The junk DNA myth (or lack thereof), explained one more time.

It appears that one of my previous posts was rather confusing for some readers (see this and this, also this for rebuttal).  In the post “The Junk DNA myth strikes again (next up: media hype)“, I lamented the painfully cliched tendency for authors to start every paper reporting functions for some small segment of non-coding DNA with reference to the supposed long-running neglect of such DNA as “useless junk”.  About all I had to say, really, was that this is historically inaccurate — “junk DNA” was never dismissed in any major way in the scientific literature.  So, the idea that it was is a myth.  Does this mean that the concept of non-functional DNA is a myth?  Of course not.  But let me clarify:

“Junk DNA myth”, interpretation #1: There is no “junk DNA”, where “junk DNA” is defined as non-functional DNA.  That is, there is no non-functional DNA.  I do not think this is a myth — lots of non-coding DNA is probably non-functional.  However, lots isn’t.  It’s not either-or.

“Junk DNA myth”, interpretation #2: That non-coding DNA was “long dismissed as useless junk but now we’re finding functions”.  This is a myth.  There was no such period of dismissal.  Even if there was, it could only have been between about 1985 and 1995, which is less time than the period since this claim started being made.  I have tried to show this by referring directly to the primary literature of the 1970s, 1980s, and 1990s.

So, to clarify, I do not particularly like the term “junk DNA” because a) it has changed since its original meaning, and b) it clearly is too loaded to be used effectively in objective discourse.  I do think there is a large amount of DNA in most animal genomes that does not have any function at the organism level, but I also think some of it has been co-opted for very important roles. The originators of the “selfish DNA” idea thought so too:

“It would be surprising if the host genome did not occasionally find some use for particular selfish DNA sequences, especially if there were many different sequences widely distributed over the chromosomes. One obvious use … would be for control purposes at one level or another.”
- Orgel and Crick 1980

How much is functional?  I don’t know, but I can say that since there very beginning — in the first detailed discussion of “junk DNA” ever published — the proposed figure was higher than the current data suggest:

These considerations suggest that up to 20% of the genome is actively used and the remaining 80+% is junk. But being junk doesn’t mean it is entirely useless. Common sense suggests that anything that is completely useless would be discarded. There are several possible functions for junk DNA.
- Comings (1972)

I don’t know how to state it any more clearly than this.


28 comments to The junk DNA myth (or lack thereof), explained one more time.

  • It seems the “junk DNA” is just a very crappy name for a very real phenomenon.
    “Common sense suggests that anything that is completely useless would be discarded.”
    What a hyperadaptationist view of things!
    Considering that, to my knowledge, mutations are MUCH more frequent than deletions, it would be common sense that the genome would rather quickly be filled with garbage as poorly conserved chunks of it mutate their way to oblivion (‘Junk DNA – where genes go to die.’) and transposons play wild. In the latter case, while those transposons are useless to the host (and even potentially dangerous), they are quite useful to themselves, so perhaps their ‘junkness’ becomes a rather subjective question. Perhaps those long non-functional sequences can be viewed as relics of past environments and raging wars against invasions of selfish elements. Whether these relics are ‘junk’ becomes a question of semantics, and poor wording.
    Perhaps the swelling of genomes with junk later enables them to rely on whatever structural functions the ‘junk’ DNA may by then carry — ie, one wonders if the dinoflagellates first came across some way of tolerating rampant transposon activity (and accumulation of other junk), and their massive genomes then enabled them to lose a few histones and rely on the sheer length of the DNA for structural purposes (ie the very weird chromosomes of the ‘dinokaryon’). It’s hard to imagine that this massive genome swelling (~10x that of the already-not-very-compact human genome) was initially adaptive.
    On the other hand, you can infer from cases of extreme genome reduction (eg. microsporidia, nucleomorphs), that there are certain elements so ubiquitous in more familiar (and less ‘strict’) systems that may well be dispensed with once size becomes critical. The countless hours spent attempting to devise elaborate just-so stories explaining the ‘adaptive value’ of introns look very silly in light of the nearly-complete eradictation of introns in ultrasmall genomes (although the question remains why do those 10-20 introns still linger? Perhaps they’ve become quite entrenched in their host genes and are just unlikely to go away, or perhaps there are a few that have some other function…)
    Basically, “It must have a hidden value because otherwise it wouldn’t be there” is not the right way to approach these things, IMO. Evolution is a very clumsy process, and one definitely wouldn’t hire it to create anything too streamlined within a strict time limit… (after all, it has, what, a 99.99…% fail rate?)
    But even if a better word is devised to explain this ‘evolutionary fallout’, public media is bound to screw it up nonetheless. Personally, I don’t find these semantic wars to be of much interest, but they do reflect a real divide among evolutionary biologists: the adaptationist vs. neutral evolution wars. Now, those can get kind of interesting…
    -Psi-
    (It’s finals season, thus the posting/commenting rates should go up substantially as we procrastinate diligently…)

