Opposite Day: When the data in an ERV paper says the opposite of what the authors say

A paper was recently brought to my attention via a Creationist. It was the usual 'HAHAHA! Oh you silly Creationist! This paper says the opposite of what you think it says!', and I was going to write a blog post along that usual theme.

Fazale Rana, 'Vice President' of 'Research and Apologetics' at Reasons to Believe said on Facebook:

What happens when the best evidence for biological evolution becomes evidence for intelligent deign?

Retroviruses, long thought to be junk DNA, play a role in regulating gene expression in the brain (link to ScienceDaily about the article)

The article has some interesting observations about how expression a few young ERVs is restricted in some brain cells in mice:

TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells

Your genome does not 'want' ERVs to be expressed. Wayward activity can damage DNA, make proteins that disrupt normal processes, aka kill the host organism. So genomes have evolved ways to control ERV expression: Epigenetics.

Epigenetically modify histones to wrap ERV DNA up *tight*, so it cant be expressed.

Epigenetically modify ERV DNA to wrap ERV DNA up *tight*, so it cant be expressed.

These folks demonstrate another protein, Trim28, plays a role in keeping some ERVs silent.

1. If they knock out Trim28 entirely, baby mice die, straight up.

2. When they cut out Trim28 in fetal mice, and look in neuronal progenitor cells, there is increased ERV RNA expression (altering the environment in which the cells grow (culture) can alter epigenetic profiles, thus alter ERV expression-- they compared these to control animals).

3. They think ERV family MMERVK10C is the one causing trouble. When Trim28 is gone, the histones around these ERVs are not in the 'off' position. The DNA around these ERVs is not in the 'off' position.

4. In addition to the ERVs being transcribed, there was also an increase in transcription of 28% of the genes near the ERVs. Not all genes are 'on' in all cell types. Turning unnecessary genes 'on', or increasing/decreasing the expression of 'on' genes, can cause chaos in a cell.

Conclusion? Though Histone/DNA modification USUALLY controls ERVs in somatic cells, in this case (neural progenitor cells), TRIM28 needs to work too. If its not there, stuff gets messed up. Like hardcore messed up.

We have previously demonstrated that deletion of Trim28 in postmitotic forebrain neurons results in complex behavioral changes (Jakobsson et al., 2008). In addition, heterozygous germline deletion of Trim28 has been described to result in abnormal behavioral phenotypes (Whitelaw et al., 2010). In this study, we found that deletion of Trim28 during brain development is lethal (Figure S3). In addition, we also noted that heterozygous deletion of Trim28 during brain development resulted in behavioral changes characterized by hyperactivity (Figure S3). Together, these findings demonstrate that disruption of TRIM28 levels in the mouse brain results in behavioral changes that are similar to impairments found in humans with certain psychiatric disorders.

Many genes (in mice!) are disrupted when TRIM28 is deleted, some ERVs are too. And it is a train-wreck. Dead baby mice. Behavioral changes. Train-wreck. ERVs making noise are assholes. YAY for shutting them up!

Pretty straight forward paper.

I thought a Creationist just read 'junk DNA' 'ERV expression' and was somehow arguing that 1) dead baby mice, 2) abnormal behavior in mice, is evidence for Intelligent Design.

But this Creationist didnt get his idea out of thin air. The authors of this paper also have some strange interpretations of their data.

I think the authors might be somewhat confused-- They seem very excited about the fact that when they got rid of TRIM28, some of the genes around ERVs are over-expressed. We have known for a very, very, very long time that retroviral/ERV promoters can act as promoters for nearby genes. This is, to my knowledge, been universally bad. This is one of the ways retroviruses, and ERVs, can cause cancer and other diseases. Disrupting normal gene expression.

The data in this paper also supports the idea that wayward retroviral promoter activity is bad. When they disrupted control of ERVs, mice *die* or, if control is disrupted later, have behavioral abnormalities.

But the authors speak as if the *opposite* were true.

ScienceDaily--A new study from Lund University in Sweden indicates that inherited viruses that are millions of years old play an important role in building up the complex networks that characterise the human brain.

Researchers have long been aware that endogenous retroviruses constitute around five per cent of our DNA. For many years, they were considered junk DNA of no real use, a side-effect of our evolutionary journey.

In the current study, Johan Jakobsson and his colleagues show that retroviruses seem to play a central role in the basic functions of the brain, more specifically in the regulation of which genes are to be expressed, and when. The findings indicate that, over the course of evolution, the viruses took an increasingly firm hold on the steering wheel in our cellular machinery. The reason the viruses are activated specifically in the brain is probably due to the fact that tumours cannot form in nerve cells, unlike in other tissues.

