Exploring genetic suppression interactions on a global scale

Jolanda Van Leeuwen; Carles Pons; Joseph C. Mellor; Takafumi N. Yamaguchi; Helena Friesen; John Koschwanez; Mojca Mattiazzi Ušaj; Maria Pechlaner; Mehmet Takar; Matej Ušaj; Benjamin Vander Sluis; Kerry Andrusiak; Pritpal Bansal; Anastasia Baryshnikova; Claire E. Boone; Jessica Cao; Atina Cote; Marinella Gebbia; Gene Horecka; Ira Horecka; Elena Kuzmin; Nicole Legro; Wendy Liang; Natascha Van Lieshout; Margaret McNee; Bryan Joseph San Luis; Fatemeh Shaeri; Ermira Shuteriqi; Song Sun; Lu Yang; Ji Young Youn; Michael Yuen; Michael Costanzo; Anne Claude Gingras; Patrick Aloy; Chris Oostenbrink; Andrew Murray; Todd R. Graham; Chad L. Myers; Brenda J. Andrews; Frederick P. Roth; Charles Boone

doi:10.1126/science.aag0839

Exploring genetic suppression interactions on a global scale

Jolanda Van Leeuwen, Carles Pons, Joseph C. Mellor, Takafumi N. Yamaguchi, Helena Friesen, John Koschwanez, Mojca Mattiazzi Ušaj, Maria Pechlaner, Mehmet Takar, Matej Ušaj, Benjamin Vander Sluis, Kerry Andrusiak, Pritpal Bansal, Anastasia Baryshnikova, Claire E. Boone, Jessica Cao, Atina Cote, Marinella Gebbia, Gene Horecka, Ira HoreckaElena Kuzmin, Nicole Legro, Wendy Liang, Natascha Van Lieshout, Margaret McNee, Bryan Joseph San Luis, Fatemeh Shaeri, Ermira Shuteriqi, Song Sun, Lu Yang, Ji Young Youn, Michael Yuen, Michael Costanzo, Anne Claude Gingras, Patrick Aloy, Chris Oostenbrink, Andrew Murray, Todd R. Graham, Chad L. Myers, Brenda J. Andrews, Frederick P. Roth, Charles Boone

Computer Science and Engineering

Research output: Contribution to journal › Article › peer-review

114 Scopus citations

Abstract

Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene.To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations, in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population.These findings allow us to formulate and quantify general mechanisms of genetic suppression.

Original language	English (US)
Article number	aag0839
Journal	Science
Volume	354
Issue number	6312
DOIs	https://doi.org/10.1126/science.aag0839
State	Published - Nov 4 2016

Bibliographical note

Funding Information:
We thank G. Fairn, C. Dunn, N. Pascoe, and E. Styles for reagents and technical assistance. This work was primarily supported by grants from the NIH (R01HG005853, R01HG005084, P50HG004233, and U01HG001715) (C.B., B.J.A., C.L.M., and F.P.R.); the Canadian Institutes of Health Research (FDN-143264 and FDN-143265) (C.B. and B.J.A.); the Ontario Research Fund (Research Excellence Grant) (F.P.R.); the Canada Excellence Research Chairs Program (F.P.R.); and a postdoctoral fellowship from the Canadian Institutes of Health Research (J.v.L.). Additional support was provided by the Canadian Institutes of Health Research (FDN-143301) (A.-C.G.), the Vienna Science and Technology Fund (LS08-QM03) (C.O. and M.P.), and the NIH (R01GM107978) (T.R.G.). C.B., B.J.A., F.P.R., and C.L.M. are Senior Fellows in the Canadian Institute for Advanced Research Genetic Networks program. All whole-genome sequencing data are publicly available at NCBI's Sequencing Read Archive, under accession number SRP067030. All suppression interaction data are included in tables S1 and S2.

Publisher Copyright:
Copyright © 2016 by the American Association for the Advancement of Science.

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Van Leeuwen, J., Pons, C., Mellor, J. C., Yamaguchi, T. N., Friesen, H., Koschwanez, J., Ušaj, M. M., Pechlaner, M., Takar, M., Ušaj, M., Vander Sluis, B., Andrusiak, K., Bansal, P., Baryshnikova, A., Boone, C. E., Cao, J., Cote, A., Gebbia, M., Horecka, G., ... Boone, C. (2016). Exploring genetic suppression interactions on a global scale. Science, 354(6312), [aag0839]. https://doi.org/10.1126/science.aag0839

Van Leeuwen, J, Pons, C, Mellor, JC, Yamaguchi, TN, Friesen, H, Koschwanez, J, Ušaj, MM, Pechlaner, M, Takar, M, Ušaj, M, Vander Sluis, B, Andrusiak, K, Bansal, P, Baryshnikova, A, Boone, CE, Cao, J, Cote, A, Gebbia, M, Horecka, G, Horecka, I, Kuzmin, E, Legro, N, Liang, W, Van Lieshout, N, McNee, M, San Luis, BJ, Shaeri, F, Shuteriqi, E, Sun, S, Yang, L, Youn, JY, Yuen, M, Costanzo, M, Gingras, AC, Aloy, P, Oostenbrink, C, Murray, A, Graham, TR, Myers, CL, Andrews, BJ, Roth, FP & Boone, C 2016, 'Exploring genetic suppression interactions on a global scale', Science, vol. 354, no. 6312, aag0839. https://doi.org/10.1126/science.aag0839

