Ploidy dynamics and evolvability in fungi

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 371, Issue 1709, 2016, Pages

  Wertheimer, Noa Blutraich ^a   Stone, Neil ^b   Berman, Judith ^a  

^a TEL AVIV UNIVERSITY   (Israel)

^b ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Adaptation; Aneuploidy; Drug resistance; Loss of heterozygosity; Trimeras

Indexed keywords

ADAPTATION; CHROMOSOME; DRUG RESISTANCE; FUNGUS; GENE EXPRESSION; HETEROZYGOSITY; MUTATION; PATHOGEN; PLOIDY; SURVIVAL;

ANIMALIA; FUNGI;

ANTIFUNGAL AGENT;

ANEUPLOIDY; ANTIFUNGAL RESISTANCE; EVOLUTION; FUNGUS; GENETICS; MOLECULAR EVOLUTION; PHENOTYPE; PLOIDY;

ANEUPLOIDY; ANTIFUNGAL AGENTS; BIOLOGICAL EVOLUTION; DRUG RESISTANCE, FUNGAL; EVOLUTION, MOLECULAR; FUNGI; PHENOTYPE; PLOIDIES;

EID: 84992455343     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2015.0461     Document Type: Review

References (114)

1. Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCraw SL, Gurr SJ. 2012 Emerging fungal threats to animal, plant and ecosystem health. Nature 484, 186–194. (doi:10.1038/nature10947)
2. Institute of Medicine (US) Forum on Microbial Threats. 2011 Fungal diseases: an emerging threat to human, animal, and plant health: workshop summary. (doi:10.17226/13147)
3. Rosenblum EB et al. 2013 Complex history of the amphibian-killing chytrid fungus revealed with genome resequencing data. Proc. Natl Acad. Sci. USA 110, 9385–9390. (doi:10.1073/pnas.1300130110)
4. Ormerod KL, Fraser JA. 2013 Balancing stability and flexibility within the genome of the pathogen Cryptococcus neoformans. PLoS Pathog. 9, e1003764. (doi:10.1371/journal.ppat.1003764)
5. 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, 5127–5130. (doi:10.1128/AAC.00694-13)
6. Ma L-J et al. 2010 Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium. Nature 464, 367–373. (doi:10.1038/nature08850)
7. Rustchenko E. 2007 Chromosome instability in Candida albicans. FEMS Yeast Res 7, 2–11. (doi:10.1111/j.1567-1364.2006.00150.x)
8. Zhu YO, Sherlock GJ, Petrov DA. 2016 Whole genome analysis of 132 clinical Saccharomyces cerevisiae strains reveals extensive ploidy variation. G3 6, 2421–2434. (doi:10.1534/g3.116.029397)
9. 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, e1000893. (doi:10.1371/journal.pgen.1000893)
10. Dobzhansky T. 1973 Nothing in biology makes sense except in the light of evolution. Am. Biol. Teacher 35, 125–129. (doi:10.2307/4444260)
11. Yona AH, Manor YS, Herbst RH, Romano GH, Mitchell A, Kupiec M, Pilpel Y, Dahan O. 2012 Chromosomal duplication is a transient evolutionary solution to stress. Proc. Natl Acad. Sci. USA 109, 21 010–21 015. (doi:10.1073/pnas.1211150109)
12. Wright S. 1932 The roles of mutation, inbreeding, crossbreeding, and selection in evolution. Proceedings of the VI International Congress of Genetics, Ithaca, New York, volume 1, pp. 356–366. Menasha, WI: Brooklyn Botanic Garden.
13. Simpson GG. 1944 Tempo and mode in evolution. Columbia, NY: Columbia University Press.
14. 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, 809–815. (doi:10.1016/j.ceb.2010.06.003)
15. Pachauri RK, Resinger A. 2007 Climate change 2007. Synthesis report (Intermgovernmental Panel on Climate Change 2007), 1–71.
16. Van Mulders SE, Christianen E, Saerens SMG, Daenen L, Verbelen PJ, Willaert R, Verstrepen KJ, Delvaux FR. 2009 Phenotypic diversity of Flo protein family-mediated adhesion in Saccharomyces cerevisiae. FEMS Yeast Res. 9, 178–190. (doi:10.1111/j.1567-1364.2008.00462.x)
17. 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. (doi:10.7554/eLife.05462)
