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A genome wide dosage suppressor network reveals genomic robustness

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Title A genome wide dosage suppressor network reveals genomic robustness
 
Creator 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
 
Subject Genomic robustness
 
Description Accepted date: November 7, 2016
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.
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.
 
Date 2016-12-15T11:24:03Z
2016-12-15T11:24:03Z
2017
 
Type Article
 
Identifier Nucl. Acids Res., 45(1): 255-270
1362-4962
http://59.163.192.83:8080/jspui/handle/123456789/699
https://academic.oup.com/nar/article/45/1/255/2605800/A-genome-wide-dosage-suppressor-network-reveals
10.1093/nar/gkw1148
 
Language en_US
 
Publisher Oxford University Press