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Rob Sheldon on Larry Moran and the junk DNA

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No, not a tale, rather a reflection.

Recently, we learned that biochemist emeritus and (at one time) Uncommon Descent commenter Larry Moran is writing a book (2022) arguing that human DNA is 90% junk. Non-functional junk.

Our physics commentator Rob Sheldon writes to reflect on the many meanings of the word “function” in biology:


If I recall correctly, the original definition of “functional” was whether that piece of DNA was turned into a protein, which depended on finding a “start” and a “stop” codon. The Human Genome Project reported that some 90% of the human genome didn’t have these “start/stop” features, and hence was “non-functional”.

a) However, there was extensive editing of RNA in the “spliceosome” with the removal of introns and customization of proteins such that one “start/stop” strand of DNA could make 100 distinct proteins. So the first piece of news is that the mapping is “one to many”.

b) Since the function of start/stop was to tell the DNA polymerase where to start/stop reading, then the fact that the “spliceosome” is spitting out chunks of RNA totally indiscriminately of start/stop codons, means that start/stop is not a good way to characterize functional DNA. Some pieces were still being transcribed into protein without these markers.

The Long Ascent, Volume 2

So that led to the second method of defining “functional”. Let’s cut out that piece of DNA using CRISPR (or more likely, blocking it with a small anti-sense RNA fragment). Is the edited critter still viable after that DNA is rendered inoperable?

c) Again, a person is “still viable” without legs, just not very competitive. So what exactly does viable mean? If a bacterium lives for 2 weeks but doesn’t reproduce, is it viable? If a bacterium lives indefinitely in a Petri dish but dies when injected into a host, is that viable? If a bacterium lives in a host but dies when the host runs a fever, is that viable?

So we are back to not really knowing when something is functional or not.

So that led to a third method of defining “functional”. Let’s see if there are any protein strands in the organism that are derived from that piece of DNA.

d) But then we discovered that RNA does a million other things — it builds the ribosome, it brings in marked amino acids, it regulates transcription, it carries information outside the cell. Just because a piece of DNA isn’t converted to protein doesn’t mean that it has no function.

So we are up to our fourth method of defining “functional”. If that DNA is turned into RNA then it is functional.

e) That’s where ENCODE comes in and says that 80% and more of the DNA is converted to RNA, which is where Dan Graur loses it and starts ranting about creationists and TV sets. He builds a toy population genetics model and says that 80% destroys his model, and therefore the data is wrong. (No, he isn’t unique, all theorists harbor dark thoughts about experimentalists.)

f) But as experimentalists showed all the new things RNA does, Dan’s model gets less and less compelling. For one example, a piece of “junk DNA” was found to regulate cancer. When that junk DNA was removed, the organism died early of cancer. It was viable, just not competitive.

My analogy is that DNA is like a tool box. Just because we don’t have a hammer in our hand all day, doesn’t mean that the hammer is junk. When you need a hammer, a screwdriver just won’t do. I’ve used pipe wrenches as a hammer in a pinch, but I’ll tell you, it was ugly. My brother spent ten years as a truck mechanic, and as he would gladly tell you, he was often hired because of his toolbox.

So why should the genome be any different? Shouldn’t the default be that if some item is found in his toolbox, it has a function? Why is Dan Graur so adamant to tell my brother that his toolbox is full of junk? Whose reputation is he spitting on anyway?


Dan Graur had announced in 2014 that he didn’t “do politeness” on this topic so maybe forewarned is forearmed.

Rob Sheldon is the author of Genesis: The Long Ascent and The Long Ascent, Volume II.

See also: Larry Moran to write new book: Claims genome is 90% junk If he wants to pick a fight with ENCODE, grab a seat.

