Yeast as a Window into Changes in Genome Complexity Due to Polyploidization

  • Corey M. Hudson
  • Gavin C. Conant


Due to the long history of genetic analyses in yeasts and their experimental tractability, the yeast genome duplication provides important perspectives on the genome and population-level processes that follow whole-genome duplication (WGD). We discuss the history of the discovery of the Saccharomyces cerevisiae WGD, with special emphasis on the role of comparative genomics in its analysis. We then explore models of the WGD shaped population and species divergence, both at a gene level (e.g., Dobzhansky-Muller incompatibility) and from the perspective of recent work on secondary allopolyploidy in Saccharomyces pastorianus. Finally, we explore the selective forces that act on the WGD-produced paralogs and shape their patterns of loss and retention. In addition to discussing the dosage balance hypothesis as it applies to the yeast WGD, we explore the role of the WGD in shaping several complex metabolic and regulatory phenotypes.


Debaryomyces Hansenii Lager Yeast Independent Duplication Core Histone Gene Massive Gene Loss 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank Michaël Bekaert, Patrick Edger, and Chris Pires for helpful discussions. This work was supported by the National Library of Medicine Biomedical and Health Informatics Training Fellowship [LM007089-19] (CMH) and the Reproductive Biology Group of the Food for the twenty-first century program at the University of Missouri (GCC).


  1. Amoutzias GD, He Y, Gordon J, Mossialos D, Oliver SG, Van de Peer Y (2010) Posttranslational regulation impacts the fate of duplicated genes. Proc Natl acad sci U.S.A 107:2967–2971PubMedCrossRefGoogle Scholar
  2. Anderson JB, Funt J, Thompson DA et al (2010) Determinants of divergent adaptation and Dobzhansky-Muller interaction in experimental yeast populations. Curr Biol 20:1383–1388PubMedCrossRefGoogle Scholar
  3. Aury JM, Jaillon O, Duret L et al (2006) Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia. Nature 444:171–178PubMedCrossRefGoogle Scholar
  4. Birchler JA, Veitia RA (2007) The gene balance hypothesis: from classical genetics to modern genomics. Plant Cell 19:395–402PubMedCrossRefGoogle Scholar
  5. Blanc G, Wolfe KH (2004) Functional divergence of duplicated genes formed by polyploidy during Arabidopsis evolution. Plant Cell 16:1679–1691PubMedCrossRefGoogle Scholar
  6. Blank LM, Lehmbeck F, Sauer U (2005) Metabolic-flux and network analysis of fourteen hemiascomycetous yeasts. FEMS Yeast Res 5:545–558PubMedCrossRefGoogle Scholar
  7. Boles E, Schulte F, Miosga T, Freidel K, Schlüter E, Zimmermann FK, Hollenberg CP, Heinisch JJ (1997) Characterization of a glucose-repressed pyruvate kinase (Pyk2p) in Saccharomyces cerevisiae that is catalytically insensitive to fructose-1-6-biphosphate. J Bacteriol 179:2987–2993PubMedGoogle Scholar
  8. Byrne KP, Wolfe KH (2005) The yeast gene order browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15:1456–1461PubMedCrossRefGoogle Scholar
  9. Byrne KP, Wolfe KH (2007) Consistent patterns of rate asymmetry and gene loss indicate widespread neofunctionalization of yeast genes after whole-genome duplication. Genetics 175:1341–1350PubMedCrossRefGoogle Scholar
  10. Casaregola S, Nguyen HV, Lapathitis G, Kotyk A, Gaillardin C (2001) Analysis of the constitution of the beer yeast genome by PCR, sequencing and subtelomeric sequence hybridization. Int J Syst Evol Microbiol 51:1607–1618PubMedGoogle Scholar
  11. Chou J-Y, Hung Y-S, Lin K-H, Lee H-Y, Leu J-Y (2010) Multiple molecular mechanisms cause reproductive isolation between three yeast species. PLoS Biol 8:e1000432PubMedCrossRefGoogle Scholar
  12. Coissac E, Maillier E, Netter P (1997) A comparative study of duplications in bacteria and eukaryotes: the importance of telomeres. Mol Biol Evol 14:1062–1074PubMedCrossRefGoogle Scholar
