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Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan

Science  02 May 2014:
Vol. 344, Issue 6183, pp. 523-527
DOI: 10.1126/science.1250368

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Methylating the Family Tree

DNA sequences show a high level of similarities between humans and ancient hominids but the degree to which there are differences between methylated regions in their genomes that may explain phenotypic differences is unclear. Gokhman et al. (p. 523, published online 17 April) demonstrate that naturally degraded methylated cytosines in ancient DNA are converted to thymines and can be used to reconstruct ancient methylomes. The results suggest differences in methylation in bone tissues between modern humans and ancient hominids in a set of genes important for limb development.

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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