title: Systematic Genetic Screens Reveal the Dynamic Global Functional Organization of the Bacterial Translation Machinery.
abstract: Bacterial protein synthesis is an essential, conserved, and environmentally responsive process. Yet, many of its components and dependencies remain unidentified. To address this gap, we used quantitative synthetic genetic arrays to map functional relationships among >48,000 gene pairs in Escherichia coli under four culture conditions differing in temperature and nutrient availability. The resulting data provide global functional insights into the roles and associations of genes, pathways, and processes important for efficient translation, growth, and environmental adaptation. We predict and independently verify the requirement of unannotated genes for normal translation, including a previously unappreciated role of YhbY in 30S biogenesis. Dynamic changes in the patterns of genetic dependencies across the four growth conditions and data projections onto other species reveal overarching functional and evolutionary pressures impacting the translation system and bacterial fitness, underscoring the utility of systematic screens for investigating protein synthesis, adaptation, and evolution.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors.forename: Alla
authors.initials: A
authors.lastname: Gagarinova
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Geordie
authors.initials: G
authors.lastname: Stewart
authors.affiliation: Department of Biology and the Ottawa Institute of Systems Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Agriculture and Agri-Food Canada, Ottawa Research and Development Centre, Ottawa, ON K1A 0C6, Canada.
authors.forename: Bahram
authors.initials: B
authors.lastname: Samanfar
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, SK S4S 0A2, Canada.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Phanse
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors.forename: Carl A
authors.initials: CA
authors.lastname: White
authors.affiliation: Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, SK S4S 0A2, Canada.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, SK S4S 0A2, Canada.
authors.forename: Viktor
authors.initials: V
authors.lastname: Deineko
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Beloglazova
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Yakunin
authors.affiliation: Department of Biology and the Ottawa Institute of Systems Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Golshani
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Brown
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Agriculture and Agri-Food Canada, Ottawa Research and Development Centre, Ottawa, ON K1A 0C6, Canada.
authors.forename: Mohan
authors.initials: M
authors.lastname: Babu
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada. Electronic address: andrew.emili@utoronto.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
mesh_terms: D002478:Cells, Cultured; D004777:Environment; D004843:Epistasis, Genetic; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D053263:Gene Regulatory Networks; D005820:Genetic Testing; D014176:Protein Biosynthesis
chemical_list: D029968:Escherichia coli Proteins
keywords: E. coli; conditional rewiring; double mutant; fitness; genetic interaction; growth; protein synthesis; ribosome biogenesis; synthetic genetic array; translational fidelity