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Not dead yet: junk DNA is back

A controversy at last: most of our DNA is junk, no it isn’t, yes it is. Actually, I think it is – up to 90% really is junk. Last year The Conversation published an article with an exciting headline: Human…

The use of the term “junk DNA” has always been controversial. Nick Kidd

A controversy at last: most of our DNA is junk, no it isn’t, yes it is. Actually, I think it is – up to 90% really is junk.

Last year The Conversation published an article with an exciting headline:

Human Genome 2.0: ENCODE project debunks “junk” DNA.

ENCODE, in this case, referred to the Encyclopedia of DNA Elements, a large international research project that undertook new mapping of the genome in terms of features associated with gene regulation.

But one odd thing about the article was that – apart from the title and first line – it hardly mentioned junk DNA.

The most important statement came from an insightful comment, from Brendan Zietsch, a post-doctoral researcher at the University of Queensland, who pointed out that it was misleading to say the ENCODE project had debunked junk DNA.

He referenced some excellent work by genomics expert Sean Eddy explaining that junk DNA lives on (for details, see Eddy’s blog and his published commentary).

Last month another top geneticist, Dan Graur from the University of Houston, Texas, and his colleagues published a great paper in Genome Biology and Evolution that also countered the ENCODE conclusions about the death of junk DNA.

Graur’s is one of the most spirited demolition jobs I have ever read. If you have time it is worth reading it in full. If not, the title gives you a taste:

On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE.

Graur’s is a bitingly witty paper. It runs for 40 withering pages and doesn’t hold back.

Below are some of my thoughts on junk DNA. In short, it looks like the Eulogy for junk DNA, published in Science last September, together with the catchy paper No more junk DNA, could win prizes for the most misleading headlines of the year.

What is junk DNA?

Viruses and other small things that replicate rapidly and have large populations, have genomes with very little junk DNA. Viruses can’t afford to carry unnecessary baggage. Competing viruses without baggage take over.

dullhunk

Bacterial, and many - but not all - fungal genomes are also pretty compact. Big things, like us, seem to have accumulated DNA, and done so at a much faster rate than we jettison it.

Since we lumber along slowly and only reproduce every 20 years or so, the extra load hasn’t seemed to matter.

Think of DNA as being like computer data or code. Since your phone is small it just can’t store that much, but in the case of your office hard-drive or server, there is no need to delete every spam email or every draft copy of every document you write.

It is an effort to find things and delete them. You don’t want to delete the wrong thing or something that you might need one day. Gradually stuff builds up.

Every now and then email attachments, computer viruses or worms arrive. They are inactivated or quarantined, but lifeless copies of them pile up as well.

It is estimated that perhaps two-thirds of our genome is made up of parasitic virus-like sequences - transposable elements (or jumping genes), which are simply selfish entities that replicate themselves, much like computer viruses or worms. Nearly all of them are now inactive and harmless.

It isn’t easy for our genomes to actually throw them out because they are stitched in among more valuable DNA – so we simply leave them there.

Then there are extra copies of genes – sometimes replication goes wrong and extra copies arise. Some of these acquire new functions but most just lose function altogether and are called pseudogenes.

There are lots of repeated sequences in our genomes.

As a general rule the genome hangs onto things rather than throwing them out. All the machinery is blind.

Since some of the stuff in our genomic shed is so important our life depends on it, it is usually best not to throw things away.

Junk and garbage

The non-functional bits are termed junk DNA. The expression was coined by the respected geneticist Susumu Ohno in 1972.

The term has always been controversial. The Nobel Laureate Sydney Brenner made the distinction between junk and garbage.

Junk is stuff you keep – because you don’t get round to throwing it out and perhaps a few bits and pieces will become useful.

Garbage is stuff that begins to smell and you get rid of it. There isn’t much garbage on computer drives and there isn’t much garbage in genomes – but there is lots of junk.

So why did the ENCODE project and the media announce that 80% of our DNA is functional and that junk is dead? Mostly because they defined the word “function” loosely.

What is function?

