title: Gene Architectures that Minimize Cost of Gene Expression.
abstract: Gene expression burdens cells by consuming resources and energy. While numerous studies have investigated regulation of expression level, little is known about gene design elements that govern expression costs. Here, we ask how cells minimize production costs while maintaining a given protein expression level and whether there are gene architectures that optimize this process. We measured fitness of ∼14,000 E. coli strains, each expressing a reporter gene with a unique 5' architecture. By comparing cost-effective and ineffective architectures, we found that cost per protein molecule could be minimized by lowering transcription levels, regulating translation speeds, and utilizing amino acids that are cheap to synthesize and that are less hydrophobic. We then examined natural E. coli genes and found that highly expressed genes have evolved more forcefully to minimize costs associated with their expression. Our study thus elucidates gene design elements that improve the economy of protein expression in natural and heterologous systems.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Frumkin
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Dvir
authors.initials: D
authors.lastname: Schirman
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Aviv
authors.initials: A
authors.lastname: Rotman
authors.affiliation: Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, USA; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Fangfei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Liron
authors.initials: L
authors.lastname: Zahavi
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Ernest
authors.initials: E
authors.lastname: Mordret
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Omer
authors.initials: O
authors.lastname: Asraf
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.affiliation: Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, USA; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Sasha F
authors.initials: SF
authors.lastname: Levy
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel. Electronic address: pilpel@weizmann.ac.il.
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Pilpel
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D004734:Energy Metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D056084:Genetic Fitness; D057927:Hydrophobic and Hydrophilic Interactions; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D000596:Amino Acids; D029968:Escherichia coli Proteins; D012333:RNA, Messenger
keywords: expression cost; gene expression; genome evolution; optimal gene architecture; synthetic biology; synthetic library; systems biology; translation efficiency