Systematic analysis of bypass suppression of essential genes.

Autor: van Leeuwen J; Center for Integrative Genomics, Bâtiment Génopode, University of Lausanne, Lausanne, Switzerland.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Pons C; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology, Barcelona, Spain., Tan G; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Wang ZY; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Hou J; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Weile J; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada., Gebbia M; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada., Liang W; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Shuteriqi E; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Li Z; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Lopes M; Center for Integrative Genomics, Bâtiment Génopode, University of Lausanne, Lausanne, Switzerland., Ušaj M; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Dos Santos Lopes A; Center for Integrative Genomics, Bâtiment Génopode, University of Lausanne, Lausanne, Switzerland., van Lieshout N; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada., Myers CL; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA., Roth FP; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.; Department of Computer Science, University of Toronto, Toronto, ON, Canada., Aloy P; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology, Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., Andrews BJ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Boone C; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2020 Sep; Vol. 16 (9), pp. e9828.
DOI: 10.15252/msb.20209828
Abstrakt: 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.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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