Comments
Hi UB I sent you an email, not sure if you still monitor that inbox. It didn't bounce back so it seems to be functioning. Eugene S As to this thread, what the ID critics here need to see is the Dunning-Krueger curve of how confidence depends on experience. Currently they are sitting on top of Mt Stupid that zero experience coupled with highest confidence is characteristic of. If they really want to engage though, what follows is a dramatic drop of confidence as real experience gets accumulated (the so called Valley of Dispair), and finally the long and steady ascent on the Slope of Enlightenment, as an internet critic painfully turns into a real expert. It takes one years to undergo all these changes. As of now though, they are looking down on us off the top of Mt Stupid.EugeneS
April 19, 2021
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Orthomyxo Not sure what value there is in asking someone without a highschool level of understanding about biology to share their opinion about a biological question. Start codons have nothing to do with DNA polymerase, and DNApol isn’t involved in gene expression. It’s also bizarry to imagine people using crispr shortly after the publication of the human genome
What are you talking about? What "level" of biology when scientists thought that coding proteins (2 -3 % of total) DNA are functional and enough for life . They tought ink and paper is enough to appear a Shakespeare 's book or bricks and cement are enough for building a Cathedral. On the contrary without the mind of the playwright or the mind of the architect ink ,paper and bricks will remain unchanged. What level and quantity of information do you need to make paper or ink ? Not to much compared with "magical" combination of ink and paper made by Shackespeare. And no Shakespeare didn't put a piece of paper and ink in a box and then shaked de box to obtain a book .Sandy
April 17, 2021
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The genetic code is a set of rules involved in the transcription of DNA into mRNA (via RNA polymerase) and the subsequent translation of the processed mRNA into a polypeptide, ie a sequence of amino acids. mRNAs REPRESENT amino acids. That is what makes it a code- the symbolic representation of of one thing for another. There isn't anything in physics or chemistry that determined the pairings. Just because purely physical and chemical processes are used to carry it out doesn't mean the genetic code is reducible to those processes.ET
April 17, 2021
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. As the genuine semiotic system that the gene system was predicted (and experimentally confirmed) to be, each object specified by the system requires one material object to serve as a rate-independent symbol vehicle, and second object (a non-integrable constraint) to establish what is being specified ... correct? This is the point where you get to deny recorded science and history. Let us watch.Upright BiPed
April 17, 2021
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The thread is about (Barry's ignorance of) the genetic code. Your post isn't about the genetic code and UB took tens of posts to present a distinction without a difference about one detail of the code.orthomyxo
April 17, 2021
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ortho
I can only repeat my first comment in that thread, do you understand what is meant by “genetic code”?
I wouldn't call that a substantive response to questions posed to you on that entire thread as well as the discussion here. But that you "can only repeat" - yes, we have discovered that.Silver Asiatic
April 17, 2021
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It appears to me that ortho is making the case that how a car functions is entirely determined by the physical properties of the car, and UB is arguing that the functional qualities of the car cannot be reduced to the properties of the materials of the car.William J Murray
April 17, 2021
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. (My earlier comment somehow appeared on the wrong thread. I repeat it here) - - - - - - - - - - - - - - - - - - - Ortho is certainly not the first person on UD to state explicitly (or imply) that the gene system is the product of pure chemistry. My issue with Ortho on that particular thread (which originated from a heated exchange between two other participants) is that he claimed, more than once, that the next amino acid bound to a nascent polypeptide is determined by dynamic forces of base pair complementarity. That is flatly incorrect (i.e. it is determined by the physical properties of the aaRS). He begrudgingly conceded that point, then quickly punted away any value to the observation. He asked me why I thought it was important and I gave him the answer – among other things, it helped confirm (along with many other observations) the prediction of a symbol system as the fundamental requirement of the gene system. He had no further comments.Upright BiPed
April 16, 2021
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I can only repeat my first comment in that thread, do you understand what is meant by "genetic code"?orthomyxo
April 16, 2021
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Ortho
You might want to read the actual thread, with non clipped comments:
Thanks. I read the entire thing. I'm surprised you referred me to it. You and Ed George repeated the single argument (paraphrasing) "the entire process is determined by chemical properties and reactions". Barry, Upright BiPed and ET attempted to explain why this is not the case. I think every IDist here on UD could see how you had entirely missed the point and had no response to it. To me it is crystal clear and blatantly obvious. But maybe you don't understand or see what the argument against you was saying. I find that hard to accept because you didn't ask any questions about the details of what was presented. Again and again, arguments and evidence were provided, but there was no engagement, no buy-in from you guys. You just fell back on the one argument: "all chemicals". After a while, as UBP explained more and more, you stopped asking about what he meant. If you needed clarification, why not explain what you didn't understand, or how much of it you did understand? But then you and Ed George just became quiet - holding to the same argument "it's all just chemical properties and reactions". Again, being charitable, most the IDists here have seen this argument many times so for us it puts a radiant spotlight on the major problem of the materialist story -- but someone new to the concept might not understand the terminology or what, precisely it is pointing to. The fact that you directed me to read the thread tells me that. So perhaps if you work in the field of biology (as it seems), all of your intellectual work is done from some starting assumptions, and from that you just analyze what is seen, using those rules and concepts. You wouldn't normally question the rules of your work - you just accept what is there. Plus, you wouldn't look at the deeper problems that are with regard to the origin of such processes (that's what ID looks at - how could they evolve). You just accept that "they evolved and here they are". But we're asking for some evidence on how a discontinuous process of code-sender-translation-receiver resulting in variable, specified functions can be the product of modifications over time, or even of blind, unintelligent matter and regularities (chemical properties and reactions). Maybe it's just the level of study in a field making it hard to see outside of those assumptions. It's like a guy who works a printing press - all day long, analyzing the quality, improving flow, darkness of print, duration of paper, speed, cost. Then someone says "you know, I really wonder how Shakespeare could produce such beautiful poetry and incredible literature". The guy says "Duh. He had a good pen, ink and some paper. What do you think?" No, we're talking about what he wrote. The vocabulary, rhythm, diction, clarity of images, his influences, surprising plot twists, unity of theme, characterization, historical accuracy, how he connected one theme to another, sub-texts, hidden references. The guy: "Like I said! When the ink goes on the paper, it makes very dark marks and it stays there. The paper is light, the ink is dark. The pen distributes the ink. His hand moved it. 100% of what he did is just that. What do you think it's some kind of non-ink and paper magic?" If you're looking just at one thing all the time - if that's your work, I can understand how you would see the answer to those questions in that light. The idea that it's the creative intelligence that generates the work would be lost to a person in that situation. I don't know - again, I'm trying to be charitable. You think your view was vindicated on that thread so both sides are talking past each other.Silver Asiatic
April 16, 2021
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. I second that motion. Read it.Upright BiPed
April 16, 2021
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You might want to read the actual thread, with non clipped comments: https://uncommondescent.com/intelligent-design/stunning-levels-of-ignorance-regarding-the-genetic-code The topic was Barry's ignorance of the genetic code, UB tried to salvage something but never made a clear statement of what he was trying to say or why it matters. Not a very useful way to spend time, so I asked him to make a clear statement instead of asking leading questions.orthomyxo
April 16, 2021
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You might want to read the actual thread, with non clipped comments: https://uncommondescent.com/intelligent-design/stunning-levels-of-ignorance-regarding-the-genetic-code The topic was Barry's ignorance of the genetic code, UB tried to salvage something but never made a clear statement of what he was trying to say or why it matters. Not a very useful way to spend time, so I asked him to make a clear statement instead of asking leading questions.orthomyxo
April 16, 2021
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UBP
UB: They are independent, Ortho. The establishment of the code is physicochemically independent of the reading of the codons, right? Ortho: I ahve work to do today, so I’m not very interested …
Ok, that was brilliant and hilarious ... reading that I literally LOL.Silver Asiatic
April 16, 2021
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. Hi Ortho, Firstly your opening comment on this thread was opportunistic and unnecessarily condescending. Secondly, this is not the first time you’ve appeared on this board with a razor and an attitude. And when you get called out on the things you say, your pattern is to become suddenly disinterested and far too busy polishing your smugness to respond. I suppose that’s all fine, but you shouldn’t expect a free pass — not when you are being unnecessarily aggressive, nor when you are being unnecessarily aggressive and simultaneously misinformed.
