Scholar]
  82. 82.
    Morrow CA, Fraser JA. 2013. Ploidy variation as an adaptive mechanism in human pathogenic fungi. Semin. Cell Dev. Biol. 24:4339–46
    [Google Scholar]
  83. 83.
    Muenzner J, Trébulle P, Agostini F, Messner CB, Steger M et al. 2022. The natural diversity of the yeast proteome reveals chromosome-wide dosage compensation in aneuploids. bioRxiv 2022.04.06.487392. https://doi.org/10.1101/2022.04.06.487392 By collecting transcriptomic and proteomic data corresponding to previous genomic data from 1,011 S. cerevisiae genomes, this study finds that gene expression is buffered not at the transcriptional level but rather at the translational level.
  84. 84.
    Muller H, Thierry A, Coppée J-Y, Gouyette C, Hennequin C et al. 2009. Genomic polymorphism in the population of Candida glabrata: gene copy-number variation and chromosomal translocations. Fungal Genet. Biol. 46:3264–76
    [Google Scholar]
  85. 85.
    Muñoz JF, Gade L, Chow NA, Loparev VN, Juieng P et al. 2018. Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat. Commun. 9:5346
    [Google Scholar]
  86. 86.
    Natesuntorn W, Iwami K, Matsubara Y, Sasano Y, Sugiyama M et al. 2015. Genome-wide construction of a series of designed segmental aneuploids in Saccharomyces cerevisiae. Sci. Rep. 5:12510
    [Google Scholar]
  87. 87.
    Niwa O, Tange Y, Kurabayashi A. 2006. Growth arrest and chromosome instability in aneuploid yeast. Yeast 23:13937–50
    [Google Scholar]
  88. 88.
    O'Duibhir E, Lijnzaad P, Benschop JJ, Lenstra TL, van Leenen D et al. 2014. Cell cycle population effects in perturbation studies. Mol. Syst. Biol. 10:6732
    [Google Scholar]
  89. 89.
    Okagaki LH, Strain AK, Nielsen JN, Charlier C, Baltes NJ et al. 2010. Cryptococcal cell morphology affects host cell interactions and pathogenicity. PLOS Pathog. 6:6e1000953
    [Google Scholar]
  90. 90.
    Omrane S, Audéon C, Ignace A, Duplaix C, Aouini L et al. 2017. Plasticity of the MFS1 promoter leads to multidrug resistance in the wheat pathogen. Zymoseptoria tritici. mSphere 2:5e00393
    [Google Scholar]
  91. 91.
    Omrane S, Sghyer H, Audéon C, Lanen C, Duplaix C et al. 2015. Fungicide efflux and the MgMFS1 transporter contribute to the multidrug resistance phenotype in Zymoseptoria tritici field isolates. Environ. Microbiol. 17:82805–23
    [Google Scholar]
  92. 92.
    Papp B, Pál C, Hurst LD. 2003. Dosage sensitivity and the evolution of gene families in yeast. Nature 424:6945194–97
    [Google Scholar]
  93. 93.
    Pavelka N, Rancati G, Li R. 2010. Dr Jekyll and Mr Hyde: role of aneuploidy in cellular adaptation and cancer. Curr. Opin. Cell Biol. 22:6809–15
    [Google Scholar]
  94. 94.
    Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A et al. 2010. Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468:7321321–25
    [Google Scholar]
  95. 95.
    Payen C, Di Rienzi SC, Ong GT, Pogachar JL, Sanchez JC et al. 2014. The dynamics of diverse segmental amplifications in populations of Saccharomyces cerevisiae adapting to strong selection. G3 4:3399–409
    [Google Scholar]
  96. 96.
    Peng CA, Gaertner AAE, Henriquez SA, Fang D, Colon-Reyes RJ et al. 2018. Fluconazole induces ROS in Cryptococcus neoformans and contributes to DNA damage in vitro. PLOS ONE 13:12e0208471
    [Google Scholar]
  97. 97.
    Peter J, De Chiara M, Friedrich A, Yue J-X, Pflieger D et al. 2018. Genome evolution across 1,011 Saccharomyces cerevisiae isolates. Nature 556:7701339–44Performs a large-scale genome survey across 1,011 S. cerevisiae isolates, revealing a high frequency of ploidy, aneuploidy, and CNV; establishes that copy number changes have a greater impact on phenotypes than single-nucleotide mutations.
    [Google Scholar]
  98. 98.
