Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Nat Biotechnol. 2011 May 15;29(6):505-11. doi: 10.1038/nbt.1855.
Dosage suppression is a genetic interaction in which overproduction of one gene rescues a mutant phenotype of another gene. Although dosage suppression is known to map functional connections among genes, the extent to which it might illuminate global cellular functions is unclear. Here we analyze a network of interactions linking dosage suppressors to 437 essential genes in yeast. For 424 genes, we curated interactions from the literature. Analyses revealed that many dosage suppression interactions occur between functionally related genes and that the majority do not overlap with other types of genetic or physical interactions. To confirm the generality of these network properties, we experimentally identified dosage suppressors for 29 genes from pooled populations of temperature-sensitive mutant cells transformed with a high-copy molecular-barcoded open reading frame library, MoBY-ORF 2.0. We classified 87% of the 1,640 total interactions into four general types of suppression mechanisms, which provided insight into their relative frequencies. This work suggests that integrating the results of dosage suppression studies with other interaction networks could generate insights into the functional wiring diagram of a cell.
剂量抑制是一种遗传相互作用，其中一个基因的过度表达可以挽救另一个基因的突变表型。尽管已知剂量抑制可以映射基因之间的功能连接，但它在多大程度上可以阐明全局细胞功能尚不清楚。在这里，我们分析了一个将剂量抑制剂与酵母中 437 个必需基因联系起来的相互作用网络。对于 424 个基因，我们从文献中整理了相互作用。分析表明，许多剂量抑制相互作用发生在功能相关的基因之间，而且大多数相互作用与其他类型的遗传或物理相互作用不重叠。为了确认这些网络特性的普遍性，我们从用高拷贝分子条形码开放阅读框文库 MoBY-ORF 2.0 转化的温度敏感突变细胞的混合群体中，通过实验鉴定了 29 个基因的剂量抑制剂。我们将 1640 个总相互作用中的 87%分为四种一般抑制机制类型，这为它们的相对频率提供了深入了解。这项工作表明，将剂量抑制研究的结果与其他相互作用网络整合起来，可以深入了解细胞的功能连接图。