Ortho: It’s absolutely the case that the next amino acid in a developing protein is determined by chemistry. That’s how the genetic code works. UB: Neither the physical properties of the DNA nor RNA triplet establish which amino acid is presented for binding in the ribosome. That is established independently (spatially and temporally) by the physical properties of the aaRS. This means the system is not reducible to dynamics, but to a specific type of organization, and further, to simultaneous coordination within that organization. Ortho: Well, I’m not actually here to teach you high school biology. But binding of codons to anti codons and the action of RNApol is all well-documented in many places. Upright BiPed’s comment gets us one layer deeper into the chemical reactions. The tRNA-ligases (also called aminoacyl-tRNA synthetase or aaRS) are the enzymes that link amino acids to a specific tRNA, but that’s chemistry too. UB: Ortho, is the codon-to-anticodon association spatially and temporally independent of the anticodon-to-amino acid association? Ortho: I don’t really know what you are getting at Upright, do you want to spell it out instead? UB: Ortho, I am having a hard time grasping how much more clear I can be. To specify a particular amino acid for binding during synthesis there must be (as you clearly suggest and seem to understand) two associations made. One of those associations is the codon-to-anticodon association, and the other is the anticodon-to-amino acid association. I am simply asking if those two chemical events are spatially and temporally independent of one another? Ortho: I mean they are happening in a cell with lots of fluxes across time and heterogeneity in space. If you are trying to make some specific point that takes us beyond chemistry, please go ahead. UB: They are independent, Ortho. The establishment of the code is physicochemically independent of the reading of the codons, right? Ortho: I ahve work to do today, so I’m not very interested … UB: Ortho, by all means go on and do your work When you’ve freed up your mind from your work, you’ll find that the association between the codon and the amino acid is a discontinuous association. It is not established by dynamics, but by a) a specific type of organization, and b) simultaneous coordination between two independent sets of multiple sequences. That’s the way the system “works”.
lol “fluxes across time”, that’s a good one.Upright BiPed
April 15, 2021
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cutting and running from what, exactly. You asked a wildly off-topic question about something that doesn't interest me very much.orthomyxo
April 15, 2021
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. Yes, cutting and running seems to be your best move.Upright BiPed
April 15, 2021
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Well, even if he meant RNApol (maybe), there is still the issue that start codons aren't associated with transcription start sites (apart from being relatively nearby). The whole text is full of equally horrible confusions. I'm not really very interested in the origin of life questions like the first aaRS, and given our last conversation served to be a massive waste of time I'm even less interested in this one.orthomyxo
April 15, 2021
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. Yep, lug nuts don’t have anything to do with tires either. I can spot, all the way across the room, that the writer very likely meant “RNA” polymerase. And no one in biology has ever made that mistake, writing DNA when they meant RNA, or vice versa. But while you are gracing us with your presence, can you answer a question: when the first ever aaRS was synthesized from memory, how many of the other aaRS had to be in place? Some fellas down at the bar were asking.Upright BiPed
April 15, 2021
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Not sure what value there is in asking someone without a highschool level of understanding about biology to share their opinion about a biological question. Start codons have nothing to do with DNA polymerase, and DNApol isn't involved in gene expression. It's also bizarry to imagine people using crispr shortly after the publication of the human genomeorthomyxo
April 15, 2021
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Not sure what value there is in asking someone without a highschool level of understanding about biology to share their opinion about a biological question. Start codons have nothing to do with DNA polymerase, and DNApol isn't involved in gene expression. It's also bizarry to imagine people using crispr shortly after the publication of the human genomeorthomyxo
April 15, 2021
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On the spliceosome, does anyone have a link explaining how the spliceosome knows how to cut a pre-mRNA strand into mRNA? Presumably, it needs some sort of marker on the pre-mRNA, but I don't haven't seen anything written about this.efalken
April 15, 2021
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Of note to 'functionality, and as I cited on the other thread this morning,
,,,, as with the structural considerations cited above, functionality is not limited a particular sequence being transcribed. In fact, what is termed ‘poly-functionality’, (John Sanford), is ubiquitous in and for DNA and is completely inexplicable on Darwinian presuppositions.
