Jan 12 2010

Endogenous Viruses and “Junk” DNA

A recent report in Nature discusses the finding of a new type of viral inclusion in animal DNA, including humans. About 8% of the human genome is actually comprised of viral DNA – bits of viral genetic code that have been inserted at sometime in the past through a process called endogenization.

Up until now the only source of these viral endogenous elements was retroviruses – virsues that can take their RNA and make it into DNA that can be inserted into the DNA of the host organism it is infecting. Retroviruses then exploit the replicating machinery of the host to crank out more copies of themselves.

So it makes sense that these retroviruses can have their DNA occasionally wind up in the genomes of the animals they infect – which can happen when the viral DNA is inserted into a germline cell (sperm or egg) and then can be passed onto the next generation. Usually cells that are so infected die, but it can happen that a mutation occurs in the viral DNA after it is inserted rendering it non-functional. It is therefore stuck there and gets pass on as “junk” in the DNA.

Now researchers report the first evidence of non-retroviral endogenous regions from many animal species, including humans – from the bornavirus, or borna disease virus (BDV). BDV is not a retrovirus and does not have reverse transcriptase – the enzyme necessary to turn RNA into DNA – but its life cycle takes place in the nucleus of host cells. Apparently it spends so much time replicating in the nucleus that bits of its RNA can get converted to DNA and stuck in the host genome. This is a less common event than with retroviruses, but it happens. BDV DNA has been found in infected cells.

They also found two instances in humans of endogenous BDV sequences that had open reading frames – which means they were functional enough to actually code for proteins. These proteins are actually being made inside cells, but they have no apparent function.

This is not the first instance of this phenomenon. Essentially, viral bits get stuck in genomes where they mutate and degenerate and become useless bits of junk. But occasionally mutations may render these bits viable – able to make proteins. These proteins probably start out as useless, and may mutate back into uselessness. But they also may be co-opted by the host (through chance mutations) to serve some useful purpose.

Implications for Evolution

Creationists don’t like the notion of junk DNA, any more than they like the concept of vestigial organs – the two concepts are closely related. Both imply an evolutionary past. Both also are partly founded upon an argument of exclusion, which they try to present as an argument from ignorance (but there is a subtle difference). An argument from exclusion basically says that we do not know of any function for junk DNA therefore it probably has none. Such arguments are only as good as the extent to which we have searched for a function. After about a century of genetics, and half a century of studying DNA, we have a reasonable level of confidence that much of junk DNA is indeed junk. You cannot prove once and forever a negative claim, but you can get to high levels of confidence.

An argument from ignorance takes the form – we do not know what the function of junk DNA is, therefore it has this specific function (for which there is no positive evidence).

It is also true that over the years we have discovered functions for some of what was previously considered junk DNA, but only a small fraction. This was to be expected. Initially scientists identified the coding regions of DNA – those bits for the parts of genes that directly code for proteins. Near these coding genes were also identified regulatory regions – these determine when and how the gene is expressed. But between these coding and regulatory regions are vast sections of DNA with no apparent function, despite extensive efforts to find one. This is the so-called junk DNA.

But it is not surprising that over the years, as we learn more and more about the complexity of DNA, its function and regulation, we would discover that some parts of that junk DNA do play a role in DNA function (for example, in regulating gene expression). What creationists do is immediately extrapolate from such discoveries to the unwarranted conclusion that all of junk DNA has some hidden function. This is a position they can maintain forever, as it does not require any evidence on their part.

But there is also more to our knowledge of junk DNA than just that we cannot find a function for it – such as the identification of viral endogenes and pseudogenes. These are stretches of DNA that not only have no known function but also correspond to known segments of viral RNA. Why would there be a stretch of DNA in the human genome that looks like a bit of a viral gene, but incomplete and apparently non-functioning? This is more than an argument of exclusion. Also – why would it be that the only viral segments we have discovered are from retroviruses and now BVDs?. If you make the argument that the creator is recycling some viral code, why only from those that either place their RNA in animal genomes as part of their lifecycle, or at least replicate in the nucleus and occasionally make some DNA?

