年龄和性别对人类和许多其他物种的胞嘧啶甲基化水平有深远的影响。在这里,我们分析了来自37种灵长类动物物种的2400个组织的DNA甲基化谱,其中包括11种单亲鱼(狒狒,Marmosets,Vervets,恒河猴,黑猩猩,大猩猩,猩猩,人类)和26种链霉菌属(亚目Lemuriformes和Lorisiformes)。从我们这里介绍的这些,泛灵长类动物表观遗传时钟对包括人类在内的所有灵长类动物都非常准确(年龄相关性R=0.98)。我们还对狒狒DNA甲基化谱进行了深入分析,并为狒狒(橄榄黄狒狒杂种)产生了5个表观遗传时钟,其中之一,泛组织表观遗传时钟,接受了七种组织类型的训练(胎儿大脑皮层,成人大脑皮层,小脑,脂肪,心,肝脏,和骨骼肌),年龄从胎儿晚期到22.8岁不等。利用灵长类动物的数据,我们描述了年龄和性别对高度保守区域中单个胞嘧啶的影响。我们在基因附近的常染色体上鉴定出11个与性别相关的CpG(POU3F2,CDYL,MYCL,FBXL4,ZC3H10,ZXDC,RRAS,FAM217A,RBM39、GRIA2、UHRF2)。在年龄和性别相关的CpG之间可以观察到低重叠。总的来说,这项研究促进了我们对灵长类动物保守的年龄和性别相关表观遗传变化的理解,并为所有灵长类动物提供衰老的生物标志物。
Age and sex have a profound effect on cytosine methylation levels in humans and many other species. Here we analyzed DNA methylation profiles of 2400 tissues derived from 37 primate species including 11 haplorhine species (baboons, marmosets, vervets, rhesus macaque, chimpanzees, gorillas, orangutan, humans) and 26 strepsirrhine species (suborders Lemuriformes and Lorisiformes). From these we present here, pan-primate epigenetic clocks which are highly accurate for all primates including humans (age correlation R = 0.98). We also carried out in-depth analysis of
baboon DNA methylation profiles and generated five epigenetic clocks for baboons (Olive-yellow
baboon hybrid), one of which, the pan-tissue epigenetic clock, was trained on seven tissue types (fetal cerebral cortex, adult cerebral cortex, cerebellum, adipose, heart, liver, and skeletal muscle) with ages ranging from late fetal life to 22.8 years of age. Using the primate data, we characterize the effect of age and sex on individual cytosines in highly conserved regions. We identify 11 sex-related CpGs on autosomes near genes (POU3F2, CDYL, MYCL, FBXL4, ZC3H10, ZXDC, RRAS, FAM217A, RBM39, GRIA2, UHRF2). Low overlap can be observed between age- and sex-related CpGs. Overall, this study advances our understanding of conserved age- and sex-related epigenetic changes in primates, and provides biomarkers of aging for all primates.