Another accidental use for “junk DNA”

_{Denyse O'Leary

October 7, 2016

'Junk DNA', Intelligent Design, News}

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mouse embryo showing enhancer activity (blue stain) in heart/Berkeley Labs

Researchers have shown that when parts of a genome known as enhancers are missing, the heart works abnormally, a finding that bolsters the importance of DNA segments once considered “junk” because they do not code for specific proteins.

…

“The cardiac changes that we observed in knockout mice lacking these enhancers highlight the role of noncoding sequences in processes that are important in human disease,” said study co-senior author Axel Visel, senior staff scientist and one of three lead researchers at the Mammalian Functional Genomics Laboratory, part of Berkeley Lab’s Environmental Genomics and Systems Biology (EGSB) Division. “Identifying and interpreting sequence changes affecting noncoding sequences is increasingly a challenge in human genetics. The genome-wide catalog of heart enhancers provided through this study will facilitate the interpretation of human genetic data sets.” Paper. (public access) – Diane E. Dickel, et al., Genome-wide compendium and functional assessment of in vivo heart enhancers. Nature Communications, 2016; 7: 12923 DOI: 10.1038/NCOMMS12923 More.

See also: Formerly thought “junk DNA,” lncRNA guides development of heart muscle cells

and

The latest in functional junk DNA

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Comments

BTW, do you know that they have HIV virus from the 1920's? Why didn't AIDS appear in the 20's? Can anyone answer that?PaV_{October 13, 2016
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Just out today: Formation of new chromatin domains determines pathogenicity of genomic duplicationsPaV_{October 13, 2016
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When the only place you can find support is an article from an HIV/AIDs denier hosted by an anti-vaccination website you might be a long way out on a very thin limb... # Really PaV? HIV/AIDs denialist, and anti-vaccer site?
When did the genetic fallacy become a logical argument against anything?Vy_{October 12, 2016
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rvb8: Peter Duesberg was the preeminent virologist in the United States at the time of HIV discovery. But because he thought Robert Gallo was wrong in his assertion that HIV caused AIDs, he was systematically marginalized, his lab resources were reduced, and graduate students taken away from him. Why? Had he had a stroke, or a brain tumor that affected his thinking? No. Had he had some kind of psychotic break? No. He just didn't agree with the "consensus" view. So they set out to destroy him. And what was the "consensus" view in the middle 80's? That a vaccine would be developed in two years time. Tell me, rvb8, are you aware of any vaccine for HIV? I'm not. Fascism, even if it is practiced by scientists, is unhealthy and harmful. That's the whole point of UD.PaV_{October 12, 2016
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I've just been following this exchange and can not add to the argument, I believe 'wd', has things well in hand. Really PaV? HIV/AIDs denialist, and anti-vaccer site?rvb8_{October 11, 2016
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I knew that is exactly how you would respond. The "only" place. Really. Go put your head back into the sand.PaV_{October 10, 2016
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When the only place you can find support is an article from an HIV/AIDs denier hosted by an anti-vaccination website you might be a long way out on a very thin limb...wd400_{October 10, 2016
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Here's what they say:
'In many cases, translocations are what turn a normal cell into a cancer cell,' co-author Albino Bacolla said. Bacolla is a research associate in the Vasquez Lab. 'What we found in our study was that the sites of chromosome breaks are not random along the DNA double helix; instead, they occur preferentially at specific locations,' Bacolla said. 'Cruciforms structures in the DNA, built by the short inverted repeats, mark the spots for chromosome breaks, mutations, and potentially initiate cancer development.'
Not random, eh? Sounds like epigenetics to me---and not neo-Darwinism.PaV_{October 10, 2016
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Sampling "the aneuploid fitness landscape. . . ," though it involves mutations, is outside the 'gene-centric' view of traditional population genetics. Neo-Darwinism explains very little. Please consult Behe's book: The Edge of Evolution.PaV_{October 10, 2016
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From the web:
The current emphasis in cancer research on the search for mutant genes in a perpetual background of aneuploidy is a classic example of not seeing the forest for the trees. Thomas Kuhn remarked that the great theoretical advances of Copernicus, Newton, Lavoisier, and Einstein had less to do with definitive experiments than with looking at old data from a new perspective.Sufficient (indeed overwhelming) evidence is already in hand to convict aneuploidy of the crime of cancer and release gene mutations from custody [6-17]. Nevertheless, the gene-mutation theorists, when faced with the undeniable evidence that aneuploidy is necessary for cancer, have adopted a fall-back position. They argue that gene mutations must initiate the aneuploidy [18], or as the Scientific American reported, referring to a researcher in Vogelstein’s lab, "[Christoph] Lengauer insists aneuploidy must be a consequence of gene mutations" [1].
Here's the citation #18 from the quote above. And this is also interesting.PaV_{October 10, 2016
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BrianFraser @18: As a follow up to the comments @20 --confirming that the answer you got @19 is grossly incomplete and inaccurate at the best-- you may want to look at the paper reference posted @2117 in this link: https://uncommondescent.com/intelligent-design/mystery-at-the-heart-of-life/#comment-618883 Enjoy it!Dionisio_{October 10, 2016
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I know about CIN and other cancer cell karyotypes... what I was asking for was evidence for your claim that a "gene centric" view had lead cancer biologists to ignore chromosomes. You're own links mention that this has been a topic of investigation for many decades. That last paper you link is pretty interesting though, isnt' it. Good example of how evolutionary biology informs cancer biology, and how cancer phenotypes (like chomromosome misegration) are brought about by genetic mutations.wd400_{October 9, 2016
