Evolutionary and biomedical implications of sex differences in the primate brain transcriptome
Alex R. DeCasien, Kenneth L. Chiou, Camille Testard, Arianne Mercer, Josué E. Negrón-Del Valle, Samuel E. Bauman Surratt, Olga González, Michala K. Stock, Angelina Ruíz-Lambides, Melween I. Martínez, Susan C. Antón, Christopher S. Walker, Jérôme Sallet, Melissa Wilson, Lauren J. N. Brent, Michael J. Montague, Chet C. Sherwood, Michael L. Platt, James P. Higham, Noah Snyder‐Mackler
Abstract
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.