Systematic analysis reveals the prevalence and principles of bypassable gene essentiality
Systematic analysis reveals the prevalence and principles of bypassable gene essentiality
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系统分析揭示可绕过基因必要性的普遍性和原理
DOI：
10.1038/s41467-019-08928-1
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发表时间：
2019-03-01
影响因子：
16.6
通讯作者：
Du, Li-Lin
中科院分区：
文献类型：
--
作者：
Li, Jun;Wang, Hai-Tao;Du, Li-Lin
基因必需性是一种可变的表型性状，但必需基因在多大程度上以及如何变得对于生存能力来说是可有可无的仍不清楚。在这里，我们研究了“绕过必要性（BOE）”——一种尚未充分研究的双基因遗传相互作用类型，它使得必要基因变得可有可无。通过分析裂殖酵母裂殖酵母六个染色体臂之一上的必需基因，我们发现，引人注目的是，其中多达 27% 的基因可以通过 BOE 相互作用转化为非必需基因。使用该数据集，我们确定了重要性绕过的三个原则：可绕过的必需基因往往具有较低的重要性，往往在物种之间表现出差异的重要性，并且往往与其他可绕过的基因一起作用。此外，我们描述了可绕过必要性的潜在机制，包括以前未被重视的旁系同源物之间的休眠冗余机制。对可绕过重要性的新见解加深了我们对基因型-表型关系的理解，并将促进与必需基因相关的药物开发。
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.