Intelligent Design

Synergistic Modifications Of Nuclear Histone Proteins Display Functional Design

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The word ‘compaction’ is one that in my mind conjures up images of vacations long-passed when I would cram as many clothes as I could into the smallest suitcases I could find. Such a task has become even more irksome in recent years with the hefty restrictions in place that limit the amount of luggage we can now take onto airplanes. But in at least one context- that of DNA biology- compaction refers to something much more exquisite and desirable.

The diploid eukaryotic cell faces the challenge of squeezing and compacting about two meters of DNA into the tiny space of the nucleus (Ref 1). As DNA structuralists Chris Calladine and Horace Drew described many years ago, DNA in most eukaryotic genomes is compressed 10,000-fold (Ref 2). This is partially achieved by highly specialized proteins called histones (denoted as H1, H2a, H2b, H3, H4) around which the DNA is wrapped (Ref 2). The resulting DNA/Histone complex, called a nucleosome subunit, is repeated tens of millions of times across the human genome to form chromatin, which is further compacted into ordered fibers 250-300 Angstroms in diameter (Refs 1-4). Such compaction is crucial if the billions of base pairs of DNA that make up, say, the human genome are to fit into the tiny space of the nucleus (Ref 1).

Much work still needs to be done to elucidate the precise mechanisms through which DNA becomes accessible to RNA polymerases and subsequently gets transcribed. Yet in a seminal paper co-authored by Wistar Institute molecular biologist Ronen Marmorstein, it has become clear that this increased accessibility of chromosomal DNA to the transcription machinery is dependent upon complex modifications of the histone proteins- a feature of transcriptional regulation that forms the basis of what is more commonly referred to as the ‘histone code’ (Refs 3-5).

Several classes of histone modification have now been documented in the scientific literature notably acetylation, phosphorylation and methylation (Ref 3). Of all, acetylation is perhaps the best characterized within the context of transcriptional regulation (Ref 3) although H3 and H4 acetylation also appears to play a key role in other cellular processes such as DNA replication (Ref 4). The synergistic nature of histone modifications has been extensively discussed (Refs 4,7). We now know for example that methylated, non-acetylated H4 tends to be associated with regions of the genome that are transcriptionally inactive. Conversely phosphorylated, acetylated H3 is usually present in transcriptionally active regions (Refs 4,6).

Histone modifications may be sensitive to external environmental cues, resulting in a rapid modulation of gene expression (Ref 7). Moreover they can exert long term, stable effects, maintaining DNA in either a transcriptionally active or inactive state over many rounds of cell division (Ref 7). Importantly, the histone code parallels the everyday usage of symbols in human communication systems (Ref 7). Just as traffic lights use an established code (green, yellow, red) to produce a desired outcome, for example, so too do histone modifications produce functionally-relevant outcomes in gene expression (Ref 7). In both cases there is a need for an ‘interpreter’ of the code. In the same way that a driver’s brain interprets traffic light signals, modification-dependent binding proteins interpret modified histones, effectively kick-starting processes such as cellular differentiation (Ref 7).

Whether all histone modifications are involved in defining gene expression patterns is currently a matter of deep debate (Ref 7). Moreover, there are numerous other epigenetic factors such as DNA methylation that influence which genes are actively transcribed (Ref 7). What is clear however is that the histone code provides the foundations for a sound, logical thread of reasoning that ultimately leads us to infer the activity of an intelligent agency. As Discovery Institute philosopher Stephen Meyer remarked:

“Our experience-based knowledge of information-flow confirms that systems with large amounts of specified complexity (especially codes and languages) invariably originate from an intelligent source – that is, from a mind or personal agent. Clearly, intelligent agents have the causal powers to generate novel linear information-rich sequences of characters. To quote Henry Quastler…the “creation of new information is habitually associated with conscious activity”. Experience teaches this obvious truth” (Ref 8).

It is with the acceptance of such a thread of reasoning that we can begin a more fruitful approach to understanding the molecular underpinnings of life.

