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

By Xu, Jianping | Genetics, November 2004 | Go to article overview

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


Xu, Jianping, Genetics


ABSTRACT

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.

SPONTANEOUS mutations can occur during every cell division in all living organisms. These mutations are the ultimate source of genetic variation in natural populations. Therefore, understanding the effect of spontaneous mutations on individuals and populations of living organisms is of fundamental biological importance. It has been demonstrated that most spontaneous mutations with an effect on the phenotype are typically deleterious (Crow 1992). Many important biological phenomena are thought to be at least in part the outcomes of evolutionary responses to deleterious mutations. These phenomena include: (i) the evolution and maintenance of genetic recombination and sexual reproduction (e.g., CHARLESWORTH and BARTON 1996; KONDRASHOV 1997); (ii) the evolution of diploidy (KONDRASHOV and CROW 1991); (iii) the evolution and maintenance of mating systems in fungi, plants, and animals (CHARLESWORTH et al. 1990; ZEYL and BELL 1997; XU 2002); (iv) aging (PARTRIDGE and BARTON 1993); and (v) the viability of fragmented or captive populations (LANDE 1995). Except in a few model species such as Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Escherichia coli, Saccharomyces cerevisiae, mouse, and humans, very little is known about the patterns of spontaneous mutations in the vast majority of living organisms, including human pathogens (LYNCH and WALSH 1998). Even less is known about how environmental factors influence estimates of mutational parameters. The objective of this study was to investigate the patterns of spontaneous mutations and the genotype-environment interactions of these mutations in the human fungal pathogen Cryptococcus neoformans.

Genotype-environment interactions are widespread in natural populations. For example, studies in plants and animals have shown that the levels of inbreeding depression and heterosis were greater under harsher conditions than those in more benign environments (e.g., MITTON and GRANT 1984; DUDASH 1990). However, relatively little has been investigated on how spontaneous mutations interact with environmental factors. So far, most data have come from the model organism D. …

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