18. Mitchell A, Romano GH, Groisman B, Yona A, Dekel E, Kupiec M, Dahan O, Pilpel Y. 2009 Adaptive prediction of environmental changes by microorganisms. Nature 460, 220–224. (doi:10.1038/nature08112)
19. Suzuki T, Kobayashi I, Kanbe T, Takana K. 1989 High frequency variation of colony morphology and chromosome reorganization in the pathogenic yeast Candida albicans. J. Gen. Microbiol. 135, 425–434. (doi:10.1099/00221287-135-2-425)
20. Selmecki A, Bergmann S, Berman J. 2005 Comparative genome hybridization reveals widespread aneuploidy in Candida albicans laboratory strains. Mol. Microbiol. 55, 1553–1565. (doi:10.1111/j.1365-2958.2005.04492.x)
21. Chu WS, Magee BB, Magee PT. 1993 Construction of an SfiI macrorestriction map of the Candida albicans genome. J. Bacteriol. 175, 6637–6651.
22. Chibana H, Beckerman JL, Magee PT. 2000 Fineresolution physical mapping of genomic diversity in Candida albicans. Genome Res. 10, 1865–1877. (doi:10.1101/gr.148600)
23. Selmecki A, Forche A, Berman J. 2010 Genomic plasticity of the human fungal pathogen Candida albicans. Eukaryotic Cell 9, 991–1008. (doi:10.1128/EC.00060-10)
24. Forche A, Steinbach M, Berman J. 2009 Efficient and rapid identification of Candida albicans allelic status using SNP-RFLP. FEMS Yeast Res. 9, 1061–1069. (doi:10.1111/j.1567-1364.2009.00542.x)
25. Brunke S, Hube B. 2013 Two unlike cousins: Candida albicans and C. glabratainfection strategies. Cell Microbiol. 15, 701–708. (doi:10.1111/cmi.12091)
26. Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M. 2011 Candida bloodstream infections: comparison of species distributions and antifungal resistance patterns in community-onset and nosocomial isolates in the SENTRY antimicrobial surveillance program, 2008–2009. Antimicrob. Agents Chemother. 55, 561–566. (doi:10.1128/AAC.01079-10)
27. Martins N, Ferreira ICFR, Barros L, Silva S, Henriques M. 2014 Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment. Mycopathologia 177, 223–240. (doi:10.1007/s11046-014-9749-1)
28. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. 2009 Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23, 525–530. (doi:10.1097/QAD.0b013e328322ffac)
29. 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, e110. (doi:10.1371/journal.pbio.0060110)
30. 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, 781–794. (doi:10.1534/genetics.115.178020)
31. Hickman MA et al. 2013 The ‘obligate diploid’ Candida albicans forms mating-competent haploids. Nature 494, 55–59. (doi:10.1038/nature11865)
32. Chen X, Magee BB, Dawson D, Magee PT, Kumamoto CA. 2004 Chromosome 1 trisomy compromises the virulence of Candida albicans. Mol. Microbiol. 51, 551–565. (doi:10.1046/j.1365-2958.2003.03852.x)
33. Janbon G, Sherman F, Rustchenko E. 1998 Monosomy of a specific chromosome determines L-sorbose utilization: a novel regulatory mechanism in Candida albicans. Proc. Natl Acad. Sci. USA 95, 5150–5155. (doi:10.1073/pnas.95.9.5150)
34. 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, 624–641. (doi:10.1111/j.1365-2958.2008.06176.x)
35. Perepnikhatka V, Fischer FJ, Niimi M, Baker RA, Cannon RD, Wang YK, Sherman F, Rustchenko E. 1999 Specific chromosome alterations in fluconazole-resistant mutants of Candida albicans. J. Bacteriol. 181, 4041–4049.
36. Tan Z, Hays M, Cromie GA, Jeffery EW, Scott AC, Ahyong V, Sirr A, Skupin A, Dudley AM. 2013 Aneuploidy underlies a multicellular phenotypic switch. Proc. Natl Acad. Sci. USA 110, 12 367-12 372. (doi:10.1073/pnas.1301047110)
37. Hirakawa MP et al. 2015 Genetic and phenotypic intra-species variation in Candida albicans. Genome Res. 25, 413–425. (doi:10.1101/gr.174623.114)
