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The Epigenome: Evolution's Newest Nightmare

The epigenome looks like it could be the evolutionists' newest nightmare -- and the latest icon of intelligent design. Back in the 1950s, the genome coded in DNA could well have finished off Darwin. Its digital code, faithfully copied and reproduced by a host of molecular machines, was not the kind of sophistication that Darwinian theory expected, or seemed capable of explaining. Nevertheless, fancy footwork and rhetorical swordsmanship has kept the theory in a standoff with versions of ID for some sixty years.

Enter the epigenome, with its codes, upon codes, upon codes. Discovery Institute's Richard Sternberg has made this the focus of his research lately and, as Casey described the other day, it's also the subject of a new book based on Sternberg's work, by Tom Woodward and James Gills, The Mysterious Epigenome: What Lies Beyond DNA.

[Editors note: CSC Fellows Michael Behe and Richard Sternberg will join Tom Woodward and James Gills to speak at a conference about epigenetics titled: Shaping Your DNA Destiny - Exploring Epigenetic Keys to Improving Your Health, Feb. 24-25 in Tampa Bay, FL.]

When all else fails, look brave. Three Harvard biologists, Ben Hunter, Jesse D. Hollister, and Kirsten Bomblies, have now sought to face the daunting new challenge with an essay in Current Biology, "Epigenetic Inheritance: What News for Evolution?"

The epigenome has no clear boundaries at this point. "Epigenetics" could refer to any heritable condition beyond DNA. Scientists now know that gene expression is controlled by numerous mechanisms, including histone tags (sometimes called the "histone code"), the "zygote code," various types of small RNAs, alternative splicing, pre- and post-transcriptional modification, and an army of transcription factors. The old "central dogma" that information flows from gene to protein has been defunct for some time, but much remains to be understood. How does the environment influence epigenetic markers? How are they passed on, and how stable are they? How do "epialleles" (a new term extending Mendel's paired gene concept) affect the phenotype?

Epigenetic marks such as cytosine methylation or histone modifications can be very dynamic and can alter gene expression in response to environmental and developmental cues without changes in DNA sequence; in some cases epigenetic changes can be heritable through meiosis. This has spurred interest -- and heated debates -- about whether epigenetic variation may play a significant role in adaptive evolution. The need to formally consider epialleles in population genetics and evolutionary theory has been emphasized ... however, more empirical data are necessary to parameterize models and assess the actual impacts of epigenetic variation on adaptive phenotypes.
So far, only a couple of transgenerational studies on the lab plant Arabidopsis thaliana provide detailed data on long-term inheritance of epigenetic tags. They show that some tags are dynamic and some static, with the static markers tending to reside with non-coding regions of DNA. There appear to be "hotspots" for epigenetic change. Some markers can revert; others appear to be metastable. Without a clear view of the threat (just the echo of its approaching footsteps), the Harvard team decided to engage in possibility thinking. Maybe it's something they can throw the "epigenetic junk" weapon at.
It has been known for some time that epialleles at some loci are "metastable" and can change dramatically over generations. Such instability suggests it is unlikely that alternative epialleles can contribute appreciably to stable evolutionary change.

While instability speaks against the idea that individual epialleles would contribute to long-term adaptive evolution, it does beg the question why there is variation among loci in epigenetic stability in the first place. As Richards has pointed out, one possibility is that the unstable epialleles are really just phenotypically inconsequential "genomic clutter" that is reset with passing generations. On the other hand, such variation could also be part of a plastic environmental response system or, if selection can stabilize epigenetic states, then it becomes a standing supply of potentially heritable, adaptive epialleles. A particularly intriguing possible explanation when considering the role that epigenetic variation may play in long-term evolution is that it is the propensity to vary, rather than any particular allelic state, that is under selection. Simulations have shown that phenotypic variation and plasticity generated by epigenetic instability can be beneficial in variable environments, and thus instability may itself be a target of selection.

Without evidence linking unguided, undirected "epimutations" to phenotypic fitness, such hopes amount to little more than whistling in the dark. If history is any guide, evolutionists will have just as much success in obtaining the evidence they need as they have had linking genetic mutations with phenotypic fitness.

At this point, evolutionists do not know which human instinct to follow: fight or flight. The look on their faces is curiosity instead of terror.

Having realistic numbers for parameters such as allele stability, epimutation rates and reversion rates is critical for incorporating epigenetics into evolutionary theory. Studies such as the recent A. thaliana variation accumulation studies provide such vital empirical data. Moving forward, we need methods for assessing whether epigenetic marks are evolving neutrally or under selection. How do we quantify selection on methylation patterns or other epigenetic marks? What is the neutral expectation? When we observe divergence in methylation, how can we assess whether this happened under selection or via random "noise" or plasticity in the regulatory system? Having a formal body of evolutionary theory that incorporates epigenetics, as well as developing a clearer quantification of the connection between epigenetic variation and phenotypes will allow us to more rigorously ask whether or how epigenetics plays an important role in adaptive evolution. This area promises interesting new angles in the study of evolution.
We pause this epic drama right before the wizard, facing the oncoming Balrog, shouts to his companions, "Fly! This is a foe beyond any of you. I must hold the narrow way. Fly!"