{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:28:20Z","timestamp":1787239700941,"version":"build-2736575974"},"reference-count":121,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science and Engineering Research Council (NSERC) of Canada","award":["RGPIN-2020-05732"],"award-info":[{"award-number":["RGPIN-2020-05732"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Genetic variation underlies the capacity of populations to adapt, yet what drives how this variation is generated and maintained in natural populations remains poorly understood. Fundamental processes such as mutation, ploidy, and recombination are known to shape genetic variation and adaptive potential but are typically studied in isolation and under controlled laboratory conditions. How these processes act together under varying environmental conditions to structure genetic variation across complex natural populations remains unresolved. In yeasts, these processes are dependent on reproductive mode, ploidy shifts, and environmental stressors, which jointly shape genomic stability and adaptive potential. Here, we review our current knowledge on the roles of mutation, ploidy, and recombination in adaptation in the model yeasts Saccharomyces cerevisiae and the human pathogenic Cryptococcus. We highlight heterogeneity in mutation rates, recombination, and ploidy states across strains, environments, and populations, challenging the assumption that these parameters are uniform. We argue that fluctuating environments, increasingly driven by climate change, are likely to intensify interactions among these processes to impact evolution in ways that remain difficult to predict. Integrating population genomics with ecologically realistic frameworks will be essential for understanding natural evolutionary dynamics and anticipating fungal adaptation and disease emergence.<\/jats:p>","DOI":"10.3390\/genes17020204","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T09:41:02Z","timestamp":1770630062000},"page":"204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Roles of Mutation, Ploidy, and Recombination in Adaptive Evolution in Two Divergent Model Yeasts"],"prefix":"10.3390","volume":"17","author":[{"given":"Megan","family":"Hitchcock","sequence":"first","affiliation":[{"name":"Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2915-2780","authenticated-orcid":false,"given":"Jianping","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"ref_1","unstructured":"Darwin, C. (1859). The Origin of Species, Random House of Canada Limited."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1084\/jem.79.2.137","article-title":"Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III","volume":"79","author":"Avery","year":"1944","journal-title":"J. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1017\/S0016672300010284","article-title":"On the evolutionary adjustment of spontaneous mutation rates","volume":"9","author":"Kimura","year":"1967","journal-title":"Genet. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1126\/science.164.3881.788","article-title":"Non-Darwinian evolution","volume":"164","author":"King","year":"1969","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s12052-009-0128-1","article-title":"Understanding Natural Selection: Essential Concepts and Common Misconceptions","volume":"2","author":"Gregory","year":"2009","journal-title":"Evol. Educ. Outreach"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"fov067","DOI":"10.1093\/femsyr\/fov067","article-title":"Diversity and adaptive evolution of Saccharomyces wine yeast: A review","volume":"15","author":"Marsit","year":"2015","journal-title":"FEMS Yeast Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Giannakou, K., Cotterrell, M., and Delneri, D. (2020). Genomic Adaptation of Saccharomyces Species to Industrial Environments. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00916"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bai, F.-Y., Han, D.-Y., Duan, S.-F., and Wang, Q.-M. (2022). The Ecology and Evolution of the Baker\u2019s Yeast Saccharomyces cerevisiae. Genes, 13.","DOI":"10.3390\/genes13020230"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17593","DOI":"10.1073\/pnas.0407921102","article-title":"Fermented beverages of pre- and proto-historic China","volume":"101","author":"McGovern","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3934\/microbiol.2020001","article-title":"Saccharomyces cerevisiae and its industrial applications","volume":"6","author":"Parapouli","year":"2020","journal-title":"AIMS Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lahue, C., Madden, A., Dunn, R.R., and Smukowski Heil, C. (2020). History and Domestication of Saccharomyces cerevisiae in Bread Baking. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.584718"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/yea.3368","article-title":"Cheese yeasts","volume":"36","author":"Jakob","year":"2019","journal-title":"Yeast"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00029-17","DOI":"10.1128\/CMR.00029-17","article-title":"Candida auris: A Review of the Literature","volume":"31","author":"Taori","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_14","unstructured":"World Health Organization (2022). WHO Fungal Priority Pathogens List to Guide Research, Development and Public Health Action, World Health Organization. Available online: https:\/\/iris.who.int\/bitstream\/handle\/10665\/363682\/9789240060241eng.pdf?sequence=1."