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.

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Fascinating article.

....but for a moment I thought you were forming a band and just expected I would dust off my accordion.

By Prometheus (not verified) on 29 Feb 2012 #permalink

What epigenetic drugs have been developed for other diseases? They said there were many.

So according to this article, how is XMRV 100% sure to cause alcoholism along with autism?

By Poodle Stomper (not verified) on 29 Feb 2012 #permalink

can anyone respond to this post from the link above..thanks.

45. peter borger Says:
February 23rd, 2012 at 4:27 am
Dear Mr Zimmer,

Thanks for spreading âthe VIGEâ>RNA-virus memeâ on twitter.

Question to you: where do viruses have their origin. I mean, before they start to evolve (change) they must have their origin somewhere, isnât it?

Some believe they come from space. The better solution is: they come from the genome. They have their origin in transposable elements knowns as ERVs. Look into the genetics of HIV, influenza and other RNA viruses. You will observe that they have the usual core genes (gag and pol) like the harmless VIGE-family known as ERVs.

In addition, the RNA viruses have acquired genes from the genome in which they reside. HIV has acquired a piece of the CCR5 ligand (to be exact: a piece of the interleukin-8 gene) to enter immune cells. Influenza acquired the neuramidase gene, which is an essential gene found in the genome of mammals and functions to modificy proteins.

In my opinion, evolutionists have turned the world upside down. They believe that viruses made mammals, but the opposite is true. Viruses destroy mammals. The origin of RNA viruses can be found in harmless TEs (type: ERV), which are particularly good at putting genes in new regulatory contexts (to generate novel variation in offspring). Hence, RNA viruses are derailed VIGEs.

I do not know who you are but your information about ERVs is terribly in error. Without HERV W or FRD no mammal could reproduce. What about the LTR of HERVE upregulating cellular genes of the neural development by 40-60% There are ERVS upregulated in the course of several diseases but there is no causal data. My students keep finding links like this and thinking that this is real science and it is such a disservice to those who are just learning this field. DNA junk maybe junk but Retroids are not junk and have not been for several decades now !

By lilyofgallatin (not verified) on 02 Mar 2012 #permalink

Lily, please read the second paragraph, in particular the (probably) blue text that is underlined. That text is a link to how a few ERVs are used by mammals.