Science2014-06-10 5:31 PM

科学家比较远古与现代人的甲基化图谱 Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan 

论文摘要 

对远古DNA进行测序已经帮助科学家们了解将现代人与他们已灭绝的最近亲族尼安德特人与丹尼索瓦人分开的遗传改变;如今,据一项新的报告,科学家们也已经更好地理解了表观遗传学是如何影响这些群组之间的差异的。

表观遗传学调控可改变基因的表达方式,但它并非通过改变基础的DNA序列,而是通过包括DNA甲基化等过程来影响基因的。科学家们不太知道表观遗传学调控是如何随着时间而变化的,但有可能它的演变凸显了在远古与现代人之间的特质差异。

现在,通过利用甲基化及非甲基化胞嘧啶(它是DNA中发现的4种主要碱基之一)的自然降解过程,David Gokhman及其同事重新构建了尼安德特人与丹尼索瓦人的全部的DNA甲基化图谱。

通过将这些图谱与现代人的甲基化图谱(另外还与现代人的骨样本)进行比较,该团队发现了大约2000个差异性甲基化区域,它们中包括了在发育上重要的HoxD基因簇,后者会影响身体结构及肢体定位。Gokhman及其同事观察到,HoxD基因簇在现代人中的甲基化较少。

他们还发现,在现代人中具有甲基化最大差异的区域与疾病相关基因有关系的可能性大约会增加两倍,它们中许多与精神科及神经科疾病有关联。Gokhman等人的工作可帮助解释在尼安德特人、丹尼索瓦人和现代人中形态学差异的基因基础。

Abstract 

Ancient DNA sequencing has recently provided high-coverage archaic human genomes. However, the evolution of epigenetic regulation along the human lineage remains largely unexplored. We reconstructed the full DNA methylation maps of the Neandertal and the Denisovan by harnessing the natural degradation processes of methylated and unmethylated cytosines. Comparing these ancient methylation maps to those of present-day humans, we identified ~2000 differentially methylated regions (DMRs). Particularly, we found substantial methylation changes in the HOXD cluster that may explain anatomical differences between archaic and present-day humans. Additionally, we found that DMRs are significantly more likely to be associated with diseases. This study provides insight into the epigenetic landscape of our closest evolutionary relatives and opens a window to explore the epigenomes of extinct species.

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