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In contrast to a majority of species in the phylum Basidiomycota that have tetrapolar mating-type systems, the opportunistic human pathogen\n                      <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                      employs a bipolar mating-type system, with two mating types (\n                      <jats:bold>a<\/jats:bold>\n                      and \u03b1) determined by a single\n                      <jats:italic>MAT<\/jats:italic>\n                      locus that is unusually large (~120 kb) and contains more than 20 genes. While several\n                      <jats:italic>MAT<\/jats:italic>\n                      genes are associated with mating and sexual development, others control conserved cellular processes (e.g., cargo transport and protein synthesis), of which five (\n                      <jats:italic>MYO2<\/jats:italic>\n                      ,\n                      <jats:italic>PRT1<\/jats:italic>\n                      ,\n                      <jats:italic>RPL22<\/jats:italic>\n                      ,\n                      <jats:italic>RPL39<\/jats:italic>\n                      , and\n                      <jats:italic>RPO41<\/jats:italic>\n                      ) have been hypothesized to be essential. In this study, through genetic analysis involving sporulation of heterozygous diploid deletion mutants, as well as in some cases construction and analyses of conditional expression alleles of these genes, we confirmed that with the exception of\n                      <jats:italic>MYO2<\/jats:italic>\n                      , both alleles of the other four\n                      <jats:italic>MAT<\/jats:italic>\n                      genes are indeed essential for cell viability. We further showed that while\n                      <jats:italic>MYO2<\/jats:italic>\n                      is not essential, its function is critical for infectious spore production, faithful cytokinesis, adaptation for growth at high temperature, and pathogenicity\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Our results demonstrate the presence of essential genes in the\n                      <jats:italic>MAT<\/jats:italic>\n                      locus that are divergent between cells of opposite mating types. We discuss possible mechanisms to maintain functional alleles of these essential genes in a rapidly evolving genomic region in the context of fungal sexual reproduction and mating-type evolution.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Sexual reproduction is essential for long-term evolutionary success. Fungal cell-type identity is governed by the\n                        <jats:italic>MAT<\/jats:italic>\n                        locus, which is typically rapidly evolving and highly divergent between different mating types. In this study, we show that the\n                        <jats:bold>a<\/jats:bold>\n                        and \u03b1 alleles of four genes encoded in the\n                        <jats:italic>MAT<\/jats:italic>\n                        locus of the opportunistic human fungal pathogen\n                        <jats:italic>C. neoformans<\/jats:italic>\n                        are essential. We demonstrate that a fifth gene,\n                        <jats:italic>MYO2<\/jats:italic>\n                        , which had been predicted to be essential, is in fact dispensable for cell viability. However, a functional\n                        <jats:italic>MYO2<\/jats:italic>\n                        allele is important for cytokinesis and fungal pathogenicity. Our study highlights the need for careful genetic analyses in determining essential genes, which is complementary to high-throughput approaches. Additionally, the presence of essential genes in the\n                        <jats:italic>MAT<\/jats:italic>\n                        locus of\n                        <jats:italic>C. neoformans<\/jats:italic>\n                        provides insights into the function, maintenance, and evolution of these fast-evolving genomic regions.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00223-25","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T09:14:18Z","timestamp":1740474858000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Essential genes encoded by the mating-type locus of the human fungal pathogen\n                    <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4320-8296","authenticated-orcid":false,"given":"Zhuyun","family":"Bian","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushka","family":"Peer","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center","place":["Durham, 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