"junk" DNA

Discussion in 'Science' started by Helen, Oct 11, 2004.

  1. Helen

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    With the publication of the sequence of human chromosome 5, there is fresh recognition that junk DNA is not junk but has "a powerful regulatory influence".

    Thought some of you might be interested in the following. I remember a few years ago, for instance, when Galatian under one of his other names and I were on another forum and he was propunding about how junk DNA was a powerful evidence for evolution...

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    Human genome hits halfway mark
    BBC News, Wednesday, 15 September, 2004 http://news.bbc.co.uk/1/hi/sci/tech/3658386.stm

    Extract on Junk DNA: It is not just the genes in chromosome five that the scientists are interested in. Volumes of genetic material lie in between the genes, which for a long time were dismissed as "junk" by researchers.
    But on closer inspection, it seems this judgement was premature. The fact that sequences of junk were conserved for hundreds of generations suggests they have a function worth holding on to.
    "Important genetic motifs gleaned from vast stretches of non-coding sequence have been found on chromosome five," said Eddy Rubin, JGI's director.
    "Comparative studies conducted by our scientists of the vast gene desert... have shown these regions, conserved across many mammals, actually have a powerful regulatory influence."


    Human chromosome 5 final sequence analysis released to public Disease genes, important regulatory elements populate vast terrain EurekAlert, Sepember 15 2004. http://www.eurekalert.org/pub_releases/2004-09/dgi-hc5091404.php

    Extract on Junk DNA: The spaces between the genes are as important as the genes themselves, said Eddy Rubin, JGI's director. "In addition to disease genes, other important genetic motifs gleaned from vast stretches of noncoding sequence have been found on Chromosome 5. Comparative studies conducted by our scientists of the vast gene deserts where it was thought there was little of value have shown that these regions, conserved across many mammals, actually have powerful regulatory influence."
    These gene-free stretches were previously considered "junk DNA," but in recent years those seemingly barren regions have taken on greater prominence as researchers have learned that they can control the activity of distant genes. Some of the noncoding regions have also stayed remarkably consistent compared with those in mice or fish rather than accumulating mutations over the course of evolution.
    "If you have such large human regions that stay conserved over vast evolutionary distances, it strongly supports the idea that they must contain something important," said Jeremy Schmutz, the informatics group leader at SHGC. Any mutation that appeared in those conserved regions was likely to have either killed the animal or made it less able to reproduce, preventing the mutation from making it to the next generation. So far, nobody has shown what role the conserved regions play. "What this says is that we don't know as much about this conserved stuff as we think we do," Schmutz said.


    The DNA sequence and comparative analysis of human chromosome 5 JEREMY SCHMUTZ, JOEL MARTIN, ASTRID TERRY, OLIVIER COURONNE, JANE GRIMWOOD, STEVE LOWRY, LAURIE A. GORDON, DUNCAN SCOTT, GARY XIE, WAYNE HUANG, UFFE HELLSTEN, MARY TRAN-GYAMFI, XINWEI SHE, SHYAM PRABHAKAR, ANDREA AERTS, MICHAEL ALTHERR, EVA BAJOREK, STACEY BLACK, ELBERT BRANSCOMB, CHENIER CAOILE, JEAN F. CHALLACOMBE, YEE MAN CHAN, MIRIAN DENYS, JOHN C. DETTER, JULIO ESCOBAR, DAVE FLOWERS, DEA FOTOPULOS, TIJANA GLAVINA, MARIA GOMEZ, EIDELYN GONZALES, DAVID GOODSTEIN, IGOR GRIGORIEV, MATTHEW GROZA, NANCY HAMMON, TREVOR HAWKINS, LAUREN HAYDU, SANJAY ISRANI, JAMIE JETT, KRISTEN KADNER, HEATHER KIMBALL, ARTHUR KOBAYASHI,, FREDERICK LOPEZ, YUNIAN LOU, DIEGO MARTINEZ, CATHERINE MEDINA, JENNA MORGAN, RICHARD NANDKESHWAR, JAMES P. NOONAN7, SAM PITLUCK, MARTIN POLLARD, PAUL PREDKI, JAMES PRIEST, LUCIA RAMIREZ, JAMES RETTERER, ALEX RODRIGUEZ, STEPHANIE ROGERS, ASAF SALAMOV, ANGELICA SALAZAR, NINA THAYER,, HOPE TICE, MING TSAI, ANNA USTASZEWSKA, NU VO, JEREMY WHEELER, KEVIN WU, JOAN YANG, MARK DICKSON, JAN-FANG CHENG, EVAN E. EICHLER6, ANNE OLSEN,, LEN A. PENNACCHIO,, DANIEL S. ROKHSAR, PAUL RICHARDSON, SUSAN M. LUCAS, RICHARD M. MYERS & EDWARD M. RUBIN. Nature 431, 268 - 274 (16 September 2004)

    Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.
     
