Coig Rene, Harrison Benjamin R, Johnson Richard S, MacCoss Michael J, Promislow Daniel E L
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, United States.
Department of Genome Sciences, University of Washington, Seattle, WA, United States.
bioRxiv. 2024 Sep 16:2024.09.11.612537. doi: 10.1101/2024.09.11.612537.
Sex has a major effect on the metabolome. However, we do not yet understand the degree to which these quantitative sex differences in metabolism are associated with anatomical dimorphism and modulated by sex-specific tissues. In the fruit fly, , knocking out the () gene gives rise to adults with intermediate sex characteristics. Here we sought to determine the degree to which this key node in sexual development leads to sex differences in the fly metabolome. We measured 91 metabolites across head, thorax and abdomen in , comparing the differences between distinctly sex-dimorphic flies with those of reduced sexual dimorphism: null flies. Notably, in the reduced dimorphism flies, we observed a sex difference in only 1 of 91 metabolites, kynurenate, whereas 51% of metabolites (46/91) were significantly different between wildtype XX and XY flies in at least one tissue, suggesting that plays a major role in sex differences in fly metabolism. Kynurenate was consistently higher in XX flies in both the presence and absence of functioning . We observed tissue-specific consequences of knocking out . Metabolites affected by sex were significantly enriched in branched chain amino acid metabolism and the mTOR pathway. This highlights the importance of considering variation in genes that cause anatomical sexual dimorphism when analyzing sex differences in metabolic profiles and interpreting their biological significance.
性别对代谢组有重大影响。然而，我们尚未了解这些代谢方面的定量性别差异与解剖学上的二态性相关的程度，以及它们如何受到性别特异性组织的调节。在果蝇中，敲除（）基因会产生具有中间性别特征的成虫。在这里，我们试图确定性发育中的这个关键节点在多大程度上导致果蝇代谢组中的性别差异。我们测量了果蝇头部、胸部和腹部的91种代谢物，比较了明显具有性别二态性的果蝇与性别二态性降低的果蝇（即基因敲除果蝇）之间的差异。值得注意的是，在性别二态性降低的果蝇中，我们在91种代谢物中仅观察到1种代谢物（犬尿酸）存在性别差异，而在至少一个组织中，野生型XX和XY果蝇之间有51%的代谢物（46/91）存在显著差异，这表明该基因在果蝇代谢的性别差异中起主要作用。无论是否存在功能正常的该基因，XX果蝇中的犬尿酸含量始终较高。我们观察到了敲除该基因的组织特异性后果。受性别影响的代谢物在支链氨基酸代谢和mTOR途径中显著富集。这突出了在分析代谢谱中的性别差异并解释其生物学意义时，考虑导致解剖学性别二态性的基因变异的重要性。
