Cell biology News

DNA’s scissors’ lock mechanism

Spread the love

From Phys.org:

Alyssa Ward, a graduate student in Desiderio’s laboratory, says that the system works like the bolt on a door. The PHD piece is the lock, H3K4me3 is the key and the deleted piece is the actual bolt. When all of the pieces are normal, H3K4me3 unlocks the PHD segment, which moves the bolt so that the door can open— i.e., so that RAG can cut. If there is a mutation in the PHD, the key won’t fit the lock, so the door remains bolted. But, if the lock or bolt is removed entirely, the door can open and close freely.

Follow UD News at Twitter!

Hat tip: Timothy Kershner

80 Replies to “DNA’s scissors’ lock mechanism

  1. 1
    ppolish says:

    “If there is a mutation in the PHD, the key won’t fit the lock, so the door remains bolted.”

    Mutations locking out Evolution? Mutations leading to cancer? Well, look on the bright side, mutations gives you wings. Open that lock, we got wings coming through.

  2. 2
    polistra says:

    Nature invented Tenure!

  3. 3
    AVS says:

    Once again, a scientist’s layman-terms explanation is quoted as evidence that the innerworkings of cells are similar to something of our own intelligent creation.
    You guys love to take over-simplified comparisons that are meant to help you understand the results, and use it as evidence that cells are just like the intelligently designed machines of the human world.
    They’re not. They have very little in common actually.
    Many cellular processes could be explained by the statement that was quoted; allosteric binding induces conformational change, which activates the catalytic domain of a protein complex.
    If you guys understood basic molecular biology, you would know this.

  4. 4
    ppolish says:

    “just like the intelligently designed machines of the human world”

    It’s not just humans, AVS. Others show ID. Chimp sticks, beaver dams, ant colony, etc etc etc. How does ID enter Nature? At what level?

  5. 5
    AVS says:

    PP, are you trying to compare molecular machinery to chimp sticks, beaver dams, etc. now?
    I’m not really sure where you’re going with that, but sure.

    Intelligence and its use by different species has evolved just like everything else in nature.
    You’re two questions don’t really make sense to me.

  6. 6
    ppolish says:

    AVS, I’m saying that ID in Nature can obviously be seen in chimp sticks, human sporks, etc etc. I’m asking at what level does ID emerge in Nature?

    At the level of consciousness?

    Hard Core IDer would put ID at the very start. Fine Tuning just another way of saying Intelligent Design.

    Hard Core Materialist would deny ID completely – a spork the result of random action giving an appearance of design.

  7. 7
    AVS says:

    Intelligent designs emerge in nature when intelligence evolves. Different levels of intelligence evolve, corresponding with different levels of intelligence in designs, tool use, etc.

  8. 8
    ppolish says:

    Fair enough, AVS. You put ID downstream from I. Agree with you there. Can’t be having an ID without an I:)

  9. 9
    AVS says:

    Which brings us back to the original problem: that IDers like to pretend that the inner workings of the cell are intelligently designed, and use layman-terms explanations (like the one above) as evidence.
    In reality, though, these explanations are simply meant to aid in understanding, and are more often than not, far from what is really going on.
    As I said, the quoted explanation of how the transposase works could be an explanation for a number of enzymes in the cell. Not to mention the fact that the researchers don’t even know what the protein looks like. It is simply an analogy meant to explain their results to you in an extremely simplified manner.

  10. 10
    ppolish says:

    AVS, it is very common for materialist biologists themselves to use design metaphors when describing the inner workings of nature. Terms like “factories”, “assembly lines”, “bolt lock scissors” show up all the time.
    It’s very hard to avoid using design terms. Especially since the design terms are appropriate.

  11. 11
    AVS says:

    As I’ve already said, these design terms are used to explain findings in a way that those unfamiliar with the topic can understand. These analogies only work at a superficial level.
    “Factories” is a very general term and sure you can apply it to the mitochondria for example because it converts energy and generates a product.
    The phrase “assembly lines” can be used to describe reaction pathways, but in reality, the chemical pathways in the cell are not linear, often flow in both directions and even do so simultaneously.
    Sure the transposase mentioned in the original post cuts something into two pieces, but it does not do so in any way similar to scissors and the “unlocking/locking” mechanism is surely nothing like that of a deadbolt. As I said, it works just like many other enzymes; allosteric binding induces a conformational change, which activates a catalytic site.

    Using design terms is only appropriate when explaining a process to someone unfamiliar with the topic. This is because most people are familiar with these basic design terms. When you get down to it, however, the molecular functioning of cells is nothing like the man-made world. The problem is, most people have no clue how molecular biology actually works and this fact is preyed upon by you and your fellow IDers.

  12. 12
    Joe says:

    AVS- Explaining how the system works is a far cry from explaining how it came to be. We can explain how computers work in terms of physical properties but that doesn’t mean computers are reducible to those physical properties.

    ID will go away as soon as someone comes up with a way to test the claim that living organisms emerged from interactions of matter and energy.

    And did you ever find out how to test your claim pertaining to what makes an organism what it is? Developmental biology hasn’t been able to answer that question but perhaps you have found something they missed.

  13. 13
    AVS says:

    Ah yes, Joe, the good ol’ “you haven’t explained how it evolved yet” argument. My favorite ID debating tactic at work again.