Literature Cited
1. Anthony Anumziato (2008), DNA Packaging: Nucleosomes And Chromatin, Nature Education (1), See http://www.nature.com/scitable/topicpage/DNA-Packaging-Nucleosomes-and-Chromatin-310

2. Chris Calladine & Horace Drew (1992), Understanding DNA: The Molecule And How It Works, 1st Edition, Academic Press, London, pp.138-143

3. Brian D. Strahl and C. David Allis (2000), The Language Of Covalent Histone Modifications, Nature, Vol 403, pp.41-45

4. ‘The Histone Code- Genetics, Epigenetics And Histones’, See http://www.histonecode.com

5. Adrienne Clements, Arienne N. Poux, Wan-Sheng Lo, Lorraine Pillus, Shelley L. Berger, Ronen Marmostein (2003), Structural Basis For Histone And Phophohistone Binding By The GCN5 Histone Acetyltransferase, Molecular Cell, Vol 12, pp.461-473

6. Raymond H Jacobson, Andreas G. Ladurner, David S. King, Robert Tjian (2000), Structure and Function of a Human TAFII250 Double Bromodomain Module, Science, Vol 288, pp.1422-1425

7. Bryan M Turner (2007), Defining An Epigenetic Code, Nature Cell Biology, Vol 9(1), pp.2-6

8. Stephen C. Meyer, Marcus Ross, Paul Nelson, and Paul Chien (2003), The Cambrian Explosion: Biology’s Big Bang, Appears in the peer-reviewed volume Darwinism, Design, and Public Education, Michigan State University Press p.381. See
http://www.discovery.org/scripts/viewDB/filesDB-download.php?command=download&id=639

14 Replies to “Synergistic Modifications Of Nuclear Histone Proteins Display Functional Design

  1. 1
    Khan says:

    Robert,

    It is with the acceptance of such a thread of reasoning that we can begin a more fruitful approach to understanding the molecular underpinnings of life.

    All of the research you cited was done without the acceptance of this thread of reasoning. Can you please explain how thinking of molecular packaging as the work of an intelligent agent would improve research in this area? Please use specific examples. Thanks.

  2. 2
    tragic mishap says:

    Anything known about how histones are modified? You mentioned “environmental cues”. It seems modifications like that would require enzymes.

  3. 3
    George L Farquhar says:

    Robert,
    Most, if not all, of your references have had standard “peer review” applied. Except the last, which from what I can tell was “peer reviewed” by ardent supporters of ID. The purpose of peer review is to expose errors, weaknesses, and significant omissions in fact and argument. That purpose is not served if the reviewers are uncritical.

    In another thread Atom said that ID supporting papers are rejected out of hand by publications such as “Nature”, “Science” etc. When asked for evidence of that he pretended to ignore the question.

    Are you not also using a “bait’n’switch” tatic by claiming support for your position by using papers which have been peer reviewed but which don’t claim to support ID and then mixing in another book which you imply has also had the same standard of peer review applied as the other articles?

    Appears in the peer-reviewed volume Darwinism, Design, and Public Education

    Do you know who did the peer-review on that volume then? Were they ID supporters?

  4. 4
    PaulN says:

    Does the author of a peer reviewed article need to explicitly state his philosophical alignment or interpretation of the evidence? Following that, is it possible that the evidence can implicitly infer ideas different than what the researcher intentions? If so, then why should it matter if an article doesn’t explicitly state something that can easily be implied by an independently objective view of the data?

    If the current worldview paradigm trumpets one interpretation of any particular set of data, does that automatically disqualify other interpretations of the data that don’t fit the paradigm? Following this, does the popularity of a particular paradigm make the data a more suitable fit, or is the suitability of the data in regards to a particular worldview defined by something other than popular consensus? In other words, can evidence objectively support a position regardless of the opinions that it is subjected to, including the position of the opposing paradigm? If so, then ultimately why does it matter that the author (of a peer reviewed paper) doesn’t claim to support ID if and when the evidence plainly does?