38. Reedy JL, Floyd AM, Heitman J. 2009 Mechanistic plasticity of sexual reproduction and meiosis in the Candida pathogenic species complex. Curr. Biol. 19, 891–899. (doi:10.1016/j.cub.2009.04.058)
39. Hu G et al. 2011 Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients. BMC Genomics 12, 526. (doi:10.1186/1471-2164-12-526)
40. Selmecki A, Forche A, Berman J. 2006 Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313, 367–370. (doi:10.1126/science.1128242)
41. Ford CB et al. 2015 The evolution of drug resistance in clinical isolates of Candida albicans. eLife 4, 3178. (doi:10.7554/eLife.00662.023)
42. Rustchenko-Bulgac EP, Sherman F, Hicks JB. 1990 Chromosomal rearrangements associated with morphological mutants provide a means for genetic variation of Candida albicans. J. Bacteriol. 172, 1276–1283.
43. Coste A, Turner V, Ischer F, Morschhaüser J, Forche A, Selmecki A, Berman J, Bille J, Sanglard D. 2006 A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans. Genetics 172, 2139–2156. (doi:10.1534/genetics.105.054767)
44. Datta K et al. 2009 Spread of Cryptococcus gattii into Pacific Northwest region of the United States. Emerg. Infect. Dis. 15, 1185–1191. (doi:10.3201/eid1508.081384)
45. Rancati G et al. 2008 Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor. Cell 135, 879–893. (doi:10.1016/j.cell.2008.09.039)
46. Liu G et al. 2015 Gene essentiality is a quantitative property linked to cellular evolvability. Cell 163, 1388–1399. (doi:10.1016/j.cell.2015.10.069)
47. Chen G, Bradford WD, Seidel CW, Li R. 2012 Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy. Nature 482, 246–250. (doi:10.1038/nature10795)
48. Ormerod KL, Morrow CA, Chow E, Lee IR. 2013 Comparative genomics of serial isolates of Cryptococcus neoformans reveals gene associated with carbon utilization and virulence. G3: Genes Genomes 4, 675–686. (doi:10.1534/g3.113.005660)
49. Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A, Florens L, Sanderson BW, Hattem GL, Li R. 2010 Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468, 321–325. (doi:10.1038/nature09529)
50. Yang F, Kravets A, Bethlendy G, Welle S, Rustchenko E. 2013 Chromosome 5 monosomy of Candida albicans controls susceptibility to various toxic agents, including major antifungals. Antimicrob. Agents Chemother. 57, 5026–5036. (doi:10.1128/AAC.00516-13)
51. Anderson JB, Sirjusingh C, Ricker N. 2004 Haploidy, diploidy and evolution of antifungal drug resistance in Saccharomyces cerevisiae. Genetics 168, 1915–1923. (doi:10.1534/genetics.104.033266)
52. Anderson JB, Sirjusingh C, Parsons AB, Boone C, Wickens C, Cowen LE, Kohn LM. 2003 Mode of selection and experimental evolution of antifungal drug resistance in Saccharomyces cerevisiae. Genetics 163, 1287–1298.
53. Tscherner M, Schwarzmüller T, Kuchler K. 2011 Pathogenesis and antifungal drug resistance of the human fungal pathogen Candida glabrata. Pharmaceuticals 4, 169–186. (doi:10.3390/ph4010169)
54. Sanguinetti M, Posteraro B, Fiori B, Ranno S, Torelli R, Fadda G. 2005 Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrob. Agents Chemother. 49, 668–679. (doi:10.1128/AAC.49.2.668-679.2005)
55. Otto SP, Gerstein AC. 2006 Why have sex? The population genetics of sex and recombination. Biochem. Soc. Trans. 34, 519–522. (doi:10.1042/BST0340519)
56. Selmecki AM et al. 2015 Polyploidy can drive rapid adaptation in yeast. Nature 519, 349–352. (doi:10.1038/nature14187)
