- THIS ARTICLE
- Full Text
- Full Text (PDF)
-
All Versions of this Article:
genetics.104.033266v1
168/4/1915 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Email this article to a friend
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Anderson, J. B.
- Articles by Ricker, N.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Anderson, J. B.
- Articles by Ricker, N.
Originally published as Genetics Published Articles Ahead of Print on September 15, 2004.
Genetics, Vol. 168, 1915-1923, December 2004, Copyright © 2004
doi:10.1534/genetics.104.033266
Haploidy, Diploidy and Evolution of Antifungal Drug Resistance in Saccharomyces cerevisiae
James B. Anderson1, Caroline Sirjusingh and Nicole Ricker
Department of Botany, University of Toronto, Mississauga, Ontario L5L 1C6, Canada
1 Corresponding author: Department of Botany, University of Toronto, 3359 Mississauga Rd., North Mississauga, ON L5L 1C6, Canada.
E-mail: janderso{at}utm.utoronto.ca
We tested the hypothesis that the time course of the evolution of antifungal drug resistance depends on the ploidy of the fungus. The experiments were designed to measure the initial response to the selection imposed by the antifungal drug fluconazole up to and including the fixation of the first resistance mutation in populations of Saccharomyces cerevisiae. Under conditions of low drug concentration, mutations in the genes PDR1 and PDR3, which regulate the ABC transporters implicated in resistance to fluconazole, are favored. In this environment, diploid populations of defined size consistently became fixed for a resistance mutation sooner than haploid populations. Experiments manipulating population sizes showed that this advantage of diploids was due to increased mutation availability relative to that of haploids; in effect, diploids have twice the number of mutational targets as haploids and hence have a reduced waiting time for mutations to occur. Under conditions of high drug concentration, recessive mutations in ERG3, which result in resistance through altered sterol synthesis, are favored. In this environment, haploids consistently achieved resistance much sooner than diploids. When 29 haploid and 29 diploid populations were evolved for 100 generations in low drug concentration, the mutations fixed in diploid populations were all dominant, while the mutations fixed in haploid populations were either recessive (16 populations) or dominant (13 populations). Further, the spectrum of the 53 nonsynonymous mutations identified at the sequence level was different between haploids and diploids. These results fit existing theory on the relative abilities of haploids and diploids to adapt and suggest that the ploidy of the fungal pathogen has a strong impact on the evolution of fluconazole resistance.
This article has been cited by other articles:
 |
|
 |
|
  J. B. Anderson, C. Sirjusingh, N. Syed, and S. Lafayette Gene Expression and Evolution of Antifungal Drug Resistance Antimicrob. Agents Chemother., May 1, 2009; 53(5): 1931 - 1936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Anderson, N. Ricker, and C. Sirjusingh Antagonism between Two Mechanisms of Antifungal Drug Resistance. Eukaryot. Cell, August 1, 2006; 5(8): 1243 - 1251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Cowen and S. Lindquist Hsp90 Potentiates the Rapid Evolution of New Traits: Drug Resistance in Diverse Fungi Science, September 30, 2005; 309(5744): 2185 - 2189. [Abstract] [Full Text] [PDF]
|
|