National Institute of Biological Sciences, 102206, Beijing, China.
Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
Nat Commun. 2019 Mar 1;10(1):1002. doi: 10.1038/s41467-019-08928-1.
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.
基因的必需性是一个可变的表型特征，但必需基因在多大程度上以及如何变得可有可无仍然不清楚。在这里，我们研究了“必需性回避（BOE）”——一种未被充分探索的双基因遗传相互作用类型，它使必需基因变得可有可无。通过分析裂殖酵母 Schizosaccharomyces pombe 的六条染色体臂之一上的必需基因，我们惊人地发现，多达 27%的必需基因可以通过 BOE 相互作用转化为非必需基因。利用这个数据集，我们确定了必需性回避的三个原则：可回避的必需基因往往重要性较低，在物种间往往表现出不同的必需性，并且往往与其他可回避的基因一起作用。此外，我们还阐明了可回避必需性的潜在机制，包括以前未被重视的同源基因之间休眠冗余的机制。在可回避必需性方面获得的新见解加深了我们对基因型-表型关系的理解，并将有助于与必需基因相关的药物开发。