57. Zörgö E, Gjuvsland A, Cubillos FA, Louis EJ, Liti G, Blomberg A, Omholt SW, Warringer J. 2012 Life history shapes trait heredity by accumulation of loss-of-function alleles in yeast. Mol. Biol. Evol. 29, 1781–1789. (doi:10.1093/molbev/mss019)
58. May RC, Stone NRH, Wiesner DL, Bicanic T, Nielsen K. 2016 Cryptococcus: from environmental saprophyte to global pathogen. Nat. Rev. Microbiol. 14, 106–117. (doi:10.1038/nrmicro.2015.6)
59. Okagaki LH, Strain AK, Nielsen JN, Charlier C, Baltes NJ, Chrétien F, Heitman J, Dromer F, Nielsen K. 2010 Cryptococcal cell morphology affects host cell interactions and pathogenicity. PLoS Pathog. 6, e1000953. (doi:10.1371/journal.ppat.1000953)
60. 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, e1000945. (doi:10.1371/journal.ppat.1000945)
61. Gerstein AC, Fu MS, Mukaremera L, Li Z, Ormerod KL, Fraser JA, Berman J, Nielsen K. 2015 Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation. mBio 6, e01340-15. (doi:10.1128/mBio.01340-15)
62. 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, 1554–1566. (doi:10.1128/EC.00209-09)
63. Cowen LE, Kohn LM, Anderson JB. 2001 Divergence in fitness and evolution of drug resistance in experimental populations of Candida albicans. J. Bacteriol. 183, 2971–2978. (doi:10.1128/JB.183.10.2971-2978.2001)
64. 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, e1000705. (doi:10.1371/journal.pgen.1000705)
65. Dunkel N, Morschhaüser J. 2011 Loss of heterozygosity at an unlinked genomic locus is responsible for the phenotype of a Candida albicans sap4D sap5D sap6D mutant. Eukaryot. Cell 10, 54–62. (doi:10.1128/EC.00281-10)
66. Sampaio P, Santos M, Correia A, Amaral FE, Chavéz-Galarza J, Costa-de-Oliveira S, Castro AG, Pedrosa J, Pais C. 2010 Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection. PLoS ONE 5, e10155. (doi:10.1371/journal.pone.0010155)
67. Ferrari S et al. 2009 Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog. 5, e1000268. (doi:10.1371/journal.ppat.1000268)
68. Abbey D, Hickman M, Gresham D, Berman J. 2011 High-resolution SNP/CGH microarrays reveal the accumulation of loss of heterozygosity in commonly used Candida albicans strains. G3 (Bethesda) 1, 523–530. (doi:10.1534/g3.111.000885)
69. Pierce JV, Dignard D, Whiteway M, Kumamoto CA. 2013 Normal adaptation of Candida albicans to the murine gastrointestinal tract requires Efg1pdependent regulation of metabolic and host defense genes. Eukaryot. Cell 12, 37–49. (doi:10.1128/EC.00236-12)
70. Muzzey D, Sherlock G, Weissman JS. 2014 Extensive and coordinated control of allele-specific expression by both transcription and translation in Candida albicans. Genome Res. 24, 963–973. (doi:10.1101/gr.166322.113)
71. Ciudad T, Hickman M, Bellido A, Berman J, Larriba G. 2016 The phenotypic consequences of a spontaneous loss of heterozygosity in a common laboratory strain of Candida albicans. Genetics 203, 1161–1176. (doi:10.1534/genetics.116.189274)
72. Sunshine AB, Payen C, Ong GT, Liachko I, Tan KM, Dunham MJ. 2015 The fitness consequences of aneuploidy are driven by condition-dependent gene effects. PLoS Biol. 13, e1002155. (doi:10.1371/journal.pbio.1002155)
73. Torres EM, Williams BR, Amon A. 2008 Aneuploidy: cells losing their balance. Genetics 179, 737–746. (doi:10.1534/genetics.108.090878)
74. 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. (doi:10.7554/eLife.14409)
75. Sterkers Y, Lachaud L, Bourgeois N, Crobu L, Bastien P, Pagès M. 2012 Novel insights into genome plasticity in eukaryotes: mosaic aneuploidy in Leishmania. Mol. Microbiol. 86, 15–23. (doi:10.1111/j.1365-2958.2012.08185.x)
