Systematic analysis of bypass suppression of essential genes

Jolanda van Leeuwen; Carles Pons; Guihong Tan; Jason Zi Wang; Jing Hou; Jochen Weile; Marinella Gebbia; Wendy Liang; Ermira Shuteriqi; Zhijian Li; Maykel Lopes; Matej Ušaj; Andreia Dos Santos Lopes; Natascha van Lieshout; Chad L. Myers; Frederick P. Roth; Patrick Aloy; Brenda J. Andrews; Charles Boone

doi:10.15252/msb.20209828

Systematic analysis of bypass suppression of essential genes

Jolanda van Leeuwen, Carles Pons, Guihong Tan, Jason Zi Wang, Jing Hou, Jochen Weile, Marinella Gebbia, Wendy Liang, Ermira Shuteriqi, Zhijian Li, Maykel Lopes, Matej Ušaj, Andreia Dos Santos Lopes, Natascha van Lieshout, Chad L. Myers, Frederick P. Roth, Patrick Aloy, Brenda J. Andrews, Charles Boone

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Abstract

Essential genes tend to be highly conserved across eukaryotes, but, in some cases, their critical roles can be bypassed through genetic rewiring. From a systematic analysis of 728 different essential yeast genes, we discovered that 124 (17%) were dispensable essential genes. Through whole-genome sequencing and detailed genetic analysis, we investigated the genetic interactions and genome alterations underlying bypass suppression. Dispensable essential genes often had paralogs, were enriched for genes encoding membrane-associated proteins, and were depleted for members of protein complexes. Functionally related genes frequently drove the bypass suppression interactions. These gene properties were predictive of essential gene dispensability and of specific suppressors among hundreds of genes on aneuploid chromosomes. Our findings identify yeast's core essential gene set and reveal that the properties of dispensable essential genes are conserved from yeast to human cells, correlating with human genes that display cell line-specific essentiality in the Cancer Dependency Map (DepMap) project.

Original language	English (US)
Article number	e9828
Journal	Molecular Systems Biology
Volume	16
Issue number	9
DOIs	https://doi.org/10.15252/msb.20209828
State	Published - Sep 1 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Published under the terms of the CC BY 4.0 license

Keywords

compensatory evolution
gene essentiality
genetic interactions
genetic networks
genetic suppression

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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van Leeuwen, J., Pons, C., Tan, G., Wang, J. Z., Hou, J., Weile, J., Gebbia, M., Liang, W., Shuteriqi, E., Li, Z., Lopes, M., Ušaj, M., Dos Santos Lopes, A., van Lieshout, N., Myers, C. L., Roth, F. P., Aloy, P., Andrews, B. J., & Boone, C. (2020). Systematic analysis of bypass suppression of essential genes. Molecular Systems Biology, 16(9), Article e9828. https://doi.org/10.15252/msb.20209828

van Leeuwen, J, Pons, C, Tan, G, Wang, JZ, Hou, J, Weile, J, Gebbia, M, Liang, W, Shuteriqi, E, Li, Z, Lopes, M, Ušaj, M, Dos Santos Lopes, A, van Lieshout, N, Myers, CL, Roth, FP, Aloy, P, Andrews, BJ & Boone, C 2020, 'Systematic analysis of bypass suppression of essential genes', Molecular Systems Biology, vol. 16, no. 9, e9828. https://doi.org/10.15252/msb.20209828

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Systematic analysis of bypass suppression of essential genes

Abstract

Bibliographical note

Keywords

UN SDGs

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