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In summary, it is evident that chromosome missegregation may be as important a factor in tumor development as DNA mutations and chromosomal translocations. Until recently, little attention has been paid to the process of whole-chromosome imbalance. Given the widespread relevance of CIN in human cancers, understanding the mechanisms that lead to chromosome missegregation, the role it plays in the evolution of tumors, and the potential for therapeutic intervention will provide a significant improvement in our ability to find cures for resistant cancers.
Here's the paper.PaV_{October 9, 2016
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From: from a two-minute google search:
The most striking visual hallmark of cancer cells is their abnormal number of chromosomes and chromosome arms. This feature, known as aneuploidy, was first seen in 1914 by Theodor Boveri who observed that tumor cells consistently display an abnormal number of chromosomes—either missing entirely, missing parts, or copied over as extras—compared to normal diploid cells. Yet a century after Boveri, scientists still aren’t exactly sure if aneuploidy and other kinds of related chromosomal mayhem drive tumorigenesis or if they are simple bystanders. An answer to this longstanding conundrum has now emerged from a new computational study by Howard Hughes Medical Institute investigator Stephen J. Elledge and colleagues at Harvard Medical School who present evidence that aneuploidy patterns of chromosome deletion or amplification that are recurrent among tumors actually represent a driving force during tumor evolution and are very frequent in cancer.
One hundred years of looking for point mutations, when all along, aneuploidy was staring everyone in the face. That's how scientific dogma (mutations are the cause of all that ails us) can prove harmful.PaV_{October 9, 2016
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So your game is to put words into my mouth? And you're too lazy to look things up?PaV_{October 9, 2016
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So it's dangerous to be knowledgeable, and you have no intention of providing evidence to support your claims?wd400_{October 9, 2016
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wd400:
Sure, though of course my perspective in this case has the advantage of being informed by reality.
Isn't also possible, if not likely, that this "informed" position is a disadvantage since it is filled with presuppositions that go unchallenged? It was not an "informed" and "knowledgeable" adult who told the Emperor that he had no clothes, but a simple child.
You’ll have to provide details about how gene-centric view blinkered doctors and scientists from studying chromosomes in cancer, or indeed what progress might have been made with the technologies available to researchers when they were so blinkered if they’d focused on chormosomes instead of genes.
No, I don't. You can look for the information yourself. I'm quoting authors who have studied the field and written papers. Just look around.PaV_{October 9, 2016
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butifnot, You may want to look at the paper reference posted @2109-2111 here: https://uncommondescent.com/intelligent-design/mystery-at-the-heart-of-life/#comment-618798 As you can see, the comment @19 is embarrassingly off the target. :) Genuine humility is a required attitude for approaching scientific research seriously. Unfortunately it's very rare these days. That's why we see so much pseudoscientific hogwash within otherwise interesting research papers. Really pathetic.Dionisio_{October 9, 2016
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butifnot, @24 I was referring to your comments @23. Regarding your comments @22:
Which is more amazing – The blithe dismissal of the stunningly incredible engineering we are discovering Or the engineering of life itself ?
I believe the former is just the natural human rebellious attitude against our responsibility to test everything and hold onto what's right. I don't think there's anything amazing in that. The latter is indeed far beyond amazing, which should lead us to contemplate it in awe and worship the Creator.Dionisio_{October 9, 2016
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butifnot, Yes, that's a good analogy. Thank you. However, in this case it's much worse than that. We humans (including scientists) still don't know all the ingredients that go into the enchilada. But definitely are clueless about the recipe and many don't realize it takes a knowledgeable chef to get the enchilada ready to eat. :) All that said, I won't be surprised if there's some mess in the biological systems, after the messy history since the beginning of humanity. Portions of the genome could be messed up too. Historically we haven't taken good care of ourselves or the environment. Instead we have messed things up badly. Had we stayed in Eden, things would have been much cleaner and in good shape. But we prefer to do things our way instead of our Creator's way. Too late, can't complain now. Actually, it's amazing how robust the biological systems are. After so much messing things up through human history, a less robust system would have stopped functioning long ago. BTW, the robustness is another layer of complexity added to a complex system. The whole enchilada is complex complexity on steroids. We look forward with increasing anticipation to reading future research papers describing new discoveries that shed more light on the beautifully elaborate informational choreographies orchestrated within the biological systems. :)Dionisio_{October 9, 2016
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Origenes #21 et all Ingredients versus the recipe, and the 'cook'butifnot_{October 9, 2016
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Which is more amazing - The blithe dismissal of the stunningly incredible engineering we are discovering Or the engineering of life itself ?butifnot_{October 9, 2016
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Brian Faser #18,
Brian Faser: What part of DNA codes for shapes? What encodes the shape and length and location of a bone? What encodes facial features? Doesn’t DNA code for things besides proteins?
I have asked very similar questions to Larry Moran and wd400:
If most of our genome is junk, then where is the information stored for the (adult) body plan? Where is the information stored for e.g. the brain? And where is the information stored for how to build all this?
Their answers:
Larry Moran: …. experts do not see a need to encode body plans and brain in our genome …

