Genetic Mapping of MAPK-mediated Complex Traits Across S. Cerevisiae

Overview

Journal PLoS Genet

Specialty Genetics

Date 2015 Jan 9

PMID 25569670

Citations 27

Authors

Sebastian Treusch

Frank W Albert

Joshua S Bloom

Iulia E Kotenko

Leonid Kruglyak

Affiliations

Soon will be listed here.

Abstract

Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic variation on signaling pathways remains to be conducted. In S. cerevisiae, both response and resistance to stressors that activate signaling pathways differ between diverse isolates. Here, we present a quantitative trait locus (QTL) mapping approach that enables us to identify genetic variants underlying such phenotypic differences across the genetic and phenotypic diversity of S. cerevisiae. Using a Round-robin cross between twelve diverse strains, we identified QTL that influence phenotypes critically dependent on MAPK signaling cascades. Genetic variants under these QTL fall within MAPK signaling networks themselves as well as other interconnected signaling pathways. Finally, we demonstrate how the mapping results from multiple strain background can be leveraged to narrow the search space of causal genetic variants.

Citing Articles

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References

Teng X, Dayhoff-Brannigan M, Cheng W, Gilbert C, Sing C, Diny N . Genome-wide consequences of deleting any single gene. Mol Cell. 2013; 52(4):485-94. PMC: 3975072. DOI: 10.1016/j.molcel.2013.09.026. View

Wilkening S, Lin G, Fritsch E, Tekkedil M, Anders S, Kuehn R . An evaluation of high-throughput approaches to QTL mapping in Saccharomyces cerevisiae. Genetics. 2013; 196(3):853-65. PMC: 3948811. DOI: 10.1534/genetics.113.160291. View

Erdeniz N, Mortensen U, Rothstein R . Cloning-free PCR-based allele replacement methods. Genome Res. 1998; 7(12):1174-83. PMC: 310678. DOI: 10.1101/gr.7.12.1174. View

Meyer M, Kircher M . Illumina sequencing library preparation for highly multiplexed target capture and sequencing. Cold Spring Harb Protoc. 2010; 2010(6):pdb.prot5448. DOI: 10.1101/pdb.prot5448. View

Michelmore R, Paran I, Kesseli R . Identification of markers linked to disease-resistance genes by bulked segregant analysis: a rapid method to detect markers in specific genomic regions by using segregating populations. Proc Natl Acad Sci U S A. 1991; 88(21):9828-32. PMC: 52814. DOI: 10.1073/pnas.88.21.9828. View

ORourke S, Herskowitz I, OShea E . Yeast go the whole HOG for the hyperosmotic response. Trends Genet. 2002; 18(8):405-12. DOI: 10.1016/s0168-9525(02)02723-3. View

Bloom J, Ehrenreich I, Loo W, Lite T, Kruglyak L . Finding the sources of missing heritability in a yeast cross. Nature. 2013; 494(7436):234-7. PMC: 4001867. DOI: 10.1038/nature11867. View

Smith C, Greig D . The cost of sexual signaling in yeast. Evolution. 2010; 64(11):3114-22. DOI: 10.1111/j.1558-5646.2010.01069.x. View

Levin D . Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 2005; 69(2):262-91. PMC: 1197416. DOI: 10.1128/MMBR.69.2.262-291.2005. View

10.

Audhya A, Emr S . Regulation of PI4,5P2 synthesis by nuclear-cytoplasmic shuttling of the Mss4 lipid kinase. EMBO J. 2003; 22(16):4223-36. PMC: 175787. DOI: 10.1093/emboj/cdg397. View

11.

Mackay T, Stone E, Ayroles J . The genetics of quantitative traits: challenges and prospects. Nat Rev Genet. 2009; 10(8):565-77. DOI: 10.1038/nrg2612. View

12.

Chen R, Thorner J . Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae. Biochim Biophys Acta. 2007; 1773(8):1311-40. PMC: 2031910. DOI: 10.1016/j.bbamcr.2007.05.003. View

13.

Albertyn J, Hohmann S, Thevelein J, Prior B . GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol. 1994; 14(6):4135-44. PMC: 358779. DOI: 10.1128/mcb.14.6.4135-4144.1994. View

14.

Cherry J, Hong E, Amundsen C, Balakrishnan R, Binkley G, Chan E . Saccharomyces Genome Database: the genomics resource of budding yeast. Nucleic Acids Res. 2011; 40(Database issue):D700-5. PMC: 3245034. DOI: 10.1093/nar/gkr1029. View

15.

Kaida D, Yashiroda H, Toh-E A, Kikuchi Y . Yeast Whi2 and Psr1-phosphatase form a complex and regulate STRE-mediated gene expression. Genes Cells. 2002; 7(6):543-52. DOI: 10.1046/j.1365-2443.2002.00538.x. View

16.

Seger R, KREBS E . The MAPK signaling cascade. FASEB J. 1995; 9(9):726-35. View

17.

Rodicio R, Heinisch J . Together we are strong--cell wall integrity sensors in yeasts. Yeast. 2010; 27(8):531-40. DOI: 10.1002/yea.1785. View

18.

Yvert G, Brem R, Whittle J, Akey J, Foss E, Smith E . Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nat Genet. 2003; 35(1):57-64. DOI: 10.1038/ng1222. View

19.

Yalcin B, Flint J, Mott R . Using progenitor strain information to identify quantitative trait nucleotides in outbred mice. Genetics. 2005; 171(2):673-81. PMC: 1456780. DOI: 10.1534/genetics.104.028902. View

20.

Yang Y, Foulquie-Moreno M, Clement L, Erdei E, Tanghe A, Schaerlaekens K . QTL analysis of high thermotolerance with superior and downgraded parental yeast strains reveals new minor QTLs and converges on novel causative alleles involved in RNA processing. PLoS Genet. 2013; 9(8):e1003693. PMC: 3744412. DOI: 10.1371/journal.pgen.1003693. View