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

IF 11.1 Q1 CELL BIOLOGY Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-27 DOI:10.1016/j.xgen.2024.100589
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 V Ruiz-Lambides, Melween I Martínez, Susan C Antón, Christopher S Walker, Jérôme Sallet, Melissa A Wilson, Lauren J N Brent, Michael J Montague, Chet C Sherwood, Michael L Platt, James P Higham, Noah Snyder-Mackler
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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.

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灵长类动物大脑转录组性别差异对进化和生物医学的影响。
人类在许多神经发育障碍和神经退行性疾病的发病率方面存在性别差异。在这里,我们为猕猴生成了一个最大的多脑区批量转录数据集,并描述了性别差异基因表达模式,以研究该物种对性别差异神经疾病的可转化性。我们发现了与人类相似的模式,这些模式与包括自闭症在内的人类性别偏向性疾病的重叠调控机制、生物过程和相关基因有关。我们还发现,性别偏向基因在表达方面表现出更大的遗传变异和更多的组织特异性表达模式,这可能会促进性别偏向基因的快速进化。我们的研究结果为性别偏见疾病的生物学机制提供了见解,并支持将猕猴模型用于这些疾病的转化研究。
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