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Yet, their degree of involvement remains elusive partly because chromosomal sex (e.g. XX\/XY) and gonadal sex (ovaries or testes) are usually inextricably intertwined. They are, however, dissociated in the African pygmy mouse, Mus minutoides, in which a feminizing X (X*) has evolved, resulting in three female genotypes (XX, XX*, and X*Y) and one male genotype (XY). Furthermore, all sex chromosomes are fused to autosomes (neo-sex chromosomes: neo-X, neo-X* and neo-Y). Despite complete sex reversal, X*Y females show distinctive phenotypes with greater fertility, divergent maternal care strategies, and the masculinization of some traits (e.g. enhanced aggressiveness). By comparing the brain transcriptome of the four sexual genotypes, we show that differential gene expression is mainly linked to gonadal sex but also, and significantly, to chromosomal sex. Genes influenced by chromosomal sex are overrepresented on sex-linked genomic regions, and some are strong candidates to explain X*Y-specific behavioral and reproductive traits. Our results also suggest the preferential inactivation of the X* chromosome in XX* females, only in the brain, which could explain their trait similarities with XX females. Overall, we show that sex and neo-sex chromosomes have profoundly impacted the brain transcriptome in ways that reflect their new transmission modes, evolutionary trajectories, and resulting genomic conflicts.<\/jats:p>","DOI":"10.1093\/molbev\/msaf208","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T11:48:34Z","timestamp":1756381714000},"source":"Crossref","is-referenced-by-count":2,"title":["Influence of Gonadal and Chromosomal Sex on the Brain Transcriptome in a Mouse Species with Natural Sex Reversal"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3280-2289","authenticated-orcid":false,"given":"Louise D","family":"Heitzmann","sequence":"first","affiliation":[{"name":"Institut des Sciences de l\u2019Evolution de Montpellier (ISEM), Universit\u00e9 de Montpellier, CNRS, IRD , Montpellier 34095 ,","place":["France"]},{"name":"Department of Evolution, Ecology and Organismal Biology, University of California Riverside , Riverside, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-0472","authenticated-orcid":false,"given":"Paul A","family":"Saunders","sequence":"additional","affiliation":[{"name":"Institut des Sciences de l\u2019Evolution de Montpellier (ISEM), Universit\u00e9 de Montpellier, CNRS, IRD , Montpellier 34095 ,","place":["France"]},{"name":"Discipline of Biological Sciences, University of Tasmania , Sandy Bay, Tasmania 7000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Perez","sequence":"additional","affiliation":[{"name":"Institut des Sciences de l\u2019Evolution de Montpellier (ISEM), Universit\u00e9 de Montpellier, CNRS, IRD , Montpellier 34095 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6366-2341","authenticated-orcid":false,"given":"Pierre","family":"Boursot","sequence":"additional","affiliation":[{"name":"Institut des Sciences de l\u2019Evolution de Montpellier (ISEM), Universit\u00e9 de Montpellier, CNRS, IRD , Montpellier 34095 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1706-9915","authenticated-orcid":false,"given":"Frederic","family":"Veyrunes","sequence":"additional","affiliation":[{"name":"Institut des Sciences de l\u2019Evolution de Montpellier (ISEM), Universit\u00e9 de Montpellier, CNRS, IRD , Montpellier 34095 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"issue":"5","key":"2025092506431818900_msaf208-B1","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.yhbeh.2009.03.011","article-title":"The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues","volume":"55","author":"Arnold","year":"2009","journal-title":"Horm Behav."},{"issue":"3","key":"2025092506431818900_msaf208-B2","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00412-019-00699-4","article-title":"Sex chromosome quadrivalents in oocytes of the African pygmy mouse Mus minutoides that harbors non-conventional sex chromosomes","volume":"128","author":"Baudat","year":"2019","journal-title":"Chromosoma"},{"issue":"1688","key":"2025092506431818900_msaf208-B3","doi-asserted-by":"publisher","first-page":"20150109","DOI":"10.1098\/rstb.2015.0109","article-title":"Genetic dissection of neural circuits underlying sexually dimorphic social behaviors","volume":"371","author":"Bayless","year":"2016","journal-title":"Philos. 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