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1128\/CMR.8.4.462","article-title":"New and emerging yeast pathogens","volume":"8","author":"Hazen","year":"1995","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Torrado, R., and Querol, A. (2016). Opportunistic Strains of Saccharomyces cerevisiae: A Potential Risk Sold in Food Products. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.01522"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1093\/infdis\/169.4.859","article-title":"Comparative Pathogenesis of Clinical and Nonclinical Isolates of Saccharomyces cerevisiae","volume":"169","author":"Clemons","year":"1994","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e428","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global incidence and mortality of severe fungal disease","volume":"24","author":"Denning","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.fgb.2015.02.009","article-title":"Recognition of seven species in the Cryptococcus gattii\/Cryptococcus neoformans species complex","volume":"78","author":"Hagen","year":"2015","journal-title":"Fungal Genet. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"myae043","DOI":"10.1093\/mmy\/myae043","article-title":"Cryptococcosis\u2014A systematic review to inform the World Health Organization Fungal Priority Pathogens List","volume":"62","author":"Dao","year":"2024","journal-title":"Med. Mycol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.4014\/jmb.2404.04040","article-title":"Comprehensive Overview of Candida auris: An Emerging Multidrug-Resistant Fungal Pathogen","volume":"34","author":"Kim","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e594","DOI":"10.1016\/S2666-5247(24)00039-9","article-title":"Impact of climate change and natural disasters on fungal infections","volume":"5","author":"Seidel","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-micro-041522-102707","article-title":"From Petri Dishes to Patients to Populations: Scales and Evolutionary Mechanisms Driving Antibiotic Resistance","volume":"78","author":"Souque","year":"2024","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/mec.13474","article-title":"The population genetics of drug resistance evolution in natural populations of viral, bacterial and eukaryotic pathogens","volume":"25","author":"Wilson","year":"2016","journal-title":"Mol. Ecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev-micro-020518-120210","article-title":"Life Cycle of Cryptococcus neoforman","volume":"73","author":"Zhao","year":"2019","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1128\/mr.52.4.536-553.1988","article-title":"Life cycle of the budding yeast Saccharomyces cerevisiae","volume":"52","author":"Herskowitz","year":"1988","journal-title":"Microbiol. Rev."},{"key":"ref_27","first-page":"821","article-title":"Morphogenesis of Filobasidiella Neoformans, the Sexual State of Cryptococcus Neoformans","volume":"68","year":"1976","journal-title":"Mycologia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev-genet-110410-132536","article-title":"Sex in fungi","volume":"45","author":"Ni","year":"2011","journal-title":"Annu. Rev. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev-genet-120116-024755","article-title":"The Evolution of Sexual Reproduction and the Mating-Type Locus: Links to Pathogenesis of Cryptococcus Human Pathogenic Fungi","volume":"53","author":"Sun","year":"2019","journal-title":"Annu. Rev. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gray, J.C., and Goddard, M.R. (2012). Sex enhances adaptation by unlinking beneficial from detrimental mutations in experimental yeast populations. BMC Evol. Biol., 12.","DOI":"10.1186\/1471-2148-12-43"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1098\/rstb.2009.0317","article-title":"The population genetics of mutations: Good, bad and indifferent","volume":"365","author":"Loewe","year":"2010","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1093\/genetics\/148.4.1667","article-title":"Rates of spontaneous mutation","volume":"148","author":"Drake","year":"1998","journal-title":"Genetics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16895","DOI":"10.1074\/jbc.R400006200","article-title":"DNA Replication Fidelity","volume":"279","author":"Kunkel","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1146\/annurev.biochem.74.082803.133243","article-title":"DNA Mismatch Repair*","volume":"74","author":"Kunkel","year":"2005","journal-title":"Annu. Rev. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"gkv1136","DOI":"10.1093\/nar\/gkv1136","article-title":"The current state of eukaryotic DNA base damage and repair","volume":"43","author":"Bauer","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101953","DOI":"10.1016\/j.gde.2022.101953","article-title":"Recent insights into the evolution of mutation rates in yeast","volume":"76","author":"Melde","year":"2022","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Shor, E., Fox, C.A., and Broach, J.R. (2013). The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003680"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1007\/BF00284197","article-title":"Hydrogen peroxide induces G:C to TA and G:C to C:G transversions in the supF gene of Escherichia coli","volume":"243","author":"Akasaka","year":"1994","journal-title":"Molec. Gen. Genet."