A genome wide dosage suppressor network reveals genomic robustness
Creators
- 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.
-
Ray, Animesh
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.
Additional Information
© 2016 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Received July 29, 2016. Revision received October 17, 2016. Accepted November 7, 2016. First published online: November 29, 2016. We thank Dr C. Boone (U. Toronto) for discussion, for sharing strains and their suppressor data before publication, B. Kraynack and K. Svay for initial work in suppressor discovery and C. Cordova, R. Vasudevan, V. Padmakumar, K. Bheda, K. Datta, A. Kamra, D. Lev, M. Pollock and S. Russell for technical assistance, and Dr C. Murre (UCSD) for comments on an earlier version of the manuscript. Author contributions: B.P., Y.K., A.W.S., G.Y. J.P.F., R.R.V., A.H., B.Ø., A.B., B.M. and J.K.T. conducted experiments and analyzed data, A.K. conducted experiments; B.P., Y.K., A.W.S., J.P.F., R.R.V., A.H., B.Ø., A.B., B.M., N.S.B., E.J.G., D.J.G., G.Y., A.Rav., C.A., E.M.P and A.Ray designed experiments and analyzed data; B.P., A.W.S., G.Y., J.P.F., A.H., B.Ø., A.B., D.J.G., A.Rav., C.A. and A.Ray wrote the manuscript; E.J.G., D.J.G., A.Rav., C.A., E.M.P. and A.Ray. procured funding. Funding: 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.). Funding for open access charge: Internal institutional sources. Conflict of interest statement. None declared.Attached Files
Published - gkw1148.pdf
Supplemental Material - nar-02141-h-2016-File007.pdf
Supplemental Material - nar-02141-h-2016-File008.pdf
Supplemental Material - nar-02141-h-2016-File009.zip
Files
gkw1148.pdf
Additional details
Identifiers
- PMCID
- PMC5224485
- Eprint ID
- 72621
- DOI
- 10.1093/nar/gkw1148
- Resolver ID
- CaltechAUTHORS:20161207-074147204
Related works
- Describes
- 10.1093/nar/gkw1148 (DOI)
Funding
- NSF
- EF-0527023
- NSF
- CCF-0523643
- NSF
- EAGR-0941078
- NIH
- 1R01GM084881-01
Dates
- Created
-
2016-12-07Created from EPrint's datestamp field
- Updated
-
2022-04-07Created from EPrint's last_modified field