Function is a tricky word. The junk in the bottom layer of my shed has a function – it serves as a shelf for the top layer and keeps it off the damp floor. The top layer has a function too – it serves as a cover for the bottom layer and keeps it free from dust. My junk has also recently acquired a new function – that is, causing my house to fill up with stuff since the shed is now full.

But those functions are ridiculous. In Dan Graur’s paper he uses other nice examples of ludicrous functions. The biological function of the heart is to pump blood but one could argue that another function of the heart is to make a noise.

He points out that the ENCODE team defined function in the wrong way and this in part led them to suggest most of the genome is functional and therefore not junk.

For the ENCODE team DNA was considered functional if it is:

  • transcribed (i.e. copied into RNA)
  • binds a DNA-binding protein, or lacks associated packaging proteins called histones, or has histones with special marks
  • is methylated.

j.e.proctor

But none of these characteristics, or these activities, is a good measure of function. The junk in my shed may be looked at occasionally (or photographed even, like being copied into RNA), it may be labelled by a post-it note – fragile or do not touch – (analogous to being tagged with a DNA-binding protein, or a histone or by methylation).

Both Sean Eddy and Dan Graur point out that if ENCODE had included the ability to be replicated (copied into DNA) rather than simply transcribed (copied into RNA), ENCODE could quickly have declared 100% of the genome to be functional.

But being subjected to these activities, or having markers such as methylation or histones are not functions.

The key point is that the bits of junk in my shed are not things I would miss if they were broken. Thus they are non-functional.

Big science

What has gone wrong here? The fact is that ENCODE was a “big science” reference data collection exercise that checked for genomic labels and activity but not for function. Previous work had considered function by looking at conservation. Useful things are conserved and one misses them when they are gone.

Current estimates suggest only about 9% of our genome shows evidence of being under selective pressure and functional, not 80%. In other words up to 91% is junk and it is still junk despite the headlines.

So was ENCODE bad? Not at all. The purpose of ENCODE was not to determine whether or not our DNA is junk: the purpose was to catalogue the markings. A great deal of cataloguing was done, and done very well. The data will be useful. The problem was that the work was published in 30 papers.

Lawrence OP

Exciting headlines and take-home messages had to be squeezed out. Big investments in big science demand big outcomes, and this can cause problems.

In a world of “publish or perish” it wasn’t enough to just say: “the data is now available on the web” and leave it at that. There had to be headlines. Nothing is more exciting than the idea that most of our genome has a secret function waiting to be discovered.

What could be better than overturning the idea that most of our genomes are junk and rewriting all the textbooks?

Science is driven by the hope of discovery. Humans are motivated by hope and hype. But that is not such a bad thing. Columbus may have wanted to find a short cut to India; Burke and Wills wanted to find the inland sea, thought to be in the middle of Australia.

Newspaper articles frequently declare that we only use 10% of our brains. These hopes were not well-founded but I rather admire the people who go out on a limb and are always looking for new things.

Columbus made a big discovery and although Burke and Wills didn’t find rich farmlands, the land they mapped is rich in minerals. And there will be new discoveries in the genome too. Junkyards can become evolution’s playgrounds.

Every now and then a bit of DNA that was termed junk will be found to have acquired a genuine function - it will be a real treasure, and that will make the headlines.

And, yes, there may be some functional bits amid the junk that we have overlooked. But most of our DNA will still be junk.

So in my view junk is junk and I expect that at least 80% of our DNA is junk.

But don’t worry: I also predict at least 80% of the mysteries of the genome remain to be discovered. So genetics, too, is far from dead.

Join the conversation

42 Comments sorted by

  1. Baron Pike

    logged in via Facebook

    Spoken like a true neo-Darwinist.

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  2. Alex Cannara

    logged in via Facebook

    "Junk DNA is back" -- really?

    "What could be better than overturning the idea that most of our genomes are junk" -- maybe studying what actually goes on it the overall genetic and cellular systems?