},{"key":"ref_39","unstructured":"Tervo, A.A. (2024). Average Mutation Rates of Saccharomyces cerevisiae in Industrially Relevant Stressful Environments. [Master\u2019s Thesis, Aalto University Findland]."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100209","DOI":"10.1016\/j.cellin.2024.100209","article-title":"Spontaneous and environment induced genomic alterations in yeast model","volume":"4","author":"Li","year":"2025","journal-title":"Cell Insight"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/em.22087","article-title":"Mechanisms of DNA damage, repair, and mutagenesis","volume":"58","author":"Chatterjee","year":"2017","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"75","DOI":"10.32607\/20758251-2016-8-2-75-78","article-title":"Heat Stress-Induced DNA Damage","volume":"8","author":"Kantidze","year":"2016","journal-title":"Acta Nat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nrg.2016.104","article-title":"Genetic drift, selection and the evolution of the mutation rate","volume":"17","author":"Lynch","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.tig.2010.05.003","article-title":"Evolution of the mutation rate","volume":"26","author":"Lynch","year":"2010","journal-title":"Trends Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0076-6879(05)09012-9","article-title":"Methods for determining spontaneous mutation rates","volume":"409","author":"Foster","year":"2006","journal-title":"Methods Enzymol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e68285","DOI":"10.7554\/eLife.68285","article-title":"A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae","volume":"10","author":"Jiang","year":"2021","journal-title":"eLife"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1534\/genetics.107.071506","article-title":"Estimating the Per-Base-Pair Mutation Rate in the Yeast Saccharomyces cerevisiae","volume":"178","author":"Lang","year":"2008","journal-title":"Genetics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/genetics\/28.6.491","article-title":"Mutations of Bacteria from Virus Sensitivity to Virus Resistance","volume":"28","author":"Luria","year":"1943","journal-title":"Genetics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"E2310","DOI":"10.1073\/pnas.1323011111","article-title":"Precise estimates of mutation rate and spectrum in yeast","volume":"111","author":"Zhu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.ecolsys.39.110707.173437","article-title":"Spontaneous Mutation Accumulation Studies in Evolutionary Genetics","volume":"40","author":"Halligan","year":"2009","journal-title":"Annu. Rev. Ecol. Evol. Syst."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1016\/j.cub.2019.03.054","article-title":"Yeast Spontaneous Mutation Rate and Spectrum Vary with Environment","volume":"29","author":"Liu","year":"2019","journal-title":"Curr. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1534\/genetics.118.301609","article-title":"The Genetic Basis of Mutation Rate Variation in Yeast","volume":"211","author":"Gou","year":"2019","journal-title":"Genetics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1128\/AAC.45.2.420-427.2001","article-title":"Dynamic and Heterogeneous Mutations to Fluconazole Resistance in Cryptococcus neoformans","volume":"45","author":"Xu","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"18488","DOI":"10.1073\/pnas.1216223109","article-title":"Drift-barrier hypothesis and mutation-rate evolution","volume":"109","author":"Sung","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1038\/s41467-021-24364-6","article-title":"The rate and molecular spectrum of mutation are selectively maintained in yeast","volume":"12","author":"Liu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/42696","article-title":"Role of mutator alleles in adaptive evolution","volume":"387","author":"Taddei","year":"1997","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00595-17","DOI":"10.1128\/mBio.00595-17","article-title":"Mismatch Repair of DNA Replication Errors Contributes to Microevolution in the Pathogenic Fungus Cryptococcus neoformans","volume":"8","author":"Boyce","year":"2017","journal-title":"mBio"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e28802","DOI":"10.7554\/eLife.28802","article-title":"Natural mismatch repair mutations mediate phenotypic diversity and drug resistance in Cryptococcus deuterogattii","volume":"6","author":"Billmyre","year":"2017","journal-title":"eLife"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1101\/gr.185538.114","article-title":"The 100-genomes strains, an S. cerevisiae resource that illuminates its natural phenotypic and genotypic variation and emergence as an opportunistic pathogen","volume":"25","author":"Strope","year":"2015","journal-title":"Genome Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1073\/pnas.0510998103","article-title":"Negative