Current Genetics

, Volume 62, Issue 1, pp 81–85 | Cite as

Last hope for the doomed? Thoughts on the importance of a parasexual cycle for the yeast Candida albicans

  • Jan Schmid
  • Paul T. Magee
  • Barbara R. Holland
  • Ningxin Zhang
  • Richard D. Cannon
  • Beatrice B. Magee


The yeast Candida albicans, a commensal colonizer and occasional pathogen of humans, has a rudimentary mating ability. However, mating is a cumbersome process that has never been observed outside the laboratory, and the population structure of the species is predominantly clonal. Here we discuss recent findings that indicate that mating ability is under selection in C. albicans, i.e. that it is a biologically relevant process. C. albicans strains can only mate after they have sustained genetic damage. We propose that the rescue of such damaged strains by mating may be the primary reason why mating ability is under selection.


Candida albicans Parasexual cycle Mating Evolution Clonality 


  1. Agrawal AA, Conner JK, Rasmann S (2010) Tradeoffs and negative correlations in evolutionary ecology. In: Bell G, Eanes WF, Futuyma DJ, Levinton JS (eds) Evolution after Darwin: the first 150 years. Sinauer Associates Sunderland, Massachusetts, pp 243–268Google Scholar
  2. Alby K, Schaefer D, Bennett RJ (2009) Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans. Nature 460:890–893PubMedCentralCrossRefPubMedGoogle Scholar
  3. Bennett RJ, Johnson AD (2003) Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains. EMBO J 22:2505–2515PubMedCentralCrossRefPubMedGoogle Scholar
  4. Bennett RJ, Miller MG, Chua PR, Maxon ME, Johnson AD (2005) Nuclear fusion occurs during mating in Candida albicans and is dependent on the KAR3 gene. Mol Microbiol 55:1046–1059CrossRefPubMedGoogle Scholar
  5. Bougnoux M-E, Pujol C, Diogo D, Bouchier C, Soll DR, d’Enfert C (2008) Mating is rare within as well as between clades of the human pathogen Candida albicans. Fungal Genet Biol 45:221–231PubMedCentralCrossRefPubMedGoogle Scholar
  6. Chibana H, Beckerman JL, Magee PT (2000) Fine-resolution physical mapping of genomic diversity in Candida albicans. Genome Res 10(12):1865–1877CrossRefPubMedGoogle Scholar
  7. Cox MP, Holland BR, Wilkins MC, Schmid J (2013) Reconstructing historic changes in locus-specific recombination rates. BMC Genet 14:11PubMedCentralCrossRefPubMedGoogle Scholar
  8. de Visser JA, Elena SF (2007) The evolution of sex: empirical insights into the roles of epistasis and drift. Nat Rev Genet 8:139–149CrossRefPubMedGoogle Scholar
  9. Diogo D, Bouchier C, d’Enfert C, Bougnoux M-E (2009) Loss of heterozygosity in commensal isolates of the asexual diploid yeast Candida albicans. Fungal Genet Biol 46:159–168CrossRefPubMedGoogle Scholar
  10. Forche A, May G, Magee PT (2005) Demonstration of loss of heterozygosity by single-nucleotide polymorphism microarray analysis and alterations in strain morphology in Candida albicans strains during Infection. Eukaryot Cell 4(1): 156–165PubMedCentralCrossRefPubMedGoogle Scholar
  11. 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 PubMedCentralCrossRefPubMedGoogle Scholar
  12. 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 182:799–811. doi: 10.1534/genetics.109.103325 PubMedCentralCrossRefPubMedGoogle Scholar
  13. Forche A, Abbey D, Pisithkul T, Weinzierl MA, Ringstrom T, Bruck D, Petersen K, Berman J (2011) Stress alters rates and types of loss of heterozygosity in Candida albicans. MBio 2:e00200–e00211. doi: 10.1128/mBio.00129-11 CrossRefGoogle Scholar
  14. Goddard MR, Godfray HC, Burt A (2005) Sex increases the efficacy of natural selection in experimental yeast populations. Nature 434:636–640CrossRefPubMedGoogle Scholar
  15. Gräser Y, Volovsek M, Arrington J, Schönian G, Presber W, Mitchell TG, Vilgalys R (1996) Molecular markers reveal that population structure of the human pathogen Candida albicans exhibits both clonality and recombination. Proc Natl Acad Sci USA 93:12473–12477PubMedCentralCrossRefPubMedGoogle Scholar