    I don’t need to test my claim. It’s already been proven that the genome and differential gene expression of that genome is what makes an organism what it is.

    In fact, I just read a paper showing a little bit of “how it came to be,” enjoy:

    “Deep conservation of wrist and digit enhancers in fish”
    Gherke et al. 2014

  14. 14
    Joe says:

    AVS- Obviously you are just willfully ignorant of both what is being debated and what science is.

    It’s already been proven that the genome and differential gene expression of that genome is what makes an organism what it is.

    Bull- that is pure nonsensical bull. The sad part is you really believe it.

    And Gherke can’t explain fish nor those enhancers so perhaps he should start there. Yours can’t get beyond populations of prokaryotes given starting populations of prokaryotes

    Ahh, AVS, all bluff and bluster and still no clue what is going on

  15. 15
    AVS says:

    “that’s bull”
    “evolution hasn’t explain this, evolution hasn’t explained that.”
    “you haven’t reproduced the evolution of eukaryotes from prokaryotes”
    Ha. More of my favorite ID debating tactics. When are you guys going to start a series of posts on them?
    You have demonstrated your complete lack of knowldge on the subject of biology time and time again to the point where your “arguments” no longer merit a response.
    Let me know when PPolish returns would ya? At least he was making some sense.

  16. 16
    Mung says:

    AVS:

    Which brings us back to the original problem: that IDers like to pretend that the inner workings of the cell are intelligently designed, and use layman-terms explanations (like the one above) as evidence.

    Are you one of those who have your own subjective morality like keiths? Why OUGHT NOT IDers pretend whatever they like, including that the inner workings of the cell are intelligently designed?

    And by the way, it’s not just the inner workings.

    I’m still waiting for an even remotely plausible account of the origin of cell membranes. Do you know of one?

    Do you think the first cells just had anything and everything passing across the barrier? Not much of a barrier that.

  17. 17
    AVS says:

    You’re right mungy, IDers can pretend whatever they like. Certainly don’t let things like “facts” get in the way!

    In FACT =) there is evidence that simple lipids can be synthesized from hydrogen gas and carbon dioxide, in a reaction catalyzed by minerals within hydrothermal vents. Meteorites have also been found to harbor lipids if you’re into panspermia-type ideas. Most importantly is that these lipids are amphipathic molecules, which means their hydrophobic portion drives them together in aqueos solution and the hydrophilic portion controls their alignment. These are the current thoughts on how the first plasma membranes came about and are backed by scientific evidence.
    Also when the first cells came about their early membranes certainly were less of a barrier than they are today but they have been shown to allow ribonucleotides to enter the cell. The formation of RNA from these monomers can then occur and these larger molecules are impermeable. Experiments have also shown that free lipids can also be incorporated into these early protocell membranes and that simple shearing forces can cause the protocells to divide.
    Anything else?

  18. 18
    Mung says:

    Well AVS, on the first question you’ve merely moved the goalposts.

    Why OUGHT NOT IDers not let things like “facts” get in the way? And the question of “fact” leads to the question of truth. Or do you believe in false facts, my dear AVS?

    At some point your whining ought to come to an end, don’t you think?

  19. 19
    Mung says:

    …there is evidence that simple lipids can be synthesized from hydrogen gas and carbon dioxide, in a reaction catalyzed by minerals within hydrothermal vents.

    So? Cell membranes are not simple lipids. Or do you say they are?

    AVS:

    Meteorites have also been found to harbor lipids if you’re into panspermia-type ideas.

    Lipids everywhere then! So what? What is the connection between these “cosmic lipids” and cell membranes?

    AVS:

    Most importantly is that these lipids are amphipathic molecules, which means their hydrophobic portion drives them together in aqueos solution and the hydrophilic portion controls their alignment.

    IOW, they act like lipids. And their water loving parts love water and their water hating parts hate water. Sort of true by definition, don’t you think? And this is relevant to cell membranes how?

    AVS:

    These are the current thoughts on how the first plasma membranes came about and are backed by scientific evidence.

    Lipids. Plasma membranes. Hand waving. Got it.

    AVS:

    Also when the first cells came about their early membranes certainly were less of a barrier than they are today …

    Oh yes. certainly.

    And the earliest membranes allowed what and restricted what from crossing the barrier?

    AVS:

    Experiments have also shown that free lipids can also be incorporated into these early protocell membranes and that simple shearing forces can cause the protocells to divide.

    Are we back to talking about lipids or are we talking about membranes? I bet all sorts of forces can cause things to divide. So what?

  20. 20
    AVS says:

    Current cell membranes consist of more complicated lipids, early cell membranes consisted of simple lipids. The synthesis of these simple lipids has already been demonstrated to occur in early Earth conditions. The most important thing is that all these lipids, were amphipathic molecules.

    The connection between the cosmic lipids, the simple lipids and cell membranes is that these lipids come together on their own, due to their chemical properties to form the first plasma membrane.
    Yes they act like lipids, which is exactly why they come together to form lipid membranes on their own. You can call it hand-waving all you want, but everything I say is backed by experimental evidence thank you very much.

    The early membranes were simple, they were less of a barrier, they allowed more molecules to cross such as simple monomers and ions as I said, but restricted large molecules, as I said. Do I need to spell everything out for you?

    We are talking about lipids and their function in plasma membranes, try to keep up.