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  • Earrnz

    What does function mean in this context?
    I’m very ignorant about genetics, so as an outsider, I have some trouble with an intuitive notion of function and the way discussions about “junk DNA” usually go.
    I use to think about function in general [I repeat, in a very intuitive, non-technical way,] as anything that modulates the development or the output of a process. Following this definition, I think you can say that all non-coding DNA has many functions. The most obvious for me is that it slows down the cell cycle. If there’s more DNA to replicate, the S phase gets longer and more expensive for the cell. So, non-coding DNA would always be functional, but it wouldn’t always have a sequence-specific function.
    What do you think about this?

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    • I think this confuses function and effect. I agree 100% that it will have an effect (most of my own research investigates that) but this is not the same as a function in all cases.

      Effect versus function

      Non-functional DNA: non-functional vs. inconsequential

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      • Earrnz

        Thanks! I really liked both articles. I missed them as I discovered your blog just about last year.
        So, following that definition of function, there can be functions only in teleonomic systems.
        Would you say that there’re no functions in ecosystems*? Just effects or “roles”?
        * I don’t see ecosystems as teleonomic systems, but I guess that’s arguable. Organisms are adapted to their niches (and construct them), so <em>there’s a close fit between cause and outcome shaped by NS</em>, but they don’t produce a <em>positive result</em>, as the ecosystem has no aparent purpose whatsoever.

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  • If “junk” DNA didn’t exist it would need to be invented. Occam’s razor: If all we had was “functional” DNA then the daily mutation rate inside cells would be destructive – if it does nothing else but provide fodder for DNA dmaage that already makes it valuable

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  • Shorter life span?

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  • Earnz says,
    <i>If there’s more DNA to replicate, the S phase gets longer and more expensive for the cell. So, non-coding DNA would always be functional, but it wouldn’t always have a sequence-specific function. What do you think about this?</i>
    If you have more DNA then you can have more replication origins. They are pretty evenly spaced out in most eukaryotic genomes.  If you want to replicate the genome quickly then all you need are lots of replication complexes (replisomes) to bind to the thousand or origins that exist in a large genome.
    The speed of replicating eukaryotic DNA should not be dependent on the size of the genome.
    Furthermore, the cell cycle isn’t limited by the duration of S phase except in some very unusual cases.
     
     

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  • Keith Grimaldi says,

    <I>If all we had was “functional” DNA then the daily mutation rate inside cells would be destructive – if it does nothing else but provide fodder for DNA damage that already makes it valuable.</I>
     
    This makes no sense.  The error rate is “per nucleotide.” Let’s assume that 5% of our genome is functional; that means 160,000 kb of functional DNA. The chance that it will acquire a mutation during DNA replication is about 1/100,000 based on an error rate of 10^-10 per nucleotide per replication.
     
    If our genome consisted entirely of functional DNA then the chance of mutating it would be 1/100,000. If our genome contained this amount of functional DNA plus 20X more non-functional DNA then the chance of mutating the functional DNA would still be 1/100,000. Junk DNA doesn’t stop mutations from happening in functional DNA.
     
    Why did you think it would?
     

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  • The problem is not the error rate in replication but the error rate in repair of damaged DNA. If all we had was “functional” DNA all damage (UV, oxidation, carcinogens, etc) would occur there, increasing enormously the chances of dangerous mutations. The “junk” soaks up the damage

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    • Protection against mutations in genes is probably the armchair hypothesis I hear most frequently.  It makes some predictions, none of which seem to be met.  For example, species exposed to UV don’t seem to have more DNA, species with high metabolisms has less DNA, etc.

