Evolutionary and biomedical implications of sex differences in the primate brain transcriptome.
DeCasien AR., Chiou KL., Testard C., Mercer A., Negrón-Del Valle JE., Bauman Surratt SE., González O., Stock MK., Ruiz-Lambides AV., Martínez MI., Cayo Biobank Research Unit None., Antón SC., Walker CS., Sallet J., Wilson MA., Brent LJN., Montague MJ., Sherwood CC., Platt ML., Higham JP., Snyder-Mackler N.
Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.