    All sorts of forces can completely destroy micelles and bicelles, but simple shearing forces allow them to break apart in a much more orderly fashion and reform into smaller protocells.
    Apparently I do need to spell everything out for you.

  21. 21
    Dionisio says:

    An Autoregulatory Mechanism Imposes Allosteric Control on the V(D)J Recombinase by Histone H3 Methylation

    DOI: http://dx.doi.org/10.1016/j.celrep.2014.12.001

    V(D)J recombination is initiated by a specialized transposase consisting of the subunits RAG-1 and RAG-2.

    The susceptibility of gene segments to DNA cleavage by the V(D)J recombinase is correlated with epigenetic modifications characteristic of active chromatin, including trimethylation of histone H3 on lysine 4 (H3K4me3).

    Engagement of H3K4me3 by a plant homeodomain (PHD) in RAG-2 promotes recombination in vivo and stimulates DNA cleavage by RAG in vitro.

    We now show that H3K4me3 acts allosterically at the PHD finger to relieve autoinhibition imposed by a separate domain within RAG-2.

    Disruption of this autoinhibitory domain was associated with constitutive increases in recombination frequency, DNA cleavage activity, substrate binding affinity, and catalytic rate, thus mimicking the stimulatory effects of H3K4me3.

    Our observations support a model in which allosteric control of RAG is enforced by an autoinhibitory domain whose action is relieved by engagement of active chromatin.

    http://www.cell.com/cell-repor.....all%3Dtrue

  22. 22
    AVS says:

    Yes that is the abstract of the original paper…..thanks Dio……

  23. 23
    Dionisio says:

    AVS,

    Are you aware of any papers where they describe in details how those mechanisms appeared? Can you provide the links to those sources? Thanks.
    🙂

  24. 24
    AVS says:

    Sure Dio, here you go.
    Enjoy!

    “Primordial emergence of the recombination activating gene 1 (RAG1): sequence of the complete shark gene indicates homology to microbial integrases”

    “Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system”

    “Recombination-Activating Genes, Transposition, and the Lymphoid-Specific Combinatorial Immune System: A Common Evolutionary Connection”

    “The recombination activating gene 2 (RAG2) of the rainbow trout Oncorhynchus mykiss”

    “Structure and Intrinsic Disorder in Protein Autoinhibition”

  25. 25
    gpuccio says:

    AVS:

    My compliments! What a wealth of literature!

    So, thanks to a huge collection of papers of about 20 years ago, now we know that:

    a) RAG1 and RAG2, two proteins which appear suddenly in jawed fishes, and which are 1043 and 527 AA long (in humans), and are highly conserved in vertebrates (68% identities and 81% similarities between shark and humans), probably share a few AAs similarity, barely detectable, in a very restricted segment of their sequence, with some bacterial integrases. That certainly explains all.

    b) Transposons are probably implied in the engineering of the immune system (I definitely agree!).

    c) Trouts have an immune system, like all other vertebrates.

    d) ?

    I am still trying to understand how the last paper, which is the only recent one, is relevant to our discussion here. Can you help?

    Certainly, the true character of the neo darwinian theory is well illustrated by the cognitive value of its explanations.

  26. 26
    Dionisio says:

    Immunological memory within the innate immune system.

    Immune memory has traditionally been the domain of the adaptive immune system, present only in antigen-specific T and B cells.

    The purpose of this review is to summarize the evidence for immunological memory in lower organisms (which are not thought to possess adaptive immunity) and within specific cell subsets of the innate immune system.

    A special focus will be given to recent findings in both mouse and humans for specificity and memory in natural killer (NK) cells, which have resided under the umbrella of innate immunity for decades.

    The surprising [?] longevity and enhanced responses of previously primed NK cells will be discussed in the context of several immunization settings.

    doi: 10.1002/embj.201387651

    http://www.ncbi.nlm.nih.gov/pubmed/24674969

    surprising ?

    Why surprising? Did they expect something different?

  27. 27
    Dionisio says:

    The origins of the RAG genes – from transposition to V(D)J recombination

    doi:10.1016/j.smim.2009.11.004

    The recombination activating genes 1 and 2 (Rag1 and Rag2) encode the key enzyme that is required for the generation of the highly diversified antigen receptor repertoire central to adaptive immunity.

    The longstanding model proposed that this gene pair was acquired by horizontal gene transfer to explain its abrupt appearance in the vertebrate lineage.

    The analyses of the enormous amount of sequence data created by many genome sequencing projects now provide the basis for a more refined model as to how this unique gene pair evolved from a selfish DNA transposon into a sophisticated DNA recombinase essential for immunity.

    http://www.sciencedirect.com/s.....2309001195

    http://www.ncbi.nlm.nih.gov/pm.....MC2823946/

  28. 28
    gpuccio says:

    Dionisio (and AVS):

    From the paper:

    “While this had suggested that at least this domain of Rag1 originated from a bacterial DNA recombinase, a recent report of the crystal structure of the NBD disproved this idea as its protein fold differs from that of the Hin DNA binding domain”.

