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Sex differentiation is regulated by sex chromosomes, but their presence creates a dosage imbalance between males (XY) and females (XX). Dosage compensation (DC) can re-equilibrate the expression of sex chromosomal genes. However, because DC mechanisms have only been fully characterized in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved<jats:sup>1<\/jats:sup>. Here we report the discovery of a previously uncharacterized gene (<jats:italic>sex chromosome activation<\/jats:italic> (<jats:italic>SOA<\/jats:italic>)) as a master regulator of DC in the malaria\u00a0mosquito <jats:italic>Anopheles gambiae<\/jats:italic>. Sex-specific alternative splicing prevents functional SOA protein expression in females. The male isoform encodes a DNA-binding protein that binds the promoters of active X\u2009chromosomal genes. Expressing male SOA is sufficient to induce DC in female cells. Male mosquitoes lacking SOA or female mosquitoes ectopically expressing the male isoform exhibit X\u2009chromosome misregulation, which is compatible with viability but causes developmental delay. Thus, our molecular analyses of a DC master regulator in a non-model organism elucidates the evolutionary steps that lead to the establishment of a chromosome-specific fine-tuning mechanism.<\/jats:p>","DOI":"10.1038\/s41586-023-06641-0","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T16:02:40Z","timestamp":1695916960000},"page":"175-182","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The sex-specific factor SOA controls dosage compensation in Anopheles mosquitoes"],"prefix":"10.1038","volume":"623","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0231-3428","authenticated-orcid":false,"given":"Agata Izabela","family":"Kalita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4147-3747","authenticated-orcid":false,"given":"Eric","family":"Marois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0137-5379","authenticated-orcid":false,"given":"Magdalena","family":"Kozielska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3281-663X","authenticated-orcid":false,"given":"Franz J.","family":"Weissing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Jaouen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1237-2410","authenticated-orcid":false,"given":"Martin M.","family":"M\u00f6ckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7688-2394","authenticated-orcid":false,"given":"Frank","family":"R\u00fchle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7197-7279","authenticated-orcid":false,"given":"Falk","family":"Butter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1111-9459","authenticated-orcid":false,"given":"M. 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