76. Mannaert A, Downing T, Imamura H, Dujardin J-C. 2012 Adaptive mechanisms in pathogens: universal aneuploidy in Leishmania. Trends Parasitol. 28, 370–376. (doi:10.1016/j.pt.2012.06.003)
77. Lee SC, Corradi N, Doan S, Dietrich FS, Keeling PJ, Heitman J. 2010 Evolution of the sex-related locus and genomic features shared in microsporidia and fungi. PLoS ONE 5, e10539. (doi:10.1371/journal.pone.0010539)
78. Refsnider JM, Poorten TJ, Langhammer PF, Burrowes PA, Rosenblum EB. 2015 Genomic correlates of virulence attenuation in the deadly amphibian chytrid fungus, Batrachochytrium dendrobatidis. G3 (Bethesda) 5, 2291–2298. (doi:10.1534/g3.115.021808)
79. Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M, Dunham MJ, Amon A. 2007 Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317, 916–924. (doi:10.1126/science.1142210)
80. Braun BR, Johnson AD. 2000 TUP1, CPH1 and EFG1 make independent contributions to filamentation in Candida albicans. Genetics 155, 57–67.
81. Korting HC, Hube B, Oberbauer S, Januschke E, Hamm G, Albrecht A, Borelli C, Schaller M. 2003 Reduced expression of the hyphal-independent Candida albicans proteinase genes SAP1 and SAP3 in the efg1 mutant is associated with attenuated virulence during infection of oral epithelium. J. Med. Microbiol. 52, 623–632. (doi:10.1099/jmm.0.05125-0)
82. Lo HJ, Köhler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR. 1997 Nonfilamentous C. albicans mutants are avirulent. Cell 90, 939–949. (doi:10.1016/S0092-8674(00)80358-X)
83. Noffz CS, Liedschulte V, Lengeler K, Ernst JF. 2008 Functional mapping of the Candida albicans Efg1 regulator. Eukaryot. Cell 7, 881–893. (doi:10.1128/EC.00033-08)
84. Stoldt VR, Sonneborn A, Leuker CE, Ernst JF. 1997 Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. EMBO J. 16, 1982–1991. (doi:10.1093/emboj/16.8.1982)
85. Pande K, Chen C, Noble SM. 2013 Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism. Nat. Genet. 45, 1088–1091. (doi:10.1038/ng.2710)
86. Ormerod KL, Morrow CA, Chow EWL, Lee IR, Arras SDM, Schirra HJ, Cox GM, Fries BC, Fraser JA. 2013 Comparative genomics of serial isolates of Cryptococcus neoformans reveals gene associated with carbon utilization and virulence. G3 (Bethesda) 3, 675–686. (doi:10.1534/g3.113.005660)
87. Sionov E, Chang YC, Garraffo HM, Kwon-Chung KJ. 2009 Heteroresistance to fluconazole in Cryptococcus neoformans is intrinsic and associated with virulence. Antimicrob. Agents Chemother. 53, 2804–2815. (doi:10.1128/AAC.00295-09)
88. Meyer W. 2015 Cryptococcus gattii in the age of whole-genome sequencing. mBio 6, e01761-15. (doi:10.1128/mBio.01761-15)
89. Varma A, Kwon-Chung KJ. 2010 Heteroresistance of Cryptococcus gattii to fluconazole. Antimicrob. Agents Chemother. 54, 2303–2311. (doi:10.1128/AAC.00153-10)
90. Croll D, Zala M, McDonald BA. 2013 Breakagefusion-bridge cycles and large insertions contribute to the rapid evolution of accessory chromosomes in a fungal pathogen. PLoS Genet. 9, e1003567. (doi:10.1371/journal.pgen.1003567)
91. Kasuga T et al. 2016 Host-induced aneuploidy and phenotypic diversification in the sudden oak death pathogen Phytophthora ramorum. BMC Genomics 17, 385. (doi:10.1186/s12864-016-2717-z)
92. Santaguida S, Amon A. 2015 Short-and long-term effects of chromosome mis-segregation and aneuploidy. Nat. Rev. Mol. Cell Biol. 16, 473–485. (doi:10.1038/nrm4025)
93. White TC. 1997 The presence of an R467 K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14a demethylase in Candida albicans. Antimicrob. Agents Chemother. 41, 1488–1494.
