A genome wide dosage suppressor network reveals genomic robustness.
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Authors
Patra, Biranchi
Kon, Yoshiko
Yadav, Gitanjali
Sevold, Anthony W
Frumkin, Jesse P
Vallabhajosyula, Ravishankar R
Hintze, Arend
Østman, Bjørn
Schossau, Jory
Bhan, Ashish
Marzolf, Bruz
Tamashiro, Jenna K
Kaur, Amardeep
Baliga, Nitin S
Grayhack, Elizabeth J
Adami, Christoph
Galas, David J
Raval, Alpan
Phizicky, Eric M
Publication Date
2017-01-09Journal Title
Nucleic Acids Res
ISSN
0305-1048
Publisher
Oxford University Press (OUP)
Volume
45
Issue
1
Pages
255-270
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Patra, B., Kon, Y., Yadav, G., Sevold, A. W., Frumkin, J. P., Vallabhajosyula, R. R., Hintze, A., et al. (2017). A genome wide dosage suppressor network reveals genomic robustness.. Nucleic Acids Res, 45 (1), 255-270. https://doi.org/10.1093/nar/gkw1148
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.
Keywords
Saccharomyces cerevisiae, RNA Polymerase II, Saccharomyces cerevisiae Proteins, Gene Expression Profiling, Computational Biology, Cell Division, Gene Expression Regulation, Fungal, Gene Dosage, Mutation, Genome, Fungal, Genes, Lethal, Gene Regulatory Networks, Genetic Fitness
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.).
Identifiers
External DOI: https://doi.org/10.1093/nar/gkw1148
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284478
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