    “Although there is almost no conservation between Rag1 and any of the well-studied prokaryotic transposases at the level of their primary amino acid sequences, secondary structure prediction allowed the identification of a triad of acidic residues within mouse Rag1 (D600, D708, and E962) forming the catalytic center of the Rag1/Rag2 complex [29–31]. These two aspartates and one glutamate form a so called DDE motif that chelates two divalent metal ions essential for catalysis [32]. Importantly, DDE (and the related DDD) motifs represent the common active site shared by many cut-and-paste transposase superfamilies [33, 34]. As all three residues reside within Rag1, this finding provides a strong argument that this protein is closely related to transposases and thus may share a common evolutionary origin.”

    “The sequence similarity between vertebrate Rag1 and the Transib elements is limited to its core region [35]. Surprisingly, an analysis of transcripts and genomic fragments from the mollusk Aplysia californica revealed a new class of transposable element, named NRAG1-TP that shows a striking similarity with the N-terminal conserved non-core region of Rag1 [37]. This includes the RING domain, but all the remaining parts of NRAG1-TP, including the region thought to contain its active site, show no discernible similarities to Rag1. This finding raises the idea that the ancient Rag1 transposon might have been generated by a recombination event between a Transib and an NRAG1-TP element. Several sequence matches with limited similarity to the N-terminus of Rag1 (though lacking similarity to Rag1 core) were also found in the genomes of sea urchin, lancelet, sea anemone, and hydra [35], but whether they share a genetic origin with Rag1 and/or NRag1-TP elements is unclear. This, however, suggests another attractive model, namely that Rag1 could also have originated from the integration of a Transib element into the 3?end of a ubiquitin ligase gene that was located next to the ancestral Rag2”

    Long live transposons, wonderful tools of Intelligent Design!

  29. 29
    Box says:

    Aurelio Smith,

    Is the coming into existence of the universe observable or just imaginary? What is the mechanism?

    IOW if we don’t how it happened, must we therefor conclude that it didn’t happen?

  30. 30
    Box says:

    Aurelio,

    The products of design in nature and the cosmos are equally observable. How the designer operates is beyond the scope of science – like many other phenomena.

  31. 31
    Box says:

    Which definition? Please, be precise.

  32. 32
    Joe says:

    Aurelio- what definition of science are you referring to? Oops, thanks Box!

    ID is about the DESIGN and the design is open to scientific investigation.

  33. 33
    Axel says:

    There are many simple souls, Aurelio, naive in terms of worldly intelligence, who throng to see an angel or the face of Christ in a pattern of leaves or some such, some haphazard, usually not very convincing, configuration in nature.

    However, their simplicity is wiser, immeasurably more intelligent, yes, even in terms of worldly wisdom, immeasurably, than an atheists’ wilful blindness to the uniformly-manifest designs of the highest calibre throughout nature, which only an omnipotent Creator could have created. Utterly, utterly surreal. ‘Cep ‘God scatters the proud in the imagination of their hearts.’

    Even quantum mechanics, with its myriad paradoxes and mathematical confirmation of theistic truths, such as the priority of mind over matter and consequent inter-subjective observation, teaches you nothing leaves you none the wiser. And that, after 80 plus years.

  34. 34
    Box says:

    Aurelio,

    By pointing out that we cannot observe the coming into existence of the universe I intended to show you that your question “observable or just imaginary” contains a false dichotomy. Did you get that?

    edit: in quantum mechanics there are multiple unknown and unobserved mechanisms (‘entanglement’ comes to mind), but that doesn’t mean that the effects are “just imaginary” – nor does it disqualify physics as science.

  35. 35
    Joe says:

    I see that AVS refuses to supports its claims. How typical…

  36. 36
    gpuccio says:

    Aurelio Smith:

    “How does that work? How does the “Intelligent Designer” use these tools? What is the mechanism? Is it observable or just imaginary?”

    Of course, I am synthesizing here a conclusion which is tentative, and which I have defended here for years.

    The main reasons for my conviction of the important role of transposons as ID tools are the following:

    a) ID can be inferred when functional results are achieved which are well beyond the scope of any non design explanation (this is the basic point in ID theory, so I will not deal with it in detail here).

    b) Transposons are increasingly implied in important remodeling of the genome which, in the course of evolution, generates new important functional configurations, which are well beyond the scope of any non design explanation.

    c) Therefore, it is perfectly natural to hypothesize that the working of transposons, when it generates new complex functional configurations, is guided, and not random.

    IOWs, I hypothesize, at least in many cases, ID through guided transposon activity, rather than through guided mutations.

    Is the “mechanism” observable? In a sense, it is.

    The best scenario for biological ID is an intervention of the designer’s consciousness in biological events through a consciousness-matter interface at quantum level. That is not so strange, because it is exactly what has been hypothesized as an explanation of the consciousness-matter interface in the human brain (see, for example, Eccles).

    Now, while in the future we could be able to detect those quantum interface directly, for the moment we can observe its results: the input of functional information into material events which could never generate that information. That is the essence of ID theory, and it is observable.

  37. 37
    Zachriel says:

    Box: How the designer operates is beyond the scope of science – like many other phenomena.

    Beyond scientific investigation? Why is that?

  38. 38
    gpuccio says:

    Zachriel:

    If I can say what I think, I would not say that “how the designer operates” is necessarily beyond scientific investigation.

