Abstract: While sex-biased gene expression and its evolutionary dynamics across taxa have been extensively investigated, systematic separate characterization of the evolutionary patterns in transcriptome divergence between male and female lineages remains underexplored. Here, we analyze a comprehensive RNA-seq data set from the house mouse complex, spanning multiple organs across subspecies and species, to delineate the evolutionary trajectories of gene expression in males and females in intra- and inter-species contrasts. For both sexes, we find specific gene expression divergence patterns across the surveyed organs, with a particularly high divergence rate at early evolutionary stages of separation. Comparative analysis between sexes demonstrates male reproductive organs, particularly the testis, displaying accelerated evolutionary rates of expression divergence. Strikingly, testicular long non-coding RNA genes show the most pronounced acceleration, with differences emerging already after a few thousand years of population separation. In contrast, somatic organs and female reproductive auxiliary tissues show no major sex-specific evolutionary dynamics. Genes with sex-biased expression substantially contribute to differentially expressed genes across evolutionary transitions, though without predominant directional bias toward either sex. Notably, these differentially expressed genes display significant over-representation on autosomes. A general functional divergence process is found between male and female transcriptomes across organs mainly driven by sex-specific differentially expressed genes. Collectively, our findings establish a new evolutionary framework for sex-specific expression divergence and provide novel insights into the role of reproductive constraints in shaping transcriptome evolution in mammals.

Key words: house mouse complex, population transcriptomics, sex‐biased gene expression, sex‐specific gene expression evolution, transcriptome divergence