But it also gets better, because these viral endogenous DNA segments are not sprinkled at random throughout the animal kingdom – they occur in a pattern consistent with our picture of common descent. In other words, we find the same endogenous viruses in the same locations in related species – in an evolutionary pattern.

There is a coherence to the evolutionary explanation of endogenous viruses, with multiple lines of evidence converging on evolution as the answer.

Conclusion

We are likely to find more functions, or at least effects, of some of what is now called junk DNA, but not all of it. Nature is resourceful and makes use of what is there, but it is also messy and clutter does not go away unless it provides a significant enough disadvantage to survival. So our DNA is a bit cluttered.

But there is useful information in that junk DNA – it is partly a record of our evolutionary past, and it provides powerful evidence for common descent. In fact, common descent is the only viable explanation for the pattern of endogenous viruses we have discovered in various species. Creationists don’t have a viable alternative scientific hypothesis (just their go-to default untestable explanati0n – goddidit) – they can only take pot shots at the science in order to generate confusion and doubt. That is because creationism is not a science, it is denialism, and confusion and doubt is all they have.

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29 responses so far

29 Responses to “Endogenous Viruses and “Junk” DNA”

  1. Justin L.on 12 Jan 2010 at 9:15 am

    I find this extremely interesting. However, I’m sure that sometime in the near future I’m going to hear a creationist complain about the lack of transitional fossils. Having read this, I’m going to pull out my hair out, and scream at the computer screen, “what about stretches of DNA that not only have no known function but also correspond to known segments of viral RNA!” Maybe I’m better off not knowing.

  2. canadiaon 12 Jan 2010 at 9:52 am

    if only the creationists weren’t going to outlive us :(

    So, interesting speculation…would it be beneficial, in the future, to clean up our DNA by removing the junk? I can’t help but think of the ability to take control of our own evolution as an important species milestone. It seems like getting rid of the useless stuff would be an inherent part of that process.

  3. DSimonon 12 Jan 2010 at 11:04 am

    Canadia, I’m not so sure that would be helpful. From a CS perspective, that would be like using compression so that the data storage requirements are reduced but you still get the same output on demand. The advantages of doing that to save space and access time on your hard drive don’t really apply to our genome, I think; it’s not like we can fill up free space in our DNA with Beatles albums and vacation photos.

    I suppose one possible benefit is that it might make protein production faster. Maybe whatever is responsible for producing the proteins would have to spend less time skipping over garbage, thereby increasing the rate of healing and cell regrowth? I have no idea if this makes any sense.

  4. CWon 12 Jan 2010 at 12:00 pm

    Another nail in the Creationism coffin. This casket is becoming comprised of more metal than wood.

  5. Ashon 12 Jan 2010 at 12:01 pm

    Canadia – I think we’d want to demonstrate pretty conclusively that the “junk” has no function before taking it out of our DNA (and even then I think we’d need a reason to do it). It might be interesting to do an animal study (or even a plant study would work) when we get the capability though – if you created a version of an organism with all its junk DNA removed you could compare it to a “normal” version of the organism and see whether there is any significant function.

  6. leoneton 12 Jan 2010 at 12:19 pm

    canadia: I certainly hope that we progres to the point where we can become editors of our own evolution, but it’s possible even completely nonfunctional DNA is useful in the sense that it provides “bulk” in the genome. It’s a blank space for mutations, insertions of viral code, transposition etc. to occur without disrupting essential genes.

    I’m not a molecular biologist, but I suspect that a larger, less efficient genome is a necessary price for leading a long, multicellular life :-P

  7. Jeff Keoghon 12 Jan 2010 at 3:53 pm

    GodHead,

    You said, “To conserve such huge areas of non-coding information within our genome would require an incredibly strong selection pressure.”

    Why?

    As I understand it, natural selection only acts when there is an effect upon which it can act.

    In other words, non-coding DNA has no phenotypic effect and is therefore not available for selection. In other words, there is not selective penalty for having a large portion of DNA as non-coding.

  8. Jeff Keoghon 12 Jan 2010 at 3:55 pm

    Ugh.