"We have been able to observe that these viruses are activated specifically in the brain cells and have an important regulatory role. We believe that the role of retroviruses can contribute to explaining why brain cells in particular are so dynamic and multifaceted in their function. It may also be the case that the viruses' more or less complex functions in various species can help us to understand why we are so different," says Johan Jakobsson, head of the research team for molecular neurogenetics at Lund University.

Scientific American-- By manipulating mice genetics, researchers found evidence that some endogenous retroviruses gained new roles that are important for brain development in our not-so-distant rodent relatives. “Brain cells are very complex compared to other cells,” says Johan Jakobsson, a researcher at Lund University in Sweden and lead author of the study. “Co-opting endogenous retroviruses allows for much more complexity, especially since they make up so much of the genome.”

Press Release-- "Do viruses make us smarter?"

If, when they *silenced* ERVs, there was death/abnormalities, *that* would support the idea that ERVs play a role in brain development. But that is simply not what they, or anyone else as far as I know, have observed. They observed what we already know: Wayward ERV expression is virtually universally BAD. ERVs=Death. ERVs=Disease.

I literally have no clue where the authors are getting the idea that ERV expression is a good thing. Thats not what their data says. If anything, their data says neural progenetor cells require an extra level of protection from ERVs.

So, its opposite day.

Scientists are saying their data says the opposite of what it says.

And Im looking at scientists, baffled, and telling Creationists "Its not your fault you said something stupid."

Categories

More like this

So Ive been over the basics of ERVs (Intro, gag, pol, env), but Im still missing a 'basic' aspect of ERVs, even though I talk about them all the friggen time on this blag: LTRs. In exogenous retroviruses, LTRs act as promoters. Genome has all the genes (gag, pol, env), LTRs make sure they, and…
This is a repost from the old ERV. A retrotransposed ERV :P I dont trust them staying up at Blogger, and the SEED overlords are letting me have 4 reposts a week, so Im gonna take advantage of that! I am going to try to add more comments to these posts for the old readers-- Think of these as '…
What is it about ERVs that makes kooks cling desperately to them, like little 'gag-pol-env' life-rafts, as the kooks FAILboats sink into even further obscurity? I think the general populations ignorance about ERVs is what kooks find so attractive. Kooks, like Creationists, can say any damn thing…
My god, epigenetics is a woo-magnet. Its not epigenetics fault, its just science. But the word 'epigenetics' gets put on this ('chambery thing' heh.). And this. And this. And... well, just Google it. Find your own favorite bit of self-help/explain all/magic epigenetic crap. Attention woo-meisters…

Hi gil,

I tried to find where there was any discussion of ERVs (or indeed any retroelements) in the linked opinion piece or in the full article it referenced. I searched for "ERV", "insertion", "shared", "14", "fourteen", and a number of other terms, hoping to find what it was you were referring to. However, my search has yielded nothing to support what you're saying. I looked in the Supplemental, too.

Perhaps I'm missing something. Would you mind pointing out, specifically, what data you're referring to?

The study you are referencing is about convergent evolution, not retrotransposon insertions. You are correct, we know independent insertions can happen in the same locus, but the vast majority of these are imprecise independent insertions, having inserted within the distance of a PCR amplicon, but not precisely at the same nucleotide. These are easily resolvable by comparing the sequence architecture. There are a small fraction of insertions that truly are precise independent insertions. But, these homoplasious insertions are factored into all models and easily pop out in our analyses. Further, we expect a certain number of such events given the size of the target genomes and the non-random mechanisms by which insertions occur. Lastly, precise independent insertions are vanishingly rare. Hardly the observation one would want to use to support so extraordinary a claim that common descent is false.

For example, one study looking into the rates of precise parallel independent insertions (and other potentially confounding events) is linked below. Out of more than 11,000 insertion loci examined, only 5 were found to be precise parallel independent insertions. Cherry-picking 5 insertions out of 11,000+ and claiming that these support a failure of common descent when the other 10995+ insertions don't would be either a failure to comprehend the subject material or a disingenuous attempt to misrepresent the subject material.

http://www.ncbi.nlm.nih.gov/pubmed/17345674

hi baka.

i get the data from this paper:

http://www.sciencedirect.com/science/article/pii/S0960982209020740

"Out of more than 11,000 insertion loci examined, only 5 were found to be precise parallel independent insertions."

