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Such switches are key to the success of environmental pathogens, which encounter disparate conditions as they transition between the environment and host. We determine that the copy number of chromosome seven in the thermally dimorphic fungus\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    dramatically affects the rate of transition. Though\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    is haploid, a second copy of this chromosome is present in natural isolates of multiple\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    species and is gained and lost at a high rate. Cells carrying two copies of this chromosome exhibit aspects of the environmental transcriptome even under host-like conditions and have a competitive advantage in the transition to the environmental form. Conversely, these cells are considerably less virulent than euploid cells and have a competitive disadvantage in the mouse model of infection. Chromosome seven contains a previously unstudied transcription factor that, when expressed at higher copy number in euploid\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    , is sufficient to promote some of the key phenotypes of aneuploidy. We hypothesize that rapid gain and loss of this chromosome benefits\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    by increasing phenotypic variation, thus helping populations of cells survive abrupt transitions between environment and host.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003224","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T19:40:26Z","timestamp":1767642026000},"page":"e3003224","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rapid gain and loss of a chromosome drives key morphology and virulence phenotypes in the fungal pathogen Histoplasma"],"prefix":"10.1371","volume":"24","author":[{"given":"Sarah","family":"Heater","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Voorhies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa A.","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bevin C.","family":"English","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-7534","authenticated-orcid":true,"given":"Anita","family":"Sil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"issue":"11","key":"pbio.3003224.ref001","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2218163120","article-title":"Aneuploidy and gene dosage regulate filamentation and host colonization by Candida albicans","volume":"120","author":"P Kakade","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pbio.3003224.ref002","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1038\/s41564-024-01795-7","article-title":"Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans","volume":"9","author":"X Zhou","year":"2024","journal-title":"Nat Microbiol"},{"issue":"6","key":"pbio.3003224.ref003","article-title":"Environmental change drives accelerated adaptation through stimulated copy number variation","volume":"15","author":"RM Hull","year":"2017","journal-title":"PLoS Biol"},{"issue":"7384","key":"pbio.3003224.ref004","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nature10795","article-title":"Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy","volume":"482","author":"G Chen","year":"2012","journal-title":"Nature"},{"issue":"3","key":"pbio.3003224.ref005","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1128\/EC.00286-14","article-title":"A FACS-optimized screen identifies regulators of genome stability in Candida albicans","volume":"14","author":"R Loll-Krippleber","year":"2015","journal-title":"Eukaryot Cell"},{"key":"pbio.3003224.ref006","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1146\/annurev-micro-041320-112443","article-title":"The dynamic fungal genome: polyploidy, aneuploidy and copy number variation in response to stress","volume":"77","author":"P Vande Zande","year":"2023","journal-title":"Annu Rev Microbiol"},{"issue":"8","key":"pbio.3003224.ref007","doi-asserted-by":"crossref","DOI":"10.1093\/mmy\/myad080","article-title":"Infection of bats with Histoplasma species","volume":"61","author":"HC Gugnani","year":"2023","journal-title":"Med Mycol"},{"key":"pbio.3003224.ref008","doi-asserted-by":"crossref","DOI":"10.1093\/mmy\/myy039","article-title":"The endozoan, small-mammal reservoir hypothesis and the life cycle of Coccidioides species","volume":"57","author":"JW Taylor","year":"2019","journal-title":"Med Mycol"},{"key":"pbio.3003224.ref009","unstructured":"WHO fungal priority pathogens list to guide research, development and public health action. 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