Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Genetic dissection of acetic acid tolerance in Saccharomyces cerevisiae


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.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3


  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 35:1777–1780

  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–R15

  3. Causton HC et al (2001) Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12:323–337

  4. Deutschbauer AM, Davis RW (2005) Quantitative trait loci mapped to single-nucleotide resolution in yeast. Nat Genet 37:1333–1340

  5. Flint J, Mott R (2001) Finding the molecular basis of quatitative traits: successes and pitfalls. Nat Rev Genet 2:437–445

  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:e35

  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 181:4644–4652

  8. Hu X et al (2007) Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces cerevisiae. Genetics 175:1479–1487

  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

  10. Katou T, Namise M, Kitagaki H, Akao T, Shimoi H (2009) QTL mapping of sake brewing characteristics of yeast. J Biosci Bioeng 107:383–393

  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 6:924–936

  12. Kren A et al (2003) War1p, a novel transcription factor controlling weak acid stress response in yeast. Mol Cell Biol 23:1775–1785

  13. Lander E, Schork N (1994) Genetic dissection of complex traits. Science (New York, NY) 265:2037

  14. Mauricio R (2001) Mapping quantitative trait loci in plants: uses and caveats for evolutionary biology. Nat Rev Genet 2:370–381

  15. McCusker JH, Clemons KV, Stevens DA, Davis RW (1994) Genetic characterization of pathogenic Saccharomyces cerevisiae isolates. Genetics 136:1261–1269

  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

  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 9:13

  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

  19. Mollapour M, Piper PW (2006) Hog1p mitogen-activated protein kinase determines acetic acid resistance in Saccharomyces cerevisiae. FEMS Yeast Res 6:1274–1280

  20. Pampulha M, Loureiro-Dias M (1990) Activity of glycolytic enzymes of Saccharomyces cerevisiae in the presence of acetic acid. Appl Microbiol Biotechnol 34:375–380

  21. Pampulha ME, Loureiro-Dias MC (2000) Energetics of the effect of acetic acid on growth of Saccharomyces cerevisiae. FEMS Microbiol Lett 184:69–72

  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 13:319–327

  23. Piper P et al (1998) The Pdr12 ABC transporter is required for the development of weak organic acid resistance in yeast. EMBO J 17:4257–4265

  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 147:2635–2642

  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

  26. Schlotterer C (2000) Evolutionary dynamics of microsatellite DNA. Chromosoma 109:365–371. doi:10.1007/s004120000089

  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 238–248

  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 416:326–330

  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

  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 16:1469–1481

  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

Download references


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).

Author information

Correspondence to Liang Zhang.

Additional information

Peng Geng and Yin Xiao have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 45 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Geng, P., Xiao, Y., Hu, Y. et al. Genetic dissection of acetic acid tolerance in Saccharomyces cerevisiae . World J Microbiol Biotechnol 32, 145 (2016). https://doi.org/10.1007/s11274-016-2101-9

Download citation


  • Acetic acid tolerance
  • Phenotypic analysis
  • QTL
  • Saccharomyces cerevisiae
  • SSR markers