  13. Conant GC (2010) Rapid reorganization of the transcriptional regulatory network after genome duplication in yeast. Proc R Soc B 277:869–876PubMedCrossRefGoogle Scholar
  14. Conant GC, Wolfe KH (2006a) Functional partitioning of yeast co-expression networks after genome duplication. PLoS Biol 4:e109PubMedCrossRefGoogle Scholar
  15. Conant GC, Wolfe KH (2006b) Functional partitioning of yeast co-expression networks after genome duplication. PLoS Biol 4:e109PubMedCrossRefGoogle Scholar
  16. Conant GC, Wolfe KH (2007) Increased glycolytic flux as an outcome of whole-genome duplication in yeast. Mol Syst Biol 3:129PubMedCrossRefGoogle Scholar
  17. Conant GC, Wolfe KH (2008a) Probabilistic cross-species inference of orthologous genomic regions created by whole-genome duplication in yeast. Genetics 179:1681–1692PubMedCrossRefGoogle Scholar
  18. Conant GC, Wolfe KH (2008b) Turning a hobby into a job: how duplicated genes find new functions. Nat Rev Genet 9:938–950PubMedCrossRefGoogle Scholar
  19. Deluna A, Vetsigian K, Shoresh N, Hegreness M, Colon-Gonzalez M, Chao S, Kishony R (2008) Exposing the fitness contribution of duplicated genes. Nat Genet 40(5):676–681PubMedCrossRefGoogle Scholar
  20. Dequin S, Casaregola S (2011) The genomes of fermentative Saccharomyces. CR Biol 334:687–693CrossRefGoogle Scholar
  21. Des Marais DL, Rausher MD (2008) Escape from adaptive conflict after duplication in an anthocyanin pathway gene. Nature 454:762–765PubMedGoogle Scholar
  22. Dettman JR, Sirjusingh C, Kohn LM, Anderson JB (2007) Incipient speciation by divergent adaptation and antagonistic epistasis in yeast. Nature 447:585–588PubMedCrossRefGoogle Scholar
  23. Dietrich FS, Voegeli S, Brachat S et al (2004) The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces cerevisiae genome. Science 304:304–307PubMedCrossRefGoogle Scholar
  24. Dujon B, Sherman D, Fischer G et al (2004) Genome evolution in yeasts. Nature 430:35–44PubMedCrossRefGoogle Scholar
  25. Evangelisti AM, Conant GC (2010) Nonrandom survival of gene conversions among yeast ribosomal proteins duplicated through genome doubling. Genome Biol Evol 2:826–834PubMedCrossRefGoogle Scholar
  26. Fares MA, Byrne KP, Wolfe KH (2006) Rate asymmetry after genome duplication causes substantial long-branch attraction artifacts in the phylogeny of Saccharomyces species. Mol Biol Evol 23:245–253PubMedCrossRefGoogle Scholar
  27. Fitzpatrick D, Logue M, Stajich J, Butler G (2006) A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis. BMC Evol Biol 6:99PubMedCrossRefGoogle Scholar
  28. Force A, Lynch M, Pickett FB, Amores A, Yan Y, Postlethwait J (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151:1531–1545PubMedGoogle Scholar
  29. Freeling M (2009) Bias in plant gene content following different sorts of duplication: tandem, whole-genome, segmental, or by transposition. Annu Rev Plant Biol 60:433–453PubMedCrossRefGoogle Scholar
  30. Freeling M, Thomas BC (2006) Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity. Genome Res 16:805–814PubMedCrossRefGoogle Scholar
  31. Friedman R, Hughes AL (2001) Gene duplication and the structure of eukaryotic genomes. Genome Res 11:373–381PubMedCrossRefGoogle Scholar
  32. Furlong RF, Holland PWH (2002) Were vertebrates octoploid? Philos Trans R Soc Lond B 357:531–544CrossRefGoogle Scholar
  33. Fusco D, Grassi L, Bassetti B, Caselle M, Lagomarsino MC (2010) Ordered structure of the transcription network inherited from the yeast whole-genome duplication. BMC Syst Biol 4:77PubMedCrossRefGoogle Scholar
  34. Gao LZ, Innan H (2004) Very low gene duplicaiton rate in the yeast genome. Science 306:1367–1370PubMedCrossRefGoogle Scholar
  35. Geladé R, Van De Velde S, Van Dijck P, Thevelein JM (2003) Multi-level response of the yeast genome to glucose. Genome Biol 4:233PubMedCrossRefGoogle Scholar