    "There are lots of repeated sequences in our genomes." -- indeed, and these author doesn't seem to get that some repetitions are there to trap short sequences that can be trouble, like viral transposons.

    But this is good...

    "As a general rule the genome hangs onto things rather than throwing…

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  3. Stephen Ralph

    carer at n/a

    and all this time i thought i was just unwell.

    damn that junk dna.

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  4. Dale Bloom

    Analyst

    I have sometimes wondered if dinosaurs were more or less evolved than present day animals.

    We tend to think of dinosaurs as being primitive animals, but that could be a matter of subjective opinion only, and dinosaurs seemed to find a use for more DNA than present day animals.

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  5. Chris Booker

    Research scientist

    Arrrhhh.. junk DNA, again! I really wish this term would hurry up and run off to die. And I mean that as a biologist who is genuinely interested in evolution and all the mystery of genetic material that it entails. Also, I'm actually reading Ohno's work right now, and have a lot of respect for the guy, but I think this 'junk DNA' term was the mistake of his career. Now, that rant aside, here's my more serious response:

    We really need to do away with the term 'junk DNA'. Let's face it, we're still…

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    1. Dan Smith

      Network Engineer

      In reply to Chris Booker

      I'm getting the impression you're not a fan of the term. :)

      Junk DNA is a bold, media-friendly phrase, and like "selfish gene", its original purpose as a slightly provocative analogy is sadly crowded out by semantic arguments and misunderstandings. The distinction between junk and garbage is useful but, ironically, perhaps only to those who accept the original term in its more humble role as analogy. To those set against the description in the first place, it probably makes things worse to break…

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    2. Mike Swinbourne

      logged in via Facebook

      In reply to Chris Booker

      Chris

      I am by no means an expert on this subject, but as an interested lay person I would appreciate the thoughts of an expert on a thought I once had.

      A lot of small animals (eg spiders) have 'innate intelligence' which enables them to undertake quite complex tasks like spinning a web. They aren't taught how to do this, which means it must be inherent in them somehow, and must therefore be passed somehow from generation to generation. The only way I know of that can do this is in the genes/DNA.

      Could it be that the so-called 'junk DNA' contains a lot of the code for knowledge and capabilities which are passed from generation to generation without the necessity to be taught by their parents?

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    3. Chris Booker

      Research scientist

      In reply to Mike Swinbourne

      Re: Dan Smith. Yes I see your points. I guess I just wonder sometimes whether this whole 'media-friendly' term approach, God particle, junk DNA, etc. actually ends up doing harm in the process by creating an unrealistic picture of the science. It seems to me you could communicate something clearer without the need to use these kinds of phrases, although obviously I see why they get picked up in the mainstream media.

      And as for the spider idea Mike, it seems to me the only way they could be able to do this is via genetic information, but I have no idea how they manage to pull off those feats of web-building!

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  6. Cris Kerr

    Volunteer Advocate for the value of Patient Testimony & Sustaining our Public Healthcare Systems

    It's junk DNA until proven otherwise, either individually or collectively, then at that time it is deemed to have value.

    Not being able to determine what something does or how it does it is not evidence that it does nothing and has no purpose.

    Hopefully no-one will patent our 'junk DNA' or decide to design a new human life without 'junk DNA' before this riddle can be solved :-)

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  7. Mark King

    Senior Lecturer, Psychology and Counselling and Researcher, CARRSQ at Queensland University of Technology

    A good article. For me, one of your key statements was "All the machinery is blind", a point which is often misunderstood and frequently obscured by the intentional language used by scientists as well as non-scientists (and especially the media). As an example, Maeterlinck's "Life of the Bee" is a classic in ethology, but employs highly unscientific and intentional language. Arguments that all DNA must have a function are similar, and smack strongly of the fallacious assumptions that characterise a lot of evolutionary psychology, where it is often assumed that every human characteristic must have an evolutionarily selected purpose. This kind of assumption has been around since Darwin (Spencer was an obvious exponent). It is unfortunate that many scientists think of philosophy as irrelevant to science - it has a lot to teach about logic, theorisation and fallacies.