  2. The Galatian

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    If you remember, Helen, I told you that "Junk DNA" was a misnomer; that evolution often takes unused features and reworks them to useful purposes. I suggested that this would be true of "junk" DNA (and many geneticists were arguing this before I did)

    From your link:
    "These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy."

    It is gratifying to know that it was true, after all.
     
  3. Helen

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    You have a very short term memory, Galatian. I recall you saying other things....but that's OK.

    At any rate, you will please note that all changes are harmful. Doesn't do well as evidence for evolution.
     
  4. Charles Meadows

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    Changes in DNA are not always harmful. There are certainly sequences of DNA for which we do not know a purpose - but that doesn't mean one doesn't exist.

    Mutation in DNA is definitely a cause of "microevolution". Take Staphylococcus aureus. This germ was one one many bacteria sensitive to penicillin in the 1940s when it came out. By 1951 most all Staph were resistant. In 1961 a Staph aureus strain resistant to nearly all antibiotics (except vancomycin) arose.

    These different Staph didn't just mutate from "normal ones". Changes in DNA occurred at random. Most of these mutations caused death of the bacteria - but a few were livable and just happened to confer resistance to antibiotics. When a patient got antibiotics most of the germs got killed so the only ones to replicate were the resistant ones which could grow despite the presence of the antibiotics.

    Now nearly 50% of Staph aureus are "MRSA", very resistant germs. This is microevolution at work!

    The big picture is interesting. DNA definitely points toward an evolution of some sorts - but it doesn't seem to jive with evolution over millions of years! Interesting!!
     
  5. The Galatian

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    Well, as you get older Helen, your recall may not work as it did, but yes, that's what I told you.

    And as Charles notes, there are many instances of useful mutations.

    Would you like to hear about some of them? As you once mentioned, there are often dozens of useful alleles for many human loci.

    Yet Adam and Eve could have contributed at most, four of them. From where do you think the others came?
     
  6. Gup20

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    You should know by now, Helen... that what Galation says and what Galation "SAYS" are different ;)

    It's a natural byproduct when one has comprimised and undermined themselves into oblivion.

    Evolutionists have long thought and maintained that these 'junk DNA' sections are left overs of miscellaneous strings left over from built up failed mutations. Indeed them being useful - even harmful if changed - indicates that this is not evidence of mutational leftovers, but specificly sequenced and needed information. It also serves to further decrease the mathmatical probability of evolution as well because this eliminates the 'scratch pad' which evolutionists have clung to as the junk bin for miscue mutations. It indicates that - if mutations did arise, they were perfect mutations with no wiggle room ... essentially that each of these millions of mutations that supposedly happened were a 1 in a million shot, and succeeded in spite of probability, and without error.

    Moreover junk DNA has also been considered 'evidence' of evolution as a convincer to built up mutations. Here is yet another evolutionary evidence that eventually contradicts evolution once more understanding comes.
     
  7. UTEOTW

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    I just do not see how finding that some genetic material that was not known to previously have a function in fact does have a function is supposed to be a blow to evolution. Yes much of what was previously considered to be "junk" has been found found to be useful. Much of it useful for coding RNA that regulatory in nature. But much of it really is junk. There are psuedogenes and long repetitions and retroviral insertions and other stuff that really is evolutionary leftovers. Sometimes a use is even found for some of this junk. But not ususally.
     
  8. UTEOTW

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    "At any rate, you will please note that all changes are harmful. Doesn't do well as evidence for evolution."

    Huh?

    A few that I have put on another thread recently that you may not have seen.

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=15353580&dopt=Abstract

    "Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4,000 m," Beall CM, Song K, Elston RC, Goldstein MC, Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14300-4. Epub 2004 Sep 07

    Another beneficial mutation that is spreading its way through the population. In this case, an increased ability to carry oxygen in the blood for a population living at high altitude that makes survival to child bearing age more likely.
     