  36. Goffeau A, Barrell B, Russey H et al (1996) Life with 6000 genes. Science 274:562–567CrossRefGoogle Scholar
  37. Gordon JL, Byrne KP, Wolfe KH (2009) Additions, losses and rearrangements on the evolutionary route from a reconstructed ancestor to the modern Saccharomyces cerevisiae genome. PLoS Genet 5:e1000485PubMedCrossRefGoogle Scholar
  38. Gordon JL, Byrne KP, Wolfe KH (2011) Mechanisms of chromosome number evolution in yeast. PLoS Genet 7:e1002190PubMedCrossRefGoogle Scholar
  39. Gordon JL, Wolfe KH (2008) Recent allopolyploid origin of Zygosaccharomyces rouxii strain ATCC 42981. Yeast 25:449–456PubMedCrossRefGoogle Scholar
  40. Greig D (2008) Reproductive isolation in Saccharomyces. Heredity 102:39–44PubMedCrossRefGoogle Scholar
  41. Guan Y, Dunham MJ, Troyanskaya OG (2007) Functional analysis of gene duplications in Saccharomyces cerevisiae. Genetics 175:933–943PubMedCrossRefGoogle Scholar
  42. Hakes L, Pinney JW, Lovell SC, Oliver SG, Robertson DL (2007) All duplicates are not equal: the difference between small-scale and genome duplication. Genome Biol 8:R209PubMedCrossRefGoogle Scholar
  43. Hittinger CT, Carroll SB (2007) Gene duplication and the adaptive evolution of a classic genetic switch. Nature 449:677–681PubMedCrossRefGoogle Scholar
  44. Hughes AL (1999) Phylogenies of developmentally important proteins do not support the hypothesis of two rounds of genome duplication early in vertebrate history. J Mol Evol 48:565–576PubMedCrossRefGoogle Scholar
  45. Hughes TR, Roberts CJ, Dai H et al (2000) Widespread aneuploidy revealed by DNA microarray expression profiling. Nat Genet 25:333–337PubMedCrossRefGoogle Scholar
  46. Ihmels J, Bergmann S, Gerami-Nejad M, Yanai I, McClellan M, Berman J, Barkai N (2005) Rewiring of the yeast transcriptional network through the evolution of motif usage. Science 309:938–940PubMedCrossRefGoogle Scholar
  47. Jaillon O, Aury J-M, Brunet F et al (2004) Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature 431:946–957PubMedCrossRefGoogle Scholar
  48. James SA, Bond CJ, Stratford M, Roberts IN (2005) Molecular evidence for the existence of natural hybrids in the genus Zygosaccharomyces. FEMS Yeast Res 5:747–755PubMedCrossRefGoogle Scholar
  49. Johnston M, Kim J-H (2005) Glucose as a hormone: Receptor-mediated glucose sensing in the yeast Saccharomyces cerevisiae. Biochem Soc Trans 33:247–252PubMedCrossRefGoogle Scholar
  50. Kao KC, Schwartz K, Sherlock G (2010) A genome-wide analysis reveals no nuclear Dobzhansky-Muller pairs of determinants of speciation between S. cerevisiae and S. paradoxus, but suggests more complex incompatibilities. PLoS Genet 6:e1001038PubMedCrossRefGoogle Scholar
  51. Kellis M, Birren BW, Lander ES (2004) Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 428:617–624PubMedCrossRefGoogle Scholar
  52. Kielland-Brandt MC, Nilsson-Tillgren T, Gjermansen C, Holmberg S, Pedersen MB (1995) Genetics of brewing yeasts. In: Rose AH, Wheals AE, Harrison JS (eds) The Yeasts, vol 6, 2nd edn. Academic, London, pp 223–254Google Scholar
  53. Kim S-H, Yi SV (2006) Correlated asymmetry of sequence and functional divergence between duplicate proteins of Saccharomyces cerevisiae. Mol Biol Evol 23:1068–1075PubMedCrossRefGoogle Scholar
  54. Kim T-Y, Ha CW, Huh W-K (2009) Differential subcellular localization of ribosomal protein L7 paralogs in Saccharomyces cerevisiae. Mol Cells 27:539–546PubMedCrossRefGoogle Scholar
  55. Komili S, Farny NG, Roth FP, Silver PA (2007) Functional specificity among ribosomal proteins regulates gene expression. Cell 131:557–571PubMedCrossRefGoogle Scholar
  56. Koszul R, Caburet S, Dujon B, Fischer G (2004) Eucaryotic genome evolution through the spontaneous duplication of large chromosomal segments. EMBO J 23:234–243PubMedCrossRefGoogle Scholar
  57. Kuepfer L, Sauer U, Blank LM (2005) Metabolic functions of duplicate genes in Saccharomyces cerevisiae. Genome Res 15:1421–1430PubMedCrossRefGoogle Scholar
