Haploidy, diploidy and evolution of antifungal drug resistance in Saccharomyces cerevisiae

Genetics
James B AndersonNicole Ricker

Abstract

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 population...Continue Reading

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Citations

Jun 15, 2005·Nature Reviews. Microbiology·James B Anderson
Jul 25, 2009·The Journal of Heredity·Aleeza C Gerstein, Sarah P Otto
Oct 12, 2012·Biology Letters·Aleeza C Gerstein
Mar 11, 2009·Antimicrobial Agents and Chemotherapy·James B AndersonShantelle Lafayette
Aug 10, 2006·Eukaryotic Cell·James B AndersonCaroline Sirjusingh
May 18, 2006·Annual Review of Microbiology·Xiaorong Lin, Joseph Heitman
Feb 28, 2009·PLoS Computational Biology·Kerry J Kim, Vilaiwan M Fernandes
Sep 28, 2006·PLoS Genetics·Aleeza C GersteinSarah P Otto
May 1, 2007·PLoS Genetics·Sijmen E SchoustraRolf F Hoekstra
Apr 5, 2013·PLoS Genetics·Enikö ZörgöJonas Warringer
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Sep 28, 2007·Molecular Microbiology·Sadri ZnaidiMartine Raymond
Aug 25, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Michael Knop
Jan 29, 2011·Molecular Microbiology·E AndaluzG Larriba
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Nov 6, 2007·Cell·Sarah P Otto
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Feb 19, 2014·FEMS Yeast Research·Lisa SolieriSilvio Bicciato
Nov 7, 2015·PLoS Genetics·Karin VoordeckersKevin J Verstrepen
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May 16, 2018·Proceedings of the National Academy of Sciences of the United States of America·Nathaniel P SharpSarah P Otto
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Jun 26, 2018·Frontiers in Cellular and Infection Microbiology·Thuyen TruongChaminda J Seneviratne

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