    As far as Khan’s question, have you ever seen a program or a set of functions whose purpose is to intelligently derive the optimal arrangement for a set of structures within a 2 or 3 dimensional plane in regards to the conservation of space? Believe it or not, some modern video games have this type of programming. I’m not sure if you’re familiar with a game called “Diablo 2,” but the simple “auto sort” button for optimizing space within the character’s inventory is possibly the most rudimentary example of this being done on a 2 dimensional plane. Even this admittedly weaker example shows the by-products of ingenuity and purposeful goal-oriented procedure. However, trying to constrict 6 feet worth of DNA into a space of 6 micrometers, also accounting for rotation, structural integrity, and conservation of the ability to express genes is a far more complex and specified than what most computer programs could account for.

  5. 5
    George L Farquhar says:

    PaulN,
    I don’t really understand the point you are trying to make in your first two paragraphs.

    However, trying to constrict 6 feet worth of DNA into a space of 6 micrometers, also accounting for rotation, structural integrity, and conservation of the ability to express genes is a far more complex and specified than what most computer programs could account for.

    Perhaps you are thinking about it the wrong way. In fact, perhaps you have it backwards. Literally.

    What if there was much less then 6 feet worth of DNA. Much less. It seems to me it becomes an easier problem to solve, perhaps even within the weak power of micro-evolution. I.E. a 2 micrometer space and 10nm of DNA. Or whatever. Less, much less.

    Of course, when you get to the scale of “feet” it suddenly seems much more of a difficult problem, perhaps even impossible. It must have been designed.

    It’s a fallacy that’s very popular here – a tornado in a junkyard is unlikely to create a 747, but it might create a kite out of a car bonnet. And if the metric is “flying ability”….

  6. 6
    kairosfocus says:

    Re GLF, 5:

    It’s a fallacy that’s very popular here – a tornado in a junkyard is unlikely to create a 747, but it might create a kite out of a car bonnet. And if the metric is “flying ability”….

    His strawmanised and dismissed “fallacy” is in fact a serious and unanswered challenge to evolutionary materialist origins ideas, posed by A Nobel Prize equivalent holder — Sir Fred Hoyle — on an area of his expertise {statistical thermodynamics] — one that he would seemingly rather dismiss than address on the merits.

    As to the strawman argument that would compare kiting of a car bonnet in a storm with spontaneous assembly of a flyable (i.e fully functional) 747 by a tornado in a junkyard, the fact that GLF and ilk evidently cannot see the difference between the cases is itself utterly revealing.

    I suggest that those wishing to evaluate the quality of such assertions by GLF and co from Anti -Evo would as a first level find the remarks here and here (as well as on the more specific case here) to be helpful. (And this, too.)

    GEM of TKI

  7. 7
    George L Farquhar says:

    Kairofocus,

    His strawmanised and dismissed “fallacy” is in fact a serious and unanswered challenge to evolutionary materialist origins ideas

    In fact this “challenge” has been fully addressed. In fact, the phrase “Hoyle’s fallacy” has been coined to describe his errors.
    http://en.wikipedia.org/wiki/Hoyle%27s_Fallacy

    In summary:

    1. They calculate the probability of the formation of a “modern” protein, or even a complete bacterium with all “modern” proteins, by random events. This is not the abiogenesis theory at all.
    2. They assume that there is a fixed number of proteins, with fixed sequences for each protein, that are required for life.
    3. They calculate the probability of sequential trials, rather than simultaneous trials.
    4. They misunderstand what is meant by a probability calculation.
    5. They seriously underestimate the number of functional enzymes/ribozymes present in a group of random sequences.[1]

    Sir Fred Hoyle — on an area of his expertise {statistical thermodynamics] —

    It’s important that the onlookers note that Sir Fred Hoyle (who I consider a genius in general) was not a biologist and as such his errors in this regard should be forgiven.

    As to the strawman argument that would compare kiting of a car bonnet in a storm with spontaneous assembly of a flyable (i.e fully functional) 747 by a tornado in a junkyard, the fact that GLF and ilk evidently cannot see the difference between the cases is itself utterly revealing.

    It is equally revealing that you cannot see the difference between a fully formed 747 coming about by chance and a much simpler arrangement but with some of the relevant functionaly coming about by chance.

