Different sets of QTLs influence fitness variation in yeast.
Most of the phenotypes in nature are complex and are determined by many quantitative trait loci (QTLs). In this study we identify gene sets that contribute to one important complex trait: the ability of yeast cells to survive under alkali stress. We carried out an in-lab evolution (ILE) experiment, in which we grew yeast populations under increasing alkali stress to enrich for beneficial mutations. The populations acquired different sets of affecting alleles, showing that evolution can provide alternative solutions to the same challenge. We measured the contribution of each allele to the phenotype. The sum of the effects of the QTLs was larger than the difference between the ancestor phenotype and the evolved strains, suggesting epistatic interactions between the QTLs. In parallel, a clinical isolated strain was used to map natural QTLs affecting growth at high pH. In all, 17 candidate regions were found. Using a predictive algorithm based on the distances in protein-interaction networks, candidate genes were defined and validated by gene disruption. Many of the QTLs found by both methods are not directly implied in pH homeostasis but have more general, and often regulatory, roles.
Romano
Gal Hagit
GH
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel.
Gurvich
Yonat
Y
Lavi
Ofer
O
Ulitsky
Igor
I
Shamir
Ron
R
Kupiec
Martin
M
D000465:Algorithms; D017920:Antiporters / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003470:Culture Media / Q000378:metabolism; D019020:Directed Molecular Evolution / Q000379:methods*; D056084:Genetic Fitness / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D010641:Phenotype; D040641:Quantitative Trait Loci; D015203:Reproducibility of Results; D000080083:SLC31 Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D049490:Systems Biology / Q000379:methods
D017920:Antiporters; C100982:CTR3 protein, S cerevisiae; D027682:Cation Transport Proteins; D003470:Culture Media; D000080083:SLC31 Proteins; D029701:Saccharomyces cerevisiae Proteins