Weyrich Alexandra, Guerrero-Altamirano Tania P, Yasar Selma, Czirják Gábor Á, Wachter Bettina, Fickel Jörns
Department of Evolutionary Genetics, Leibniz Institute for Zoo and Wildlife Research, Alfred-Kowalke-Str. 17, 10315 Berlin, Germany.
Program in Genetics and Genomics, Duke University, Durham, NC 27708, USA.
Life (Basel). 2022 Jun 20;12(6):920. doi: 10.3390/life12060920.
Free-ranging cheetahs () are generally healthy, whereas cheetahs under human care, such as those in zoological gardens, suffer from ill-defined infectious and degenerative pathologies. These differences are only partially explained by husbandry management programs because both groups share low genetic diversity. However, mounting evidence suggests that physiological differences between populations in different environments can be tracked down to differences in epigenetic signatures. Here, we identified differentially methylated regions (DMRs) between free-ranging cheetahs and conspecifics in zoological gardens and prospect putative links to pathways relevant to immunity, energy balance and homeostasis. Comparing epigenomic DNA methylation profiles obtained from peripheral blood mononuclear cells (PBMCs) from eight free-ranging female cheetahs from Namibia and seven female cheetahs living in zoological gardens within Europe, we identified DMRs of which 22 were hypermethylated and 23 hypomethylated. Hypermethylated regions in cheetahs under human care were located in the promoter region of a gene involved in host-pathogen interactions () and in an intron of a transcription factor relevant for the development of pancreatic β-cells, liver, and kidney (). The most canonical mechanism of DNA methylation in promoter regions is assumed to repress gene transcription. Taken together, this could indicate that hypermethylation at the promoter region of is involved in the reduced immunity in cheetahs under human care. This approach can be generalized to characterize DNA methylation profiles in larger cheetah populations under human care with a more granular longitudinal data collection, which, in the future, could be used to monitor the early onset of pathologies, and ultimately translate into the development of biomarkers with prophylactic and/or therapeutic potential.
自由放养的猎豹通常很健康，而在人类照料下的猎豹，比如动物园里的猎豹，却患有一些病因不明的传染病和退行性疾病。这些差异只能部分地由饲养管理方案来解释，因为这两组猎豹的基因多样性都很低。然而，越来越多的证据表明，不同环境中猎豹种群之间的生理差异可以追溯到表观遗传特征的差异。在这里，我们鉴定了自由放养的猎豹和动物园里的同种猎豹之间的差异甲基化区域（DMRs），并探寻其与免疫、能量平衡和内稳态相关通路的潜在联系。通过比较从纳米比亚的八只自由放养的雌性猎豹和欧洲动物园里的七只雌性猎豹的外周血单核细胞（PBMCs）中获得的表观基因组DNA甲基化图谱，我们鉴定出了DMRs，其中22个是高甲基化的，23个是低甲基化的。在人类照料下的猎豹中，高甲基化区域位于一个参与宿主-病原体相互作用的基因的启动子区域，以及一个与胰腺β细胞、肝脏和肾脏发育相关的转录因子的内含子中。启动子区域DNA甲基化最典型的机制被认为是抑制基因转录。综上所述，这可能表明 基因启动子区域的高甲基化与人类照料下的猎豹免疫力下降有关。这种方法可以推广到以更细致的纵向数据收集来表征更多人类照料下的猎豹种群的DNA甲基化图谱，未来可用于监测疾病的早期发作，并最终转化为具有预防和/或治疗潜力的生物标志物的开发。
