{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:13:57Z","timestamp":1784175237511,"version":"3.55.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["188666959"],"award-info":[{"award-number":["188666959"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["515890405"],"award-info":[{"award-number":["515890405"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In male heterogametic species, the difference in ploidy of the X chromosome between females (XX) and males (XY) has led to the evolution of sex chromosome-specific regulatory mechanisms. In Drosophila melanogaster, expression of the single X chromosome is upregulated in male somatic cells by the well-known process of dosage compensation. In contrast, expression of the X chromosome in the male germline is suppressed by an as yet unknown mechanism that has similarities to mammalian meiotic sex chromosome inactivation. To gain insight into this suppression, we carried out a forward mutagenesis screen for males exhibiting increased expression of a testis-specific, X-linked reporter gene. Two independent mutants were recovered that showed global upregulation of the X chromosome in the male germline and male-specific sterility. Expression of the gene-poor Y chromosome was also upregulated in the mutants. Despite the use of chemical mutagenesis to induce point mutations, both mutants were found to have large, reciprocal translocations between the X chromosome and chromosome arm 3R. Genes on the translocated regions of the X chromosome, encompassing approximately 20 Mb, showed uniform upregulation in testis, which is consistent with a regulatory interaction between the centromeric heterochromatin and the euchromatin. Our observations lend support to classical genetic studies that posited the functional significance of X chromosome suppression in the male germline and its link to male fertility.<\/jats:p>","DOI":"10.1093\/genetics\/iyag011","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:50:34Z","timestamp":1768481434000},"source":"Crossref","is-referenced-by-count":3,"title":["Disruption of meiotic sex chromosome inactivation by X-autosome translocations in\n                    <i>Drosophila melanogaster<\/i>"],"prefix":"10.1093","volume":"232","author":[{"given":"Zhihui","family":"Bao","sequence":"first","affiliation":[{"name":"Division of Evolutionary Biology, Faculty of Biology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen , Planegg-Martinsried 82152 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksei","family":"Belyi","sequence":"additional","affiliation":[{"name":"Division of Evolutionary Biology, Faculty of Biology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen , Planegg-Martinsried 82152 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza","family":"Argyridou","sequence":"additional","affiliation":[{"name":"Division of Evolutionary Biology, Faculty of Biology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen , Planegg-Martinsried 82152 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-5549","authenticated-orcid":false,"given":"John","family":"Parsch","sequence":"additional","affiliation":[{"name":"Division of Evolutionary Biology, Faculty of Biology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen , Planegg-Martinsried 82152 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"2026030400563669700_iyag011-B1","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3390\/genes9050242","article-title":"Regulation of the X chromosome in the germline and soma of Drosophila melanogaster Males","volume":"9","author":"Argyridou","year":"2018","journal-title":"Genes (Basel)"},{"key":"2026030400563669700_iyag011-B2","doi-asserted-by":"publisher","first-page":"e1011511","DOI":"10.1371\/journal.pgen.1011511","article-title":"Meiotic sex chromosome inactivation: conservation across the Drosophila genus","volume":"21","author":"Avelino","year":"2025","journal-title":"PLoS Genet"},{"key":"2026030400563669700_iyag011-B3","doi-asserted-by":"publisher","first-page":"13239","DOI":"10.1073\/pnas.230438397","article-title":"Y chromosomal fertility factors kl-2 and kl-3 of Drosophila melanogaster encode dynein heavy chain polypeptides","volume":"97","author":"Carvalho","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026030400563669700_iyag011-B4","doi-asserted-by":"publisher","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"2026030400563669700_iyag011-B5","doi-asserted-by":"publisher","first-page":"e1011615","DOI":"10.1371\/journal.pgen.1011615","article-title":"Dynamics of X chromosome hyper-expression and inactivation in male tissues during stick insect development","volume":"21","author":"Djordjevic","year":"2025","journal-title":"PLoS Genet"},{"key":"2026030400563669700_iyag011-B6","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.cels.2016.07.002","article-title":"Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments","volume":"3","author":"Durand","year":"2016","journal-title":"Cell Syst"},{"key":"2026030400563669700_iyag011-B7","doi-asserted-by":"publisher","first-page":"e1011376","DOI":"10.1371\/journal.pgen.1011376","article-title":"Single-nucleus atlas of the Artemia female reproductive system suggests germline repression of the Z chromosome","volume":"20","author":"Elkrewi","year":"2024","journal-title":"PLoS