  16. Heitman J (2010) Evolution of eukaryotic microbial pathogens via covert sexual reproduction. Cell Host Microbe 8:86–99PubMedCentralCrossRefPubMedGoogle Scholar
  17. Hickman MA, Zeng G, Forche A, Hirakawa MP, Abbey D, Harrison BD, Wang YM, Su CH, Bennett RJ, Wang Y, Berman J (2013) The ’obligate diploid’ Candida albicans forms mating-competent haploids. Nature 494:55–59. doi: 10.1038/nature11865 PubMedCentralCrossRefPubMedGoogle Scholar
  18. Hill J, O’Meara TR, Cowen EL (2015) Fitness trade-offs associated with the evolution of resistance to antifungal drug combinations. Cell Rep 10:809–819. doi: 10.1016/j.celrep.2015.01.009 CrossRefGoogle Scholar
  19. Holmes AR, Tsao S, Ong S-W, Lamping E, Niimi K, Monk BC, Niimi M, Kaneko A, Holland BR, Schmid J, Cannon RD (2006) Heterozygosity and functional allelic variation in the Candida albicans efflux pump genes CDR1 and CDR2. Mol Microbiol 62:170–186CrossRefPubMedGoogle Scholar
  20. Hull CM, Johnson AD (1999) Identification of a mating type-like locus in the asexual pathogenic yeast Candida albicans. Science 285:1271–1276CrossRefPubMedGoogle Scholar
  21. Hull CM, Raisner RM, Johnson AD (2000) Evidence for mating of the “asexual” yeast Candida albicans in a mammalian host. Science 289:307–310CrossRefPubMedGoogle Scholar
  22. Jacobsen MD, Duncan AD, Bain J, Johnson EM, Naglik JR, Shaw DJ, Odds FC (2008) Mixed Candida albicans strain populations in colonized and infected mucosal tissues. FEMS Yeast Res 8(8):1334–1338. doi: 10.1111/j.1567-1364.2008.00438.x PubMedCentralCrossRefPubMedGoogle Scholar
  23. Kimura M, Ohta T (1969) The average number of generations until fixation of a mutant gene in a finite population. Genetics 61:763–771PubMedCentralPubMedGoogle Scholar
  24. Kurtzman CP, Smiley MJ, Johnson CJ (1980) Emendation of the genus Issatchenkia Kudriavzev and comparison of species by deoxyribonucleic acid reassociation, mating reaction, and ascospore ultrastructure. Int J Syst Evol Microbiol 30:503–513. doi: 10.1099/00207713-30-2-503 Google Scholar
  25. Lang GI, Murray AW, Botstein D (2009) The cost of gene expression underlies a fitness trade-off in yeast. Proc Natl Acad Sci USA 106:5755–5760. doi: 10.1073/pnas.0901620106 PubMedCentralCrossRefPubMedGoogle Scholar
  26. Lockhart SR, Daniels KJ, Zhao R, Wessels D, Soll DR (2003) Cell biology of mating in Candida albicans. Eukaryot Cell 2:49–61PubMedCentralCrossRefPubMedGoogle Scholar
  27. Magee BB, Magee PT (2000) Induction of mating in Candida albicans by construction of MTLa and MTLalpha strains. Science 289:310–313CrossRefPubMedGoogle Scholar
  28. Magee PT, Magee BB (2004) Through a glass opaquely: the biological significance of mating in Candida albicans. Curr Opin Microbiol 7:661–665CrossRefPubMedGoogle Scholar
  29. Miller M, Johnson A (2002) White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110:293CrossRefPubMedGoogle Scholar
  30. Morran LT, Schmidt OG, Gelarden IA, Parrish RC, Lively CM (2011) Running with the Red Queen: host-parasite coevolution selects for biparental sex. Science 333:216–218PubMedCentralCrossRefPubMedGoogle Scholar
  31. Muller HJ (1964) The relation of recombination to mutational advance. Mutat Res 1:2–9CrossRefGoogle Scholar
  32. Odds FC (1988) Candida and candidosis, 2nd edn. Bailliere Tindall, LondonGoogle Scholar
  33. Odds FC, Bougnoux ME, Shaw DJ, Bain JM, Davidson AD, Diogo D, Jacobsen MD, Lecomte M, Li SY, Tavanti A, Maiden MC, Gow NA, d’Enfert C (2007) Molecular phylogenetics of Candida albicans. Eukaryot Cell 6:1041–1052PubMedCentralCrossRefPubMedGoogle Scholar
  34. Otto SP, Lenormand T (2002) Resolving the paradox of sex and recombination. Nat Rev Genet 3:252–261CrossRefPubMedGoogle Scholar