  9. UTEOTW

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    "Selective sweep of a newly evolved sperm-specific gene in Drosophila," Nurminsky DI, Nurminskaya MV, De Aguiar D, Hartl DL, Nature. 1998 Dec 10;396(6711):572-5.

    In this case, two adjacent genes were duplicated in a mutation. After this, one of the copies had the non-coding DNA between the two removed. The two genes were then combined into one new, functional gene. So two genes became three. New function, new information.
     
  10. UTEOTW

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    "Adaptive evolution after gene duplication," Hughes AL, Trends Genetics, 2002 Sep.18(9):433-4.

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12175796&dopt=Abstract

    In this case a gene, RNASE1, was duplicated such that we had a new gene, RNASE1B. These genes occur in the colobine monkey, douc langur, and make pancreatic ribonuclease. Through a change in diet, the conditions within the digestive tract of the monkey were altered. Through delective pressure, the B copy of the gene mutated until it was adapted to digest single stranded bacterial RNA.

    Again, we have new information. The original gene still exists to perform its original function. The gene was duplicated. When the copy mutated, then there was information that was not there previously, namely the new DNA sequence. The second copy eventually mutated until it performed a new digestive process.
     
  11. UTEOTW

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    An example of "junk" being changed to become useful.

    "Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis," Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S, Keith JC Jr, McCoy JM, Nature 2000 Feb 17;403(6771):785-9.

    In this case, a retrovirus inserted a section of DNA into the genome. In this case, humans have co-opted the gene to serve an important role in the area of human placental morphogenesis. The purpose of the original gene was as the envelope gene of the virus. So humans gained a gene and a function which they previously did not have. The information of the human genome was thus increased.
     
  12. UTEOTW

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    In this case, parts of a gene for a pancreatic protein were used to make a new gene that makes "antifreeze" for cold water fish.

    "Origin of antifreeze protein genes: A cool tale in molecular evolution," John M. Logsdon Jr. and W. Ford Doolittle, Proceedings of the National Academy of Science, USA,Vol. 94, pp. 3485-3487, April 1997.

    If you are curious, the reference for the other "antifreeze" mentioned is DeVries, A. L. & Wohlschlag, D. E. (1969) Science 163, 1073-1075.
     
  13. Helen

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    Coming down the line here:

    Charles, I should have clarified myself a bit: all changes mentioned in the article in the lead post were shown to be harmful. I do know that not all mutations are apparently harmful. I am willing to go out on this limb, however, -- all changes involve a loss of function in one way or another.

    The staph you mentioned is NOT the example you want it to be. It is well known that single-celled organisms have hot spots on their genes where they mutate and then back-mutate with frequency. This provides a natural variation in the organism not available otherwise. Thus the staph which ALREADY had the combination of these mutations and back mutations which allowed it to resist antibiotics became the survivors under assault from antibiotics. They will still mutate and back mutate, but in the presence of antibiotics, those most antibiotic resistant will continue and propagate. They are still staph, they are still back mutating into variations of the wild form -- it's just that those individual organisms don't make it under antibiotic assault. They will never be completely wiped out because of the back and forth swing at the genetic hot spots, but as long as we use the antibiotics we use, they will remain the minority.

    Galatian, You still seem to be laboring under the misconception of one gene per trait. We know that even in the loss of function, such as the eyeless cave fish, there is a complex pathway of interactions associated with just about every trait. Thus it was not necessary for Adam and Eve to have all the variations you seem to feel are necessary. The interactions caused by slight differences and timing variations at different points along any given chromosome would be quite enough to spark quite a diversity.

    Gup20 Amen on all counts.

    UTE, You couldn't have done your research and gotten it all in one post? Nevertheless...

    "Much of it really is junk" -- please remember those words, OK?

    I am aware of the Tibetan women. If you want to call this evolution, that's fine. I consider it variation that was available in our genetic package all the time. Can you prove that different? But whatever it is, are you trying to say they have varied a step away from human beings as we know them? If not, then it is simply a human variation and has nothing to do with the sort of evolution which is being argued by evolutionists regarding a common ancestor.

    My past copies of Nature are in storage until we get into our permanent residence here (we are living in the home our kids are buying at the present, while ours is being remodeled). But if what you are saying is what I think you are saying about this article, they got a gene to divide and then, essentially, put it back together again, OK. This was done without any intelligent interaction on the part of humans, right.... :D If the answer to that is no, we keep coming back to intelligent design, a Creator, etc. I'm not surprised man can fool around with a lot of things. Why should I be?

    ditto on the monkey gene

    as far as the article in Nature 2000, I need to get the material out of storage to see if you are reporting it correctly or what. I generally go through my Natures fairly quickly and would want to go back to that one and see what actually is being reported.

