Resurrection from lethal knockouts: Bypass of gene essentiality

• Published in: Biochemical and biophysical research communications Vol. 528; no. 3; pp. 405 - 412
• Main Author: Du, Li-Lin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.07.2020
• Subjects: Animals; death; Epistasis, Genetic; Evolution, Molecular; Gene Knockout Techniques; gene targeting; Genes, Essential; Genes, Fungal; Genes, Lethal; Genes, Synthetic; genetic suppression; genotype; genotype-phenotype correlation; loss-of-function mutation; Models, Genetic; Phenotype; Saccharomyces cerevisiae - genetics; Schizosaccharomyces - genetics; Schizosaccharomyces pombe; Suppression, Genetic
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2020.05.207

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.