ERVs, epigenetics, and the alcoholic brain

Let me make this clear, for like the millionth time:

You do not want transposable elements in your genome (DNA transposons, ERVs, LINEs, SINEs, etc) to be active and functional. You are happy, happy, happy that these elements are junk. Yes, occasionally a transposable element has been domesticated for the hosts purposes. Yes, I know, Creationists think this means every last nucleotide to be there For A Reason by The Designer. But if what they wanted was a reality, we would all be dead right now. Expression of the vast, vast majority of transposable elements is a sign that something has gone very, very wrong.

This paper is another example of how expression of Junk DNA is a sign something is very wrong, and might even be playing a role in the pathogenesis of alcoholism:

Gene coexpression networks in human brain identify epigenetic modifications in alcohol dependence.

These scientists compared regions of postmortem brains of 17 alcoholics and 15 non-alcoholics-- they were not only looking for differences in gene expression, but also differences in gene networks AND differences in epigenetic profiles.

I am very pleased to see that they controlled for so many things between the alcoholics and the non-alcoholics-- not just age/gender/etc, but smoking (which might also have an effect on brain epigenetic profiles) AND they controlled for the ways of death that screw with your epigenetic profiles, rendering further study useless, like hypoxia. Nice.

So, what did they find?

The epigenetics of the cells in the brains of alcoholics is messed up-- both the epigenetic markers on the DNA and epigenetic markers on histones (the beach-ball like things DNA wraps itself around). Well, epigenetics is one of the main ways our genomes have for restricting the expression and movement of transposable elements. So when they zoomed in on ERVs they found that ERVs were stripped of their DNA methylation in the alcoholic brain, and saw the expected huge increase in ERV mRNA as a result of this.

So, take home message-- they found a ton of ERV mRNA floating around in the brain cells of alcoholics.

But what does this mean? Are ERVs playing a role in the brain damage associated with alcoholism? Are ERVs playing a role in alcoholism itself? Or is expression of ERV mRNA just a side-effect of the global epigenetic 'things are messed up up in here' that happens as a result of chronic alcoholism?

The authors think that ERVs are not just a marker of the damage caused by alcoholism, but that the ERVs are actively contributing to the brain damage due to alcoholism. They hypothesize that expression of ERV proteins is activating microglia and astrocytes and inducing neuroinflammation. They also think that their observations weave with others findings, suggesting in the discussion that putative neuroinflammation induced by ERV proteins could play a role in alcohol addiction itself.

Happily, they made it clear that they are just hypothesizing here, there are other interpretations of their data. Its so refreshing when other scientists arent wildly overstating their results! My main concern is that while ERV mRNA might be upregulated in the alcoholic brain, they have no data demonstrating that any of this mRNA is translated into a protein that could even serve as a marker for the damage induced by alcoholism, much less protein that is actively participating in the pathogenesis of alcoholism. That is obviously the next step.

But I am just as hopeful as the authors for the future direction of their research:

One implication is that epigenetic interventions may effectively correct the widespread changes in brain gene expression and functional abnormalities produced by chronic alcohol abuse. Many epigenetic therapeutics have been developed for other diseases, and our study may direct some of these therapeutics toward alcoholism and drug addiction.