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  • it may well just be an armchair hypothesis but mutation is not necessarily a bad thing, after all, it drives adaptation, selection and evolution. Species with long life spans though need protection against DNA damage because repair mechanisms are not error free. You are an expert on genome sizes and species, are there any long life span species with very little “junk” DNA? How long would a human survive with 10% of the genome (if of course 90% had no other important function other than damage limitation?).

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    • Well, birds and bats have exceptionally long lifespans for their body sizes, but smaller genomes compared to non-flying mammals of similar size. And there are plenty of animals with much larger genomes than humans — salamanders with 40x as much DNA, in fact.

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  • <blockquote cite=”Keith Grimaldi”>The problem is not the error rate in replication but the error rate in repair of damaged DNA. If all we had was “functional” DNA all damage (UV, oxidation, carcinogens, etc) would occur there, increasing enormously the chances of dangerous mutations. The “junk” soaks up the damage.</blockquote>
     
    Let’s take UV irradiation as an example to see if your explanation makes sense.  Imagine a photon of ultraviolet light passing through the body of a cell. It has to pass through all kinds of obstacles before it hits the target of 160 Mb of functional DNA. Are you saying that adding some extra DNA to the huge amount of proteins and lipids that are already in the cell will provide some significant shielding effect?
     
    Let’s think about X-rays. The worst damage is strand breakage&mdash;this is also one of the important kinds of damage with many carcinogens. Broken DNA strands can be lethal and they are hard to repair.
     
    If you expand the genome with a lot of junk DNA then you increase the chances of severe damage because the target size for strand breakage is the whole genome and not just the functional DNA.  It’s difficult to see how this jibes with your hypothesis. Can you explain?
     
     

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  •  The difference in size between 160 million bp and 3 billion bp is not that great relative to total cell size and both UV and X-rays do get to the DNA and damage it, despite the many obstacles, and if the DNA was only composed of genes then the damage would always be potentially serious. UV does damage DNA as do external carcinogens from tobacco smoke, food, pollution etc, and the most common cause of DNA adduction is endogenous oxidative damage – these are all mainly repaired by excision mechanisms which don’t involve strand breaks. X-rays cause breaks which can be lethal – and it is good that they are lethal, much better to sacrifice a single cell via apoptosis than allow it to divide with a damaged genome. But if there are strand breaks in gene(s) important for apoptosis, the chances of which would be much higher in the smaller “functional only” genome, then the chances of allowing the creation of transformed cells would be much greater too. With a larger genome the chances of any X-ray damage may be higher, but the chances of life threatening (to the organism, not just the cell) damage would actually be lower. So yes, depsite all the various barriers I am saying that adding a lot of extra DNA will provide a shield to protect the coding parts of the genome.

    The “armchair” hypothesis may be boring, too simple and unexciting but it seems possible until it is refuted. Is a  “functional only” genome compatible with a long life span? Thanks to Dr Gregory we know that the smallest bird genome is .91pg (approx 1 billion bp, is that correct?) – so it’s still not that small and the lifespan of the hummingbird is what, about 5 yrs, 10yrs? Why a newt has 10x more DNA is not really an issue for disproving this possible role of “junk” DNA

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  • The goalposts are moving so fast, I’m not even sure where they stand now.  Why don’t you provide the following, and we’ll go from there:

    1) What specific, testable predictions does your hypothesis make?

    2) What evidence would you accept as refuting the hypothesis?

     

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  • I think Keith’s understanding is that there are a set number of mutations per cell and therefore more “junk DNA” means fewer of those mutations will take place in functional genes. Not only do I find this unconvincing, I think that long stretches of non-coding DNA will increase the chances of higher-level replication errors (e.g. Fragile X syndrome, Down syndrome).

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  • Estimates of endogenous oxidative damage (8-hydroxydeoxyguanosine) range from a low end of 100 events per cell per day to 10,000 per day. Multiplied by trillions of cells coupled with the not 100% fidelity of DNA repair mechanisms mean that mutation is not a rare event. DNA damage limitation is very important for human aging as seen in the cases of the various DNA repair deficiency diseases (XP, Cockayne’s, etc). DNA is a target for oxidative damage, reducing the size of the genome e.g. by 50% would not reduce the amount of oxidative damage by 50% but would increase the levels of damage on the remaining genome (mitochondrial DNA is very small but has high damage rates, even accounting for the oxidative reactions taking place locally.
     Testable hypotheses are not so easy but i suppose there are some. It’s not of course my theory, that would be ridiculous to propose, it’s something that has been going around for ages (not surprising as it’s an obvious possibility) and does not yet seem to have been refuted. It just seems to be one of the simplest explanations that should be dismissed (with evidence) before proposing more complex hypotheses (without real evidence). It has been discussed by many others, including more recently – Patrushev, 2006, Russian Journal of Bioorganic Chemistry, Volume 32, Number 4 / July, 2006.

