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A genome wide dosage suppressor network reveals genomic robustness.


Type

Article

Change log

Authors

Patra, Biranchi 
Kon, Yoshiko 
Yadav, Gitanjali 
Sevold, Anthony W 
Frumkin, Jesse P 

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.

Description

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

Journal Title

Nucleic Acids Res

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

45

Publisher

Oxford University Press (OUP)
Sponsorship
National Science Foundation (Frontiers in Integrative Biological Research) [0527023 to D.J.G, E.J.G., E.M.P., C.A., A.Rav., A.Ray.; 0523643 to A.Rav., A.Ray.; 0941078 to A.Ray.]; National Institutes of Health [1R01GM084881-01 to A.Ray.).