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Chromosome-level genome assemblies were generated for multiple species, covering virtually all known diversity within these genera. Although\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    and\n                    <jats:italic>Kwoniella<\/jats:italic>\n                    have comparable genome sizes (about 19.2 and 22.9 Mb) and similar gene content, hinting at preadaptive pathogenic potential, our analysis found evidence of gene gain (via horizontal gene transfer) and gene loss in pathogenic\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    species, which might represent evolutionary signatures of pathogenic development. Genome analysis also revealed a significant variation in chromosome number and structure between the 2 genera. By combining synteny analysis and experimental centromere validation, we found that most\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    species have 14 chromosomes, whereas most\n                    <jats:italic>Kwoniella<\/jats:italic>\n                    species have fewer (11, 8, 5, or even as few as 3). Reduced chromosome number in\n                    <jats:italic>Kwoniella<\/jats:italic>\n                    is associated with formation of giant chromosomes (up to 18 Mb) through repeated chromosome fusion events, each marked by a pericentric inversion and centromere loss. While similar chromosome inversion\u2013fusion patterns were observed in all\n                    <jats:italic>Kwoniella<\/jats:italic>\n                    species with fewer than 14 chromosomes, no such pattern was detected in\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    . Instead,\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    species with less than 14 chromosomes showed reductions primarily through rearrangements associated with the loss of repeat-rich centromeres. Additionally,\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    genomes exhibited frequent interchromosomal translocations, including intercentromeric recombination facilitated by transposons shared between centromeres. Overall, our findings advance our understanding of genetic changes possibly associated with pathogenicity in\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    and provide a foundation to elucidate mechanisms of centromere loss and chromosome fusion driving distinct karyotypes in closely related fungal species, including prominent global human pathogens.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3002682","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T14:00:00Z","timestamp":1717682400000},"page":"e3002682","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Comparative genomics of the closely related fungal genera Cryptococcus and Kwoniella reveals karyotype dynamics and suggests evolutionary mechanisms of pathogenesis"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5716-0561","authenticated-orcid":true,"given":"Marco A.","family":"Coelho","sequence":"first","affiliation":[]},{"given":"M\u00e1rcia","family":"David-Palma","sequence":"additional","affiliation":[]},{"given":"Terrance","family":"Shea","sequence":"additional","affiliation":[]},{"given":"Katharine","family":"Bowers","sequence":"additional","affiliation":[]},{"given":"Sage","family":"McGinley-Smith","sequence":"additional","affiliation":[]},{"given":"Arman W.","family":"Mohammad","sequence":"additional","affiliation":[]},{"given":"Andreas","family":"Gnirke","sequence":"additional","affiliation":[]},{"given":"Andrey M.","family":"Yurkov","sequence":"additional","affiliation":[]},{"given":"Minou","family":"Nowrousian","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2895-1153","authenticated-orcid":true,"given":"Sheng","family":"Sun","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5778-960X","authenticated-orcid":true,"given":"Christina A.","family":"Cuomo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6369-5995","authenticated-orcid":true,"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"issue":"1","key":"pbio.3002682.ref001","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofab593","article-title":"Prevalence and healthcare burden of fungal infections in the United States, 2018.","volume":"9","author":"E Rayens","year":"2022","journal-title":"Open Forum Infect Dis."},{"issue":"4","key":"pbio.3002682.ref002","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41579-023-00861-x","article-title":"The WHO fungal priority pathogens list as a game-changer","volume":"21","author":"MC Fisher","year":"2023","journal-title":"Nat Rev Microbiol"},{"issue":"7","key":"pbio.3002682.ref003","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.tim.2012.04.005","article-title":"Evolution of virulence in opportunistic pathogens: generalism, plasticity, and control","volume":"20","author":"SP Brown","year":"2012","journal-title":"Trends Microbiol"},{"issue":"12","key":"pbio.3002682.ref004","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1007\/s00018-015-1860-z","article-title":"Opportunistic yeast pathogens: reservoirs, virulence mechanisms, and therapeutic strategies","volume":"72","author":"EJ Polvi","year":"2015","journal-title":"Cell Mol Life Sci"},{"issue":"5","key":"pbio.3002682.ref005","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s11046-021-00577-7","volume":"186","author":"EC Francisco","year":"2021","journal-title":"Cryptococcosis and Cryptococcus. 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