title: Genomics of Compensatory Adaptation in Experimental Populations ofAspergillus nidulans.
abstract: Knowledge of the number and nature of genetic changes responsible for adaptation is essential for understanding and predicting evolutionary trajectories. Here, we study the genomic basis of compensatory adaptation to the fitness cost of fungicide resistance in experimentally evolved strains of the filamentous fungusAspergillus nidulansThe original selection experiment tracked the fitness recovery of lines founded by an ancestral strain that was resistant to fludioxonil, but paid a fitness cost in the absence of the fungicide. We obtained whole-genome sequence data for the ancestralA. nidulansstrain and eight experimentally evolved strains. We find that fludioxonil resistance in the ancestor was likely conferred by a mutation in histidine kinasenikA, part of the two-component signal transduction system of the high-osmolarity glycerol (HOG) stress response pathway. To compensate for the pleiotropic negative effects of the resistance mutation, the subsequent fitness gains observed in the evolved lines were likely caused by secondary modification of HOG pathway activity. Candidate genes for the compensatory fitness increases were significantly overrepresented by stress response functions, and some were specifically associated with the HOG pathway itself. Parallel evolution at the gene level was rare among evolved lines. There was a positive relationship between the predicted number of adaptive steps, estimated from fitness data, and the number of genomic mutations, determined by whole-genome sequencing. However, the number of genomic mutations was, on average, 8.45 times greater than the number of adaptive steps inferred from fitness data. This research expands our understanding of the genetic basis of adaptation in multicellular eukaryotes and lays out a framework for future work on the genomics of compensatory adaptation inA. nidulans.
authors.affiliation: Department of Biology, University of Ottawa, Ontario K1N 6N5, Canada jdettman@uottawa.ca.|Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Dettman
authors.affiliation: Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodrigue
authors.affiliation: Laboratory of Genetics, Wageningen University, NL-6708 PB, The Netherlands.
authors.forename: Sijmen E
authors.initials: SE
authors.lastname: Schoustra
authors.affiliation: Department of Biology, University of Ottawa, Ontario K1N 6N5, Canada.|Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Rees
authors.initials: R
authors.lastname: Kassen
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D001233:Aspergillus nidulans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D004149:Dioxoles / Q000494:pharmacology; D025141:Drug Resistance, Fungal; D019143:Evolution, Molecular; D056084:Genetic Fitness; D016681:Genome, Fungal; D023281:Genomics; D009997:Osmotic Pressure / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology
chemical_list: D004149:Dioxoles; D011758:Pyrroles; C108339:fludioxonil
keywords: adaptive walks; fludioxonil; fungicide resistance; trade-offs