yep. but if we can get 14 mutations in the same site from a 10^9 bp genome, then we can get thousant of share insertion without a commondescent.

another important point is that we acctually find contradict data to the primate phylogeny:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1054887/

"Several lines of evidence indicate that chimpanzee and gorilla PTERV1 copies arose from an exogenous source. First, there is virtually no overlap (less than 4%) between the location of insertions among chimpanzee, gorilla, macaque, and baboon, making it unlikely that endogenous copies existed in a common ancestor and then became subsequently deleted in the human lineage and orangutan lineage. Second, the PTERV1 phylogenetic tree is inconsistent with the generally accepted species tree for primates, suggesting a horizontal transmission as opposed to a vertical transmission from a common ape ancestor. An alternative explanation may be that the primate phylogeny is grossly incorrect, as has been proposed by a minority of anthropologists".

so if its true- then a lots the share erv between chimp and human may be a result of independent insertions.

what did you think about this option? have a nice day

There are a lot of pop-sci sites that are repeating that same article. I don't see any independent interviews of the researchers by other journalists. I wonder if some rookie journalist, or perhaps even a creationist, got involved in editing that piece.

Abbie: Perhaps you could take a moment from your busy schedule and contact one of the authors for clarification and see if this was just a journalistic hatchet job?

By Fair Witness (not verified) on 28 Jan 2015 #permalink

It is important to note that the premise of design, while not constrained by anything we know about the designer, predicts nothing about what happens in DNA.

Designers are free to design things that have anything from no functionality at all to something highly essential. In fact human designers design things that are non-functional. Or have components that are non-functional.

What people miss is that a hypothesis is not testable on a prediction unless that prediction comes through logical necessity from the premises. In this case, if functionality is the prediction, one would have to show the logic for why the design premise would fail if something were found that is not functional. Premises would need to be in the hypothesis to show why the hypothesis would forbid non-functionality.

So in summary, the naked unconstrained premise of design predicts nothing through logical necessity about what might be found or not found in DNA. As such, no tests for anything in DNA could cause the design hypothesis to fail.

A hypothesis that cannot fail is not testable.

Regards,
Dudley

By Dudley Chapman (not verified) on 29 Jan 2015 #permalink

hi dudley.

i think you can say this about the evolution theory too. we can expect both similarity and non-similarity from evolution prespective.

what about this test (for both evolution and id): if we can show that there is step wise way to a complex system through mutations and natural selection(or any kind of change)- then the evolution is possible but id is not. i think darwin claim this in is book the origin of species. a perfect analogy will be a cell-phone. can we get from a self replicat material(with dna and self replicat system) a cell phone over bilions of years of mutations? i dont think so because there is no step wise from a self replicat material to a cell-phone. a minimal cell phone will need at least 4-5 parts for minimal function. so a biological system will need also 4-5 parts to a minimal function. we cant even get a cell phone by combination of parts because a cell phone have also unique parts.

GIl.
Trying to compare independent mutations to independent VIRAL INSERTIONS is pretty stupid. It's an apple to orange comparison. As explained here: http://www.evolutionarymodel.com/evolutionnews.htm
''An even more striking example comes from Wang et al. (2007), where an unprecedented “40,569 unique integration site sequences” were analyzed. Of all those integration events, only 41 “hosted two independent integration events at exactly the same base pair in the human genome (Wang et al., 2007, p. 1188).” Again, shared insertions resulting from parallel integration is rare—not as rare as so many misinformed individuals on the internet that use the ERV argument claim—but rare enough to make it unambiguously clear that retroviral insertion is not locus specific.''
So independent insertion of a virus into the same loci in two species is 41 to 40,569, or about 0.1% So no, just because it's possible that it is an independent event, doesn't mean it is, especially when the odds are so low. Even lower with the odds Baka gave you. 11,000 similar viral insertions and only 5 are independent? Those odds are about .05%. So yeah, it's more likly that shared ERVs in the same loci indicate common descent. Especially since we share over 200000 of them with chimps. Can you really make the case that they all are independent events? I think you can't
So pointing to shared mutations that arised independently (especially since convergent evolution is allowed since we all share the same universal DNA code, and they are in somewhat similiar environments), isn't proving ID since while it did happen, the odds were very, very low, so it's unlikly that it would happen again.