Multiple genetic codes Excerpt: Trifonov,, was also the first one to demonstrate[20] that there are multiple codes present in the DNA. He points out that even so called non-coding DNA has a function, i.e. contains codes, although different from the triplet code. Trifonov recognizes[19]:5–10 specific codes in the DNA, RNA and proteins:,, chromatin code (Trifonov 1980) RNA-to-protein translation code (triplet code) framing code (Trifonov 1987) translation pausing code (Makhoul & Trifonov 2002) protein folding code (Berezovsky, Grosberg & Trifonov 2000) fast adaptation codes (Trifonov 1989) binary code (Trifonov 2006) genome segmentation code (Kolker & Trifonov 1995) The codes can overlap[19]:10 each other so that up to 4 different codes can be identified in one DNA sequence (specifically a sequence involved in a nucleosome). According to Trifonov, other codes are yet to be discovered. http://en.wikipedia.org/wiki/E.....etic_codes Multiple Overlapping Genetic Codes Profoundly Reduce the Probability of Beneficial Mutation George Montañez 1, Robert J. Marks II 2, Jorge Fernandez 3 and John C. Sanford 4 – May 2013 Excerpt: In the last decade, we have discovered still another aspect of the multi- dimensional genome. We now know that DNA sequences are typically “ poly-functional” [38]. Trifanov previously had described at least 12 genetic codes that any given nucleotide can contribute to [39,40], and showed that a given base-pair can contribute to multiple overlapping codes simultaneously. The first evidence of overlapping protein-coding sequences in viruses caused quite a stir, but since then it has become recognized as typical. According to Kapronov et al., “it is not unusual that a single base-pair can be part of an intricate network of multiple isoforms of overlapping sense and antisense transcripts, the majority of which are unannotated” [41]. The ENCODE project [42] has confirmed that this phenomenon is ubiquitous in higher genomes, wherein a given DNA sequence routinely encodes multiple overlapping messages, meaning that a single nucleotide can contribute to two or more genetic codes. Most recently, Itzkovitz et al. analyzed protein coding regions of 700 species, and showed that virtually all forms of life have extensive overlapping information in their genomes [43]. 38. Sanford J (2008) Genetic Entropy and the Mystery of the Genome. FMS Publications, NY. Pages 131–142. 39. Trifonov EN (1989) Multiple codes of nucleotide sequences. Bull of Mathematical Biology 51:417–432. 40. Trifanov EN (1997) Genetic sequences as products of compression by inclusive superposition of many codes. Mol Biol 31:647–654. 41. Kapranov P, et al (2005) Examples of complex architecture of the human transcriptome revealed by RACE and high density tiling arrays. Genome Res 15:987–997. 42. Birney E, et al (2007) Encode Project Consortium: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816. 43. Itzkovitz S, Hodis E, Sega E (2010) Overlapping codes within protein-coding sequences. Genome Res. 20:1582–1589. Conclusions: Our analysis confirms mathematically what would seem intuitively obvious – multiple overlapping codes within the genome must radically change our expectations regarding the rate of beneficial mutations. As the number of overlapping codes increases, the rate of potential beneficial mutation decreases exponentially, quickly approaching zero. Therefore the new evidence for ubiquitous overlapping codes in higher genomes strongly indicates that beneficial mutations should be extremely rare. This evidence combined with increasing evidence that biological systems are highly optimized, and evidence that only relatively high-impact beneficial mutations can be effectively amplified by natural selection, lead us to conclude that mutations which are both selectable and unambiguously beneficial must be vanishingly rare. This conclusion raises serious questions. How might such vanishingly rare beneficial mutations ever be sufficient for genome building? How might genetic degeneration ever be averted, given the continuous accumulation of low impact deleterious mutations? http://www.worldscientific.com.....08728_0006
Of related interest as to what other functions that ‘junk DNA’ has now been found to have
New Book on "Junk DNA" Surveys the Functions of Non-Coding DNA - April 29, 2015 Excerpt: Carey,, goes on to explain how today we now believe that, far from being irrelevant, it's the "junk DNA" that is running the whole show: "The other shock from the sequencing of the human genome was the realisation that the extraordinary complexities of human anatomy, physiology, intelligence and behaviour cannot be explained by referring to the classical model of genes. In terms of numbers of genes that code for proteins, humans contain pretty much the same quantity (around 20,000) as simple microscopic worms. Even more remarkably, most of the genes in the worms have directly equivalent genes in humans. As researchers deepened their analyses of what differentiates humans from other organisms at the DNA level, it became apparent that genes could not provide the explanation. In fact, only one genetic factor generally scaled with complexity. The only genomic features that increased in number as animals became more complicated were the regions of junk DNA. The more sophisticated an organism, the higher the percentage of junk DNA it contains. Only now are scientists really exploring the controversial idea that junk DNA may hold the key to (increasing) complexity. (p. 4),,," She goes on to spend the bulk of the book reviewing the numerous discoveries of function for non-coding "junk" DNA. Just a few of those include: * Structural roles such as packaging chromosomes and preventing DNA "from unravelling and becoming damaged," acting as "anchor points when chromosomes are shared equally between different daughter cells and during cell division," and serving as "insulation regions, restricting gene expression to specific regions of chromosomes." * Regulating gene expression, as "Thousands and thousands of regions of junk DNA are suspected to regulate networks of gene expression." * Introns are extremely important: The bits of gobbledygook between