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Comparing Methylation Maps of Archaic and Modern Humans

Sequencing ancient DNA has helped scientists learn about the genetic changes that separate modern humans from their closest extinct relatives, Neandertals and Denisovans, and now, according to a new report, scientists better understand how epigenetics influenced differences among these groups, too. Epigenetic regulation changes how genes are expressed not by changing the underlying DNA sequence but by influencing genes through processes including DNA methylation. Scientists don't know much about how epigenetic regulation has changed over time, but it is likely that its evolution underscores differences in traits among archaic and modern-day people. Now, by taking advantage of the natural degradation processes of methylated and unmethylated cytosines (one of the four main bases found in DNA), David Gokhman and colleagues have reconstructed full DNA methylation maps of the Neandertal and the Denisovan. By comparing these maps with methylation maps of modern-day humans (and with modern-day bone samples, too), the team identified about 2,000 differentially methylated regions, among them the developmentally important HoxD gene cluster, which influences body structure and limb placement. The HoxD cluster is less methylated in modern humans, Gokhman and colleagues observed. They also found that the regions with the greatest differences in methylation in modern-day humans were about twice as likely to be associated with disease-related genes, many linked to psychiatric and neurological disorders. The work of Gokhman et al. helps explain the genetic basis of the morphological differences among Neandertals, Denisovans, and modern humans.

"Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan," by D. Gokhman; E. Lavi; E. Meshorer; L. Carmel at The Hebrew University of Jerusalem in Jerusalem, Israel; K. Prüfer; J. Kelso; S. Pääbo at Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany; M.F. Fraga at University of Oviedo in Oviedo, Spain; M.F. Fraga at CNB-CSIC in Madrid, Spain; J.A. Riancho at University of Cantabria in Santander, Spain.

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