  35. Papon N, Savini V, Lanoue A, Simkin A, Crèche J, Giglioli-Guivarc’h N, Clastre M, Courdavault V, Sibirny A (2013) Candida guilliermondii: biotechnological applications, perspectives for biological control, emerging clinical importance and recent advances in genetics. Curr Genet 59:73–90. doi: 10.1007/s00294-013-0391-0 CrossRefPubMedGoogle Scholar
  36. Rice WR (2002) Experimental tests of the adaptive significance of sexual recombination. Nat Rev Genet 3:241–251CrossRefPubMedGoogle Scholar
  37. 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(3):1276–1283PubMedCentralPubMedGoogle Scholar
  38. Schmid J, Herd S, Hunter PR, Cannon RD, Yasin MSM, Samad S, Carr M, Parr D, McKinney W, Schousboe M, Harris B, Ikram R, Harris M, Restrepo A, Hoyos G, Singh KP (1999) Evidence for a general-purpose genotype in Candida albicans, highly prevalent in multiple geographic regions, patient types and types of infection. Microbiology 145:2405–2414CrossRefPubMedGoogle Scholar
  39. Schmid J, Cannon RD, Holland B (2004) A futile act? Thoughts on the reproductive biology of Candida albicans. Mycologist 18:158–163CrossRefGoogle Scholar
  40. Soll DR, Galask R, Schmid J, Hanna C, Mac K, Morrow B (1991) Genetic dissimilarity of commensal strains of Candida spp. carried in different anatomical locations of the same healthy women. J Clin Microbiol 29(8):1702–1710PubMedCentralPubMedGoogle Scholar
  41. Tavanti A, Gow NA, Maiden MC, Odds FC, Shaw DJ (2004) Genetic evidence for recombination in Candida albicans based on haplotype analysis. Fungal Genet Biol 41:553–562CrossRefPubMedGoogle Scholar
  42. Tibayrenc M (1997) Are Candida albicans natural populations subdivided? Trends Microbiol 5:253–257CrossRefPubMedGoogle Scholar
  43. Tsai IJ, Bensasson D, Burt A, Koufopanou V (2008) Population genomics of the wild yeast Saccharomyces paradoxus: quantifying the life cycle. Proc Natl Acad Sci USA 105:4957–4962. doi: 10.1073/pnas.0707314105 PubMedCentralCrossRefPubMedGoogle Scholar
  44. Vrijenhoek RC, Parker EJ (2009) Geographical parthogenesis: general purpose genotypoes and frozen niche variation. In: Isa Schön KM, Dijk PJ, van Dijk P (eds) Lost Sex: the evolutionary biology of parthenogenesis. Springer, Berlin, pp 99–132CrossRefGoogle Scholar
  45. Wu W, Pujol C, Lockhart SR, Soll DR (2005) Chromosome loss followed by duplication is the major mechanism of spontaneous mating-type locus homozygosis in Candida albicans. Genetics 169:1311–1327PubMedCentralCrossRefPubMedGoogle Scholar
  46. Wu W, Lockhart SR, Pujol C, Srikantha T, Soll DR (2007) Heterozygosity of genes on the sex chromosome regulates Candida albicans virulence. Mol Microbiol 64:1587–1604CrossRefPubMedGoogle Scholar
  47. Xie J, Tao L, Nobile CJ, Tong Y, Guan G, Sun Y, Cao C, Hernday AD, Johnson AD, Zhang L, Bai FY, Huang G (2013) White-opaque switching in natural MTLa/alpha isolates of Candida albicans: evolutionary implications for roles in host adaptation, pathogenesis, and sex. PLoS Biol 11:e1001525. doi: 10.1371/journal.pbio.1001525 PubMedCentralCrossRefPubMedGoogle Scholar
  48. Zhang N, Cannon RD, Holland B, Patchett M, Schmid J (2010) Impact of genetic background on allele selection in a highly mutable Candida albicans gene, PNG2. PLoS One 5:e9614PubMedCentralCrossRefPubMedGoogle Scholar
  49. Zhang N, Magee BB, Magee PT, Holland BR, Rodrigues E, Holmes AR, Cannon RD, Schmid J (2015) Selective advantages of a parasexual cycle for the yeast Candida albicans. Genetics 200:1117–1132. doi: 10.1534/genetics.115.177170 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Institute of Fundamental Sciences, College of SciencesMassey UniversityPalmerston NorthNew Zealand
  2. 2.Department of Genetics, Cell Biology, and DevelopmentUniversity of MinnesotaMinneapolisUSA
  3. 3.School of Physical SciencesUniversity of TasmaniaHobartAustralia
  4. 4.Department of Oral SciencesUniversity of OtagoDunedinNew Zealand

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