Sexual Dimorphism in Gene Expression: A Genome-Wide Study of Tissue and Chromosome Dependencies

Males and females possess nearly identical genomes, yet they exhibit significant differences in disease morbidity, prevalence, severity, therapeutic response, and mortality. To explore these differences, we conducted a comprehensive analysis of gene expression data across seven tissues from BXD recombinant inbred (RI) mouse strains. Our findings revealed substantial variations in the number and functional roles of genes across tissues, as well as between autosomal and sex chromosomes. Among sex-differential genes, those located on autosomal chromosomes primarily regulate metabolic pathways specific to their host organs. In contrast, genes on sex chromosomes are predominantly involved in regulating nuclear proteins essential for DNA replication and transcription during early development. Notably, the kidney exhibited the fewest sex-differential genes on sex chromosomes. Further analysis showed that sexually dimorphic genes on the X chromosome are associated with perception, while those on autosomal chromosomes are linked to metabolic processes. Importantly, these gene expression patterns are not reflected in similarities in protein structures but are instead grouped by functional roles.