Genetic dissection of acetic acid tolerance in Saccharomyces cerevisiae

  • Peng Geng
  • Yin Xiao
  • Yun Hu
  • Haiye Sun
  • Wei Xue
  • Liang ZhangEmail author
  • Gui-yang Shi
Original Paper


Dissection of the hereditary architecture underlying Saccharomyces cerevisiae tolerance to acetic acid is essential for ethanol fermentation. In this work, a genomics approach was used to dissect hereditary variations in acetic acid tolerance between two phenotypically different strains. A total of 160 segregants derived from these two strains were obtained. Phenotypic analysis indicated that the acetic acid tolerance displayed a normal distribution in these segregants, and suggested that the acetic acid tolerant traits were controlled by multiple quantitative trait loci (QTLs). Thus, 220 SSR markers covering the whole genome were used to detect QTLs of acetic acid tolerant traits. As a result, three QTLs were located on chromosomes 9, 12, and 16, respectively, which explained 38.8–65.9 % of the range of phenotypic variation. Furthermore, twelve genes of the candidates fell into the three QTL regions by integrating the QTL analysis with candidates of acetic acid tolerant genes. These results provided a novel avenue to obtain more robust strains.


Acetic acid tolerance Phenotypic analysis QTL Saccharomyces cerevisiae SSR markers 



This work was supported by the Natural Science Foundation of Jiangsu Province (Grant No. BK2012363) and the Outstanding Youth Foundation of Jiangsu Province (Grant No. BK20140002).

Supplementary material

11274_2016_2101_MOESM1_ESM.docx (46 kb)
Supplementary material 1 (DOCX 45 kb)


