Emerging and evolving concepts in gene essentiality

• Published in: Nature reviews. Genetics Vol. 19; no. 1; pp. 34 - 49
• Main Authors: Rancati, Giulia, Moffat, Jason, Typas, Athanasios, Pavelka, Norman
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2018; Nature Publishing Group
• Subjects: 631/181/2474; 631/181/2475; 631/208/191; 631/208/2490; 631/208/325; 631/208/68; 631/326/22; 631/337/475/2290; 631/61/338/552; 631/67/1059; Agriculture; Animal Genetics and Genomics; Animals; Bacteria; Biomedicine; Cancer; Cancer Research; Conserved Sequence; Disease susceptibility; Drug Delivery Systems; Drug Resistance - genetics; Evolution, Molecular; Gene Editing; Gene expression; Gene Function; Gene Regulatory Networks; Genes, Essential; Genetic aspects; Genetic research; Genomics; Genotypes; Health aspects; High-Throughput Nucleotide Sequencing; Human Genetics; Humans; Metabolic Engineering; Models, Genetic; review-article; Screens; Synthetic Biology
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg.2017.74

Key Points
A gene is considered essential if it is required for the reproductive success of a cell or an organism. Gene essentiality is a core concept of genetics, with repercussions in evolutionary, systems and synthetic biology and with applications in drug development.
The 'essentialome' is defined as the complete set of genes that are individually essential in a given organism. Recent genome sequencing and editing technologies are enabling the identification of essentialomes in a progressively larger number of non-model organisms and higher eukaryotes.
The essentiality of many genes is dependent on the environment and/or genetic context and can be altered in the course of both short-term and long-term evolutionary processes. Hence it is not an absolute and static property of a gene.
There seems to be a gradient of gene essentiality among genes in each genome, with some essential genes being more prone to losing their essentiality than others. Hence essentiality is not a binary but a quantitative property of a gene.
The context-dependent nature of gene essentiality can be exploited to develop more effective or more specific antimicrobials and provides avenues for patient-tailored anticancer therapies.
The evolvable nature of gene essentiality has implications for drug target prioritization: genes that are less likely to lose their essentiality should be associated with a lower incidence of resistance when targeted by a drug.
Identifying which genes in a genome are essential for survival has been a long-standing goal of geneticists. This Review discusses our evolving understanding of cellular gene essentiality across diverse organisms. It describes how essentiality is often non-absolute but is instead dependent on the environment or genetic background and how this knowledge can be exploited therapeutically.
Gene essentiality is a founding concept of genetics with important implications in both fundamental and applied research. Multiple screens have been performed over the years in bacteria, yeasts, animals and more recently in human cells to identify essential genes. A mounting body of evidence suggests that gene essentiality, rather than being a static and binary property, is both context dependent and evolvable in all kingdoms of life. This concept of a non-absolute nature of gene essentiality changes our fundamental understanding of essential biological processes and could directly affect future treatment strategies for cancer and infectious diseases.