ABSTRACT

Genomes of KhoeSan individuals of the Kalahari Desert provide the greatest understanding of single nucleotide diversity in the human genome. Compared with individuals in industrialized environments, the KhoeSan have a unique foraging and hunting lifestyle. Given these dramatic environmental differences, and the responsiveness of the methylome to environmental exposures of many types, we hypothesized that DNA methylation patterns would differ between KhoeSan and neighbouring agropastoral and/or industrial Bantu. We analysed Illumina HumanMethylation 450 k array data generated from blood samples from 38 KhoeSan and 42 Bantu, and 6 Europeans. After removing CpG positions associated with annotated and novel polymorphisms and controlling for white blood cell composition, sex, age and technical variation we identified 816 differentially methylated CpG loci, out of which 133 had an absolute beta-value difference of at least 0.05. Notably SLC39A4/ZIP4, which plays a role in zinc transport, was one of the most differentially methylated loci. Although the chronological ages of the KhoeSan are not formally recorded, we compared historically estimated ages to methylation-based calculations. This study demonstrates that the epigenetic profile of KhoeSan individuals reveals differences from other populations, and along with extensive genetic diversity, this community brings increased accessibility and understanding to the diversity of the human genome.

摘要

卡拉哈里沙漠的 KhoeSan 个体的基因组提供了对人类基因组中单核苷酸多样性的最大了解。与工业化环境中的个体相比，科桑人有着独特的觅食和狩猎生活方式。鉴于这些巨大的环境差异，以及甲基化组对多种环境暴露的反应性，我们假设 KhoeSan 与邻近的农牧和/或工业班图语之间的 DNA 甲基化模式会有所不同。我们分析了从 38 名 KhoeSan 和 42 名班图人以及 6 名欧洲人的血液样本中生成的 Illumina HumanMethylation 450 k 阵列数据。在去除与注释和新的多态性相关的 CpG 位置并控制白细胞组成、性别、年龄和技术差异我们确定了 816 个差异甲基化 CpG 基因座，其中 133 个具有至少 0.05 的绝对 β 值差异。尤其在锌转运中起作用的SLC39A4 / ZIP4是差异最大的甲基化基因座之一。虽然没有正式记录 KhoeSan 的实际年龄，但我们将历史估计的年龄与基于甲基化的计算进行了比较。这项研究表明，KhoeSan 个体的表观遗传特征揭示了与其他人群的差异，并且随着广泛的遗传多样性，该社区增加了对人类基因组多样性的可及性和理解。