Evolutionary and biomedical implications of sex differences in the primate brain transcriptome

Cell Genom. 2024 Jul 10;4(7):100589. doi: 10.1016/j.xgen.2024.100589. Epub 2024 Jun 27.

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.

Keywords: animal model; autism; brain evolution; comparative neurobiology; rhesus macaque; sex-biased gene expression.

MeSH terms

  • Animals
  • Brain* / metabolism
  • Evolution, Molecular
  • Female
  • Humans
  • Macaca mulatta* / genetics
  • Male
  • Sex Characteristics*
  • Transcriptome*