    And as far as the 'antifreeze' gene is concerned, are you aware that different fish in different parts of the world have managed to achieve the same result using different genetic pathways?

    Seems it was built into fish to be able to vary in that way...

    ---------

    In the meantime, guys, the 'junk' DNA which was used as a strong argument for evolution as 'evolutionary leftovers' seems to be going the way of the 'leftover' parts of the human body -- which are not leftover at all.

    We were designed to be human beings and human beings we are, always have been, and will stay until the Lord creates the new heaven and new earth. Whether or not we will be called humans then is something I am not aware of.
     
  14. UTEOTW

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    "You couldn't have done your research and gotten it all in one post? Nevertheless..."

    Sometimes stuff like that all tends to run together if you try and put it all in one post. I am not a big fan of a bunch of short posts in a row, but sometimes I find the need.

    "This was done without any intelligent interaction on the part of humans, right.... If the answer to that is no, we keep coming back to intelligent design, a Creator, etc."

    Uh, my reading, and I could be wrong, is that the new gene was discovered on down the line after it happened in two different lines of flies. I do not think that there was an active human intervention in the gene.

    "If you want to call this evolution, that's fine. I consider it variation that was available in our genetic package all the time. Can you prove that different? But whatever it is, are you trying to say they have varied a step away from human beings as we know them? If not, then it is simply a human variation and has nothing to do with the sort of evolution which is being argued by evolutionists regarding a common ancestor."

    Well, it is hard to say yet. They have not isolated the actual gene to see if it exists elsewhere. However, there is circumstantial evidence to show that it is new. It was an argument against your statement that all change is bad. You have since clarified that statement.

    I must be honest and say that in this case I cannot be sure that I am reading it entirely correctly. Something slightly different may have happened. I don't always get technical articles exactly.

    There is also the issue that in your scenario, there can only be so many alleles of a given gene floating around. Surely something so advantageous would have been more widely spread than some folks living on top of a mountain. There wewre significant changes in mortality.

    "ditto on the monkey gene"

    No human interevention here. As I remember (I am not bothering to go back and re-read everything so this is all from memory) the change happened after a change in diet led to new selective pressures.

    "And as far as the 'antifreeze' gene is concerned, are you aware that different fish in different parts of the world have managed to achieve the same result using different genetic pathways? "

    Yes. I even gave the reference, but no further information, on another such pathway.

    "Seems it was built into fish to be able to vary in that way..."

    The variation described where a gene is duplicated and then part of the duplicate is repeatedly duplicated was a built in function. It sounds (I know you are not) like you are advocating that life is designed to evolve if that is the case.
     
  15. Charles Meadows

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    Helen,

    Resistant staph don't simply mutate back to wild-type and vice versa. This is in fact an example of microevolution based on environmental pressure. Staph either have the gene or they don't. Those that do can survive preferentially. The MRSA that exist today are clonally derived. The older MRSA are from 1961 and the newer clones from the early 90s. Some Staph are have inducible resistance - to clindamycin and not penicillin! This is a different phenomenon and does not involve mutation.

    Many of the "wild type" Staph we see in infections today are actually nutritional auxotrophs called "small-colony variants". They have lain dormant in tissues for years only to be activated by exposure to nutritional deprivation (like anti-folate antibiotics).

    The hot spot phenomenon does occur but this is not an example of it.

    This simply IS microevolution. Although the timeline of millions of years here is still a little problematic.
     
  16. The Galatian

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    Alleles are not traits, Helen. Alleles are different versions of the same gene. The point is, if we started with two people, there would be at most, 4 alleles for each gene locus. Yet many of them in humans have dozens of alleles. From where do you think the rest came?

    But all of these alleles are different, and Adam and Eve could not possibly have had all of them. Humans have, as you know, only two copies of each gene. Hence one pair could have at most four alleles. The many human alleles are, most of them, very useful and even essential to human life. So from where do you think they came?

    This would not have been sufficient to produce new alleles. That would have to have come about by mutation and natural selection.

    "Alleles are genes that reside at the same loci on homologous chromosomes and affect the same trait differently. For example, the genes that determine coat color are found at the same loci but can code for different colors."
    http://www.uark.edu/depts/anscposc/Notes/GeneticsNew.html
     
  17. UTEOTW

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    News item this week...

    http://www.cnn.com/2004/TECH/science/10/20/how.many.genes.ap/index.html

    So, there is one answer to where some of the junk really is junk.

