article published yes Carolina De Castro Barbosa Rodrigues Barata author 20565186-803f-11ed-ab7e-96a4ff7694ef0000-0003-1945-2245 Beatriz Vicoso author 49E1C5C6-F248-11E8-B48F-1D18A9856A870000-0002-4579-8306 BeVi department Does genetic drift set a limit on the adaptive evolution of sex-biased expression? project In many species, sex-biased expression is widespread and thought to contribute to sexual dimorphism. While bulk RNA-sequencing has been instrumental in identifying strongly sex-biased genes, it lacks resolution to assess variation across cell-types and tissue compartments. Using single-nucleus expression data from the Fly Cell Atlas, we investigate sex differences in adult Drosophila melanogaster. We find that differences in cell-type composition between the sexes are not a major source of sex-bias, as for the vast majority of genes, the degree of sex-bias is similar regardless of whether sex differences in cell-type composition are controlled for or not. Our analysis confirms a deficit of X-linked male-biased genes in the body’s somatic tissues that is widespread across cell-types. We also find the excess of X-linked female-biased genes to be associated with nervous system cells in the head but with epithelial cells in the body’s somatic tissues, showing that single-nucleus data crucially resolves sex-bias at the cell-type level. We investigate dosage compensation (DC) across 15 tissues and 17 cell-types. We observe that it varies throughout the body. Surprisingly, we observe a lack of DC in a cluster of main cells within the male accessory glands. This result highlights the importance of understanding context-dependent DC. https://research-explorer.ista.ac.at/download/21161/21226/2026_RoyalSocPubProceedingsB_Barata.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Royal Society of London2026 eng 1471-2954 4159277710.1098/rspb.2025.2471 2932063 de Castro Barbosa Rodrigues Barata, C., &#38; Vicoso, B. (2026). Single-nucleus resolution of sex-biased expression and dosage compensation in Drosophila melanogaster. <i>Proceedings of the Royal Society B Biological Sciences</i>. Royal Society of London. <a href="https://doi.org/10.1098/rspb.2025.2471">https://doi.org/10.1098/rspb.2025.2471</a> de Castro Barbosa Rodrigues Barata C, Vicoso B. Single-nucleus resolution of sex-biased expression and dosage compensation in Drosophila melanogaster. <i>Proceedings of the Royal Society B Biological Sciences</i>. 2026;293(2063). doi:<a href="https://doi.org/10.1098/rspb.2025.2471">10.1098/rspb.2025.2471</a> C. de Castro Barbosa Rodrigues Barata and B. Vicoso, “Single-nucleus resolution of sex-biased expression and dosage compensation in Drosophila melanogaster,” <i>Proceedings of the Royal Society B Biological Sciences</i>, vol. 293, no. 2063. Royal Society of London, 2026. Castro Barbosa Rodrigues Barata, Carolina de, and Beatriz Vicoso. “Single-Nucleus Resolution of Sex-Biased Expression and Dosage Compensation in Drosophila Melanogaster.” <i>Proceedings of the Royal Society B Biological Sciences</i>. Royal Society of London, 2026. <a href="https://doi.org/10.1098/rspb.2025.2471">https://doi.org/10.1098/rspb.2025.2471</a>. de Castro Barbosa Rodrigues Barata C, Vicoso B. 2026. Single-nucleus resolution of sex-biased expression and dosage compensation in Drosophila melanogaster. Proceedings of the Royal Society B Biological Sciences. 293(2063), 20252471. de Castro Barbosa Rodrigues Barata, Carolina, and Beatriz Vicoso. “Single-Nucleus Resolution of Sex-Biased Expression and Dosage Compensation in Drosophila Melanogaster.” <i>Proceedings of the Royal Society B Biological Sciences</i>, vol. 293, no. 2063, 20252471, Royal Society of London, 2026, doi:<a href="https://doi.org/10.1098/rspb.2025.2471">10.1098/rspb.2025.2471</a>. C. de Castro Barbosa Rodrigues Barata, B. Vicoso, Proceedings of the Royal Society B Biological Sciences 293 (2026). 211612026-02-08T23:02:49Z2026-07-08T09:17:41Z