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    1. Baron Pike

      logged in via Facebook

      In reply to Mark King

      So are you supposing that junk DNA at no time had a function, or that if even some once did, those have no purpose now as a pre-adaptive set of options?

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  8. Peter Ormonde
    Peter Ormonde is a Friend of The Conversation.

    Farmer

    People look into my shed with its mountains of gear piled in perfectly arranged chaos and say it's junk - but no - all useful, all necessary and all irreplaceable.

    The point is that just because some orderly tidy person takes a peek and recoils in horror doesn't mean it's junk or even just "held in reserve" awaiting a use to be found. It just means they don't grasp the essential value and purpose. Nor do I yet.

    Very little waste in nature's shed either. We just need to work out what it's for.

    'Cause the one iron clad Law of Sheds is that as soon as you clean it out and throw away all that "junk", the very next day you'll realise that piece of rusted flat metal that used to be stored safely over there would have been perfect for that now impossible task or purpose.

    More than "junk", more than safely stored away in endless piles of gibberish letters... it's perfect for doing something - we just don't know what. Yet.

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    1. Stephen Ralph

      carer at n/a

      In reply to Peter Ormonde

      an irrefutable law of nature peter........not just of sheds.

      but thats the physical side, sometimes junk thoughts need to be jettisoned. otherwise they pile up and become a headache.

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    2. Peter Campbell

      Scientist (researcherid B-7232-2008)

      In reply to Peter Ormonde

      Peter,
      In the case of your shed you have have review mechanism for deciding what might come in handy some time and what might not. It might not be perfect but it is there. I'm sure there are somethings you have thrown out!
      Biology isn't like that. Organisms don't really have a way to look at a sequence and decide that it might come in handy. Instead the organism with the bit of DNA either reproduces and propagates that bit of DNA or it doesn't.
      If that bit of DNA is harmless it might stay in…

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    3. Baron Pike

      logged in via Facebook

      In reply to Peter Campbell

      "Biology isn't like that. Organisms don't really have a way to look at a sequence and decide that it might come in handy. Instead the organism with the bit of DNA either reproduces and propagates that bit of DNA or it doesn't."
      Except that organisms do look at these sequences and rewrite the instructions all the time. Otherwise you have non-intelligent nature intelligently changing sequences by accident.
      And the appendix situation is nothing but a bad analogy, physical versus informational, even though it's turning out that it has current uses after all.

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    4. Peter Ormonde
      Peter Ormonde is a Friend of The Conversation.

      Farmer

      In reply to Peter Campbell

      Extraordinary claims require extraordinary proof Peter.

      And I have a notion that alleging "waste" or surplus inactive useless DNA is an extraordinary claim. Might be true. And certainly those strings opf CATGs piled up mile after mile do look pretty useless. But we have no proof... just inference. And given what we don't know I don't think that's sufficient.

      Bit like the appendix analogy which - far from being some useless primordial relic of a healthier diet actually does have some sort…

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    5. Peter Campbell

      Scientist (researcherid B-7232-2008)

      In reply to Peter Ormonde

      I guess the term I would prefer would be something like 'apparently junk' DNA. I don't disagree that much of it might be found to have some function but I don't find it an extraordinary claim that much of it might not.
      The appendix analogy may not have been ideal since it does make sense that it could have some benefit as a gut flora reserve etc. Nonetheless, my point is that life tends to be contingent and messy, not as tidy and perfect as people tend to suppose.
      I expect that you are right that…

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    6. Peter Campbell

      Scientist (researcherid B-7232-2008)

      In reply to Baron Pike

      I hope Baron Pike is not running an 'intelligent design' argument. I'll assume not.
      When DNA is replicated there are proof-reading enzymes that check for errors in the new DNA strand against the template strand.
      Also, there is a process called gene conversion. This is a bit like the process that gives gene duplications in reverse. Two somewhat similar genes, the consequence of some old gene duplication can have enough similarity of sequence to have some sequence from one used in the similar part…

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    7. Peter Ormonde
      Peter Ormonde is a Friend of The Conversation.