    It’s telling that you did not address the substantial part of my previous comment regarding the problem becoming more tractable if you consider an earlier stage of development. The reason you want to stick with “a fully formed 747” or “a fully formed bacterial flagellum” is obvious to all. If stepwise formation from simple to complex is considered your probabilties fall apart. I understand that you want to stick with “starts complex” but look at where that has got you.

    It’s ironic that you say it’s totally improbable that a 747 can come about via random chance but your explanation for how the 747 (aka Life) came about is even more improbable.

    I suggest that those wishing to evaluate the quality of such assertions by GLF and co from Anti -Evo would as a first level find the remarks here and here (as well as on the more specific case here) to be helpful. (And this, too.)

    It’s telling that the links you use to support your argument are all self referential. Do you really think that If your posts here are failing to convince then another 100,000 words written by you will convince?

    Do you have any links to peer reviewed papers (i.e. where a minimum level of quality and fact checking is present) instead?

    What does that tell you onlookers? KF has gone on the record as saying he’ll never submit his work to real journals, and so his work can only be considered alongside the likes of “timecube” until then.

    I ask you once again KF, in Hoyle’s “junkyard” what is the metric of success? It’s it “flying ability” or is it “747-ness”?

    Think about your answer carefully.

  8. 8
    kairosfocus says:

    Onlookers, re:

    GLF, 7: the phrase “Hoyle’s fallacy” has been coined to describe his errors . . .

    The above rebuttal — and labelling and listing talking points does not provide a cogent answer — is simply not relevant, but dismissive.

    (As to notions such as that a car bonnet kiting in a storm has functionality that is somehow relevant to that of a flyable 747, this is so self-refuting that I simply note that this is a claimed rebuttal point by GLF. Fellow denizens of the Clapham bus stop, take the measure of the rebuttal from that lame strawman.)

    On the summary list of Wiki talking points on the so-called fallacy:

    ________________

    1. They [Hoyle’s calculations, presumably] calculate the probability of the formation of a “modern” protein, or even a complete bacterium with all “modern” proteins, by random events. This is not the abiogenesis theory at all.

    –> Red herring, led out to a duly pummelled strawman: Hoyle’s calculations have a much broader general foundation and relevance, which is what I addressed

    –> Namely, the previously linked summary is on the general thermodynamic and statistical problem of creating ANY complex functionally specific, complex information (FSCI) – exhibiting energy converter by chance, which is where the 747 in a junkyard issue bites home.

    –> We have no ends of good experience of intelligence creating such by art, but it is fair comment to say that there is no observed case of mechanical necessity plus chance forces doing same.

    –> The above linked calculation and analysis show why that is the case.

    –> And dismissing the calcs and analysis by saying that the summary calculation is by the undersigned is plainly an ad hominem. (Where calculations are concerned, any informed person will be able to follow that they are right and are rooted in the standard foundations of thermodynamics, and in standard terms and symbols, with a bit of simplification, i.e. no stuff on d’Qrev etc . . . ]. Indeed, all one needs to understand is that dS etc means small increment in S [entropy], and that d’Q means that the increment in Q, heat, is dependent on specifics of the circumstances; so use your basic H.S. algebra with that addition, and see how the calcs follow, where the calcs point, why. if you understand calculus up rto partial differential equations, these are of course total differentials, with d’Q standing in for d-bar Q, as it is an improper.)

    –> For instance, let us observe that GLF has not addressed the import of Clausius’ 2nd Law on the merits [and any 1st level text on thermodynamics will show that I have simply drawn out he fact that his classic isolated system for showing 2nd LOT incorporates an energy-importing subsystem that in so importing energy INCREASES its entropy] , nor has he faced the relevant fact that the calculations are standard and are based on the works of men such as: Clausius, Gibbs, Boltzmann, Brillouin, Jaynes et al [with Einstein in a cameo on Brownian motion]; not to mention Thaxton and Bradley’s codicils.

    2. They assume that there is a fixed number of proteins, with fixed sequences for each protein, that are required for life.