94. Heilmann CJ, Schneider S, Barker KS. 2010 An A643T mutation in the transcription factor Upc2p causes constitutive ERG11 upregulation and increased fluconazole resistance in Candida albicans. Antimicrob. Agents Chemother. 54, 353–359. (doi:10.1128/AAC.01102-09)
95. Marr KA, Lyons CN, Rustad TR. 1999 Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Antimicrob. Agents Chemother. 42, 2584–2589.
96. Abbey DA, Funt J, Lurie-Weinberger MN, Thompson DA, Regev A, Myers CL, Berman J. 2014 YMAP: a pipeline for visualization of copy number variation and loss of heterozygosity in eukaryotic pathogens. Genome Med. 6, 100. (doi:10.1186/s13073-014-0100-8)
97. Jain C, Yun M, Politz SM, Rao RP. 2009 A pathogenesis assay using Saccharomyces cerevisiae and Caenorhabditis elegans reveals novel roles for yeast AP-1, Yap1, and host dual oxidase BLI-3 in fungal pathogenesis. Eukaryot. Cell 8, 1218–1227. (doi:10.1128/EC.00367-08)
98. Cowen LE, Sanglard D, Calabrese D, Sirjusingh C, Anderson JB, Kohn LM. 2000 Evolution of drug resistance in experimental populations of Candida albicans. J. Bacteriol. 182, 1515–1522. (doi:10.1128/JB.182.6.1515-1522.2000)
99. Sheltzer JM et al. 2011 Aneuploidy drives genomic instability in yeast. Science 333, 1026–1030. (doi:10.1126/science.1206412)
100. Yona AH, Frumkin I, Pilpel Y. 2015 Perspective. Cell 163, 549–559. (doi:10.1016/j.cell.2015.10.005)
101. Magwene PM, Kayıkçı Ö, Granek JA, Reininga JM, Scholl Z, Murray D. 2011 Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 108, 1987–1992. (doi:10.1073/pnas.1012544108)
102. Bougnoux ME, Pujol C, Diogo D, Bouchier C. 2008 Mating is rare within as well as between clades of the human pathogen Candida albicans. Fung. Genet. Biol. 45, 221–231. (doi:10.1016/j.fgb.2007.10.008)
103. Bell G. 1982 The masterpiece of nature: the evolution and genetics of sexuality. Berkeley, CA: University of California Press. (doi:10.1016/0162-3095(84)90043-8)
104. Butler G. 2010 Fungal sex and pathogenesis. Clin. Microbiol. Rev. 23, 140–159. (doi:10.1128/CMR.00053-09)
105. 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, a019604. (doi:10.1101/cshperspect.a019604)
106. Ene IV, Bennett RJ. 2014 The cryptic sexual strategies of human fungal pathogens. Nat. Rev. Microbiol. 12, 239–251. (doi:10.1038/nrmicro3236)
107. Berman J, Hadany L. 2012 Does stress induce (para)sex? Implications for Candida albicans evolution. Trends Genet. 28, 197–203. (doi:10.1016/j.tig.2012.01.004)
108. Hull CM, Johnson AD. 1999 Identification of a mating type-like locus in the asexual pathogenic yeast Candida albicans. Science 285, 1271–1275. (doi:10.1126/science.285.5431.1271)
109. Lachke SA, Lockhart SR, Daniels KJ, Soll DR. 2003 Skin facilitates Candida albicans mating. Infect. Immun. 71, 4970–4976. (doi:10.1128/IAI.71.9.4970-4976.2003)
110. Harrison BD, Hashemi J, Bibi M, Pulver R, Bavli D, Nahmias Y, Wellington M, Sapiro G, Berman J. 2014 A tetraploid intermediate precedes aneuploid formation in yeasts exposed to fluconazole. PLoS Biol. 12, e1001815. (doi:10.1371/journal.pbio.1001815)
111. Mitra S, Dolan K, Foster TH, Wellington M. 2010 Imaging morphogenesis of Candida albicans during infection in a live animal. J. Biomed. Opt. 15, 010504. (doi:10.1117/1.3290243)
112. Godinho SA, Pellman D. 2014 Causes and consequences of centrosome abnormalities in cancer. Phil. Trans. R. Soc. B 369, 20130467. (doi:10.1098/rstb.2013.0467)
113. Morrow CA, Fraser JA. 2013 Ploidy variation as an adaptive mechanism in human pathogenic fungi. Semin. Cell Dev. Biol. 24, 339–346. (doi:10.1016/j.semcdb.2013.01.008)
114. Megginson LC. 1963 Lessons from Europe for American business. Southwest Soc. Sci. Q. 44, 3–13.