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Experimental determination of codon usage?dependent selective pressure on high copy?number genes in Saccharomyces cerevisiae

Jossé, Lyne, Singh, Tarun, von der Haar, Tobias (2019) Experimental determination of codon usage?dependent selective pressure on high copy?number genes in Saccharomyces cerevisiae. Yeast, 36 . pp. 43-51. ISSN 0749-503X. (doi:10.1002/yea.3373)

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Abstract

One of the central hypotheses in the theory of codon usage evolution is that in highly expressed genes particular codon usage patterns arise because they facilitate efficient gene expression and are thus selected for in evolution. Here we use plasmid copy number assays and growth rate measurements to explore details of the relationship between codon usage, gene expression level, and selective pressure in Saccharomyces cerevisiae. We find that when high expression levels are required optimal codon usage is beneficial and provides a fitness advantage, consistent with evolutionary theory. However, when high expression levels are not required, optimal codon usage is surprisingly and strongly selected against. We show that this selection acts at the level of protein synthesis, and we exclude a number of molecular mechanisms as the source for this negative selective pressure including nutrient and ribosome limitations and proteotoxicity effects. These findings inform our understanding of the evolution of codon usage bias, as well as the design of recombinant protein expression systems.

Item Type: Article
DOI/Identification number: 10.1002/yea.3373
Uncontrolled keywords: codon usage, yeast, evolution, selective pressure, recombinant gene expression, plasmid copy number
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QR Microbiology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Tobias von der Haar
Date Deposited: 11 Jan 2019 09:55 UTC
Last Modified: 30 May 2019 08:43 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/71591 (The current URI for this page, for reference purposes)
von der Haar, Tobias: https://orcid.org/0000-0002-6031-9254
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