Archaic Epigenomes

The ongoing research on the ancient DNA of hominin fossil is continuing to provide insight into the biology of our extinct ancestors. A study by Gokman et al. (2014) details the reconstruction of DNA methylation maps of both the Neanderthals and Denisovans, and provides insight into the epigenetic basis for phenotypic differences between present-day and archaic humans. However, just like nuclear aDNA, traditional methods designed to measure full methylomes are not applicable to archaic samples due to the postmortem degradation of the DNA. Despite this, Gokman and colleagues note that unmethylated cytosines decay to uracils, whereas those that are methylated decay to thymines. Cytosines that were methylated prior to death should exhibit a higher fraction of reads with thymine in comparision to unmethylated cytosines. Therefore, the ratio of C to T substitutions provides a robust proxy for methylation level in aDNA. Using this proxy, the study revealed around 1100 differentially methylated regions that were then assigned to a species. Among these differentially methylated regions was a HOXD cluster, a key regulator in limb development. In Neanderthals and Denisovans, HOXD9 and HOXD10 were hypermethylated, whereas they are hypomethylated in present-day humans. These differentially methylated regions imply regulation of HOXD9 and HOXD10 consistent with morphological differences between Neanderthals and modern humans.