The Promise of Paleo-Epigenetics

Thanks to new research in the field of ancient DNA, we are now a step closer to understanding how ancient environments and cultural practices may have affected the health of people living in past societies. This new research applies the field of epigenetics, the study of heritable chemical modifications to DNA in response to the environment, to ancient human populations. "Paleo-epigenetics" has the potential to give us fascinating new insights into the lives of our ancestors.

The development of a human is a complex process, depending on not just which alleles (forms of a gene) are present in their genome, but also when and where genes are expressed (when the information stored in DNA sequences is converted to the proteins that make up the human body). Different genes are expressed at varying stages of an organism's development and are expressed by diverse kinds of cells (for example, neurons express different genes than skin cells, even though they have the same DNA sequence). In addition, genes may vary in expression throughout an organism's lifetime, responding to changes in its environment.

This process is regulated in multiple ways at different stages of gene expression. The transcription stage (DNA-> mRNA) is one of the most important stages of regulation, and one of the ways it is regulated is by chemical modifications to DNA that either direct the cell to begin expression, or to silence the genetic information in that region. These chemical "tags" or "marks", such as the addition of methyl groups to the DNA base cytosine, don't change the DNA sequence itself, just whether or not it is expressed. For a really nice video explanation of epigenetics, check out this page .

Some types of epigenetic modifications are directly influenced by environmental factors. Thus, characterizing and understanding the "epigenome" can help us understand the ways in which factors like diet and other life experiences affect our physical bodies. This research is still very new but we are already finding out, for example, that nutrition, stress, and social rank can have significant phenotypic effects , and that these effects can even be passed on from parent to offspring across several generations.

What if we could study the epigenome in ancient human populations? We could potentially stand to learn a great deal about past societies and individual lives in the past, in ways that we can't get at by studying archaeology or genetics alone. My labmate Rick Smith has just published a new study showing that methylation can be measured in ancient human populations. Using this approach, it may be possible to learn about how past environments affected human health.

The very early research in paleo-epigenetics has been mainly proof-of-concept. Because methylated cytosines degrade differently than un-methylated cytosines after death, DNA damage patterns have been used to infer methylation in the ancient genomes of a 43,000 year old mammoth (Briggs et al. 2010), a 38,000 year old Neandertal (Gokhman et al. 2014), and the ancient Saqqaq individual from Greenland (Pendersen et al. 2014). But damage-based approaches are somewhat crude, and can only provide general estimates of methylation. The most precise method--an approach known as bisulfite sequencing, which captures all (undamaged) methylated cytosines--had only been successfully used once on a 26,000 year old bison (Llamas et al. 2012).

Moreover, while identifying patterns of cytosine methylation in individual cases is interesting, without comparative data these patterns don't really tell us much about the individual's life history or environment. To address these questions, the field of paleo-epigenetics needs to find a way to robustly apply bisulfite sequencing methods on a population-scale.

Smith et al. (2015) have just taken the first step towards doing this. They investigated whether bisulfite sequencing could be used to identify methylated cytosines in a collection of 30 individuals from 5 different ancient North American populations, ranging in age from 200 to more than 4500 years old. They looked at how factors such as time since death, depositional context, DNA concentration, and DNA degradation affected the success of detecting methylated cytosines. They were able to identify cytosine methylation patterns using this approach in 29 out of the 30 individuals (a success rate of 97%), opening the door to a much wider application of this approach in future research.

Here is a link to their open-access paper in PLOS so you can read the results for yourself , and here's a short write up of it from the University of Texas. I'm going to venture a prediction that this field will be expanding rapidly in the near future, and we're going to start getting a lot of new insights into how ancient people lived and were affected by their environments thanks to these developments.
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I'm excited about this area of research, which has a lot of promise for teaching us more about the relationship between our environment, culture, and our biology (as well as give us glimpses of such relationships in the past). But the fact that it's so exciting unfortunately draws pseudoscientific opportunists like flies to honey. Deepak Chopra is a good example. As with his constant use of the word "quantum," he takes advantage of the fact that few people really understand epigenetics to further his brand with sciencey-sounding nonsense . Contrast his approach with this paper by Smith et al. Researchers are doing the hard work of discovering exciting new truths, using the tools of science, and doing their best to verify the facts before publishing anything. People who claim that you can use epigenetics to bring about a "self-directed biological transformation," are trying to sell books. Be cautious, therefore, when evaluating claims about this field.