epistasis between natural variants of the Saccharomyces cerevisiae MLH1 and PMS1 genes results in a defect in mismatch repair","volume":"103","author":"Heck","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","first-page":"20162672","article-title":"Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains","volume":"284","author":"Skelly","year":"2017","journal-title":"Proc. Biol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1534\/genetics.118.301550","article-title":"Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Baker\u2019s Yeast","volume":"210","author":"Raghavan","year":"2018","journal-title":"Genetics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9272","DOI":"10.1073\/pnas.0803466105","article-title":"A genome-wide view of the spectrum of spontaneous mutations in yeast","volume":"105","author":"Lynch","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Nishant, K.T., Wei, W., Mancera, E., Argueso, J.L., Schlattl, A., Delhomme, N., Ma, X., Bustamante, C.D., Korbel, J.O., and Gu, Z. (2010). The Baker\u2019s Yeast Diploid Genome Is Remarkably Stable in Vegetative Growth and Meiosis. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001109"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"E5046","DOI":"10.1073\/pnas.1801040115","article-title":"The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast","volume":"115","author":"Sharp","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1534\/g3.117.1135","article-title":"Genome Dynamics of Hybrid Saccharomyces cerevisiae During Vegetative and Meiotic Divisions","volume":"7","author":"Dutta","year":"2017","journal-title":"G3 Genes|Genomes|Genet"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1534\/g3.120.401551","article-title":"Loss of Heterozygosity and Base Mutation Rates Vary Among Saccharomyces cerevisiae Hybrid Strains","volume":"10","author":"Pankajam","year":"2020","journal-title":"G3"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.bbrc.2004.10.120","article-title":"Spontaneous mutagenesis in haploid and diploid Saccharomyces cerevisiae","volume":"325","author":"Ohnishi","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rattray, A., Santoyo, G., Shafer, B., and Strathern, J.N. (2015). Elevated Mutation Rate during Meiosis in Saccharomyces cerevisiae. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1004910"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1093\/genetics\/162.3.1157","article-title":"Estimating the spontaneous mutation rate of loss of sex in the human pathogenic fungus Cryptococcus neoformans","volume":"162","author":"Xu","year":"2002","journal-title":"Genetics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1534\/genetics.104.030031","article-title":"Genotype-Environment Interactions of Spontaneous Mutations for Vegetative Fitness in the Human Pathogenic Fungus Cryptococcus neoformans","volume":"168","author":"Xu","year":"2004","journal-title":"Genetics"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Priest, S.J., Coelho, M.A., Mix\u00e3o, V., Clancey, S.A., Xu, Y., Sun, S., Gabald\u00f3n, T., and Heitman, J. (2021). Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1008871"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Roe, C.C., Bowers, J., Oltean, H., DeBess, E., Dufresne, P.J., McBurney, S., Overy DPWanke, B., Lysen, C., Chiller, T., and Meyer WThompson, G.R. (2018). Dating the Cryptococcus gattii Dispersal to the North American Pacific Northwest. mSphere, 3.","DOI":"10.1128\/mSphere.00499-17"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e92899","DOI":"10.7554\/eLife.92899","article-title":"Evolution of haploid and diploid populations reveals common, strong, and variable pleiotropic effects in non-home environments","volume":"12","author":"Chen","year":"2023","journal-title":"eLife"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1574-6968.2004.tb09481.x","article-title":"Experimental studies of ploidy evolution in yeast","volume":"233","author":"Zeyl","year":"2004","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_76","first-page":"7.5.1","article-title":"Analysis of Cellular DNA Content by Flow Cytometry","volume":"82","author":"Darzynkiewicz","year":"2017","journal-title":"Curr. Protoc. Cytom."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Chang, Y.C., Davis, M.J., and Kwon-Chung, K.J. (2024). Determination of Ploidy Levels and Nuclear DNA Content in Cryptococcus neoformans by Flow Cytometry: Drawbacks with Variability. J. Fungi, 10.","DOI":"10.3390\/jof10040296"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Wei\u00df, C.L., Pais, M., Cano, L.M., Kamoun, S., and Burbano, H.A. (2018). nQuire: A statistical framework for ploidy estimation using next generation sequencing. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2128-z"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Todd, R.T., Forche, A., and Selmecki, A. (2017). Ploidy Variation in Fungi: Polyploidy, Aneuploidy, and Genome Evolution. Microbiol. Spectr. 