    Please excuse the dreadful expression in that last comment of mine. I ought to learn to proof-reading prior to clicking submit.

    I ought to. Doesn’t mean it’s gunna happen, though.

  9. KathyOon 12 Jan 2010 at 4:36 pm

    Having a larger genome may serve as a buffer against mutation– random mutations would be that much less likely to hit something vital.

    On the other hand, it could just be that there’s no particular pressure either way to keep the junk in or to get rid of it. We’re not like bacteria that are in a constant arms race with each other to reproduce the fastest. If it takes our cells a few extra hours to replicate all that DNA, so what? We already take nine months to replicate ourselves anyway.

    I guess a question is, how much junk DNA do other animals have? They’ve been around just as long and have just as much incentive to avoid unfavorable mutations. Maybe someone will remove the junk from a cloned animal’s genome and see what happens.

  10. KathyOon 12 Jan 2010 at 4:41 pm

    @ Happy Rationalist

    Yes, viruses do mutate (though most of them are not as variable as the flu virus), but the functional regions of proteins tend to be conserved. You can recognize that something is almost the same as a viral gene but different from any known mammalian gene.

  11. KathyOon 12 Jan 2010 at 4:44 pm

    Are these comments being entered in some weird order? Both of my previous comments appear to be stuck in the middle of the pack. My last one now seems to predate the post I was addressing. Maybe it’s only on my computer. If it looks that way to everyone, no, I’m not psychic.

  12. Happy Rationaliston 12 Jan 2010 at 4:56 pm

    When I first learned about endogenous retroviral insertions (via the talkorigins.org page in the article), I was blown away, and I still find this to be one of the most staggering lines of evidence for common descent.

    However, one question I have encountered when I enthusiastically relate this to other people is, how do we know that the stretches are actually viral insertions? If they are recent, I imagine that we can see similarities with existing viruses. But in the talkorigins article, it talks about insertions dating to the split between the big and small cat families. Since viruses mutate very quickly, presumably they are very different today than they were at the time of the insertion (if they even still exist).

    Are there telltale virus components, motifs that we find repeated throughout the virus world, and which we do not find in uninfected animal DNA? How can we really know, looking at an ancient insertion, that it was in fact a viral one?

    Thanks for any pointers!

    Brian

  13. GodHeadon 12 Jan 2010 at 5:17 pm

    I have always been partial to the theory that leonet describes.

    It provides a statistical buffer against functional damage.

    In my opinion there must be a very strong selection pressure acting to keep the junk DNA within the genome because there have been viral studies that have shown that by simply supplying viruses with necessary components such as capsid proteins is enough to delete these functional sections from their genome within a short series of generations.

    To conserve such huge areas of non-coding information within our genome would require an incredibly strong selection pressure.

    So something’s there, researchers just need to know how to look for it.

  14. weingon 12 Jan 2010 at 6:07 pm

    “A question: Does anyone know if the bornavirus would be capable of causing horizontal gene transfers between higher-level organisms?”

    I recall reading, about 3 years ago, that the adaptive immune system of vertebrates was due to such a gene transfer.

    http://prl.aps.org/abstract/PRL/v98/i5/e058101

  15. weingon 12 Jan 2010 at 6:10 pm

    canadia,

    I have no idea how I traveled back in time to post that response to you.

  16. canadiaon 12 Jan 2010 at 6:20 pm

    @ GodHead/Leonet – Love that idea!

    A question: Does anyone know if the bornavirus would be capable of causing horizontal gene transfers between higher-level organisms?

  17. artfulDon 12 Jan 2010 at 6:24 pm

    “I can’t help but think of the ability to take control of our own evolution as an important species milestone. ”
    But what we likely see here is more evidence that life has already taken a measure of such control by the incremental engineering of it’s own evolution.
    The Neo-Darwinist denial that such a process exists or even could exist will certainly prevent any discovery by them of any preadaptive function of so-called junk DNA that enables that self-engineering process.

    But happily there are others without the dogmatic mindsets of either the creationists or the “natural magic” selectionists are forging ahead regardless.

