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Systematic analysis reveals the prevalence and principles of bypassable gene essentiality

Author

Listed:
  • Jun Li

    (National Institute of Biological Sciences)

  • Hai-Tao Wang

    (National Institute of Biological Sciences
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Wei-Tao Wang

    (National Institute of Biological Sciences
    China Agricultural University)

  • 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
    Tsinghua University)

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.

Suggested Citation

  • 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 & Li-Lin Du, 2019. "Systematic analysis reveals the prevalence and principles of bypassable gene essentiality," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08928-1
    DOI: 10.1038/s41467-019-08928-1
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    Cited by:

    1. Piaopiao Chen & Agnès H. Michel & Jianzhi Zhang, 2022. "Transposon insertional mutagenesis of diverse yeast strains suggests coordinated gene essentiality polymorphisms," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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