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title = "Exploring genetic suppression interactions on a global scale",

abstract = "Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene.To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations, in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population.These findings allow us to formulate and quantify general mechanisms of genetic suppression.",

author = "{Van Leeuwen}, Jolanda and Carles Pons and Mellor, {Joseph C.} and Yamaguchi, {Takafumi N.} and Helena Friesen and John Koschwanez and U{\v s}aj, {Mojca Mattiazzi} and Maria Pechlaner and Mehmet Takar and Matej U{\v s}aj and {Vander Sluis}, Benjamin and Kerry Andrusiak and Pritpal Bansal and Anastasia Baryshnikova and Boone, {Claire E.} and Jessica Cao and Atina Cote and Marinella Gebbia and Gene Horecka and Ira Horecka and Elena Kuzmin and Nicole Legro and Wendy Liang and {Van Lieshout}, Natascha and Margaret McNee and {San Luis}, {Bryan Joseph} and Fatemeh Shaeri and Ermira Shuteriqi and Song Sun and Lu Yang and Youn, {Ji Young} and Michael Yuen and Michael Costanzo and Gingras, {Anne Claude} and Patrick Aloy and Chris Oostenbrink and Andrew Murray and Graham, {Todd R.} and Myers, {Chad L.} and Andrews, {Brenda J.} and Roth, {Frederick P.} and Charles Boone",

note = "Funding Information: We thank G. Fairn, C. Dunn, N. Pascoe, and E. Styles for reagents and technical assistance. This work was primarily supported by grants from the NIH (R01HG005853, R01HG005084, P50HG004233, and U01HG001715) (C.B., B.J.A., C.L.M., and F.P.R.); the Canadian Institutes of Health Research (FDN-143264 and FDN-143265) (C.B. and B.J.A.); the Ontario Research Fund (Research Excellence Grant) (F.P.R.); the Canada Excellence Research Chairs Program (F.P.R.); and a postdoctoral fellowship from the Canadian Institutes of Health Research (J.v.L.). Additional support was provided by the Canadian Institutes of Health Research (FDN-143301) (A.-C.G.), the Vienna Science and Technology Fund (LS08-QM03) (C.O. and M.P.), and the NIH (R01GM107978) (T.R.G.). C.B., B.J.A., F.P.R., and C.L.M. are Senior Fellows in the Canadian Institute for Advanced Research Genetic Networks program. All whole-genome sequencing data are publicly available at NCBI's Sequencing Read Archive, under accession number SRP067030. All suppression interaction data are included in tables S1 and S2. Publisher Copyright: Copyright {\textcopyright} 2016 by the American Association for the Advancement of Science.",

year = "2016",

month = nov,

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doi = "10.1126/science.aag0839",

language = "English (US)",

volume = "354",

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AU - Van Leeuwen, Jolanda

AU - Pons, Carles

AU - Mellor, Joseph C.

AU - Yamaguchi, Takafumi N.

AU - Friesen, Helena

AU - Koschwanez, John

AU - Ušaj, Mojca Mattiazzi

AU - Pechlaner, Maria

AU - Takar, Mehmet

AU - Ušaj, Matej

AU - Vander Sluis, Benjamin

AU - Andrusiak, Kerry

AU - Bansal, Pritpal

AU - Baryshnikova, Anastasia

AU - Boone, Claire E.

AU - Cao, Jessica

AU - Cote, Atina

AU - Gebbia, Marinella

AU - Horecka, Gene

AU - Horecka, Ira

AU - Kuzmin, Elena

AU - Legro, Nicole

AU - Liang, Wendy

AU - Van Lieshout, Natascha

AU - McNee, Margaret

AU - San Luis, Bryan Joseph

AU - Shaeri, Fatemeh

AU - Shuteriqi, Ermira

AU - Sun, Song

AU - Yang, Lu

AU - Youn, Ji Young

AU - Yuen, Michael

AU - Costanzo, Michael

AU - Gingras, Anne Claude

AU - Aloy, Patrick

AU - Oostenbrink, Chris

AU - Murray, Andrew

AU - Graham, Todd R.

AU - Myers, Chad L.

AU - Andrews, Brenda J.

AU - Roth, Frederick P.

AU - Boone, Charles

N1 - Funding Information: We thank G. Fairn, C. Dunn, N. Pascoe, and E. Styles for reagents and technical assistance. This work was primarily supported by grants from the NIH (R01HG005853, R01HG005084, P50HG004233, and U01HG001715) (C.B., B.J.A., C.L.M., and F.P.R.); the Canadian Institutes of Health Research (FDN-143264 and FDN-143265) (C.B. and B.J.A.); the Ontario Research Fund (Research Excellence Grant) (F.P.R.); the Canada Excellence Research Chairs Program (F.P.R.); and a postdoctoral fellowship from the Canadian Institutes of Health Research (J.v.L.). Additional support was provided by the Canadian Institutes of Health Research (FDN-143301) (A.-C.G.), the Vienna Science and Technology Fund (LS08-QM03) (C.O. and M.P.), and the NIH (R01GM107978) (T.R.G.). C.B., B.J.A., F.P.R., and C.L.M. are Senior Fellows in the Canadian Institute for Advanced Research Genetic Networks program. All whole-genome sequencing data are publicly available at NCBI's Sequencing Read Archive, under accession number SRP067030. All suppression interaction data are included in tables S1 and S2. Publisher Copyright: Copyright © 2016 by the American Association for the Advancement of Science.

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Exploring genetic suppression interactions on a global scale

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