    1. No significant lifespan is possible with a sequence dependent functional only genome – I don’t know offhand what “significant” is, but at least  it would predict that in any creature living for more than few years the genome will be mainly “junk”, or not sequence sensitive

    2. If the bulk of DNA is “junk” then sequence preservation will not be important and will not be conserved. Take some skin fibroblasts from an individual and make monoclonal cultures from them, sequence and compare coding vs “junk” regions to compare mutation rates in different genome areas between different cells from a single individual. This will be possible in the not too distant future with “next-next” gen sequencing (whole genome in sequenced in 15 mins!). For now maybe it could be speeded up a bit by culturing in a mutagenic medium and sequencing long stretches rather than whole genome.
    3. Mitochondrial DNA will not need protection because of the number of copies per cell. Random mutations will not become established, just like a single strain of e.coli will remain the same strain unless selective pressure is applied

    4. Removal of large portions of non-sequence conserved “junk” DNA should shorten life span – this i suppose would be technically tricky

    5. Refutation – any of the following:
    a) find a long lived species with no “junk”;
    b) show that majority of DNA is highly sequence sensitive;
    c) removing “junk” has no effect on damage induced aging;
    d) explain how a “coding only” genome could sustain mitochondrial levels of damage;
    e) demonstrate other functions for the majority of the non-coding DNA;

    Chris Lawson: “I think that long stretches of non-coding DNA will increase the chances of higher-level replication errors (e.g. Fragile X syndrome, Down syndrome).  ”  OK, but does it really? and does it increase mutation or are the errors detected and cells killed by apoptosis

    Who moved the goalposts and where by the way??
     

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    •  

      Keith Grimaldi: It just seems to be one of the simplest explanations that should be dismissed (with evidence) before proposing more complex hypotheses (without real evidence).

      I think your comments are on the right track, but the one quoted here is problematic.  It is not the case that this idea is held as the explanation until it is refuted when there is no supporting evidence.  The burden of proof is on proponents to show why this idea should continue to be taken seriously.

       

       

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      •  

        T. Ryan Gregory:   I think your comments are on the right track, but the one quoted here is problematic.  It is not the case that this idea is held as the explanation until it is refuted when there is no supporting evidence.  The burden of proof is on proponents to show why this idea should continue to be taken seriously.

        Yes – here I mean that more complex theories should not be proposed in preference unless there is good evidence for them – of course that is exactly what I have been doing with protective vs. null, as explained in the other post on your later edition of the junk story!
         

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    •  

      Keith Grimaldi: find a long lived species with no “junk”;

      “No junk” is a pretty strict requirement, but here’s an interesting one.  The red sea urchin, Strongylocentrotus franciscanus, has been reported to live up to 100 years.  It has an estimated genome size of only about 800Mb.

       

       

       

       

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  • MTiffany

    Instead of “junk” DNA, how about we refer to it as “baffling” DNA, is in, we’re baffled as to what particular stretches of the genome do?

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  • Paul

    You’re right it’s a myth, and so no surprise that Richard Dawkins wrote:

    “The amount of DNA in organisms is more than is strictly necessary for building them: A large fraction of the DNA is never translated into protein. From the point of view of the individual organism this seems paradoxical. If the ‘purpose’ of DNA is to supervise the building of bodies, it is surprising to find a large quantity of DNA which does no such thing. Biologists are racking their brains trying to think what useful task this apparently surplus DNA is doing. But from the point of view of the selfish genes themselves, there is no paradox. The true ‘purpose’ of DNA is to survive, no more and no less. The simplest way to explain the surplus DNA is to suppose that it is a parasite, or at best a harmless but useless passenger, hitching a ride in the survival machines created by the other DNA.” (The Selfish Gene, p. 47)

    Perhaps you need to disown Ricard in favor of those biologists racking their brains. He gets all the press. And comes out looking like a fool, and the rest of you by extension.

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