Systematic analysis reveals the prevalence and principles of bypassable gene essentiality

Jun Li, Hai-Tao Wang, Wei-Tao Wang, Xiao-Ran Zhang, Fang Suo, Jing-Yi Ren, Ying Bi, Ying-Xi Xue, Wen Hu, Meng-Qiu Dong and Li-Lin Du ()
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Jun Li: National Institute of Biological Sciences
Hai-Tao Wang: National Institute of Biological Sciences
Wei-Tao Wang: National Institute of Biological Sciences
Xiao-Ran Zhang: National Institute of Biological Sciences
Fang Suo: National Institute of Biological Sciences
Jing-Yi Ren: National Institute of Biological Sciences
Ying Bi: National Institute of Biological Sciences
Ying-Xi Xue: National Institute of Biological Sciences
Wen Hu: National Institute of Biological Sciences
Meng-Qiu Dong: National Institute of Biological Sciences
Li-Lin Du: National Institute of Biological Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Gene essentiality is a variable phenotypic trait, but to what extent and how essential genes can become dispensable for viability remain unclear. Here, we investigate ‘bypass of essentiality (BOE)’ — an underexplored type of digenic genetic interaction that renders essential genes dispensable. Through analyzing essential genes on one of the six chromosome arms of the fission yeast Schizosaccharomyces pombe, we find that, remarkably, as many as 27% of them can be converted to non-essential genes by BOE interactions. Using this dataset we identify three principles of essentiality bypass: bypassable essential genes tend to have lower importance, tend to exhibit differential essentiality between species, and tend to act with other bypassable genes. In addition, we delineate mechanisms underlying bypassable essentiality, including the previously unappreciated mechanism of dormant redundancy between paralogs. The new insights gained on bypassable essentiality deepen our understanding of genotype-phenotype relationships and will facilitate drug development related to essential genes.

Date: 2019
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DOI: 10.1038/s41467-019-08928-1

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