    Poláková S, Blume C, Zárate JA, Mentel M, Jørck-Ramberg D et al. 2009. Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata. PNAS 106:82688–93
    [Google Scholar]
  99. 99.
    Pös O, Radvanszky J, Buglyó G, Pös Z, Rusnakova D et al. 2021. DNA copy number variation: main characteristics, evolutionary significance, and pathological aspects. Biomed. J. 44:5548–59
    [Google Scholar]
  100. 100.
    Prasad K, Bloomfield M, Levi H, Keuper K, Bernhard SV et al. 2022. Whole-genome duplication shapes the aneuploidy landscape of human cancers. Cancer Res. 82:91736–52
    [Google Scholar]
  101. 101.
    Rancati G, Pavelka N, Fleharty B, Noll A, Trimble R et al. 2008. Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor. Cell 135:5879–93
    [Google Scholar]
  102. 102.
    Robbins N, Caplan T, Cowen LE. 2017. Molecular evolution of antifungal drug resistance. Annu. Rev. Microbiol. 71:753–75
    [Google Scholar]
  103. 103.
    Robinson D, Place M, Hose J, Jochem A, Gasch AP. 2021. Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories. eLife 10:e70564Surveys the fitness costs of overexpression for ∼4,000 genes in 15 different S. cerevisiae strains, finding a significant amount of natural variation in tolerance to gene overexpression.
    [Google Scholar]
  104. 104.
    Ropars J, Maufrais C, Diogo D, Marcet-Houben M, Perin A et al. 2018. Gene flow contributes to diversification of the major fungal pathogen Candida albicans. Nat. Commun. 9:2253
    [Google Scholar]
  105. 105.
    Sanchez MR, Miller AW, Liachko I, Sunshine AB, Lynch B et al. 2017. Differential paralog divergence modulates genome evolution across yeast species. PLOS Genet. 13:2 ). e1006585Shows that recurrent amplifications of sulfate transporter genes in multiple Saccharomyces species are an excellent example of both the frequency of amplification as an adaptive mechanism and the regulatory network underlying adaptation between species.
    [Google Scholar]
  106. 106.
    Santaguida S, Amon A. 2015. Short- and long-term effects of chromosome mis-segregation and aneuploidy. Nat. Rev. Mol. Cell Biol. 16:8473–85
    [Google Scholar]
  107. 107.
    Schoustra SE, Debets AJM, Slakhorst M, Hoekstra RF. 2007. Mitotic recombination accelerates adaptation in the fungus Aspergillus nidulans. PLOS Genet. 3:4e68
    [Google Scholar]
  108. 108.
    Schukken KM, Sheltzer JM. 2022. Extensive protein dosage compensation in aneuploid human cancers. Genome Res. 32:71254–70
    [Google Scholar]
  109. 109.
    Scopel EFC, Hose J, Bensasson D, Gasch AP. 2021. Genetic variation in aneuploidy prevalence and tolerance across Saccharomyces cerevisiae lineages. Genetics 217:4iyab015
    [Google Scholar]
  110. 110.
    Scott AL, Richmond PA, Dowell RD, Selmecki AM. 2017. The influence of polyploidy on the evolution of yeast grown in a sub-optimal carbon source. Mol. Biol. Evol. 34:102690–703
    [Google Scholar]
  111. 111.
    Selmecki A, Bergmann S, Berman J. 2005. Comparative genome hybridization reveals widespread aneuploidy in Candida albicans laboratory strains. Mol. Microbiol. 55:51553–65
    [Google Scholar]
  112. 112.
    Selmecki A, Forche A, Berman J. 2006. Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313:5785367–70
    [Google Scholar]
  113. 113.
    Selmecki A, Gerami-Nejad M, Paulson C, Forche A, Berman J. 2008. An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1. Mol. Microbiol. 68:3624–41
    [Google Scholar]
  114. 114.
    Selmecki AM, Dulmage K, Cowen LE, Anderson JB, Berman J. 2009. Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance. PLOS Genet. 5:10e1000705
    [Google Scholar]
  115. 115.
    Selmecki AM, Maruvka YE, Richmond PA, Guillet M, Shoresh N et al. 2015. Polyploidy can drive rapid adaptation in yeast. Nature 519:7543349–52
    [Google Scholar]
  116. 116.
    Sharp NP, Sandell L, James CG, Otto SP. 2018. The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast. PNAS 115:22E5046–55
    [Google Scholar]
  117. 117.
