BACKGROUND:Evolutionary novelties,be they morphological or biochemical,fascinate both scientists and non-scientists alike.These types of adaptations can significantly impact the biodiversity of the organisms in which they occur.While much work has been invested in the evolution of novel morphological traits,substantially less is known about the evolution of biochemical adaptations.METHODS:In this review,we present the results of literature searches relating to one such biochemical adaptation:α-amanitin tolerance/resistance in the genus Drosophila.RESULTS:Amatoxins,including α-amanitin,are one of several toxin classes found in Amanita mushrooms.They act by binding to RNA polymerase Ⅱ and inhibiting RNA transcription.Although these toxins are lethal to most eukaryotic organisms,17 mushroom-feeding Drosophila species are tolerant of natural concentrations of amatoxins and can develop in toxic mushrooms.The use of toxic mushrooms allows these species to avoid infection by parasitic nematodes and lowers competition.Their amatoxin tolerance is not due to mutations that would inhibit α-amanitin from binding to RNA polymerase Ⅱ.Furthermore,the mushroom-feeding flies are able to detoxify the other toxin classes that occur in their mushroom hosts.In addition,resistance has evolved independently in several D.melanogaster strains.Only one of the strains exhibits resistance due to mutations in the target of the toxin.CONCLUSIONS:Given our current understanding of the evolutionary relationships among the mushroom-feeding flies,it appears that amatoxin tolerance evolved multiple times.Furthermore,independent lines of evidence suggest that multiple mechanisms confer α-amanitin tolerance/resistance in Drosophila.