    –> Red herring dragged out to a strawman again: the issue is FSCI-using heat engines/energy converters originating by spontaneous forces of chance + necessity, and why we do not observe that. That is, we see per relevant thermodynamic considerations why organisation of intricate systems comprising a multitude of co-adapted interacting parts that act in a definite step by step process is qualitatively different from the order of say a huyurricane, which is the product of ordering forces of planet scale convection over a sea surface at 80 F or more, with a bit of help from Coriolis effects. [NB: Strictly the “spontaneously” rotating part of the hurricane is an artifact of our living in a rotating — i.e. accelerated, non-inertial — frame of reference.]

    –> The 747 formed by a tornado in a junkyard — or the miniaturised version I developed that explicitly works with diffusion and Brownian motion and the like — show that even where components are present, the organisation requires a work of clumping and configuring, which per the simple probabilistic implications of relative statistical weights of accessible microstates, will overwhelmingly not occur by the forces and materials available in Darwin’s warm little pond or the like.

    3. They calculate the probability of sequential trials, rather than simultaneous trials.

    –> Red herring led out to a strawman again.

    –> The 1,000 bit rule of thumb threshold for sufficient complexity for FSCI sets a level where the quantum states of all the atoms of the observed universe [~ 10^80] shifting every Planck time, will only go though some 10^150 states across its reasonable lifetime as estimated thermodynamically. [No parallel search of the observed cosmos can exceed this]

    –> 1,000 bits of stored functional information specifies a config space of 10 times the SQUARE of the 10^150 possible searched states of the whole cosmos.

    –> So, let us imagine: a whole universe, using up 10^80 atoms, comprising 1 cubic metre buckets with parts for miniature jumbo jets, and available for the duration of our cosmos. The jumbo jet obviously encodes much more than 1,000 bits of functional information [just for the code in the flight management computer!]. What are he odds of just 1 jet forming in 10^25 seconds, if he parts reshuffle every 10^-43 seconds. [Again, we are up against the number of states searched would be 10^150. Even with a great many flyable configurations, the isolation of these states tot he extent that less than 1 in 10^150 of possible states can be searched, would make the odds of getting just one flyable jet negligibly different from zero. [Try working out the accessible configurations for 1 million parts in a million possible sites, for simplicity with ten spatial orientations per part per site, and you will see why. A jumbo has a lot more than than 1 million parts, and so does a minimally complex cell.]

    –> Minimally complex observed life capable of independent existence comes in at 300,000 – 500,000 base pairs, or at plausible minimum, 9.9 * 10^180,617 states of its DNA string.

    4. They misunderstand what is meant by a probability calculation.

    –> the relevant search calculation is plain, and the probabilistic resources of the whole observed universe are grossly inadequate to get to minimal FSCI per chance + necessity

    –> but, we routinely observe FSCI-bearing entities created by intelligence.

    –> So, on inference to best empirically anchored explanation, the FSCI in cell based life is most reasonably explained by intelligent design.

    5. They seriously underestimate the number of functional enzymes/ribozymes present in a group of random sequences.[1]

    –> “functionality” here is based on an equivocation of the meaning. In life systems, mRNA, tRNA, rRNA fulfill specific functions. |Being able to replicate oneself or to catalyse some chemical reaction or another are irrelevant tot he required observed function

    –> in short this is entirely analogous to the self-refuting strawman fallacy GLF so insists on as though it were a rhetorical home-run: comparing a car bonnet kiting in a storm wind, to a flyable 747 being assembled by chance through the forces of a tornado.

    –> FYI, GLF: there is a reason we sometimes see the one — or its equivalent in flying sets of roofing materials — but not the other.

    –> The same reason why hurricanes and tornadoes are noted for destructive not constructive effects.

    __________________

    GEM of TKI

  9. 9
    PaulN says:

    Well said KF. You came right out and identified his argument primarily as a list of talking points and dismissals, something I’ve become accustomed to and somewhat desensitized from hearing on their side. Their support of Darwin’s theory is no longer focused on the evidence and logic, but rather political tactics and social engineering. Of course following that I have my own opinions on the socio-political impact this philosophical system has reaped on our country within the past few decades, but I suppose that discussion should be saved for a “big picture” topic.

