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Nat Commun. 2019 Mar 1;10(1):1002. doi: 10.1038/s41467-019-08928-1.

Systematic analysis reveals the prevalence and principles of bypassable gene essentiality.

Author information

1
National Institute of Biological Sciences, 102206, Beijing, China.
2
Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
3
College of Biological Sciences, China Agricultural University, 100193, Beijing, China.
4
National Institute of Biological Sciences, 102206, Beijing, China. dulilin@nibs.ac.cn.
5
Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, 100084, Beijing, China. dulilin@nibs.ac.cn.

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.

PMID:
30824696
PMCID:
PMC6397241
DOI:
10.1038/s41467-019-08928-1
[Indexed for MEDLINE]
Free PMC Article

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