A genome wide dosage suppressor network reveals genomic robustness.

Document Type

Article

Publication Date

1-9-2017

Publication Title

Nucleic acids research

Keywords

Cell Division; Computational Biology; Gene Dosage; Gene Expression Profiling; Gene Expression Regulation, Fungal; Gene Regulatory Networks; Genes, Lethal; Genetic Fitness; Genome, Fungal; Mutation; RNA Polymerase II; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins

Abstract

Genomic robustness is the extent to which an organism has evolved to withstand the effects of deleterious mutations. We explored the extent of genomic robustness in budding yeast by genome wide dosage suppressor analysis of 53 conditional lethal mutations in cell division cycle and RNA synthesis related genes, revealing 660 suppressor interactions of which 642 are novel. This collection has several distinctive features, including high co-occurrence of mutant-suppressor pairs within protein modules, highly correlated functions between the pairs and higher diversity of functions among the co-suppressors than previously observed. Dosage suppression of essential genes encoding RNA polymerase subunits and chromosome cohesion complex suggests a surprising degree of functional plasticity of macromolecular complexes, and the existence of numerous degenerate pathways for circumventing the effects of potentially lethal mutations. These results imply that organisms and cancer are likely able to exploit the genomic robustness properties, due the persistence of cryptic gene and pathway functions, to generate variation and adapt to selective pressures.

Department

Institute for Systems Biology

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