    Picking arguments apart point by point with rationale and logical merits like you’ve demonstrated here is how ID will eventually win this battle while maintaining honesty and integrity, not having to resort to any underhanded or deceitfully miasmic tactics.

  10. 10
    kairosfocus says:

    Dr Paul Nelson:

    Thank you.

    I ask, could you contact me through the contact in my always linked? [Issue: sci and sci edu liberation initiatives.]

    Thanks

    GEM of TKI

    PS: The notion that Sir Fred Hoyle grossly errs on what a statistical thermodynamics related probability is, would be laughable, if it were not being used in yet another Plato’s Cave rhetorical game. (BTW, why is it that discussions of the PC parable seldom bring out the overt manipulativeness and imposition of agendas in the parable?)

    (Hint to Anti-Evo advocates and Wikipedians: The Late, Great Sir Fred may err, but his errors are highly instructive; not those of mere ignorance or sloppiness of thought. Just remember, you are up against a holder of a Nobel-equivalent prize here [who in a fairer world would have been awarded the Nobel as well . . . ], a major figure on one of the two major models for cosmology in C20, whose nickname for the other model is the one we use today as the more of less official name: the Big Bang theory. My latest instructive encounter with the sheer quality of the mind of this man — unabashedly, one of my personal scientific heroes — was on his electrodynamic model on planetary formation in protosolar system models. Subtleties include what happens when a solenoid with a field in it rotates. [Further Hint: the Faraday Disk Generator has in it some subtleties that School and College science tutors seldom tell students about!])

  11. 11
    PaulN says:

    Oh my, I must say that I am terribly sorry for the misunderstanding! I’m actually not the Dr. Paul Nelson, and I hope no one else here has been under that impression, as I would hate to possibly tarnish his reputation! =)

    My name is Paul, and my last name just happens to start with an N. I kept it at that just to maintain a certain level of anonymity. I don’t aim to disappoint, but I’m actually one of the younger participants here (though I’m flattered you took me for a Doctor! =P); I just started my freshmen year in college, but I’ve been following the ID movement for almost 3 years now. Since then I’ve been absolutely thrilled with the progress and attention that you guys have been receiving, as the world truly needs to see the other side of the coin that is left mostly unmarred by a philosophically naturalistic worldview agenda.

    As a highschooler I was completely blind to any thorough and intellectually rigorous criticisms of Darwinism, and now that I’m in college I realize that this institutionally induced state of self-propagating ignorance would have continued right through a 4 year degree. Fortunately shortly after graduating high school I came across a brilliant critique of all that I had held to be true up to that point. It was an online video featuring Michael Behe, William Dembski, Stephen C. Meyer, and Dean Kenyon among other ID heavyweights who drove nails through the core components and ideas of Darwinian evolution. This was the first time in my life I had ever heard mention of positive, logical counter-points to Darwin’s theory such as irreducible complexity and complex specified information. On top of Dean Kenyon’s rebuttal to his own theory of biochemical predestination, the video focused on the workings of the bacterial flagella and how its function specified a parallel to what we know as an outboard motor.

    Since then I’ve come to know hundreds of documents and videos that solidly reinforced this new-found position with straightforward logic and evidence, as opposed to profoundly wishful narratives, stretched correlations, and enormous gaps which were traversed with elegant rhetoric.

    That’s basically my story in a nutshell. I must say, however, that it’s an honor to be able to converse with everyone here in an open forum! I am truly privileged to have access to the rich information and discourse that goes on here between all of the contributors; and, while I may not have as much to contribute yet, I feel that my understanding of all the evidence and arguments will grow exponentially as I learn more in college (particularly when it comes to math and engineering!).

    -Paul Narcisse

  12. 12
    kairosfocus says:

    Ah Paul;

    I see.

    Do contact me

    GEM of TKI

  13. 13
    PaulN says:

    My pleasure =)

  14. 14
    Oramus says:

    PaulN,

    Great post @11!

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