wd400: If it is not clear enough, there is no over-arching “plan” in the genome. There are genes, that have regulatory elements, which produce gene produces respond to environments and influence other genes and so on and so on.
Eric Anderson summarized their position as follows:
Eric Anderson: … this thread may have uncovered at least one aspect of the simplistic thinking that leads a person to believe that most DNA is junk. After all, the thinking goes, all we need to do is specify some parts in the DNA and the machine will build itself all by chemistry. It’s easy! No plan needed. No program required. Just specify some gene products and we’re done. Everything else is probably just junk. Amazing what chemistry can do.
- - - A more principled problem for neo-Darwinism (and neutral theory) is that DNA is simply at the wrong level to organize things. In his book ‘Darwin’s Doubt’, Stephen Meyer offers the following analogies:
At a construction site, builders will make use of many materials: lumber, wires, nails, drywall, piping, and windows. Yet building materials do not determine the floor plan of the house or the arrangement of houses in a neighborhood. Similarly, electronic circuits are composed of many components, such as resistors, capacitors, and transistors. But such lower-level components do not determine their own arrangement in an integrated circuit …. In a similar way, DNA does not by itself direct how individual proteins are assembled into these larger systems or structures—cell types, tissues, organs, and body plans—during animal development.

“Detailed information at the level of the gene does not serve to explain form.” [Müller and Newman, “Origination of Organismal Form,” 8]
Origenes_{October 9, 2016
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BrianFraser @18: Excellent questions. However, the answer you got @19 is incomplete at the best. Let's suppose you don't know much about music. One day you listen to Beethoven's 9th Symphony and ask how is that music produced? The answer you got @19 is analogous to saying that there is an orchestra that uses sheet music and several instruments. That wouldn't answer your question, would it? You would expect a better explanation, wouldn't you? The sentence @19 "The details are pretty complex..." is a gross understatement. The real thing is complex complexity on steroids. The final picture is not ready yet. Don't let anyone fool you. For example, check this out: https://uncommondescent.com/intelligent-design/mystery-at-the-heart-of-life/#comment-618792 If we pay attention to details, any biology research paper we read may provoke a series of "how?" and "why?" questions. Perhaps sometimes those fundamental questions are overlooked. All we need is to recover the sense of wonder we had when we were children. Keep asking questions. The more, the better. Don't worry if a professor from the U of T in Canada says that you don't ask honest questions. Actually, that would be a nice compliment. :)Dionisio_{October 9, 2016
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Hi Brian, The shape and length of bones are encoded in DNA... through protein coding genes (and functional RNAs) and through the regulation of gene expression. The details are pretty complex, but something like the action of FGF and WNT proteins in limb buds should give you and idea how these processes work.wd400_{October 8, 2016
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What part of DNA codes for shapes? What encodes the shape and length and location of a bone? What encodes facial features? Doesn't DNA code for things besides proteins? Just wondering.BrianFraser_{October 8, 2016
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Origenes, Moran is being skeptical of the claim that there a are millions of enhancers. There certainly aren't millions of known enhcnacers, GP, I'm talking about the press release and the parroting of it by News. The paper is certainly an achievement (most importantly, I think, for being able to find small effects). If 10% of the predicted enhancers turned out to be something that would be interesting, but that hasn't happened. PaV,
Obviously you have a different view of these things. Yet, it is beyond conjecture that the ‘gene-centric’ view of biologists certainly kept doctors and researchers locked into looking at particular genes when it came to cancer, and so kept them away from looking at the increasingly apparent role that chromosomes themselves play in oncogenesis.