    If we assume a “consciousness-matter” interface as an explanation for design, then the problem becomes:

    a) Is consciousness beyond scientific investigation? I would not say that, but it is perfectly possible that it is beyond investigation by the usual phenomenological procedures, which apply to “objects”. If consciousness is in some way transcendental (which is my personal view), then maybe that we should use different approaches to include it in the scientific scenario. However, IMO anything that exists can be in some way included in a scientific map of reality.

    b) Is the way that consciousness interacts with matter “beyond scientific investigation”? Certainly not. As we can observe matter and its phenomena, we can certainly investigate scientifically all that happens to matter, including what “comes” from a consciousness-matter interface. Moreover, we can also observe consciousness, although in a different way. Therefore I am sure that a lot of information about the consciousness-matter interface can be reached by scientific investigation, even if in the ultimate sense consciousness itself cannot probably be “explained” in a traditional “objective” scientific scenario.

  39. 39
    gpuccio says:

    Aurelio Smith:

    Thank you for your comments.

    My idea about the “theistic evolutionary approach” is that there is a very big difference between that and ID.

    We in ID firmly believe that there is a definite scientific way to infer design from observable properties of functional configurations of matter. IOWs, we can infer the intervention of a conscious intelligent purposeful being any time we observe some properties in matter, like for example dFSCI. This is an empirical conclusion, and has nothing to do with being “committed to a guided process”. It has only to do with searching for the right answers to the right questions.

    So, I am definitely with Behe, and absolutely not with Miller.

    I understand that sometimes Behe has expressed views which are more “near” to theistic evolution, for example in one of the final chapters of TEOE. In that, I disagree with him, but I think that that chapter does not probably express well his real position.

    In this sense, I am completely for what we could call “strong ID”: design detection is a scientific reality, completely empirical, and design can absolutely be detected in biological objects. It’s as simple as that.

  40. 40
    Zachriel says:

    gpuccio: We in ID firmly believe that there is a definite scientific way to infer design from observable properties of functional configurations of matter.

    Lacking a link of causation to the designer undermines the claim. It resembles a gap argument. It’s complicated. We don’t know a natural explanation. So design.


    edited for grammar

  41. 41
    Dionisio says:

    An amphioxus RAG1-like DNA fragment encodes a functional central domain of vertebrate core RAG1
    doi: 10.1073/pnas.1318843111
    http://www.ncbi.nlm.nih.gov/pubmed/24368847

    Evolution of Innate Immunity: Clues from Invertebrates via Fish to Mammals.
    doi: 10.3389/fimmu.2014.00459
    http://www.ncbi.nlm.nih.gov/pubmed/25295041

    Ikaros and RAG-2-Mediated Antisense Transcription Are Responsible for Lymphocyte-Specific Inactivation of NWC Promoter
    doi: 10.1371/journal.pone.0106927
    http://www.ncbi.nlm.nih.gov/pm.....MC4157847/

  42. 42
    Axel says:

    Poor AVS is confused about a laymans’ description of the functions/uses/purposes of machines, whether a cell or factory, evidently believing that if the detailed functioning of a machine, a mechanism, is sophisticated, and its details bear scant resemblance to those of a simple machine, an analogy between their functions, their uses, is invalid; as if to say that, because the mechanism of a child’s pedal car is relatively very simple, to describe it in the same way as one would a Ferrari, as a vehicle, would be inapplicable, invalid.

    E = MC2 is a simple enough equation, easily explained to a layman, yet was the product of some quite sophisticated mathematics, I believe. I was once able to do some very simple quadratic equations, and you know what? On the face of it, the answers seemed much more impressively sophisticated than E = MC2 (if only because they were non-specific conceptual representations), until you did the math on Einstein’s famous equation, and realised that the deepest truths are conveyed the most simply – albeit in QM replete with paradoxes, which very seldom seem to appear in the materialist’s lexicon, since they prefer to burble on about ‘counter-intuitiveness’.

    Yet, it is not the calculations behind E= MC2 that are significant, but its implication, so simple that it can even be expressed verbally to a layman, almost entirely in monosyllables in everyday use.

    So, whatever reservation you were seeking to convey concerning a comparison between the overarching characteristics of a cell and a factory, for example, were to all intents and purposes, quite vapid and spurious.

  43. 43
    Dionisio says:

    Science is discovering everyday, at a fast pace, many elaborate molecular choreographies, orchestrated within rationally observable bio systems. Definitely every new discovery sheds more light on those fascinating information-processing systems that on many occasions serve as sophisticate models to study through reverse engineering. However, as researchers dig deeper into biology, for every outstanding question that gets answered, new questions may arise. Sometimes that gives the impression of a never-ending story. 🙂

  44. 44
    Upright BiPed says:

    Lacking a link of causation to the designer undermines the claim. It resembles a gap argument. It’s complicated. We don’t know a natural explanation. So design.

    “Lacking a link of causation to the designer undermines the claim. It resembles a gap argument. It’s complicated. We don’t know a designer. So naturalism.”

    Goes both ways. Always.

    The distinction between the two is that the piece of evidence on the top of the pile still points to design.

  45. 45
    Dionisio says:

    #22 AVS

    Yes that is the abstract of the original paper…..thanks Dio……

    Who would have thought that such a seemingly innocent comment could trigger such a follow-up avalanche of comments?

    🙂

    Next time, try going quietly under the radar, completely undetected. Thus maybe things will remain undisturbed. 🙂

    Now it’s too late. The genie is out of the bottle.