Genet"},{"key":"2026030400563669700_iyag011-B8","doi-asserted-by":"publisher","first-page":"11132","DOI":"10.1073\/pnas.90.23.11132","article-title":"A fertility region on the Y chromosome of Drosophila melanogaster encodes a dynein microtubule motor","volume":"90","author":"Gepner","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026030400563669700_iyag011-B9","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1093\/gbe\/evx154","article-title":"Evolution of sex chromosome dosage compensation in animals: a beautiful theory, undermined by facts and bedeviled by details","volume":"9","author":"Gu","year":"2017","journal-title":"Genome Biol Evol"},{"key":"2026030400563669700_iyag011-B10","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s42003-023-05717-x","article-title":"The Drosophila melanogaster Y-linked gene, WDY, is required for sperm to swim in the female reproductive tract","volume":"7","author":"Hafezi","year":"2024","journal-title":"Commun Biol"},{"key":"2026030400563669700_iyag011-B11","doi-asserted-by":"publisher","first-page":"e273","DOI":"10.1371\/journal.pbio.0050273","article-title":"X chromosome inactivation during Drosophila spermatogenesis","volume":"5","author":"Hense","year":"2007","journal-title":"PLoS Biol"},{"key":"2026030400563669700_iyag011-B12","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1101\/gr.185579.114","article-title":"The release 6 reference sequence of the Drosophila melanogaster genome","volume":"25","author":"Hoskins","year":"2015","journal-title":"Genome Res"},{"key":"2026030400563669700_iyag011-B13","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/hdy.2013.86","article-title":"Escaping\u2019 the X chromosome leads to increased gene expression in the male germline of Drosophila melanogaster","volume":"112","author":"Kemkemer","year":"2014","journal-title":"Heredity (Edinb)"},{"key":"2026030400563669700_iyag011-B14","doi-asserted-by":"publisher","first-page":"e1002499","DOI":"10.1371\/journal.pbio.1002499","article-title":"Sex chromosome-wide transcriptional suppression and compensatory cis-regulatory evolution mediate gene expression in the Drosophila male germline","volume":"14","author":"Landeen","year":"2016","journal-title":"PLoS Biol"},{"key":"2026030400563669700_iyag011-B15","doi-asserted-by":"publisher","first-page":"4572","DOI":"10.1093\/bioinformatics\/btab705","article-title":"New strategies to improve minimap2 alignment accuracy","volume":"37","author":"Li","year":"2021","journal-title":"Bioinformatics"},{"key":"2026030400563669700_iyag011-B16","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1073\/pnas.69.1.182","article-title":"The role of X-chromosome inactivation during spermatogenesis","volume":"69","author":"Lifschytz","year":"1972","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026030400563669700_iyag011-B17","first-page":"226","volume-title":"The genetics and biology of Drosophila vol. 2d","author":"Lindsley","year":"1980"},{"key":"2026030400563669700_iyag011-B18","first-page":"275","volume-title":"International symposium on genes and chromosomes structure and function","author":"Lindsley","year":"1965"},{"key":"2026030400563669700_iyag011-B19","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2026030400563669700_iyag011-B20","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1038\/s41467-021-20897-y","article-title":"Dynamic sex chromosome expression in Drosophila male germ cells","volume":"12","author":"Mahadevaraju","year":"2021","journal-title":"Nat Commun"},{"key":"2026030400563669700_iyag011-B21","doi-asserted-by":"publisher","first-page":"e1001126","DOI":"10.1371\/journal.pbio.1001126","article-title":"Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation","volume":"9","author":"Meiklejohn","year":"2011","journal-title":"PLoS Biol"},{"key":"2026030400563669700_iyag011-B22","doi-asserted-by":"publisher","first-page":"iyad211","DOI":"10.1093\/genetics\/iyad211","article-title":"FlyBase: updates to the Drosophila genes and genomes database","volume":"227","author":"\u00d6zt\u00fcrk-\u00c7olak","year":"2024","journal-title":"Genetics"},{"key":"2026030400563669700_iyag011-B23","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1093\/oxfordjournals.molbev.a003862","article-title":"Molecular evolution of the ocnus and janus genes in the Drosophila melanogaster species subgroup","volume":"18","author":"Parsch","year":"2001","journal-title":"Mol Biol Evol"},{"key":"2026030400563669700_iyag011-B24","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1126\/science.aac7504","article-title":"An essential cell cycle regulation gene causes hybrid inviability in Drosophila","volume":"350","author":"Phadnis","year":"2015","journal-title":"Science"},{"key":"2026030400563669700_iyag011-B25","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2023"},{"key":"2026030400563669700_iyag011-B26","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/s0925-4773(98)00009-4","article-title":"An analysis of maleless and histone H4 acetylation in Drosophila melanogaster spermatogenesis","volume":"71","author":"Rastelli","year":"1998","journal-title":"Mech Dev"},{"key":"2026030400563669700_iyag011-B27","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/ng1192-192","article-title":"X inactivation in mammalian testis is correlated with inactive X-specific transcription","volume":"2","author":"Richler","year":"1992","journal-title":"Nat