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Epigenetics, a Revolution with a Long Onramp, Poised to Accelerate Design Thinking

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Some revolutions have long onramps. Modern epigenetics has been around for well over a decade, but its impact has yet to be fully explored. Which interpretation of biology -- evolution or intelligent design -- stands the best chance of advancing scientific understanding of genomics through epigenetics research?

Well, it is indeed a revolution; that's what senior reporter Heidi Ledford calls it in her Nature Outlook piece, "Epigenetics: the genome unwrapped." She ends with remarks by Tomasz Jurkowski, a biochemist and epigeneticist at the University of Stuttgart in Germany who is racing against other researchers to untangle DNA's secrets:

He takes the competition in stride -- it is the price of entry into the fast lane. Epigenetics is on the verge of a revolution, he says. "This is just the beginning," he says. With just a little more time, "It will develop into a completely new field." [Emphasis added.]

As with any field in such a revolutionary condition, the ultimate outcome is unpredictable. That's why Ledford's subtitle reads, "Epigeneticists are harnessing genome-editing technologies to tackle a central question hanging over the community -- does their field matter?"

There's reason to think it will matter -- a lot. Of the many epigenetic markers already identified, many have shown to affect an organism's phenotype. Some of them have been shown to be heritable, opening up new vistas of epigenetic inheritance. Now, with the updated CRISPR-Cas9 gene editing tool, despite its potential for ethical quandaries (see discoverer Jennifer Doudna in Nature worrying about the Pandora's box she opened), epigenetics researchers are pushing the accelerator pedal.

Ledford describes how CRISPR-Cas9 -- Science Magazine's 2015 "Breakthrough of the Year" -- has already allowed one research team to speed around another team that did things the old-fashioned way.

Ren� Maehr, an immunologist at the University of Massachusetts Medical School in Worcester and his colleagues fused an enzyme called histone demethylase, which removes methyl groups from histones, to a deactivated Cas9 enzyme, and then programmed it to target regions of DNA believed to enhance the expression of certain genes. The result was a functional map of genetic 'enhancer' sequences that allows researchers to determine what these enhancers do, how strongly, and -- most importantly -- where they are located in the genome.

Question: Why were they seeking "to determine what these enhancers do"? Answer: They didn't believe they were junk. They watched the target gene increase its expression significantly. "That result started to convince me that the acetylation of histones may be a direct cause of gene activation." This suggests a new layer of specified complexity that supersedes the old Central Dogma that viewed DNA as the master controller. Functional mapping now steps up from genes to the epigenetic markers that regulate them.

Researchers don't know if all epigenetic marks have such dramatic effects. "For all we know, they might have very minor effects on gene expression except in a few special cases," a researcher at the Fred Hutchinson Cancer Center in Seattle opines. We may not have long to find out.

Now, however, researchers have a tool to pick apart the detail. Because of its simplicity and versatility, CRISPR-Cas9 opens up an opportunity to launch the kind of large-scale projects needed to reach that level of understanding. "If we want to target a region in the genome, we can have that targeting molecule here tomorrow for five dollars," says Reddy. "We're going to get to march through every single one of these modifications and figure out what they actually do."

You don't try to figure out what pieces of junk do. Whatever the outcome of the "ambitious projects" ahead, "the rapid pace of the field is already defying expectations," Ledford writes. Let's look at some other recent articles for clues.

Epigenetic markers may shed light on the long-standing mystery of the molecular basis for caste-specific behavior in ant colonies. (Science Magazine):

These findings reveal the epigenome as a likely substrate underlying caste-based division of labor in eusocial insects. Furthermore, in light of the conserved role of CBP in learning and memory in both invertebrates and mammals, these data suggest that CBP-mediated histone acetylation may similarly facilitate the complex social interactions found in vertebrate species.

Epigenetic markers affecting the immune system change with habitat, researchers found when comparing methylation marks on forest-dwelling African tribes with sedentary farmers. (Pasteur Institute):

These results partly explain why some people are predisposed to certain diseases. "Our research shows that changing lifestyles and habitats have a major influence on our epigenome and that urbanization significantly affects the epigenetic profiles of the immune system. This demonstrates how important it is, alongside more traditional genetic research, to investigate how epigenetic changes could result in an immune system that is more prone to the development of autoimmune diseases, allergies, inflammation and so on," explains Lluis Quintana-Murci. [Italics in original.]

"Epigenetic discovery suggests DNA modifications more diverse than previously thought" (University of Cambridge):

The world of epigenetics -- where molecular 'switches' attached to DNA turn genes on and off -- has just got bigger with the discovery by a team of scientists from the University of Cambridge of a new type of epigenetic modification.... It's possible that we struck lucky with this modifier, but we believe it is more likely that there are many more modifications that directly regulate our DNA."

This is just a taste of the kind of high-level research that is attracting grant money. The project at Cambridge, for instance, was funded by the Biotechnology and Biological Sciences Research Council, Human Frontier Science Program, Isaac Newton Trust, Wellcome Trust, Cancer Research UK, and the Medical Research Council.

Four years ago, we discussed whether the epigenome is "Evolution's Newest Nightmare." Current Biology put up a brave front, claiming that epigenetics might promise "interesting new angles in the study of evolution." That's hard to support now. None of the articles quoted above had any use for evolutionary theory. Indeed, how could they? If epigenetic markers regulate genes; if they act like molecular switches; if they can be placed into functional maps -- then they represent a higher level of complex specified information that defies the neo-Darwinian mutation/selection story.

Stated explicitly or not, it's design-based thinking that leads scientists to build functional maps of epigenetic markers and motivates them to "figure out what they actually do." Who would waste time or money on junk? The downfall of the junk-DNA concept gives scientists encouragement to seek new levels of specified complexity in epigenetic regulation. The future of epigenomics looks bright -- for intelligent design.

Image: � fnalphotos.com / Dollar Photo Club.