title: Ras mutants enhance the ability of cells to anticipate future lethal stressors.
abstract: Organisms integrate information of current environmental stressors and can adjust themselves against harmful events that might occur in the future. The molecular processes that lead to such "anticipatory" behaviors, although of great interest, are mostly unexplored and the minimal genetic requirements for reconfiguring key signaling networks in order either to create or to strengthen such vital "anticipatory" capabilities is largely unknown. We identified new "anticipatory" phenotypes in yeast cells by evolving yeast strains that strongly associate a present modest stress with a future deadly one. Whole genome sequencing and classic genetic analysis revealed that two dominant negative ras2 alleles (ras2-K23N and ras2-G17C) displayed a strong "anticipatory" ability being highly resistant to oxidative stress, extremely thermotolerant and long lived only following an initial mild heat shock. We suggest that such "anticipatory" phenotypes can be easily evolved by a single point mutation in a key signaling protein, the Ras2 small GTPase, and we propose a molecular model describing how specific ras2 alleles, and not null ras2 mutants, or mutations in other components of the Ras/cAMP pathway, can enhance the "predictive ability" of cells for future lethal stressors.
authors.affiliation: Biology Department, University of Crete, Heraklion, Crete, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Zacharioudakis
authors.affiliation: Biology Department, University of Crete, Heraklion, Crete, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Papagiannidis
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion, Crete, Greece.
authors.forename: Niki
authors.initials: N
authors.lastname: Gounalaki
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion, Crete, Greece.
authors.forename: Irini
authors.initials: I
authors.lastname: Stratidaki
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion, Crete, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kafetzopoulos
authors.affiliation: Biology Department, University of Crete, Heraklion, Crete, Greece. Electronic address: Tzamaria@imbb.forth.gr.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Tzamarias
mesh_terms: D000483:Alleles; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005799:Genes, Dominant; D016678:Genome; D006360:Heat-Shock Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D050505:Mutant Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D017354:Point Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013696:Temperature; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D006360:Heat-Shock Proteins; D050505:Mutant Proteins; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C489015:RAS2 protein, S cerevisiae; D018631:ras Proteins
keywords: Anticipation; Hydrogen peroxide resistance; Ras