Sure, though of course my perspective in this case has the advantage of being informed by reality. You'll have to provide details about how gene-centric view blinkered doctors and scientists from studying chromosomes in cancer, or indeed what progress might have been made with the technologies available to researchers when they were so blinkered if they'd focused on chormosoomes instead of genes.wd400_{October 8, 2016
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wd400: Obviously you have a different view of these things. Yet, it is beyond conjecture that the 'gene-centric' view of biologists certainly kept doctors and researchers locked into looking at particular genes when it came to cancer, and so kept them away from looking at the increasingly apparent role that chromosomes themselves play in oncogenesis. This is no more than a cautionary note as to the harm that comes from being locked into the "consensus view." It affects physics, just like it affects biology. We're dealing with human beings---and, more practically with governmental funding agencies staffed by humans---and so a certain amount of this is unavoidable; however, it's up to the scientists themselves to make sure it remains limited. But, once again, you seem to miss the larger point: Moran calculates 200 enhancers per gene. Well, doesn't this paint a much more complex view of what "fitness" means---the very concept that lies at the bottom of neo-Darwinism. "Fitness" needs to be rethought. And the incredible complexity we see more and more of in cellular life needs to be reckoned with, and not just ignored. How do you get 20,000 genes and 2 million enhancers to work together? To say random forces can bring this all about just staggers the mind.PaV_{October 8, 2016
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wd400: I must disagree with you about this paper. While I certainly agree that enhancers have been known for a long time as functional DNA, this is probably the first attempt at identifying all possible enhancers involved in the function of one specific organ (the heart) by specific bioinformatic methods applied to the whole genome. The quantitative results are important. They find that about 8% of the whole genome is a candidate, and they also try to narrow that quantity by a score. Now, even is only 10% of that were confirmed as having a specific enhancer function for the heart, that would still be an important result. In the end, continuing this kind of analysis, we could reasonably find that a much bigger part of non coding DNA is involved in enhancer activity than previously thought. That would be an important achievement, don't you agree?gpuccio_{October 8, 2016
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Are “enhancers” considered to be part of “Junk-DNA” or not? Wd400 suggests in post #1 that this is obviously not the case and I, trusting that no one is his right mind would do such a thing, affirmed the obvious in post #2: “Surely, those thousands of mapped enhancers were not considered junk-DNA.” However, now I’m not so sure: Here Larry Moran discusses a paper by W. de Laat et al. Larry summarizes their position on enhancers thusly:
Larry Moran: The authors claim that there are millions of enhancers in the human genome. If we take "millions" to mean just two million then there are, on average, one hundred enhancers per gene. This means that expression of each gene in our genome is regulated, on average, by the binding of 100 transcription factors to 100 transcription factor binding sites (= enhancers). Thus, a lot of our genome (40%) is devoted to regulation.
If these “enhancers” are not considered “junk-DNA”, as wd400 claims, then the human genome has, at the very least, less than 60% junk-DNA. Right? Yet, at another blog post by Larry we can also learn the following numbers:
Total Essential/Functional (so far) = 8.7% Total Junk (so far) = 65% Unknown (probably mostly junk) = 26.3%
IOWs most of the “enhancers” that W. de Laat et al speak of is considered to be “total Junk” or “probably mostly junk”. Why? That’s not very clear. Larry again:
Larry Moran: It also can't be a general rule that the average gene is regulated by one hundred transcription factor binding sites. That doesn't make any sense. Why would most genes need this level of control?
“Why would most genes need this level of control?” Now, that’s a weird question.Origenes_{October 8, 2016
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