Fitzpatrick, David A. and O'Brien, Jennifer and Moran, Ciara and Hasin, Naushaba and Kenny, Elaine and Cormican, Paul and Gates, Amy and Morris, Derek W. and Jones, Gary W. (2011) Assessment of Inactivating Stop Codon Mutations in Forty Saccharomyces cerevisiae Strains: Implications for [PSI+] Prion-Mediated Phenotypes. PLoS ONE, 6 (12). e28684. ISSN 1932-6203

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Abstract

The yeast prion [PSI+] has been implicated in the generation of novel phenotypes by a mechanism involving a reduction in translation fidelity causing readthrough of naturally occurring stop codons. Some [PSI+] associated phenotypes may also be generated due to readthrough of inactivating stop codon mutations (ISCMs). Using next generation sequencing we have sequenced the genomes of two Saccharomyces cerevisiae strains that are commonly used for the study of the yeast [PSI+] prion. We have identified approximately 26,000 and 6,500 single nucleotide polymorphisms (SNPs) in strains 74-D694 and G600 respectively, compared to reference strain S288C. In addition to SNPs that produce non-synonymous amino acid changes we have also identified a number of SNPs that cause potential ISCMs in these strains, one of which we show is associated with a [PSI+]-dependent stress resistance phenotype in strain G600. We identified twenty-two potential ISCMs in strain 74-D694, present in genes involved in a variety of cellular processes including nitrogen metabolism, signal transduction and oxidative stress response. The presence of ISCMs in a subset of these genes provides possible explanations for previously identified [PSI+]-associated phenotypes in this strain. A comparison of ISCMs in strains G600 and 74-D694 with S. cerevisiae strains sequenced as part of the Saccharomyces Genome Resequencing Project (SGRP) shows much variation in the generation of strain-specific ISCMs and suggests this process is possible under complex genetic control. Additionally we have identified a major difference in the abilities of strains G600 and 74-D694 to grow at elevated temperatures. However, this difference appears unrelated to novel SNPs identified in strain 74-D694 present in proteins involved in the heat shock response, but may be attributed to other SNP differences in genes previously identified as playing a role in high temperature growth.

Item Type:	Article
Additional Information:	© 2011 Fitzpatrick et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The original published article is available at Fitzpatrick DA, O'Brien J, Moran C, Hasin N, Kenny E, et al. (2011) Assessment of Inactivating Stop Codon Mutations in Forty Saccharomyces cerevisiae Strains: Implications for [PSI+] Prion- Mediated Phenotypes. PLoS ONE 6(12): e28684. doi:10.1371/journal.pone.0028684 . This work was supported by a Science Foundation Ireland (www.sfi.ie) Research Frontiers grant (08/BMT/1439) awarded to GWJ. DAF acknowledges support of the Irish Health Research Board (www.hrb.ie). CM was supported by an IRCSET (www.ircset.ie) postgraduate scholarship and NH is supported by a NUI Maynooth John and Pat Hume postgraduate scholarship. The Trinity Genome Sequencing Laboratory is supported by Science Foundation Ireland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords:	Inactivating; Stop Codons; Mutations; Saccharomyces cerevisiae Strains; [PSI+]; Prion-Mediated Phenotypes; yeast prion;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	3065
Depositing User:	David Fitzpatrick
Date Deposited:	01 Feb 2012 16:15
Journal or Publication Title:	PLoS ONE
Publisher:	Public Library of Science
Refereed:	Yes
Funders:	Science Foundation Ireland, John and Pat Hume postgraduate scholarship, Irish Health Research Board, IRCSET
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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