Zacharioudakis Ioannis, Papagiannidis Dimitris, Gounalaki Niki, Stratidaki Irini, Kafetzopoulos Dimitris, Tzamarias Dimitris
Biology Department, University of Crete, Heraklion, Crete, Greece.
Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion, Crete, Greece.
Biochem Biophys Res Commun. 2017 Jan 22;482(4):1278-1283. doi: 10.1016/j.bbrc.2016.12.028. Epub 2016 Dec 7.
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.
生物体整合当前环境应激源的信息，并能够针对未来可能发生的有害事件进行自我调整。导致这种“预期性”行为的分子过程虽然备受关注，但大多尚未得到探索，而且重新配置关键信号网络以创建或增强这种重要的“预期性”能力所需的最小遗传要求在很大程度上也尚不清楚。我们通过培育酵母菌株来鉴定酵母细胞中的新“预期性”表型，这些酵母菌株将当前适度的应激与未来致命的应激紧密联系起来。全基因组测序和经典遗传分析表明，两个显性负性ras2等位基因（ras2-K23N和ras2-G17C）表现出很强的“预期性”能力，仅在经历一次初始轻度热激后就对氧化应激具有高度抗性、极其耐热且寿命延长。我们认为，这种“预期性”表型可以通过关键信号蛋白Ras2小GTP酶中的单点突变轻松进化而来，并且我们提出了一个分子模型，描述特定的ras2等位基因，而非ras2无效突变体或Ras/cAMP途径其他成分中的突变，如何能够增强细胞对未来致命应激源的“预测能力”。