  1. Bretagne S, Costa JM, Besmond C, Carsique R, Calderone R (1997) Microsatellite polymorphism in the promoter sequence of the elongation factor 3 gene of Candida albicans as the basis for a typing system. J Clin Microbiol 35:1777–1780Google Scholar
  2. Carpenter C, Broadbent J (2009) External concentration of organic acid anions and pH: key independent variables for studying how organic acids inhibit growth of bacteria in mildly acidic foods. J Food Sci 74:R12–R15CrossRefGoogle Scholar
  3. Causton HC et al (2001) Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12:323–337CrossRefGoogle Scholar
  4. Deutschbauer AM, Davis RW (2005) Quantitative trait loci mapped to single-nucleotide resolution in yeast. Nat Genet 37:1333–1340CrossRefGoogle Scholar
  5. Flint J, Mott R (2001) Finding the molecular basis of quatitative traits: successes and pitfalls. Nat Rev Genet 2:437–445CrossRefGoogle Scholar
  6. Gatbonton T et al (2006) Telomere length as a quantitative trait: genome-wide survey and genetic mapping of telomere length-control genes in yeast. PLoS Genet 2:e35CrossRefGoogle Scholar
  7. Holyoak CD, Bracey D, Piper PW, Kuchler K, Coote PJ (1999) The Saccharomyces cerevisiae weak-acid-inducible ABC transporter Pdr12 transports fluorescein and preservative anions from the cytosol by an energy-dependent mechanism. J Bacteriol 181:4644–4652Google Scholar
  8. Hu X et al (2007) Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces cerevisiae. Genetics 175:1479–1487CrossRefGoogle Scholar
  9. Jubany S et al (2008) Toward a global database for the molecular typing of Saccharomyces cerevisiae strains. FEMS Yeast Res 8:472–484. doi: 10.1111/j.1567-1364.2008.00361.x CrossRefGoogle Scholar
  10. Katou T, Namise M, Kitagaki H, Akao T, Shimoi H (2009) QTL mapping of sake brewing characteristics of yeast. J Biosci Bioeng 107:383–393CrossRefGoogle Scholar
  11. Kawahata M, Masaki K, Fujii T, Iefuji H (2006) Yeast genes involved in response to lactic acid and acetic acid: acidic conditions caused by the organic acids in Saccharomyces cerevisiae cultures induce expression of intracellular metal metabolism genes regulated by Aft1p. FEMS Yeast Res 6:924–936CrossRefGoogle Scholar
  12. Kren A et al (2003) War1p, a novel transcription factor controlling weak acid stress response in yeast. Mol Cell Biol 23:1775–1785CrossRefGoogle Scholar
  13. Lander E, Schork N (1994) Genetic dissection of complex traits. Science (New York, NY) 265:2037CrossRefGoogle Scholar
  14. Mauricio R (2001) Mapping quantitative trait loci in plants: uses and caveats for evolutionary biology. Nat Rev Genet 2:370–381CrossRefGoogle Scholar
  15. McCusker JH, Clemons KV, Stevens DA, Davis RW (1994) Genetic characterization of pathogenic Saccharomyces cerevisiae isolates. Genetics 136:1261–1269Google Scholar
  16. Meijnen J-P et al (2016) Polygenic analysis and targeted improvement of the complex trait of high acetic acid tolerance in the yeast Saccharomyces cerevisiae. Biotechnol Biofuels. doi: 10.1186/s13068-015-0421-x Google Scholar
  17. Mira NP, Palma M, Guerreiro JF, Sá-Correia I (2010a) Genome-wide identification of Saccharomyces cerevisiae genes required for tolerance to acetic acid. Microb Cell Fact 9:13CrossRefGoogle Scholar
  18. Mira NP, Palma M, Guerreiro JF, Sa-Correia I (2010b) Genome-wide identification of Saccharomyces cerevisiae genes required for tolerance to acetic acid. Microb Cell Fact 9:79. doi: 10.1186/1475-2859-9-79 CrossRefGoogle Scholar
  19. Mollapour M, Piper PW (2006) Hog1p mitogen-activated protein kinase determines acetic acid resistance in Saccharomyces cerevisiae. FEMS Yeast Res 6:1274–1280CrossRefGoogle Scholar
  20. Pampulha M, Loureiro-Dias M (1990) Activity of glycolytic enzymes of Saccharomyces cerevisiae in the presence of acetic acid. Appl Microbiol Biotechnol 34:375–380CrossRefGoogle Scholar
  21. Pampulha ME, Loureiro-Dias MC (2000) Energetics of the effect of acetic acid on growth of Saccharomyces cerevisiae. FEMS Microbiol Lett 184:69–72CrossRefGoogle Scholar
  22. Perlstein EO, Ruderfer DM, Ramachandran G, Haggarty SJ, Kruglyak L, Schreiber SL (2006) Revealing complex traits with small molecules and naturally recombinant yeast strains. Chem Biol 13:319–327CrossRefGoogle Scholar
  23. Piper P et al (1998) The Pdr12 ABC transporter is required for the development of weak organic acid resistance in yeast. EMBO J 17:4257–4265CrossRefGoogle Scholar
  24. Piper P, Calderon CO, Hatzixanthis K, Mollapour M (2001) Weak acid adaptation: the stress response that confers yeasts with resistance to organic acid food preservatives. Microbiology 147:2635–2642CrossRefGoogle Scholar
  25. Romano GH, Gurvich Y, Lavi O, Ulitsky I, Shamir R, Kupiec M (2010) Different sets of QTLs influence fitness variation in yeast. Mol Syst Biol. doi: 10.1038/msb.2010.1 Google Scholar
  26. Schlotterer C (2000) Evolutionary dynamics of microsatellite DNA. Chromosoma 109:365–371. doi: 10.1007/s004120000089 CrossRefGoogle Scholar
  27. Schlötterer C, Wiehe T (1999) Microsatellites, a neutral marker to infer selective sweeps. In: Goldstein DB, Schlötterer C (eds) Microsatellites-evolution and applications. Oxford University Press, Oxford, pp 238–248Google Scholar
  28. Steinmetz LM, Sinha H, Richards DR, Spiegelman JI, Oefner PJ, McCusker JH, Davis RW (2002) Dissecting the architecture of a quantitative trait locus in yeast. Nature 416:326–330CrossRefGoogle Scholar
  29. Strand M, Prolla TA, Liskay RM, Petes TD (1993) Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting dna mismatch repair. Nature 365:274–276. doi: 10.1038/365274a0 CrossRefGoogle Scholar
  30. Tenreiro S, Rosa PC, Viegas CA, Sá-Correia I (2000) Expression of the AZR1 gene (ORF YGR224w), encoding a plasma membrane transporter of the major facilitator superfamily, is required for adaptation to acetic acid and resistance to azoles in Saccharomyces cerevisiae. Yeast 16:1469–1481CrossRefGoogle Scholar
  31. This P et al (2004) Development of a standard set of microsatellite reference alleles for identification of grape cultivars. Theor Appl Genet 109:1448–1458. doi: 10.1007/s00122-004-1760-3 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Peng Geng
    • 2
  • Yin Xiao
    • 2
  • Yun Hu
    • 1
  • Haiye Sun
    • 2
  • Wei Xue
    • 3
  • Liang Zhang
    • 2
    Email author
  • Gui-yang Shi
    • 2
  1. 1.The Key Laboratory of Industrial Biotechnology of Ministry of EducationJiangnan UniversityWuxiChina
  2. 2.National Engineering Laboratory for Cereal Fermentation TechnologyJiangnan UniversityWuxiChina
  3. 3.School of Information Science and TechnologyNanjing Agricultural UniversityNanjingChina

Personalised recommendations