      Farmer

      In reply to Peter Campbell

      "...the balance favours a fair bit of 'apparent junk' hanging around for a long time before it is removed."

      Sounding more like my shed moment by moment Peter. I suspect that my stockpiles could do with a decent edit actually.

      It's certainly a curious business... and that's the best sort of business after all.

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    8. Peter Campbell

      Scientist (researcherid B-7232-2008)

      In reply to Peter Ormonde

      " "...the balance favours a fair bit of 'apparent junk' hanging around for a long time before it is removed."

      Sounding more like my shed moment by moment Peter. I suspect that my stockpiles could do with a decent edit actually."

      So to keep the analogy going... If you did not have a way to decide what was essential equipment and what was junk in your shed you would not last long if you kept your shed very neat and tidy by frequently and regularly tossing stuff out at random. Pretty soon you…

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    9. Peter Ormonde
      Peter Ormonde is a Friend of The Conversation.

      Farmer

      In reply to Peter Campbell

      Choose intelligently? Not quite - invariably I choose wrongly Peter. Guaranteed to be indispensable and irreplaceable once the truck disappears from view. One can never fully anticipate what needs will arise. This, at least, has been my defence of hoarding with a succession of excessively orderly partners passing through my life.

      It would of course make more sense if the "junk? DNA" we were hoarding itself made more sense. But from what I recall one of the characteristics that saw it binned…

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    10. Dale Bloom

      Analyst

      In reply to Baron Pike

      There are two interesting questions.

      Were animals supplied with a large amount of DNA, in case they needed it?

      Or did they manufacture DNA when they needed it?

      If the former, then the theory of evolution can be put into the back of the filing cabinet.

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    11. Dianna Arthur

      Environmentalist

      In reply to Peter Ormonde

      "But I'd have a hunch that we will actually discover what all this "junk DNA" does and how it works within this thrifty framework. If not - and it really is just lead in our evolutionary saddlebags -it will be unique in nature. And that requires serious underatnding and proof to convince me. Meanwhile I'm hanging on to mine - just in case."

      I'm with you Mr O - just because we don't understand something fully, doesn't mean we label it "junk" - I find that approach self-limiting - like "here be dragons".

      The comparison of mammals and other large creatures to viruses regarding DNA storage is spurious indeed. Dare I say comparing clams to fungi?

      We just don't know - yet.

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    12. Dale Bloom

      Analyst

      In reply to Dianna Arthur

      That becomes the flaw of science.

      Getting the money to carry out “further research”.

      Money is usually obtained by extracting resources from the environment, and then selling it in some form.

      Eventually, society may not be able to extract enough from the environment to fund “further research”.

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  9. Sean Lamb

    Science Denier

    It is a pretty rigorous definition of junk versus functional. After all - to the despair of PhD students around the world - there are a lot of genes you can knock out and not see much difference. Are they junk genes?
    Is it true that it is too difficult for our genomes to eliminate noise - or is it rather the cases that we developed into multicell organisms because we took a strategy of accumulating debris that makes fertile soil for evolution - while our equally successful cousins the E. coli took the strategy of a pared down genome.In other words, we can't afford to accumulate excess genetic baggage because we are large complex organisms with slow generation times, we became large complex organisms because we accumulated excess DNA.

    Probably it would have been better all round if no one had ever coined the term junk DNA - as it seems to spark debates that in the end are about nothing more interesting than semantics.

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  10. Meow-Ludo Meow-Meow

    logged in via Facebook

    I think you should have listed the fact that your research into transcription factors could create a bias in the writing of this article. I believe that the role that junk DNA may play in the role of transcription and translation presents a lot of competition to funding for your research if it turns out that 'junk DNA' plays a bigger role in these processes.

    Also, during the first three years of my time at UNSW we were taught to embrace paradigm shifts in science. I think that this article serves to reduce funding and public support towards a clearly emerging shift, and lecturers at UNSW should be encouraging students to embrace new ideas even if they challenge established ones, and even if they challenge ideas that cause the school to attract research funding.

