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Toward ancient epigenomes – University of Copenhagen

9 December 2013

Toward ancient epigenomes

In 2010, the DNA molecules preserved in a 4,000 year-old tuft of hair found in Greenland’s permafrost delivered the first ancient human genome ever characterized. This work was conducted at the Centre for GeoGenetics and represented a milestone in studying evolutionary biology and human evolution, showing that the origins of ancient cultures and civilizations could be decoded from full genome sequence information. New methods in bioinformatics dig one level deeper using the same data – and reveal new secrets about the ancient Greenlander.

Now, three years later, the same sequence data enables an international team of researchers to reconstruct the first nucleosome and methylation map of an ancient genome. Rather than informing us about the history of the Palaeo-Eskimo Saqqaq culture as a whole, those maps help reveal which genes were expressed in the hairs of the ancient individual thereby giving scientists an opportunity to look into e.g. the effects of the environment on the the ancient Greenlander.

A protecting shield of nucleosomes

The results have been published online in Genome Research on the 3rd of December and add epigenomes to the list of cellular data with genomes and proteomes, that can be used to understand the nature of evolutionary changes.

The most striking feature of the study is that the nucleosome and methylation maps have been reconstructed directly from the DNA sequences. This was made possible because of the degradation process that affects DNA after death. For detecting where nucleosomes were positioned in the genome, the researchers have simply exploited the fact that nucleosomes offer a protection from degradation.

As a result, nucleosome-protected regions will be better preserved than nucleosome-free regions, and therefore more often sequenced. Similarly, a certain type of DNA degradation will preclude sequencing unless DNA was originally methylated. The method works as the nucleosome and methylation signals recovered could recapitulate expected patterns along the genomes.

Prospects for forensic investigations

Since nucleosomes and DNA methylation marks regulate the levels of gene expression within cells, the researchers could then exploit the reconstructed maps to infer the expression levels in the hair tissue of the Palaeo-Eskimo. This confirmed the expression of a range of known hair-specific markers, suggesting that the specificities of post-mortem DNA damage can be used for quantifying gene expression levels in ancient individuals and thereby gives direct access to functional information.

Apart from revealing that the Palaeo-Eskimo died at an age of around 40 – 50 years this study opens new avenues in evolutionary biology as it now becomes possible to use ancient DNA to monitor epigenetic and genetic changes through time and disentangle their respective role in the face of major past environmental changes. Moreover, the developed methods open an alternative window into studying modern epigenomics. Finally, they pave the way for a better profiling of criminal in forensic sciences, revealing the age of suspects as well as the type of biological tissue that left exploitable traces of DNA.

This work is the result of a collaboration co-led by researchers from the Centre for GeoGenetics (University of Copenhagen) and the Department of Clinical Medicine (Aarhus University). It also involved contributions from the United States, the United Kingdom, and Russia.

The article can be downloaded free of charge here.