  58. Kurtzman C, Robnett C (2003) Phylogenetic relationships among yeasts of the ‘Saccharomyces complex’ determined from multigene sequence analyses. FEMS Yeast Res 3:417–432PubMedCrossRefGoogle Scholar
  59. Lalo D, Stettler S, Mariotte S, Slominski PP, Thuriaux P (1993) Two yeast chromosomes are related by a fossil duplication of their centromeric regions. C R Acad Sci 316:367–373Google Scholar
  60. Lee H-Y, Chou J-Y, Cheong L, Chang N-H, Yang S-Y, Leu J-Y (2008) Incompatibility of nuclear and mitochondrial genomes causes hybrid sterility between two yeast species. Cell 135:1065–1073PubMedCrossRefGoogle Scholar
  61. Libkind D, Hittinger CT, Valério E, Gonçalves C, Dover J, Johnston M, Gonçalves P, Sampaio JP (2011) Microbe domestication and the identification of the wild genetic stock of lager-brewing yeast. Proc Nat Acad Sci 108:14539–14544PubMedCrossRefGoogle Scholar
  62. Llorente B, Durrens P, Malpertuy A et al (2000a) Genomic exploration of the hemiascomycetous yeasts: 20. Evolution of gene redundancy compared to Saccharomyces cerevisiae. FEBS Lett 487:122–133PubMedCrossRefGoogle Scholar
  63. Llorente B, Malpertuy A, NeuvÈglise C et al (2000b) Genomic exploration of the hemiascomycetous yeasts: 18. Comparative analysis of chromosome maps and synteny with Saccharomyces cerevisiae. FEBS Lett 487:101–112PubMedCrossRefGoogle Scholar
  64. Lynch M, Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science 290:1151–1155PubMedCrossRefGoogle Scholar
  65. Lynch M, Force AG (2000) The origin of interspecific genomic incompatibility via gene duplication. Am Nat 156:590–605CrossRefGoogle Scholar
  66. Maclean CJ, Greig D (2011) Reciprocal gene loss following experimental whole-genome duplication causes reproductive isolation in yeast. Evolution 65:932–945PubMedCrossRefGoogle Scholar
  67. MacLean RC, Gudelj I (2006) Resource competition and social conflict in experimental populations of yeast. Nature 441:498–501PubMedCrossRefGoogle Scholar
  68. Maere S, De Bodt S, Raes J, Casneuf T, Van Montagu M, Kuiper M, Van de Peer. Y (2005) Modeling gene and genome duplications in eukaryotes. Proc Nat Acad Sci U S A 102:5454–5459CrossRefGoogle Scholar
  69. Martini AV, Kurtzman CP (1985) Deoxyribonucleic acid relatedness among species of the genus Saccharomyces sensu stricto. Int J Syst Bacteriol 35:508–511CrossRefGoogle Scholar
  70. Melnick L, Sherman F (1993) The gene clusters ARC and COR on chromosomes 5 and 10, respectively, of Saccharomyces cerevisiae share a common ancestry. J Mol Biol 233:372–388PubMedCrossRefGoogle Scholar
  71. Merico A, Sulo P, Piškur J, Compagno C (2007) Fermentative lifestyle in yeasts belonging to the Saccharomyces complex. FEBS J 274:976–989PubMedCrossRefGoogle Scholar
  72. Mewes H, Albermann K, Bähr M et al (1997) Overview of the yeast genome. Nature 387:7–65PubMedCrossRefGoogle Scholar
  73. Nakao Y, Kanamori T, Itoh T, Kodama Y, Rainieri S, Nakamura N, Shimonaga T, Hattori M, Ashikari T (2009) Genome sequence of the lager brewing yeast, an interspecies hybrid. DNA Res 16:115–129PubMedCrossRefGoogle Scholar
  74. Ni L, Snyder M (2001) A genomic study of the bipolar bud site selection pattern in Saccharomyces cerevisiae. Mol Biol Cell 12:2147–2170PubMedGoogle Scholar
  75. Ohno S (1970) Evolution by gene duplication. Springer, New YorkGoogle Scholar
  76. Oliver SG (1996) From DNA sequence to biological function. Nature 379:597–600PubMedCrossRefGoogle Scholar
  77. Özcan S, Dover J, Johnston M (1998) Glucose sensing and signaling by two glucose receptors in the yeast Saccharomyces cerevisiae. EMBO J 17:2566–2573PubMedCrossRefGoogle Scholar
  78. Papp B, Pal C, Hurst LD (2003) Evolution of cis-regulatory elements in duplicated genes of yeast. Trends Genet 19:417–422PubMedCrossRefGoogle Scholar
  79. Petes T, Hill C (1988) Recombination between repeated genes in microorganisms. Annu Rev Genet 22:147–168PubMedCrossRefGoogle Scholar