    And I view this as a problem for YE. This is because these copies are clearly the result mutations produced as evolution proceeded. But, beyond that, these copies are very conserved over the human race. In a young earth, that would mean that almost all of the these mutations occured in the lineage that lead to our last common ancestor (Noah) and then essentially none occured in the intervening time. This is very unlikely. There were what, about 10 generations listed from Adam to Noah. And how many would have occured since then? And all these thousands of extra copies were made in 10 generations and none since? And this is without even looking to see if any of these paralogs are also found in the other apes and primates. And I thought young earthers said that the rate of mutations increased with time, not that they were all at the beginning.

    This is very similar to the argument that can be made about retroviral DNA insertions. There are several insertions of viral DNA into the human genome. Again, in a YE paradigm, you must assume that all these insertions happened in the very first generations but not since. And here we have looked at the apes and primates before on this subject. There we found that you can find the same sequences in the other apes and primates. So with these LTRs, you must not only assume that the human genome was very quickly littered with these viral inserts, you must also assume that somehow the same combintation of virii infected all of the other ape "kinds" (whatever they may be), inserted the exact same DNA sequences, that the sequences were spread to the whole populations of these different species, and that these insertions did not occur again later with such frequency if at all. Repeat this for the primates.
     
  18. UTEOTW

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    This does not have to do with junk DNA, but it does apply to the above post.

    The subject I wish to explore here is chimeric retrogenes. The basics are that mRNA is turned into cDNA through reverse transcription. This sequence is then permantently integrated into the genome by endogenous integration proteins.

    The evolution of the primates and apes can then be traced by when specific sequences were integrated into the genomes of the various common ancestors.

    When looking at this 12 specific chimeric retrogenes, you get the following chart.

    http://nar.oupjournals.org/cgi/content/full/31/15/4385/GKG496F3

    The distribution of the various genes in the various primates and apes, including humans, matches that which would be predicted through other techniques. That this technique matches that as done by other genetic, molecular and fossil methods is a very powerful combination of factors that strongly indicate the descent of humans from a common ancestor with the other apes.

    "The human genome contains many types of chimeric retrogenes generated through in vivo RNA recombination," Anton Buzdin*, Elena Gogvadze, Elena Kovalskaya, Pavel Volchkov, Svetlana Ustyugova, Anna Illarionova, Alexey Fushan, Tatiana Vinogradova and Eugene Sverdlov, Nucleic Acids Research, 2003, Vol. 31, No. 15 4385-4390.

    http://nar.oupjournals.org/cgi/content/full/31/15/4385
     
  19. UTEOTW

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    New publication.

    "Megabase deletions of gene deserts result in viable mice." MARCELO A. NÓBREGA*, YIWEN ZHU*, INGRID PLAJZER-FRICK, VEENA AFZAL, EDWARD M. RUBIN, Nature 431, 988 - 993 (21 October 2004).

    Emphasis added.

    Another brick in the wall that says much of the junk really is junk.

    And these bricks are important since there really should not be ANY junk in the genome if humans were recently created. Just the handful of bricks I have mentioned in the last few posts are strong evidence against YE. Paralogs, retroviral LTRs, and the ability to delete large scale sections of DNA all show that there really is junk in there. Some YEers like to say that the genome was "rich" and that we have been losing bits of it through time. This does nothing at all to explain the first two categories and is only marginal for the third. If genes were being lost from the initial "rich: genome at such a high rate that you could make such large scale deletions, then humans would have a hard time just matching up a couple of still functioning alleles all along the chromosomes to even begin to be able to reproduce.

    [ October 25, 2004, 08:24 AM: Message edited by: UTEOTW ]
     
  20. UTEOTW

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    This is mainly to provide some support for my assertions about retroviral DNA insertions above.

    "Constructing primate phylogenies from ancient retrovirus sequences," Welkin E. Johnson and John M. Coffin, Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, Issue 18, 10254-10260, August 31, 1999.

    Here, about a dozen different retroviral DNA inserts are used to construct the evolutionary tree of human and the other apes and primates. See the following chart to see how closely the different inserts match.

    http://www.pnas.org/content/vol96/issue18/images/large/pq1892815002.jpeg

    Emphasis added.

    http://www.pnas.org/cgi/content/full/96/18/10254
     

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