  18. Jeff Keoghon 12 Jan 2010 at 8:08 pm

    Yeah; what’s with the ordering of responses?

    My contribution appeared above the post it to which it was a response.

  19. sonicon 12 Jan 2010 at 10:44 pm

    It seems that this article post overstates what the researchers have found.

    http://www.sciencedaily.com/releases/2010/01/100107103621.htm

    “They searched the 234 known eukaryotic genomes (those genomes that have been fully sequenced) for sequences that are similar to that of BDV. “The researchers unearthed a plethora of endogenous Borna-like N (EBLN) elements in many diverse mammals, ” Feschotte said.
    The scientists also were able to recover spontaneous BDV insertions in the chromosomes of human cultured cells persistently infected by BVD”

    So we can say that the researchers found sequences similar to what they were looking for. We can say that they claim they were able (an underproduced experiment, as far as I can tell) to get BDV insertions into human cells in a situation that may or may not indicate what would actually occur outside the lab.
    It seems likely that they found what they were looking for due to the fact people do that, and that the lab work won’t translate to actual life. (Certainly these sorts of things are not uncommon).

    On related topic
    It seems the notion of ‘junk DNA’ is going out the window as new discoveries are made on a regular basis–

    Some recent examples-

    http://www.sciencedaily.com/releases/2009/12/091210111148.htm

    Introns — Nonsense DNA — May Be More Important to Evolution of Genomes Than Thought

    One of the more interesting aspects of this particular study–

    “Remarkably, we have found many cases of parallel intron gains at essentially the same sites in independent genotypes,” Lynch said. “This strongly argues against the common assumption that when two species share introns at the same site, it is always due to inheritance from a common ancestor.”

    http://www.sciencedaily.com/releases/2009/05/090528203730.htm

    “To further test their theory, the researchers conducted a complex experiment aimed at mimicking biological evolution, using yeast cells as Darwinian guinea pigs…Their junk DNA saved their lives.”

    http://www.physorg.com/news162043805.html

    Research team finds important role for junk DNA

    “They have discovered that DNA sequences from regions of what had been viewed as the “dispensable genome” are actually performing functions that are central for the organism.”

  20. eiskrystalon 12 Jan 2010 at 11:40 pm

    How would we manipulate our genes in the future if the first thing we did was cut out all the raw material for doing so?

  21. Draalon 13 Jan 2010 at 9:04 am

    Junk viral DNA may serve a ‘protective’ function. Consider the following: An ancestral virus leaves it DNA in the genome. It was a fairly harmless virus. Many years later, a more virulent virus infects a decedent of the original host. The junk viral DNA is then expressed and the junk protein is packaged into new viral particles. Now, the new viral particles have the less virulent junk protein. The body may already have an antibody for the junk protein, or the virus is inefficient in infecting new cells, ect.

    +++++++++++++++
    “They also found two instances in humans of endogenous BDV sequences that had open reading frames – which means they were functional enough to actually code for proteins. These proteins are actually being made inside cells, but they have no apparent function.”
    As a technicality, the article did not prove that the N gene from the BDV virus resulted in expressed N protein. They proved expressed mRNA, not expressed protein. mRNA does not necessarily mean a functional protein is made. Case and point: riboswitches. Even if a protein is expressed, it may be non-functional: misfolded, inclusion bodies, insoluble or even immediately targeted for protein degradation. There are a number of requirements for proper translation of mRNA to occur.

  22. GodHeadon 13 Jan 2010 at 10:37 am

    The pressure to remove the extra information from the genome is the efficiency in replication and freed energy that would come about if the cells did not have to spend the energy and resources transcribing, replicating and maintaining the “junk” both as DNA as well as RNA transcripts.

    It costs a tremendous amount of energy to replicate our genome, if you multiply the cellular energy cost across an entire individual. simply removing the extra junk, which would correspondingly decrease the size of the genome, would represent a significant overall energy savings for any individual.

    Even ignoring the energy cost of transcription and replication (which is significant), a reduction in overall genome size would allow a reduction in nucleotide requirements.