    Sheltzer JM, Amon A. 2011. The aneuploidy paradox: costs and benefits of an incorrect karyotype. Trends Genet. 27:11446–53
    [Google Scholar]
  118. 118.
    Sheltzer JM, Blank HM, Pfau SJ, Tange Y, George BM et al. 2011. Aneuploidy drives genomic instability in yeast. Science 333:60451026–30
    [Google Scholar]
  119. 119.
    Sionov E, Chang YC, Kwon-Chung KJ. 2013. Azole heteroresistance in Cryptococcus neoformans: emergence of resistant clones with chromosomal disomy in the mouse brain during fluconazole treatment. Antimicrob. Agents Chemother. 57:105127–30
    [Google Scholar]
  120. 120.
    Sionov E, Lee H, Chang YC, Kwon-Chung KJ. 2010. Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. PLOS Pathog. 6:4e1000848
    [Google Scholar]
  121. 121.
    Sopko R, Huang D, Preston N, Chua G, Papp B et al. 2006. Mapping pathways and phenotypes by systematic gene overexpression. Mol. Cell 21:3319–30
    [Google Scholar]
  122. 122.
    Springer M, Weissman JS, Kirschner MW. 2010. A general lack of compensation for gene dosage in yeast. Mol. Syst. Biol. 6:368
    [Google Scholar]
  123. 123.
    Steenwyk J, Rokas A. 2017. Extensive copy number variation in fermentation-related genes among Saccharomyces cerevisiae wine strains. G3 7:51475–85
    [Google Scholar]
  124. 124.
    Stingele S, Stoehr G, Peplowska K, Cox J, Mann M, Storchova Z. 2012. Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells. Mol. Syst. Biol. 8:608
    [Google Scholar]
  125. 125.
    Sun S, Berg OG, Roth JR, Andersson DI. 2009. Contribution of gene amplification to evolution of increased antibiotic resistance in Salmonella typhimurium. Genetics 182:41183–95
    [Google Scholar]
  126. 126.
    Tan Z, Hays M, Cromie GA, Jeffery EW, Scott AC et al. 2013. Aneuploidy underlies a multicellular phenotypic switch. PNAS 110:3012367–72
    [Google Scholar]
  127. 127.
    Thompson JN. 2012. The role of coevolution. Science 335:6067410–11
    [Google Scholar]
  128. 128.
    Todd RT, Selmecki A. 2020. Expandable and reversible copy number amplification drives rapid adaptation to antifungal drugs. eLife 9:e58349Reveals that rapid acquisition of CNVs during adaptation to antifungal drugs happens through a dicentric chromosome intermediate and breakage–fusion–bridge cycles that are repaired using long repeat sequences across the C. albicans genome.
    [Google Scholar]
  129. 129.
    Todd RT, Wikoff TD, Forche A, Selmecki A. 2019. Genome plasticity in Candida albicans is driven by long repeat sequences. eLife 8:e45954
    [Google Scholar]
  130. 130.
    Torres EM, Dephoure N, Panneerselvam A, Tucker CM, Whittaker CA et al. 2010. Identification of aneuploidy-tolerating mutations. Cell 143:171–83
    [Google Scholar]
  131. 131.
    Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M et al. 2007. Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317:5840916–24
    [Google Scholar]
  132. 132.
    Trevijano-Contador N, de Oliveira HC, García-Rodas R, Rossi SA, Llorente I et al. 2018. Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals that require the activation of several transduction pathways. PLOS Pathog. 14:5e1007007
    [Google Scholar]
  133. 133.
    Tsai H-J, Nelliat A. 2019. A double-edged sword: Aneuploidy is a prevalent strategy in fungal adaptation. Genes 10:10787
    [Google Scholar]
  134. 134.
    Tsai H-J, Nelliat AR, Choudhury MI, Kucharavy A, Bradford WD et al. 2019. Hypo-osmotic-like stress underlies general cellular defects of aneuploidy. Nature 570:7759117–21Identifies a common transcriptional signature of aneuploidy stress linked to hypo-osmotic stress among diverse aneuploid strains in budding yeast.
    [Google Scholar]
  135. 135.
    Urbonaite G, Lee JTH, Liu P, Parada GE, Hemberg M, Acar M. 2021. A yeast-optimized single-cell transcriptomics platform elucidates how mycophenolic acid and guanine alter global mRNA levels. Commun. Biol. 4:822
    [Google Scholar]
  136. 136.