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  11. Will Kemp

    science student

    "Since we lumber along slowly and only reproduce every 20 years or so, the extra load hasn’t seemed to matter."

    I don't really see what reproduction's got to do with it. As i understand it, DNA gets copied every time a cell divides - and that happens a lot more than once every 20 years!

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    1. Merlin Crossley

      Dean of Science and Professor of Molecular Biology at UNSW Australia

      In reply to Will Kemp

      Hi Will
      You make a really interesting point. I think what I was trying to say was that we take so long to reach reproductive maturity that the rate at which our cells double isn’t holding us back. Our cells can double every day in the lab at least, and we need remarkably few doublings, in theory at least.
      Imagine a new born baby. The baby may be one and a half feet tall. After one doubling the baby is three feet tall. After another doubling the baby is six feet tall and full grown. So in theory…

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    2. Will Kemp

      science student

      In reply to Merlin Crossley

      Hi Merlin,

      I think you need to cube those figures - hopefully the baby grows in three dimensions! ;-) But I get the general idea. It is an interesting subject.

      Regards
      Will

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    3. Merlin Crossley

      Dean of Science and Professor of Molecular Biology at UNSW Australia

      In reply to Will Kemp

      Hi Will,

      brilliant. You're right. I'm thinking of a family of Rubik's cubes now. My one would look pretty silly compared to its parents if it only doubled twice. As you say it should double 8 times to reach adulthood. Still not that many duplications but a lot more than 2. Thanks again for your important input here.

      All the best
      Merlin

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    4. Will Kemp

      science student

      In reply to Merlin Crossley

      It would be an interesting exercise - and possibly not that hard to do - to roughly estimate the amount of energy used to copy junk DNA during, say, the first 10 years of life. I'd imagine it would probably be quite a bit - although insignificant as a proportion of the body's total energy use over that period.

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    5. Merlin Crossley

      Dean of Science and Professor of Molecular Biology at UNSW Australia

      In reply to Will Kemp

      Hi Will

      yes, that's a good idea too. Like you I expect it would be a very small fraction of total energy expenditure. But knowing the number might help illustrate why the extra DNA isn't a significant burden.

      On top of this there may well be advantages to having the extra DNA. Some people say it provides a safe place for jumping genes to crash down in - without disrupting genes, others that it provides genetic plasticity and evolutionary variation which is good in the long run. There may be other ideas too.

      All the best
      Merlin

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    6. Alex Cannara

      logged in via Facebook

      In reply to Merlin Crossley

      There's plenty of recent publication of what functions our ignorantly-named "junk DNA" performs, even in a recent Scientific American.

      So this odd near-acceptance of the thesis that seems to be: "If we don't know what it does, it must be junk", is an excellent example of how easily our minds move toward comfort, bias & lazy thought.
      ;]

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    7. Dianna Arthur

      Environmentalist

      In reply to Alex Cannara

      I do believe junk DNA is wasted on some people.
      ;)

      Alex, I do so love it when we are sympatico, makes me feel all warm and fuzzy.

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    8. Dianna Arthur

      Environmentalist

      In reply to Stephen Ralph

      Stephen

      AC would not be my first trans-Pacific encounter.

      However, as you say, this is about Junk DNA - who can say how much junk was involved when I was somewhat 'international'?

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    9. Dianna Arthur

      Environmentalist

      In reply to Stephen Ralph

      Dunno 'bout that Mr R - I do apply some discernment, whereas Alex will "take anything he can get".

      :P

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  12. Benny Vallejo

    logged in via email @yahoo.com

    It seems that you might not have actually read Sean Eddy's blog. which is a non peer reviewed opinion piece, and while it is true he is critical of the way it was reported in major News papers. If you actually read his post he remains silent on the thirty plus online papers published in Nature and other journals which confirm these findings. In fact his argument is not that its untrue, but that this should be no big news. Like T Ryan Gregory I'm sure that Eddy can point to prior research which questioned…

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