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Summary: Copyright 2003 by the Genetics Society of America
Mode of Selection and Experimental Evolution of Antifungal Drug Resistance
in Saccharomyces cerevisiae
James B. Anderson,*,1
Caroline Sirjusingh,* Ainslie B. Parsons,
Charles Boone,
Claire Wickens,*
Leah E. Cowen* and Linda M. Kohn*
*Department of Botany, University of Toronto, Mississauga, Ontario L5L 1C6, Canada and
University of Toronto, Banting and Best
Department of Medical Research, Toronto, Ontario M5G 1L6, Canada
Manuscript received September 25, 2002
Accepted for publication January 7, 2003
ABSTRACT
We show that mode of selection, degree of dominance of mutations, and ploidy are determining factors
in the evolution of resistance to the antifungal drug fluconazole in yeast. In experiment 1, yeast populations
were subjected to a stepwise increase in fluconazole concentration over 400 generations. Under this
regimen, two mutations in the same two chromosomal regions rose to high frequency in parallel in three
replicate populations. These mutations were semidominant and additive in their effect on resistance. The
first of these mutations mapped to PDR1 and resulted in the overexpression of the ABC transporter genes
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