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Here, we describe the rapid acquisition of novel, high copy number CNVs during adaptation to azole antifungal drugs. Single-cell karyotype analysis indicates that these CNVs appear to arise via a dicentric chromosome intermediate and breakage-fusion-bridge cycles that are repaired using multiple distinct long inverted repeat sequences. Subsequent removal of the antifungal drug can lead to a dramatic loss of the CNV and reversion to the progenitor genotype and drug susceptibility phenotype. These findings support a novel mechanism for the rapid acquisition of antifungal drug resistance and provide genomic evidence for the heterogeneity frequently observed in clinical settings.<\/jats:p>","DOI":"10.7554\/elife.58349","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T08:00:54Z","timestamp":1595232054000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.58349","source":"Crossref","is-referenced-by-count":149,"title":["Expandable and reversible copy number amplification drives rapid adaptation to antifungal drugs"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4522-7124","authenticated-orcid":true,"given":"Robert T","family":"Todd","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, United 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