    The good news is that gpuccio got involved in this discussion. 🙂

    Fasten your seatbelts. Get ready for the thrilling rollercoaster ride.

    We ain’t seen nothing yet.

    The party is just starting. The fun part is still ahead.

    🙂

    Let’s remember that for every research paper one reads, one should ask the most fundamental question required by the scientific method:

    https://www.youtube.com/embed/8dnUs2AqWvs

    🙂

    Happy New Year!!!

  46. 46
    dgw says:

    The evolution gap grows more and more problematic. Each discovery of a life mechanism with greater complexity than expected reduces the probability of evolution as a plausible explanation.

  47. 47
    Dionisio says:

    #48 Aurelio Smith

    I’m not so sure, but I promise to eat my hat if you succeed!

    With ketchup, mustard, balsamic vinegar? 🙂

  48. 48
    Dionisio says:

    #53 dgw

    The evolution gap grows more and more problematic. Each discovery of a life mechanism with greater complexity than expected reduces the probability of evolution as a plausible explanation.

    Well, I would say, in a more ‘politically correct’ (i.e. less confrontational) manner, that the potential alternatives seem gradually disappearing.

    🙂

  49. 49
    Dionisio says:

    #28 gpuccio

    From the paper:

    “While this had suggested that at least this domain of Rag1 originated from a bacterial DNA recombinase, a recent report of the crystal structure of the NBD disproved this idea as its protein fold differs from that of the Hin DNA binding domain”.

    “Although there is almost no conservation between Rag1 and any of the well-studied prokaryotic transposases at the level of their primary amino acid sequences, secondary structure prediction allowed the identification of a triad of acidic residues within mouse Rag1 (D600, D708, and E962) forming the catalytic center of the Rag1/Rag2 complex [29–31]. These two aspartates and one glutamate form a so called DDE motif that chelates two divalent metal ions essential for catalysis [32]. Importantly, DDE (and the related DDD) motifs represent the common active site shared by many cut-and-paste transposase superfamilies [33, 34]. As all three residues reside within Rag1, this finding provides a strong argument that this protein is closely related to transposases and thus may share a common evolutionary origin.”

    “The sequence similarity between vertebrate Rag1 and the Transib elements is limited to its core region [35]. Surprisingly, an analysis of transcripts and genomic fragments from the mollusk Aplysia californica revealed a new class of transposable element, named NRAG1-TP that shows a striking similarity with the N-terminal conserved non-core region of Rag1 [37]. This includes the RING domain, but all the remaining parts of NRAG1-TP, including the region thought to contain its active site, show no discernible similarities to Rag1. This finding raises the idea that the ancient Rag1 transposon might have been generated by a recombination event between a Transib and an NRAG1-TP element. Several sequence matches with limited similarity to the N-terminus of Rag1 (though lacking similarity to Rag1 core) were also found in the genomes of sea urchin, lancelet, sea anemone, and hydra [35], but whether they share a genetic origin with Rag1 and/or NRag1-TP elements is unclear. This, however, suggests another attractive model, namely that Rag1 could also have originated from the integration of a Transib element into the 3?end of a ubiquitin ligase gene that was located next to the ancestral Rag2?

    Long live transposons, wonderful tools of Intelligent Design!

    Really interesting. Thank you.

    Glad you’ve got involved in this discussion.

    Happy New Year to you!

    🙂

  50. 50
    gpuccio says:

    Zachriel:

    “Lacking a link of causation to the designer undermines the claim. It resembles a gap argument. It’s complicated. We don’t know a natural explanation. So design.”

    This is an old story! I am sure you know better than that. 🙂

    However, using your own words, the correct statement would be:

    It’s functionally complex. We don’t know any non design explanation for functionally complex things. But we know well that conscious, intelligent, purposeful beings can generate those kind of things. Therefore, we have a definite “link of causation” to infer design for biological objects, and that is in no way “a gap argument”.

    OK, that is better. But we are at New Year’s Eve, and probably it’s not the best time to plunge again in that old story.

    However, my best wishes to you, with sincere appreciation.

  51. 51
    gpuccio says:

    Dionisio:

    Happy New Year, my friend! 🙂

  52. 52
    Charles says:

    Upright BiPed @ 51:

    This is off topic, but, a couple times recently you mentioned in your other posts on other threads that regarding the DNA/RNA transcription apparatus, the logical separation of the code from the physical mechanism was an essential separation (or words to that effect, hopefully I’ve not so mangled your point that you realize to what I’m referring). I’ve wanted to understand that ‘separation is essential’ argument in greater detail, but I wasn’t around whenever/wherever you did, so could you kindly post a link to your most detailed explanation… please? Thank you for your assistance and patience.

  53. 53
    gpuccio says:

    Aurelio Smith:

    I hope your hat is good to digest! 🙂

    “Giving it testable entailments might be the first step on the road to making “Intelligent Design” into some sort of scientific endeavor. I wish you the best of luck if you decide to instigate or cooperate on such an exercise, sincerely.”

    Well, in a very humble way, that’s what I have been trying to do here in the last few years. For what I can. And I will go on.

