Skip to main content

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) (KAR id:71591)

PDF Author's Accepted Manuscript
Language: English
Download this file
(PDF/2MB)
[thumbnail of Josse et al 2019 AAM.pdf]
Request a format suitable for use with assistive technology e.g. a screenreader
PDF (This version is the preprint deposited on bioRxiv prior to submission to the journal) Pre-print
Language: English


Download this file
(PDF/849kB)
[thumbnail of This version is the preprint deposited on bioRxiv prior to submission to the journal]
Preview
Request a format suitable for use with assistive technology e.g. a screenreader
Official URL:
https://doi.org/10.1002/yea.3373

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: Divisions > Division of Natural Sciences > Biosciences
Funders: Royal Society (https://ror.org/03wnrjx87)
Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982)
Depositing User: Lyne Josse
Date Deposited: 11 Jan 2019 09:55 UTC
Last Modified: 04 Mar 2024 18:23 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/71591 (The current URI for this page, for reference purposes)

University of Kent Author Information

Jossé, Lyne.

Creator's ORCID:
CReDIT Contributor Roles:

von der Haar, Tobias.

Creator's ORCID: https://orcid.org/0000-0002-6031-9254
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.