Genetics, Vol. 168, 1177-1188, November 2004, Copyright © 2004
doi:10.1534/genetics.104.030031

Genotype-Environment Interactions of Spontaneous Mutations for Vegetative Fitness in the Human Pathogenic Fungus Cryptococcus neoformans

Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada

1 Address for correspondence: Department of Biology, McMaster University, 1280 Main St. W., Hamilton, Ontario L8S 4K1, Canada.
E-mail: jpxu{at}mcmaster.ca

Spontaneous mutation is the ultimate source of all genetic variation. By interacting with environmental factors, genetic variation determines the phenotype and fitness of individuals in natural populations. However, except in a few model organisms, relatively little is known about the patterns of genotype-environment interactions of spontaneous mutations. Here I examine the rates of spontaneous mutation and the patterns of genotype-environment interaction of mutations affecting vegetative growth in the human fungal pathogen Cryptococcus neoformans. Eight mutation accumulation (MA) lines were established from a single clone on the nutrient-rich medium YEPD for each of two temperatures, 25° and 37°. Cells from generations 100, 200, 400, and 600 for each of the 16 MA lines were stored and assayed for vegetative growth rates under each of four conditions: (i) 25° on SD (a synthetic dextrose minimal medium); (ii) 25° on YEPD; (iii) 37° on SD; and (iv) 37° on YEPD. Both MA conditions and assay environments for vegetative growth showed significant influence on the estimates of genomic mutation rates, average effect per mutation, and mutational heritability. Significant genotype-environment interactions were detected among the newly accumulated spontaneous mutations. Overall, clones from MA lines maintained at 37° showed less decline in vegetative fitness than those maintained at 25°. The result suggests that a high-temperature environment might be very important for the maintenance of the ability to grow at a high temperature. Results from comparisons between clinical and environmental samples of C. neoformans were consistent with laboratory experimental population analyses. This study calls into question our long-standing view that warm-blooded mammals were only occasional and accidental hosts of this human fungal pathogen.




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