Giuliani Cristina, Sazzini Marco, Bacalini Maria Giulia, Pirazzini Chiara, Marasco Elena, Fontanesi Elisa, Franceschi Claudio, Luiselli Donata, Garagnani Paolo
Department of Biological Geological and Environmental Sciences, Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Italy
Department of Biological Geological and Environmental Sciences, Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Italy.
Genome Biol Evol. 2016 Sep 19;8(9):2760-73. doi: 10.1093/gbe/evw186.
Natural epigenetic diversity has been suggested as a key mechanism in microevolutionary processes due to its capability to create phenotypic variability within individuals and populations. It constitutes an important reservoir of variation potentially useful for rapid adaptation in response to environmental stimuli. The analysis of population epigenetic structure represents a possible tool to study human adaptation and to identify external factors that are able to naturally shape human DNA methylation variability. The aim of this study is to investigate the dynamics that create epigenetic diversity between and within different human groups. To this end, we first used publicly available epigenome-wide data to explore population-specific DNA methylation changes that occur at macro-geographic scales. Results from this analysis suggest that nutrients, UVA exposure and pathogens load might represent the main environmental factors able to shape DNA methylation profiles. Then, we evaluated DNA methylation of candidate genes (KRTCAP3, MAD1L1, and BRSK2), emerged from the previous analysis, in individuals belonging to different populations from Morocco, Nigeria, Philippines, China, and Italy, but living in the same Italian city. DNA methylation of the BRSK2 gene is significantly different between Moroccans and Nigerians (pairwise t-test: CpG 6 P-value = 5.210 (-) (3); CpG 9 P-value = 2.610 (-) (3); CpG 10 P-value = 3.110 (-) (3); CpG 11 P-value = 2.810 (-) (3)). Comprehensively, these results suggest that DNA methylation diversity is a source of variability in human groups at macro and microgeographical scales and that population demographic and adaptive histories, as well as the individual ancestry, actually influence DNA methylation profiles.
自然表观遗传多样性被认为是微进化过程中的关键机制，因为它能够在个体和群体中产生表型变异。它构成了一个重要的变异库，可能有助于快速适应环境刺激。对群体表观遗传结构的分析是研究人类适应性以及识别能够自然塑造人类DNA甲基化变异的外部因素的一种可能工具。本研究的目的是调查在不同人类群体之间以及群体内部产生表观遗传多样性的动态过程。为此，我们首先使用公开可用的全表观基因组数据，探索在宏观地理尺度上发生的群体特异性DNA甲基化变化。该分析结果表明，营养物质、紫外线暴露和病原体负荷可能是能够塑造DNA甲基化图谱的主要环境因素。然后，我们评估了先前分析中出现的候选基因（KRTCAP3、MAD1L1和BRSK2）在来自摩洛哥、尼日利亚、菲律宾、中国和意大利但生活在同一意大利城市的不同群体个体中的DNA甲基化情况。摩洛哥人和尼日利亚人之间BRSK2基因的DNA甲基化存在显著差异（成对t检验：CpG 6 P值 = 5.2×10⁻³；CpG 9 P值 = 2.6×10⁻³；CpG 10 P值 = 3.1×10⁻³；CpG 11 P值 = 2.8×10⁻³）。综合来看，这些结果表明DNA甲基化多样性是宏观和微观地理尺度上人类群体变异的一个来源，并且群体人口统计学和适应性历史以及个体祖先实际上会影响DNA甲基化图谱。