"what about this test (for both evolution and id): if we can show that there is step wise way to a complex system through mutations and natural selection(or any kind of change)- then the evolution is possible but id is not" Why, id proponents would complain that these things couldn't have evolved but then we show evidance that they do, like here: http://www.sciencemeetsreligion.org/evolution/novelty.php

By Jacob Blaustein (not verified) on 16 Feb 2015 #permalink

hi jacob.

you said:

"So independent insertion of a virus into the same loci in two species is 41 to 40,569, or about 0.1% So no, just because it’s possible that it is an independent event, doesn’t mean it is, especially when the odds are so low"-

first. because english isnt my native i need to know one thing: is this paper check erv (no real time)or insertion in real time?because if its in real time- then it is not good evidence. because of the fact that erv can be beneficial then even if the insertion is random we will get non random fixations=non random erv.

" Why, id proponents would complain that these things couldn’t have evolved but then we show evidance that they do, like here"-

not realy. for example: take the lenski experiment: its need only 2 mutations to get citrit digest in oxigen environment. the gene(protein actually) that can digest citrit jump near promoter that can be activated by on(from what i remember). its like to move an abs system from into the car to outside the car. now the car get be more protect to carshs. but it isnt a new complex syste like a new gps or dvd to the car.

so again- can you show that a complex system will evolve? do you think for example that a gps can evolve step wise from a cell-phone?

have a nice day

For those who aren't aware, Gil has also been frequenting biologos boards (http://discourse.biologos.org/t/adam-eve-and-human-population-genetics-…) with the same challenge. It has been pointed out to him here that even though there is covergent evolution between dolphins and bats, these weren't identical mutations.

While these covergent mutations produced 14 of the same amino acids within the Prestin gene within dolphins and bats, the underlying DNA bases for these 14 amino acids were different, showing quite clearly that these sequences were arrived at independently.

Several years after ENCODE, the ERV= integrated virus remnants=junk mytholog is still being defended.

Of course, there is some junk in the genome due to deregulated control mechanisms, and integration of derailed TEs, but ERVs have been misinterpreted by the junk-DNA woshippers as remnants of viruses.

Rather, ERV qualifiy as variation-inducing genetic elements, as they function as alternative promoters/enhancers, as well as epigenic regulators. From these elements RNA viruses easily arise through recombination. This can be shown for HIV, influenza, etc.

Why is it so hard to get rid of the junk-myth? Because the Darwimps (the antonym of IDiots) need it for phylosophical reasons. Who invented the junk-nonsense: Darwimp Susomo Ohno. Who prpagated the junk-nonsense? The Darwimps Crick, Orgel, Dakwins. The bigger the names, the bigger the non-sense. Common factor: the atheism belief system with Darwin as the highest prophet.

Why don't you go to your lab and perform some experiments to exclude function, if you can. You cannot, because TEs and ERVs are the mechanism to induce variation...and how doe you measure variation?

Why doesn't the Darwimpscommunity make a junk-DNA free organism? I bet it will not be able to -- what they call-- evolve (due to lack of variation-inducing genetric elements).

Have a nice day,
PT

By Peer Terborg (not verified) on 04 Mar 2015 #permalink

"I think the authors might be somewhat confused– They seem very excited about the fact that when they got rid of TRIM28, some of the genes around ERVs are over-expressed. We have known for a very, very, very long time that retroviral/ERV promoters can act as promoters for nearby genes. This is, to my knowledge, been universally bad. This is one of the ways retroviruses, and ERVs, can cause cancer and other diseases. Disrupting normal gene expression."

You are wrong here. Faulkner et al showed, in 2009, that 30-70 % of the mouse and human genes, are transcriptionally associated with TEs. This shows that TEs are required to initiate the transcription. So it is a normal part of the trancriptome, known as TE-regulated trascriptome.

Further, there is now ample evidence that TEs are associated with high affinity nucleosome binding, keeping the genes that they are part of under stringent less accessible for the transcxriptional complex. Less TEs in the proximal promoter sequences, means increased transcription. This was contrary --as always-- to the Darwinian selection intuition.

Furthermore, Faulkner also demonstrated that somatic TE transposition was associated with learning.

The junk-DNA hypothesis was falsfied by thousands of observations. So stop propagating this science stopper.

Not the creationists, but you, the junk-DNA worshippers, are the science stoppers.

PT

By Peer Terborg (not verified) on 04 Mar 2015 #permalink

"And Im looking at scientists, baffled, and telling Creationists “Its not your fault you said something stupid."

Your arrogance is appaling, AS.

Let me repeat: "Not the creationists, but you, the junk-DNA worshippers, are the science stoppers."

By Peer Terborg (not verified) on 04 Mar 2015 #permalink