Triple mutations in yeast reveal broad scope of genetic interactions How many and which genes does an organism need at a minimum to sustain growth? With the identification of essential genes in a variety of organisms such as yeast (1), worms (2), and human cultured cells (3–5), the answer may seem obvious: Remove all nonessential genes, and the organism should be able to continue to survive and grow. In the yeast Saccharomyces cerevisiae, the workhorse of genetic interaction mapping, ∼1000 of the ∼6000 (∼17%) protein-coding genes are essential for viability (1). So theoretically, one might think that one could remove the other ∼5000 nonessential genes and still have a growing yeast. The reason this does not work is that genes interact with each other to drive different traits, including viability and growth. On page 283 of this issue, Kuzmin et al. (6) provide the first systematic analysis of trigenic interactions in yeast in which three gene deletions are combined in individual strains in order to ascertain the importance of multigene interactions for growth. This study shows that higher-order genetic interactions are abundant, which has implications for the interpretation of human gene variants that may interact to affect health and disease.

中文翻译：

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如果两次删除不停止增长，请尝试三个

酵母中的三重突变揭示了广泛的遗传相互作用 生物体至少需要多少和哪些基因才能维持生长？随着酵母 (1)、蠕虫 (2) 和人类培养细胞 (3-5) 等多种生物体中必需基因的鉴定，答案似乎显而易见：去除所有非必需基因，生物体应该能够继续生存和成长。在酵母酿酒酵母（遗传相互作用作图的主力）中，约 6000 个（约 17%）蛋白质编码基因中的约 1000 个对生存力至关重要 (1)。因此，理论上，人们可能会认为可以去除其他约 5000 个非必需基因，而酵母菌仍在生长。这不起作用的原因是基因彼此相互作用以驱动不同的特征，包括生存力和生长。在本期第 283 页，Kuzmin 等人。(6) 首次对酵母中的三基因相互作用进行系统分析，其中在单个菌株中组合了三个基因缺失，以确定多基因相互作用对生长的重要性。这项研究表明，高阶遗传相互作用是丰富的，这对解释可能相互作用影响健康和疾病的人类基因变异具有重要意义。