Genet"},{"key":"2026030400563669700_iyag011-B28","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.cels.2018.01.001","article-title":"Juicebox.js provides a cloud-based visualization system for Hi-C data","volume":"6","author":"Robinson","year":"2018","journal-title":"Cell Syst"},{"key":"2026030400563669700_iyag011-B29","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.1093\/bioinformatics\/btt468","article-title":"NextGenMap: fast and accurate read mapping in highly polymorphic genomes","volume":"29","author":"Sedlazeck","year":"2013","journal-title":"Bioinformatics"},{"key":"2026030400563669700_iyag011-B30","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/0165-1110(84)90007-1","article-title":"A review of the genetic effects of ethyl methanesulfonate","volume":"134","author":"Sega","year":"1984","journal-title":"Mutat Res"},{"key":"2026030400563669700_iyag011-B31","doi-asserted-by":"publisher","first-page":"101411","DOI":"10.1016\/j.cois.2025.101411","article-title":"Insect sex chromosome evolution: conservation, turnover, and mechanisms of dosage compensation","volume":"72","author":"Toups","year":"2025","journal-title":"Curr Opin Insect Sci"},{"key":"2026030400563669700_iyag011-B32","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev-genet-112414-055145","article-title":"Meiotic silencing in mammals","volume":"49","author":"Turner","year":"2015","journal-title":"Annu Rev Genet"},{"key":"2026030400563669700_iyag011-B33","doi-asserted-by":"publisher","first-page":"e1000731","DOI":"10.1371\/journal.pgen.1000731","article-title":"Stage-specific expression profiling of Drosophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic relocation of testis-expressed genes","volume":"5","author":"Vibranovski","year":"2009","journal-title":"PLoS Genet"},{"key":"2026030400563669700_iyag011-B34","doi-asserted-by":"publisher","first-page":"104","DOI":"10.7150\/jgen.8178","article-title":"Meiotic sex chromosome inactivation in Drosophila","volume":"2","author":"Vibranovski","year":"2014","journal-title":"J Genomics"},{"key":"2026030400563669700_iyag011-B35","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s10577-009-9053-y","article-title":"Progress and prospects toward our understanding of the evolution of dosage compensation","volume":"17","author":"Vicoso","year":"2009","journal-title":"Chromosome Res"},{"key":"2026030400563669700_iyag011-B36","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nature12235","article-title":"Reversal of an ancient sex chromosome to an autosome in Drosophila","volume":"499","author":"Vicoso","year":"2013","journal-title":"Nature"},{"key":"2026030400563669700_iyag011-B37","doi-asserted-by":"publisher","first-page":"e1002078","DOI":"10.1371\/journal.pbio.1002078","article-title":"Numerous transitions of sex chromosomes in Diptera","volume":"13","author":"Vicoso","year":"2015","journal-title":"PLoS Biol"},{"key":"2026030400563669700_iyag011-B38","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s12064-013-0178-3","article-title":"A model based criterion for gene expression calls using RNA-seq data","volume":"132","author":"Wagner","year":"2013","journal-title":"Theory Biosci"},{"key":"2026030400563669700_iyag011-B39","doi-asserted-by":"publisher","first-page":"e3002605","DOI":"10.1371\/journal.pbio.3002605","article-title":"Single-cell RNA-seq of Drosophila miranda testis reveals the evolution and trajectory of germline sex chromosome regulation","volume":"22","author":"Wei","year":"2024","journal-title":"PLoS Biol"},{"key":"2026030400563669700_iyag011-B40","doi-asserted-by":"publisher","first-page":"e1009728","DOI":"10.1371\/journal.pgen.1009728","article-title":"Single-cell RNA-sequencing reveals pre-meiotic X-chromosome dosage compensation in Drosophila testis","volume":"17","author":"Witt","year":"2021","journal-title":"PLoS Genet"},{"key":"2026030400563669700_iyag011-B41","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1534\/genetics.120.303324","article-title":"The role of Y chromosome genes in male fertility in Drosophila melanogaster","volume":"215","author":"Zhang","year":"2020","journal-title":"Genetics"},{"key":"2026030400563669700_iyag011-B42","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41576-024-00757-3","article-title":"Evolution and regulation of animal sex chromosomes","volume":"26","author":"Zhu","year":"2025","journal-title":"Nat Rev Genet"}],"container-title":["GENETICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/genetics\/advance-article-pdf\/doi\/10.1093\/genetics\/iyag011\/66464004\/iyag011.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/genetics\/article-pdf\/232\/3\/iyag011\/66464004\/iyag011.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/genetics\/article-pdf\/232\/3\/iyag011\/66464004\/iyag011.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:56:55Z","timestamp":1772603815000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/genetics\/article\/doi\/10.1093\/genetics\/iyag011\/8430206"}},"subtitle":[],"editor":[{"given":"M","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,19]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,1,19]]},"published-print":{"date-parts":[[2026,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/genetics\/iyag011","relation":{},"ISSN":["1943-2631"],"issn-type":[{"value":"1943-2631","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,1,19]]},"article-number":"iyag011"}}