5, 5.","DOI":"10.1128\/microbiolspec.FUNK-0051-2016"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1534\/g3.116.029397","article-title":"Whole Genome Analysis of 132 Clinical Saccharomyces cerevisiae Strains Reveals Extensive Ploidy Variation","volume":"6","author":"Zhu","year":"2016","journal-title":"G3 Genes|Genomes|Genet"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1093\/bioinformatics\/btx204","article-title":"ploidyNGS: Visually exploring ploidy with Next Generation Sequencing data","volume":"33","author":"Goldman","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.24072\/pcjournal.178","article-title":"HMMploidy: Inference of ploidy levels from short-read sequencing data","volume":"2","author":"Soraggi","year":"2022","journal-title":"Peer Community J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Mourrain, L., and Boissonneault, G. (2021). DNA Repair in Haploid Context. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212418"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1534\/genetics.110.125450","article-title":"Ploidy dictates repair pathway choice under DNA replication stress","volume":"187","author":"Li","year":"2011","journal-title":"Genetics"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"R320","DOI":"10.1016\/j.cub.2018.02.026","article-title":"Evolution: Zeroing In on the Rate of Genome Doubling","volume":"28","author":"Sharp","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1073\/pnas.1012544108","article-title":"Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae","volume":"108","author":"Magwene","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Samarasinghe, H., You, M., Jenkinson, T.S., Xu, J., and James, T.Y. (2020). Hybridization Facilitates Adaptive Evolution in Two Major Fungal Pathogens. Genes., 11.","DOI":"10.3390\/genes11010101"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Sionov, E., Lee, H., Chang, Y.C., and Kwon-Chung, K.J. (2010). Cryptococcus neoformans Overcomes Stress of Azole Drugs by Formation of Disomy in Specific Multiple Chromosomes. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000848"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"You, M., and Xu, J. (2021). What Are the Best Parents for Hybrid Progeny? An Investigation into the Human Pathogenic Fungus Cryptococcus. JoF, 7.","DOI":"10.3390\/jof7040299"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Dong, K., You, M., and Xu, J. (2020). Genetic Changes in Experimental Populations of a Hybrid in the Cryptococcus neoformans Species Complex. Pathogens, 9.","DOI":"10.3390\/pathogens9010003"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nature03405","article-title":"Sex increases the efficacy of natural selection in experimental yeast populations","volume":"434","author":"Goddard","year":"2005","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1128\/MMBR.00005-10","article-title":"The Evolution of Sex: A Perspective from the Fungal Kingdom","volume":"74","author":"Lee","year":"2010","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e02099-17","DOI":"10.1128\/mBio.02099-17","article-title":"Effects of Temperature on the Meiotic Recombination Landscape of the Yeast Saccharomyces cerevisiae","volume":"8","author":"Zhang","year":"2017","journal-title":"mBio"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.meegid.2018.10.011","article-title":"Hybrids and hybridization in the Cryptococcus neoformans and Cryptococcus gattii species complexes","volume":"66","author":"Samarasinghe","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1534\/g3.111.001255","article-title":"Genetic Diversity and Genomic Plasticity of Cryptococcus neoformans AD Hybrid Strains","volume":"2","author":"Li","year":"2012","journal-title":"G3 Genes|Genomes|Genet"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"103861","DOI":"10.1016\/j.fgb.2023.103861","article-title":"Multi-locus sequence typing and phylogenetics of Cryptococcus neoformans AD hybrids","volume":"170","author":"Cogliati","year":"2024","journal-title":"Fungal Genet. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/j.1567-1364.2006.00081.x","article-title":"the European Confederation of Medical Mycology (ECMM) Cryptococcosis Working Group Molecular analysis of 311 Cryptococcus neoformans isolates from a 30-month ECMM survey of cryptococcosis in Europe","volume":"6","author":"Viviani","year":"2006","journal-title":"FEMS Yeast Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"20160455","DOI":"10.1098\/rstb.2016.0455","article-title":"Variation in recombination frequency and distribution across eukaryotes: Patterns and processes","volume":"372","author":"Stapley","year":"2017","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3852\/12-253","article-title":"Evolution of fungal sexual reproduction","volume":"105","author":"Heitman","year":"2013","journal-title":"Mycologia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/genetics\/111.1.147","article-title":"Statistical properties of the number of recombination events in the history of a sample of DNA sequences","volume":"111","author":"Hudson","year":"1985","journal-title":"Genetics"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1017\/S0016672399003870","article-title":"Recombination and the power of statistical tests of neutrality","volume":"74","author":"Wall","year":"1999","journal-title":"Genet. Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Hitchcock, M., and Xu, J. (2023). Global Analyses of Multi-Locus Sequence Typing Data Reveal Geographic Differentiation, Hybridization, and Recombination in the Cryptococcus gattii Species Complex. JoF, 9.","DOI":"10.3390\/jof9020276"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Hitchcock, M., and Xu, J. (2022). Analyses of the Global Multilocus Genotypes of the Human Pathogenic Yeast Cryptococcus neoformans Species Complex. Genes, 13.","DOI":"10.3390\/genes13112045"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/yea.3533","article-title":"The budding yeast life cycle: More complex than anticipated?","volume":"38","author":"Fischer","year":"2021","journal-title":"Yeast"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Hitchcock, M., Thorn, V., Samarasinghe, H., Sun, S., Heitman, J., and Xu, J. (2025). Genomic evidence for a-\u03b1 heterothallic and \u03b1-\u03b1 unisexual mating and recombination in an environmental Cryptococcus deneoformans population. PLoS Genet., 21.","DOI":"10.1101\/2025.08.20.671223"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1038\/nature04220","article-title":"Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak","volume":"437","author":"Fraser","year":"2005","journal-title":"Nature"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3201\/eid1301.060823","article-title":"Cryptococcus gattii Dispersal Mechanisms, British Columbia, Canada","volume":"13","author":"Kidd","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Engelthaler, D.M., Hicks, N.D., Gillece, J.D., Roe, C.C., Schupp, J.M., Driebe, E.M., Gilgado, F., Carriconde, F., Trilles, L., and Firacative, C. (2014). Cryptococcus gattii in North American Pacific Northwest: Whole-Population Genome Analysis Provides Insights into Species Evolution and Dispersal. mBio, 5.","DOI":"10.1128\/mBio.01464-14"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Billmyre, R.B., Croll, D., Li, W., Mieczkowski, P., Carter, D.A., Cuomo, C.A., Kronstad, J.W., and Heitman, J. (2014). Highly Recombinant VGII Cryptococcus gattii Population Develops Clonal Outbreak Clusters through both Sexual Macroevolution and Asexual Microevolution. mBio, 5.","DOI":"10.1128\/mBio.01494-14"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Byrnes, E.J., Li, W., Lewit, Y., Ma, H., Voelz, K., Ren, P., Carter, D.A., Chaturvedi, V., Bildfell, R.J., and May, R.C. (2010). Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000850"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"28191","DOI":"10.1073\/pnas.2018633117","article-title":"Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells","volume":"117","author":"Sui","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Vogan, A.A., Khankhet, J., and Xu, J. (2013). Evidence for mitotic recombination within the basidia of a hybrid cross of Cryptococcus neoformans. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062790"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e00129-11","DOI":"10.1128\/mBio.00129-11","article-title":"Stress alters rates and types of loss of heterozygosity in Candida albicans","volume":"2","author":"Forche","year":"2011","journal-title":"mBio"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1093\/nar\/gkz027","article-title":"Genome-wide analysis of genomic alterations induced by oxidative DNA damage in yeast","volume":"47","author":"Zhang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1574-6968.2011.02465.x","article-title":"Horizontal gene transfer in fungi","volume":"329","author":"Fitzpatrick","year":"2012","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the emerging threat of antifungal resistance to human health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e00061-10","DOI":"10.1128\/mBio.00061-10","article-title":"Global warming will bring new fungal diseases for mammals","volume":"1","author":"Casadevall","year":"2010","journal-title":"mBio"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e01397-19","DOI":"10.1128\/mBio.01397-19","article-title":"On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and Birds","volume":"10","author":"Casadevall","year":"2019","journal-title":"mBio"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Ma, X., Cui, J., Tao, Y., Liao, G., and Wang, L. (2026). Emergence of traits in human fungal pathogens. Trends Microbiol., in press.","DOI":"10.1016\/j.tim.2025.12.005"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/mlf2.12036","article-title":"Assessing Global Fungal Threats to Humans","volume":"1","author":"Xu","year":"2022","journal-title":"mLife"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1016\/j.csbj.2022.06.030","article-title":"Population genomic analyses reveal evidence for limited recombination in the superbug Candida auris in nature","volume":"20","author":"Wang","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/2\/204\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T09:52:37Z","timestamp":1770630757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/2\/204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,8]]},"references-count":121,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["genes17020204"],"URL":"https:\/\/doi.org\/10.3390\/genes17020204","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,8]]}}}