Hit genes under well-studied stress.

Overexpression can help life adapt to stressful environments, making an examination of overexpressed genes valuable for understanding stress tolerance mechanisms. However, a systematic study of genes whose overexpression is functionally adaptive (GOFAs) under stress has yet to be conducted. We developed a new overexpression profiling method and systematically identified GOFAs in Saccharomyces cerevisiae under stress (heat, salt, and oxidative). Our results show that adaptive overexpression compensates for deficiencies and increases fitness under stress, like calcium under salt stress. We also investigated the impact of different genetic backgrounds on GOFAs, which varied among three S. cerevisiae strains reflecting differing calcium and potassium requirements for salt stress tolerance. Our study of a knockout collection also suggested that calcium prevents mitochondrial outbursts under salt stress. Mitochondria-enhancing GOFAs were only adaptive when adequate calcium was available and non-adaptive when calcium was deficient, supporting this idea. Our findings indicate that adaptive overexpression meets the cell’s needs for maximizing the organism’s adaptive capacity in the given environment and genetic context.

基因过表达可帮助生物体适应胁迫环境，因此对过表达基因的分析对于解析胁迫耐受机制具有重要价值。然而，目前尚未有针对胁迫条件下功能适应性过表达基因（GOFAs）的系统性研究开展。本研究开发了一种全新的过表达谱分析方法，系统鉴定了热、盐、氧化三种胁迫条件下酿酒酵母（Saccharomyces cerevisiae）中的功能适应性过表达基因。研究结果显示，适应性过表达可弥补胁迫环境下的生理缺陷并提升生物体适合度，盐胁迫下的钙调控即为典型实例。此外，本研究还探究了不同遗传背景对功能适应性过表达基因的影响，结果显示三种酿酒酵母菌株间的功能适应性过表达基因存在显著差异，这与其盐胁迫耐受所需的钙、钾需求差异相吻合。针对基因敲除文库的研究还表明，盐胁迫环境下钙可抑制线粒体异常释放。增强线粒体功能的功能适应性过表达基因仅在钙水平充足时具备适应性优势，而在钙缺乏时则无适应性，这一结果验证了上述推测。本研究结果表明，适应性过表达可满足细胞的生理需求，从而在特定环境与遗传背景下最大化生物体的适应能力。