    Vande Zande P, Hill MS, Wittkopp PJ. 2022. Pleiotropic effects of trans-regulatory mutations on fitness and gene expression. Science 377:6601105–9
    [Google Scholar]
  137. 137.
    Vavouri T, Semple JI, Garcia-Verdugo R, Lehner B. 2009. Intrinsic protein disorder and interaction promiscuity are widely associated with dosage sensitivity. Cell 138:1198–208
    [Google Scholar]
  138. 138.
    Wang JM, Woodruff AL, Dunn MJ, Fillinger RJ, Bennett RJ, Anderson MZ. 2021. Intraspecies transcriptional profiling reveals key regulators of Candida albicans pathogenic traits. mBio 12:2e00586
    [Google Scholar]
  139. 139.
    Will JL, Kim HS, Clarke J, Painter JC, Fay JC, Gasch AP. 2010. Incipient balancing selection through adaptive loss of aquaporins in natural Saccharomyces cerevisiae populations. PLOS Genet. 6:4e1000893
    [Google Scholar]
  140. 140.
    Yang F, Gritsenko V, Lu H, Zhen C, Gao L et al. 2021. Adaptation to fluconazole via aneuploidy enables cross-adaptation to amphotericin B and flucytosine in Cryptococcus neoformans. Microbiol. Spectr. 9:2e0072321
    [Google Scholar]
  141. 141.
    Yang F, Teoh F, Tan ASM, Cao Y, Pavelka N, Berman J. 2019. Aneuploidy enables cross-adaptation to unrelated drugs. Mol. Biol. Evol. 36:81768–82
    [Google Scholar]
  142. 142.
    Yang F, Todd RT, Selmecki A, Jiang Y-Y, Cao Y-B, Berman J. 2021. The fitness costs and benefits of trisomy of each Candida albicans chromosome. Genetics 218:2iyab056
    [Google Scholar]
  143. 143.
    Yona AH, Manor YS, Herbst RH, Romano GH, Mitchell A et al. 2012. Chromosomal duplication is a transient evolutionary solution to stress. PNAS 109:5121010–15
    [Google Scholar]
  144. 144.
    Zaragoza O, García-Rodas R, Nosanchuk JD, Cuenca-Estrella M, Rodríguez-Tudela JL, Casadevall A. 2010. Fungal cell gigantism during mammalian infection. PLOS Pathog. 6:6e1000945
    [Google Scholar]
  145. 145.
    Zaragoza O, Nielsen K. 2013. Titan cells in Cryptococcus neoformans: cells with a giant impact. Curr. Opin. Microbiol. 16:4409–13
    [Google Scholar]
  146. 146.
    Zhang H, Zeidler AFB, Song W, Puccia CM, Malc E et al. 2013. Gene copy-number variation in haploid and diploid strains of the yeast Saccharomyces cerevisiae. Genetics 193:3785–801
    [Google Scholar]
  147. 147.
    Zhou X, Ballou ER. 2018. The Cryptococcus neoformans titan cell: from in vivo phenomenon to in vitro model. Curr. Clin. Microbiol. Rep. 5:4252–60
    [Google Scholar]
  148. 148.
    Zhou X, Desanti GE, May RC, Dambuza IM, Ballou ER. 2021. Host-derived reactive nitrogen species mediate the Cryptococcus neoformans yeast-to-titan switch via fungal-derived superoxide. bioRxiv 2021.03.01.433276. https://doi.org/10.1101/2021.03.01.433276
  149. 149.
    Zhu J, Pavelka N, Bradford WD, Rancati G, Li R. 2012. Karyotypic determinants of chromosome instability in aneuploid budding yeast. PLOS Genet. 8:5e1002719
    [Google Scholar]
  150. 150.
    Zhu YO, Sherlock G, Petrov DA. 2016. Whole genome analysis of 132 clinical Saccharomyces cerevisiae strains reveals extensive ploidy variation. G3 6:82421–34
    [Google Scholar]
  151. 151.
    Zhu YO, Siegal ML, Hall DW, Petrov DA. 2014. Precise estimates of mutation rate and spectrum in yeast. PNAS 111:22E2310–18Uses mutation accumulation lines to estimate mutation rate, detecting nearly 1,000 mutations including single-nucleotide mutations and large-scale changes like aneuploidy and CNVs.
    [Google Scholar]
/content/journals/10.1146/annurev-micro-041320-112443
Loading
/content/journals/10.1146/annurev-micro-041320-112443
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error