    Happy New Year! 🙂

  54. 54
    gpuccio says:

    Upright BiPed:

    Happy New Year to you, from my heart! 🙂

  55. 55
    Dionisio says:

    Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution
    doi: 10.1371/journal.pone.0096903
    http://www.ncbi.nlm.nih.gov/pm.....MC4016189/
    http://www.plosone.org/article.....ne.0096903

    Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates.

    They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules.

    These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish.

    In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance.

    The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution.

    Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

    https://www.youtube.com/embed/8dnUs2AqWvs

    🙂

  56. 56
    Dionisio says:

    Off topic:

    If you have used EndNote for organizing research papers online, you may want to try Zotero. A friend from Canada recommended it to me. It works very well. I use it in combination with Mind Meister and a set of private WordPress web logs. I plan to share the main link with y’all when I get it well cooked (no salt added). 🙂

    Happy New Year to all! (including the interlocutors that don’t like my dumb questions). 🙂

  57. 57
    Dionisio says:

    10 years ago…

    New concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2.

    A major challenge has been to determine how the transposition activity of the RAG proteins is regulated in vivo.

    Although a variety of mechanisms have been suggested by recent studies, a clear resolution of this issue remains elusive.

    http://www.ncbi.nlm.nih.gov/pubmed/15242411

    But today we finally know how the transposition activity of the RAG proteins is regulated in vivo.

    🙂

  58. 58
    Upright BiPed says:

    Hello GP!

    Happy New Year to you my dear friend!

  59. 59
    Upright BiPed says:

    Hello Charles, Happy New Year.

    I hope this exchange might help explain it. If you have questions, I am happy to respond.

  60. 60
    Dionisio says:

    A Critical Role for the Regulated Wnt–Myc Pathway in Naive T Cell Survival

    doi: 10.4049/?jimmunol.1401238

    Wnt signaling is involved in T cell development, activation, and differentiation. However, the role for Wnt signaling in mature naive T cells has not been investigated.

    http://www.jimmunol.org/content/194/1/158.abstract

  61. 61
    Charles says:

    Upright BiPed @ 66:

    Thank you very much. That indeed looks like the argument I wanted. After I’ve studied it, I’ll likely post a question or two on that thread.

    Belated Merry Christmas and Happy New Year, to you and to all.

  62. 62
    Dionisio says:

    An Overview of the Intrathymic Intricacies of T Cell Development

    doi: 10.4049/?jimmunol.1302259

    The generation of a functional and diverse repertoire of T cells occurs in the thymus from precursors arriving from the bone marrow.

    In this article, we introduce the various stages of mouse thymocyte development and highlight recent work using various in vivo, and, where appropriate, in vitro models of T cell development that led to discoveries in the regulation afforded by transcription factors and receptor–ligand signaling pathways in specifying, maintaining, and promoting the T cell lineage and the production of T cells.

    This review also discusses the role of the thymic microenvironment in providing a niche for the successful development of T cells.

    In particular, we focus on advances in Notch signaling and developments in Notch ligand interactions in this process.

    http://www.jimmunol.org/conten.....7.abstract

  63. 63
    Joe says:

    Aurelio Smith:

    Giving it testable entailments might be the first step on the road to making “Intelligent Design” into some sort of scientific endeavor.

    And that is a road your position will never step foot on. 😛

  64. 64
    Joe says:

    Aurelio quoting Box as alleged evidence ID is not science:

    “How the designer operates is beyond the scope of science…”

    ID is about the DESIGN. Why do our opponents think their willful ignorance means something?

    How the designers of Stonehenge operated is beyond science. Does that mean archaeology isn’t science?

  65. 65
    Zachriel says:

    gpuccio: It’s functionally complex. We don’t know any non design explanation for functionally complex things. But we know well that conscious, intelligent, purposeful beings can generate those kind of things. Therefore, we have a definite “link of causation” to infer design for biological objects, and that is in no way “a gap argument”.

    The planetary orbits are functionally complex. They keep track of time and seasons and the rise and fall of empires. We don’t know any non-design explanation for something so functionally complex. But we know that we can create functionally complex mechanisms with elaborate gears and wheels and pinions that emulate the planetary movements.

    While this is *not* a link of causation (where did you get that idea?), we infer the designer of planetary orbits is obviously someone with far more design capabilities than the meager efforts of the crafters and scholars who make the pale imitation mechanisms.

  66. 66
    Dionisio says:

    KAP-1 Promotes Resection of Broken DNA Ends Not Protected by ?-H2AX and 53BP1 in G1-Phase Lymphocytes

    doi: 10.1128/MCB.00441-14

    http://mcb.asm.org/content/34/15/2811.abstract

  67. 67
    Dionisio says:

    DNA-dependent Protein Kinase Regulates DNA End Resection in Concert with Mre11-Rad50-Nbs1 (MRN) and Ataxia Telangiectasia-mutated (ATM)*

    doi: 10.1074/jbc.M113.514398

    The resection of DNA double strand breaks initiates homologous recombination (HR) and is critical for genomic stability.

    http://www.jbc.org/content/288/52/37112.abstract

  68. 68
    Dionisio says:

    Unraveling the Complexities of DNA-Dependent Protein Kinase Autophosphorylation

    doi: 10.1128/MCB.01554-13

    http://mcb.asm.org/content/34/12/2162.abstract

  69. 69
    Dionisio says:

    Small-Molecule DNA Methylation Inhibitor

    doi: 10.1158/1078-0432.CCR-14-1553

    http://clincancerres.aacrjourn.....4.abstract

  70. 70
    Dionisio says:

    Quantitation of DNA double-strand break resection intermediates in human cells

    doi: 10.1093/nar/gkt1309

    http://nar.oxfordjournals.org/.....9.abstract

  71. 71
    Dionisio says:

    Hematopoietic stem cell dysfunction underlies the progressive lymphocytopenia in XLF/Cernunnos deficiency

    DOI: http://dx.doi.org/10.1182/blood-2014-05-574863

    http://www.bloodjournal.org/co.....ecked=true

  72. 72
    gpuccio says:

    Zachriel:

    As you should know, planetary orbits are not functionally complex in the ID sense: they are the result of laws.

