Cell-Type Specific Variation in X-Chromosome Dosage Compensation in Drosophila

Male Drosophila melanogaster require dosage compensation to equalize X-linked gene expression with autosomal expression. Leveraging the single-nucleus Fly Cell Atlas (FCA) dataset, which includes 388,918 nuclei across diverse tissues, we investigated cell-type-specific patterns of X-chromosome dosage compensation. Our analysis identified a continuum of cell groups based on their X-to-autosome (X/A) expression ratios ranging from anti-compensated to effectively compensated and overcompensated. Anti-compensation was predominantly observed in male reproductive tissues, while overcompensation was prevalent in neural cells. The expression levels of the dosage compensation machinery's non-coding RNAs, RoX1 and RoX2 , correlated with compensation levels, but were insufficient to fully explain the observed patterns of compensation. These findings reveal the complexity of dosage compensation and suggest that its regulation by the RoX RNAs is nonlinear, implicating potential alternative mechanisms in certain cell types.