National Institute of Biological Sciences, Beijing, 102206, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 100084, China.
Biochem Biophys Res Commun. 2020 Jul 30;528(3):405-412. doi: 10.1016/j.bbrc.2020.05.207. Epub 2020 Jun 4.
Understanding genotype-phenotype relationships is a central pursuit in biology. Gene knockout generates a complete loss-of-function genotype and is a commonly used approach for probing gene functions. The most severe phenotypic consequence of gene knockout is lethality. Genes with a lethal knockout phenotype are called essential genes. Based on genome-wide knockout analyses in yeasts, up to approximately a quarter of genes in a genome can be essential. Like other genotype-phenotype relationships, gene essentiality is subject to background effects and can vary due to gene-gene interactions. In particular, for some essential genes, lethality caused by knockout can be rescued by extragenic suppressors. Such "bypass of essentiality" (BOE) gene-gene interactions have been an understudied type of genetic suppression. A recent systematic analysis revealed that, remarkably, the essentiality of nearly 30% of essential genes in the fission yeast Schizosaccharomyces pombe can be bypassed by BOE interactions. Here, I review the history and recent progress on uncovering and understanding the bypass of gene essentiality.
理解基因型-表型关系是生物学的核心追求。基因敲除产生完全的功能丧失基因型，是探测基因功能的常用方法。基因敲除最严重的表型后果是致死。具有致死性基因敲除表型的基因称为必需基因。基于酵母的全基因组敲除分析，基因组中多达四分之一的基因可能是必需的。与其他基因型-表型关系一样，基因的必需性受到背景效应的影响，并且可能因基因-基因相互作用而发生变化。特别是对于一些必需基因，敲除引起的致死性可以被外源抑制子拯救。这种“必需性的旁路”（BOE）基因-基因相互作用是一种研究较少的遗传抑制类型。最近的一项系统分析表明，令人惊讶的是，裂殖酵母 Schizosaccharomyces pombe 中近 30%的必需基因的必需性可以通过 BOE 相互作用来旁路。在这里，我回顾了揭示和理解基因必需性旁路的历史和最新进展。
