title: A genome wide dosage suppressor network reveals genomic robustness.
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.
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Biranchi
authors.initials: B
authors.lastname: Patra
authors.affiliation: Department of Biochemistry, University of Rochester School of Medicine, Rochester, NY 14627, USA.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kon
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.|National Institute of Plant Genome Research (NIPGR), Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Gitanjali
authors.initials: G
authors.lastname: Yadav
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Sevold
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Jesse P
authors.initials: JP
authors.lastname: Frumkin
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Ravishankar R
authors.initials: RR
authors.lastname: Vallabhajosyula
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Arend
authors.initials: A
authors.lastname: Hintze
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Østman
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Jory
authors.initials: J
authors.lastname: Schossau
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Bhan
authors.affiliation: Institute for Systems Biology, 1441 N 34th St, Seattle, WA 98103, USA.
authors.forename: Bruz
authors.initials: B
authors.lastname: Marzolf
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Jenna K
authors.initials: JK
authors.lastname: Tamashiro
authors.affiliation: Institute for Systems Biology, 1441 N 34th St, Seattle, WA 98103, USA.
authors.forename: Amardeep
authors.initials: A
authors.lastname: Kaur
authors.affiliation: Institute for Systems Biology, 1441 N 34th St, Seattle, WA 98103, USA.
authors.forename: Nitin S
authors.initials: NS
authors.lastname: Baliga
authors.affiliation: Department of Biochemistry, University of Rochester School of Medicine, Rochester, NY 14627, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Grayhack
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Adami
authors.affiliation: Institute for Systems Biology, 1441 N 34th St, Seattle, WA 98103, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Galas
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.|Institute of Mathematical Sciences, Claremont Graduate University, Claremont, CA 91711, USA.
authors.forename: Alpan
authors.initials: A
authors.lastname: Raval
authors.affiliation: Department of Biochemistry, University of Rochester School of Medicine, Rochester, NY 14627, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Phizicky
authors.affiliation: Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA aray@kgi.edu.|Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Animesh
authors.identifier: http://orcid.org/0000-0002-0120-5820
authors.initials: A
authors.lastname: Ray
mesh_terms: D002455:Cell Division; D019295:Computational Biology; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D005804:Genes, Lethal; D056084:Genetic Fitness; D016681:Genome, Fungal; D009154:Mutation; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II