Inferring Past Environments from Ancient Epigenomes

Abstract

Analyzing the conditions in which past individuals lived is key to understanding the environments and cultural transitions to which humans had to adapt. Here, we suggest a methodology to probe into past environments, using reconstructed premortem DNA methylation maps of ancient individuals. We review a large body of research showing that differential DNA methylation is associated with changes in various external and internal factors, and propose that loci whose DNA methylation level is environmentally responsive could serve as markers to infer about ancient daily life, diseases, nutrition, exposure to toxins, and more. We demonstrate this approach by showing that hunger-related DNA methylation changes are found in ancient hunter-gatherers. The strategy we present here opens a window to reconstruct previously inaccessible aspects of the lives of past individuals.

Keywords: DNA methylation; ancient DNA; ancient epigenetics; environmental epigenetics; environmental paleoepigenetics; paleoepigenetics.

Fig. 1.

Environmental paleoepigenetics builds on environmental epigenetics and paleoepigenetics. In environmental epigenetics, researchers study how extrinsic and intrinsic factors affect the epigenome (blue arrows). Paleoepigenetics harnesses degradation signals in ancient DNA to reconstruct premortem DNA methylation maps (green arrows). Environmental paleoepigenetics would use the reconstructed methylation maps of ancient individuals to infer on the unknown extrinsic and intrinsic factors that shaped them (orange arrows).

Fig. 2.

Methylation patterns in the Neanderthal and the Denisovan point to a low-calorie diet. Methylation maps are shown for a present-day human, a Neanderthal, and a Denisovan. Each lines represents a CpG position. Methylation levels are color-coded from green (unmethylated) to red (methylated). Present-day human maps are partial because the protocol used to produce the maps was reduced representation bisulfite sequencing (RRBS), which provides information for ∼10% of CpG positions. Reconstructed ancient methylation and DMRs were taken from (Gokhman etal. 2014). ERLs were taken from Dominguez-Salas etal. (2014). (a) Archaic humans are hypermethylated in the EXD3 gene compared with the present-day human. The DMR completely overlaps the ERL, where hypermethylation is associated with low-calorie diet. (b) The Neanderthal is hypermethylated in the RBM46 gene compared with the present-day human. The DMR partially overlaps with the ERL, where hypermethylation is associated with low-calorie diet. (c) The Denisovan is hypermethylated upstream of the ZNF678 gene compared with the present-day human. The DMR completely overlaps the ERL, where hypermethylation is associated with low-calorie diet. (d) Box plots of methylation levels of hunter-gatherers and sedentary individuals within the six hunger-related ERLs. In LOC654433, RBM46, and EXD3 hunter-gatherers are significantly hypermethylated compared with sedentary individuals, reflecting possible low caloric intake. Within BOLA3, however, hunter-gatherers are hypomethylated.