  80. Pfeiffer T, Schuster S (2005) Game-theoretical approaches to studying the evolution of biochemical systems. Trends Biochem Sci 30:20–25PubMedCrossRefGoogle Scholar
  81. Pfeiffer T, Schuster S, Bonhoeffer S (2001) Cooperation and competition in the evolution of ATP-producing pathways. Science 292:504–507PubMedCrossRefGoogle Scholar
  82. Pigliucci M (2010) Genotype-phenotype mapping and the end of the ‘genes as blueprint’ metaphor. Philos Trans R Soc Lond B 365:557–566CrossRefGoogle Scholar
  83. Piskur J (2001) Origin of the duplicated regions in the yeast genomes. Trends Genet 17:302–303PubMedCrossRefGoogle Scholar
  84. Piškur J, Rozpedowska E, Polakova S, Merico A, Compagno C (2006) How did Saccharomyces evolve to become a good brewer? Trends Genet 22:183–186PubMedCrossRefGoogle Scholar
  85. Rainieri S, Kodama Y, Kaneko Y, Mikata K, Nakao Y, Ashikari T (2006) Pure and mixed genetic lines of Saccharomyces bayanus and Saccharomyces pastorianus and their contribution to the lager brewing strain genome. Appl Environ Microbiol 72:3968–3974PubMedCrossRefGoogle Scholar
  86. Rolland T, Dujon B (2011) Yeasty clocks: dating genomic changes in yeasts. CR Biol 334:620–628CrossRefGoogle Scholar
  87. Scannell DR, Byrne KP, Gordon JL, Wong S, Wolfe KH (2006) Multiple rounds of speciation associated with reciprocal gene loss in polyploid yeasts. Nature 440:341–345PubMedCrossRefGoogle Scholar
  88. Scannell DR, Zill OA, Rokas A, Payen C, Dunham MJ, Eisen MB, Rine J, Johnston M, Hittinger CT (2011) The awesome power of yeast evolutionary genetics: new genome sequences and strain resources for the Saccharomyces sensu stricto genus. G3: Genes, Genomes, Genetics 1:11–25Google Scholar
  89. Seoighe C, Wolfe KH (1999) Yeast genome evolution in the post-genome era. Curr Opin Microbiol 2:548–554PubMedCrossRefGoogle Scholar
  90. Smith M (1987) Molecular evolution of the Saccharomyces cerevisiae histone gene loci. J Mol Evol 24:252–259PubMedCrossRefGoogle Scholar
  91. Taylor JW, Berbee ML (2006) Dating divergences in the fungal tree of life: review and new analyses. Mycologia 98:838–849PubMedCrossRefGoogle Scholar
  92. Van de Peer Y, Fawcett J, Proost S, Sterk L, Vandepoele K (2009) The flowering world: a tale of duplications. Trends Plant Sci 14:680–688PubMedCrossRefGoogle Scholar
  93. van Hoek MJ, Hogeweg P (2009) Metabolic adaptation after whole genome duplication. Mol Biol Evol 26:2441–2453PubMedCrossRefGoogle Scholar
  94. van Hoof A (2005a) Conserved functions of yeast genes support the duplication, degeneration and complementation model for gene duplication. Genetics 171:1455–1461PubMedCrossRefGoogle Scholar
  95. van Hoof A (2005b) Conserved functions of yeast genes support the duplication, degeneration and complementation model for gene duplication. Genetics 171:1455–1461PubMedCrossRefGoogle Scholar
  96. Wapinski I, Pfeffer A, Friedman N, Regev A (2007) Natural history and evolutionary principles of gene duplication in fungi. Nature 449:54–61PubMedCrossRefGoogle Scholar
  97. Werth CR, Windham MD (1991) A model for divergent, allopatric speciation of polyploid pteridophytes resulting from silencing of duplicate-gene expression. Am Nat 137:515–526CrossRefGoogle Scholar
  98. Wolfe KH (2000) Robustness-it’s not where you think it is. Nat Genet 25:3–4PubMedCrossRefGoogle Scholar
  99. Wolfe KH, Shields D (1997) Molecular evidence for an ancient duplication of the entire yeast genome. Nature 387:708–713PubMedCrossRefGoogle Scholar
  100. Xu M, He X (2011) Genetic incompatibility dampens hybrid fertility more than hybrid viability: yeast as a case study. PLoS ONE 6:e18341PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.MU Informatics InstituteUniversity of MissouriColumbiaUSA
  2. 2.Division of Animal SciencesUniversity of MissouriColumbiaUSA

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