the parts of a gene that code for amino acids were originally considered to be nothing but nonsense or rubbish. They were referred to as junk or garbage DNA, and pretty much dismissed as irrelevant. ... But we now know that they can have a very big impact. (pp. 17-18) * Preventing mutations by separating out gene-coding DNA. * Controlling telomere length that can serve as a "molecular clock" that helps control aging. * Forming the loci for centromeres. * Activating X chromosomes in females. * Producing long non-coding RNAs which regulate Hox genes or regulating brain development, or serving as attachment points for histone-modifying enzymes helping to turn genes on and off. * Serving as promoters or enhancers for genes, or imprinting control elements for "the expression of the protein-coding genes." * Producing RNA which acts "as a kind of scaffold, directing the activity of proteins to particular regions of the genome." * Producing RNAs which can fold into three-dimensional shapes and perform functions inside cells, much like enzymes, changing the shapes of other molecules, or helping to build ribosomes. As she notes: "We've actually known about these peculiar RNA molecules for decades, making it yet more surprising that we have maintained such a protein-centric vision of our genomic landscape." (p. 146) * Serving as tRNA genes which produce tRNA molecules. These genes can also serve as insulators or spacers to stop transcription from spreading from gene to gene. * Development of the fingers and face; changing eye, skin, and hair color; affecting obesity. * Gene splicing and generating spliceosomes. * Producing small RNAs which also affect gene expression. http://www.evolutionnews.org/2015/04/a_new_book_on_j095611.html
Also of note,
Jonathan Wells Was Right: Non-coding DNA Continues to Show Function December 10, 2019 https://evolutionnews.org/2019/12/jonathan-wells-was-right-noncoding-dna-continues-to-show-function/
bornagain77
April 15, 2021
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Our physics commentator Rob Sheldon writes to reflect on the many meanings of the word “function” in biology:
With all due respect to physicist Robert Sheldon, given that we have just been discussing how much weight should be given to the opinions of experts on matters outside their own field of expertise, might it not be more appropriate to consider the reflections of biochemist Laurence Moran on the meaning of the word "function" in the context of the human genome? He has after all written a sequence of lengthy posts on this very subject on his blog Sandwalk under the heading of "The Function Wars". For example:
On the Meaning of the Word "Function" A lot of the debate over ENCODE's publicity campaign concerns the meaning of the word "function." In the summary article published in Nature last September the authors said, "These data enabled us to assign biochemical functions for 80% of the genome ...." (The ENCODE Project Consortium, 2012). Here's how they describe function.
Operationally, we define a functional element as a discrete genome segment that encodes a defined product (for example, protein or non-coding RNA) or displays a reproducible biochemical signature (for example, protein binding, or a specific chromatin structure).
What, exactly, do the ENCODE scientists mean? Do they think that junk DNA might contain "functional elements"? If so, that doesn't make a lot of sense, does it? Ewan Birney tried to address this definitional morass on his blog [ENCODE: My own thoughts] where he says ....
It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be. This question hinges on the word “functional” so let’s try to tackle this first. Like many English language words, “functional” is a very useful but context-dependent word. Does a “functional element” in the genome mean something that changes a biochemical property of the cell (i.e., if the sequence was not here, the biochemistry would be different) or is it something that changes a phenotypically observable trait that affects the whole organism? At their limits (considering all the biochemical activities being a phenotype), these two definitions merge. Having spent a long time thinking about and discussing this, not a single definition of “functional” works for all conversations. We have to be precise about the context. Pragmatically, in ENCODE we define our criteria as “specific biochemical activity” – for example, an assay that identifies a series of bases. This is not the entire genome (so, for example, things like “having a phosphodiester bond” would not qualify). We then subset this into different classes of assay; in decreasing order of coverage these are: RNA, “broad” histone modifications, “narrow” histone modifications, DNaseI hypersensitive sites, Transcription Factor ChIP-seq peaks, DNaseI Footprints, Transcription Factor bound motifs, and finally Exons.
That's about as clear as mud. We all know what the problem is. It's whether all binding sites have a biological function or whether many of them are just noise arising as a property of DNA binding proteins. It's whether all transcripts have a biological function or whether many of those detected by ENCODE are just spurious transcripts or junk RNA. These questions were debated extensively when the ENCODE pilot project was published in 2007. Every ENCODE scientist should know about this problem so you might expect that they would take steps to distinguish between real biological function and nonfunctional noise. Their definition of "function" is not helpful. In fact, it seems deliberately designed to obfuscate.
Seversky
April 14, 2021
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