Format

Send to

Choose Destination
Mol Cell. 2017 Jan 5;65(1):142-153. doi: 10.1016/j.molcel.2016.11.007. Epub 2016 Dec 15.

Gene Architectures that Minimize Cost of Gene Expression.

Author information

1
Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel.
2
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.
3
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
4
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.
5
Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel. Electronic address: pilpel@weizmann.ac.il.

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.

KEYWORDS:

expression cost; gene expression; genome evolution; optimal gene architecture; synthetic biology; synthetic library; systems biology; translation efficiency

Comment in

PMID:
27989436
PMCID:
PMC5506554
DOI:
10.1016/j.molcel.2016.11.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center