The responses of species and populations to challenging environments are of immense interest in the face anthropogenic environmental threats, but are poorly understood. What genetic and genomic changes are associated with adaptive evolution? What is the role of phenotypic plasticity in determining adaptive outcomes? These questions are addressed here using the diverse and ecologically important fungi in the genus Tetracladium (Ascomycota). Overall, this study is designed to: identify variation associated with extreme environments; identify how populations persist in heavy metal polluted rivers; determine what separates the “winners” from the “losers” in adaptation to heavy metals. This research addresses key questions in evolutionary biology from SNPs to species, at a level of detail unrealistic to achieve in most eukaryotic organisms, and using natural populations of ecologically important non-model organisms.