    If our genome was half the size that it is, there would be more than a 50% energy savings for all replication and transcription related activities, and a lower requirement for nucleotide production and acquisition.

  23. Draalon 13 Jan 2010 at 11:49 am

    That argument seems nice and all and may very well apply to fast replicating single cell organisms. But… The shear size of some genomes is an indication that the driving force of multicellular organisms is not dependent on minimization of the energy needed to replicate a genome.

  24. Jeff Keoghon 13 Jan 2010 at 3:54 pm

    GodHead

    What you say may well be true with regard to energy/time expenditure in replication.

    My initial point remains – where is the selection pressure coming from? Unless there is some mutation which removes all (or even a fraction) of non-coding DNA (which would be a hell of a mutation!) then there is not going to be the phenotypic effect upon which selection could act.

    Also, I think Draal makes a very good point. The impact additional non-coding DNA may have has clearly not penalised mulitcellular life to this point.

  25. artfulDon 13 Jan 2010 at 4:29 pm

    sonic, your reference to the article about introns is quite interesting, especially as to the observation that introns show up in the phenotypes quite regularly even though apparently not included in the genetic transcription process. Which would seem to mean that they are reproduced for a purpose after whatever function that finds them useful has been replicated. Hardly junk just hanging on for the randomly directed ride.

  26. sonicon 13 Jan 2010 at 5:19 pm

    artfulD-
    Thanks– yeah, I agree that is an interesting aspect.
    I have a bunch of references like that– it just shows me that there are always more than one way to interpret data, and that one should keep an open mind because new discoveries will often overturn ideas that seem well established– (I submit the example of the ‘central dogma of biology’)

  27. artfulDon 13 Jan 2010 at 6:38 pm

    sonic, for a meld of physics and biology, try this very good read:
    The Rainbow and the Worm, The Physics of Organisms, Mae-Wan Ho.
    Also see her essay, Is There Purpose in Nature, http://www.cts.cuni.cz/conf98/ho.htm

    A concept foreign to this forum, I might add.

  28. Hector Moraleson 18 Jan 2010 at 4:18 am

    I hate “sayings.” Just hate ‘em, particularly when they make sense, and I don’t care to think about it. Vile!
    Like this disgusting little puke, “there are no atheists in foxholes.” Well, whoop die do!
    Just cause I pee my pants and beg god for help when someone shoots at me, doesn’t mean I actually hope some god exists. And so what if I did hope something like that momentarily? It means nothing. Temporary insanity.
    You know what else I can’t stand? The sun. I didn’t make it. Who does that star think it is, converting 600,000,000 tons of hydrogen nuclei into helium nuclei, fusing about 4,000,000 tons of mass into light and heat energy each second? I don’t recall giving permission.
    But, there it is. It had a beginning, too. And it will die. And it is a just a rather average medium size bird, not that impressive compared to “Beetle juice” and some of those big boys.
    And you are trying to tell me, that some “Thing” put it there and if I’m in a jam, this Thing could hear and help me?

  29. Hector Moraleson 18 Jan 2010 at 10:36 pm

    Having a split personality is alot of fun.
    Seriously.
    If Something could place a sun in a sky, maybe this Something has the capacity to hear a prayer or three.
    You bone head. there cannot be a god.
    Why?
    Because that type of stuff is fairy tale nonsense. Life ain’t the Wizard of Oz. There is no magic.
    Have you noticed a beautiful sunset?
    So what?
    There’s no magic? Do you recall holding your newborn in your arms?
    But, I can see those things. They are real, tangible.
    How did it all get here?
    Don’t know and neither do you.
    God started it all.
    Why? Why do you say that? Couldn’t everything have always been here?
    But, we know it began. Physics proves at a moment in time, all things burst into existence.
    Well, why do you credit god with that burst? Why couldn’t that burst have just happened?
    Nothing in the known universe has ever just burst into existence from nothingness. If you took a speed of light cruise through a worm hole and came upon a refrigerator filled with Budweiser, bologna, cheese and a t.v. turned on with the Colts playing the Packers, would you conclude, most likely, they just appeared? out of nothing?

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