    And the causal link bewtween consciousness, design and functional complexity is an inference well established by empirically observed facts.

  73. 73
    Zachriel says:

    gpuccio: As you should know, planetary orbits are not functionally complex in the ID sense: they are the result of laws.

    For those unaware of the underlying symmetries involved, it was extremely complex. That’s the whole point, of course.

  74. 74
    DATCG says:

    “Design terms” are not merely for lay people, but utilized by scientist and engineers alike for the great purpose and communication of complex ideas in systems biology.

    One need not look far today as “design terms” and design processes are routinely discussed at highest levels of academics and applied sciences in surgery, biology, regenerative medicine and biomedical engeineering. Why? Because it makes perfect sense to do so.

    Hardly an “IDer” conspiracy, but a common sense approach to real life application in science…


    A systems engineering perspective on homeostasis and disease

    Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
    2Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    3Department of Surgery, The University of Chicago, Chicago, IL, USA
    4Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA
    5Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, USA
    6Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    … there is much to be learned about biological complexity from engineered systems.

    That sentence is followed by the obligatory denial…

    This is not to say that biological systems are engineered systems: biological systems are clearly distinct and different by virtue of having resulting from evolution as opposed to design.

    What great fear the unguided live in.

  75. 75
    DATCG says:

    Looking for and applying design principles is a great educational and research heuristic going forward as seen in above links for applying systems engineering concepts, even if old guard Darwinist faithful refuse to acknowledge the ascendance of the Design Paradigm.

    Towards the rational design of synthetic cells with prescribed population dynamics

    Not only is it rational to use design terms, it is necessary among scientist, programmers and engineers developing new methods of research, treatments and solutions, including the “rational design of synthetic cells with prescribed population dynamics.”

    Why is a “programming language” or “engineering” utilized to produce new living cells? Because, treating cellular and biological functions as modular, programmable objects and systems architecture works.

    Genetic Engineering of Living Cells

    In developing programs and visual tools with languages like GEC, design terms are not denigrated, but elevated as central to solving problems.
    A spin-off of Design-centric paradigm….

    Functional Biological Parts Registry

    It is a misleading to state design terms are limited to descriptions for lay people or those uninformed about complex biological processes. That is but one use of design terms. As seen by scientific research, design terms and methodologies are at the forefront utilized by academics, programmers and engineers to collaborate and forward the understanding of life.

  76. 76
    gpuccio says:

    Zachriel:

    The whole point is that complex functional information can be exactly defined, and that it is the result of design.

  77. 77
    Zachriel says:

    gpuccio: The whole point is that complex functional information can be exactly defined, and that it is the result of design.

    As we said, planetary orbits are functionally complex. They make the days and seasons and longer periods associated with the rise and fall of civilizations. It took the very highest levels of human ingenuity and craftsmanship to make a tiny simulacrum of the heavens.

  78. 78
    Dionisio says:

    #40 gpuccio

    The main reasons for my conviction of the important role of transposons as ID tools are the following:

    a) ID can be inferred when functional results are achieved which are well beyond the scope of any non design explanation (this is the basic point in ID theory, so I will not deal with it in detail here).

    b) Transposons are increasingly implied in important remodeling of the genome which, in the course of evolution, generates new important functional configurations, which are well beyond the scope of any non design explanation.

    c) Therefore, it is perfectly natural to hypothesize that the working of transposons, when it generates new complex functional configurations, is guided, and not random.

    IOWs, I hypothesize, at least in many cases, ID through guided transposon activity, rather than through guided mutations.

    Is the “mechanism” observable? In a sense, it is.

    The best scenario for biological ID is an intervention of the designer’s consciousness in biological events through a consciousness-matter interface at quantum level. That is not so strange, because it is exactly what has been hypothesized as an explanation of the consciousness-matter interface in the human brain (see, for example, Eccles).

    Now, while in the future we could be able to detect those quantum interface directly, for the moment we can observe its results: the input of functional information into material events which could never generate that information. That is the essence of ID theory, and it is observable.

    I think the above quoted insightful compacted explanation, that you wrote at the end of last year, should be repeated at the beginning of this year. 🙂

    Here’s my first dumb question to start the new year: regarding this note “(see, for example, Eccles)”, what is Eccles? Thank you.

  79. 79
    Dionisio says:

    #82 DATCG

    Thank you for posting that interesting information.

    Happy New Year!

  80. 80
    hrun0815 says:

    Well, in a very humble way, that’s what I have been trying to do here in the last few years. For what I can. And I will go on.

    Gpuccio, I am curious. How are you actually going this– humble or not?

Leave a Reply