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A Biologic Institute challenge to Darwinism: two protein chains, combined length over 1,400 amino acid residues

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In “Intricate Co-ordination”(Biologic Perspectives,, April 30, 3012), Biologic Institute senior scientist Ann Gauger explains,

Meet carbamoyl phosphate synthetase (CPS), a remarkably complex enzyme. This enzyme uses bicarbonate, glutamine, ATP, and water to make carbamoyl phosphate via a multi-step reaction at three separate active sites, involving several unstable intermediates. [details linked]

CPS is made of two protein chains with a combined length of over 1,400 amino acid residues. We now know from extensive biochemical data that a fully coupled CPS requires the hydrolysis of one glutamine and two molecules of MgATP for every molecule of carbamoyl phosphate formed. …

How does a neo-Darwinian process evolve an enzyme like this? Even if enzymes that carried out the various partial reactions could have evolved separately, the coordination and combining of those domains into one huge enzyme is a feat of engineering beyond anything we can do. More.

Note: Biologic Institute is not to be confused with Biologos. The former is a research group that agrees that there is design in nature, and publishes journal papers on relevant issues. The latter was founded by NIH head Francis Collins to help theologians and scientists promote Darwinism to Christians.

42 Replies to “A Biologic Institute challenge to Darwinism: two protein chains, combined length over 1,400 amino acid residues

  1. 1
    nullasalus says:

    The latter was founded by NIH head Francis Collins to help theologians and scientists promote Darwinism to Christians.

    I don’t know if this is a new edition, but Biologos’ website now says under ‘our beliefs’:

    We reject ideologies such as Deism that claim the universe is self-sustaining, that God is no longer active in the natural world, or that God is not active in human history.
    We reject ideologies such as Darwinism and Evolutionism that claim that evolution is a purposeless process or that evolution replaces God.
    We reject ideologies such as Materialism and Scientism that claim science is the sole source of knowledge and truth, that science has debunked God and religion, or that the physical world constitutes the whole of reality.

  2. 2
    NickMatzke_UD says:

    Re: BioLogic’s challenge about carbomoyl phosphate synthetase evolution.

    Here, let me google that for you:
    http://lmgtfy.com/?q=evolution.....synthetase

  3. 3
    nullasalus says:

    Re: BioLogic’s challenge about carbomoyl phosphate synthetase evolution.

    Here, let me google that for you:

    Do ya find it at all damaging to your case that the links turned up in the search don’t fully address the question you know is being posed here?

    Wait a sec, Nick. I think I know what answer to expect from you. 😉

  4. 4
    NickMatzke_UD says:

    Don’t you find it disturbing that dozens of researchers have worked on the exact question that Gauger asks, and that neither Gauger, nor the DI, nor BioLogic, could be bothered to do the elementary literature review that any serious scientific endeavor would require, and thus didn’t bother to inform readers that a substantial amount of relevant work scientists have done? It’s lazy/dishonest to not know this/not cite it. No scientist will ever take you guys seriously with this kind of self-imposed ignorance as your modus operandi.

    As for “fully address”, no scientific explanation is ever complete, but it looks like we have a decent outline of how CPS evolved. It’s detailed enough to test, which is all that matters in science. The ID requirement for infinite detail in evolutionary explanations is a ridiculous phantasm they conjure up when they are desperate and have nothing else to say (it’s just a matter of time in this thread, I’m sure).

  5. 5
    nullasalus says:

    Don’t you find it disturbing that dozens of researchers have worked on the exact question that Gauger asks, and that neither Gauger, nor the DI, nor BioLogic, could be bothered to do the elementary literature review

    Okay, I want to point this out.

    Nick has a gimmick. He’s not really responding to me here, or really, to just about anyone who ever asks questions of him. He’s playing to the lurkers. Which is why he says things that I know is ludicrous, and that HE knows is ludicrous – but which he hopes anyone reading won’t realize is ludicrous. People who are glancing in, who don’t follow these topics very close. It’s a common gimmick – accuse someone you dislike of something, and even if it’s completely baseless, just hope the charge sticks among the people who encounter it and then never hear about it again.

    He’s saying that Ann Gauger and Douglas Axe – active researchers in this exact field – have “not done elementary literature review”.

    Adorable claim. Just one problem: it’s not only false, it’s demonstrably false. And in this case, all that’s necessary to do is to show the very work Ann cites, in that exact article and not only read it, but look at the references.

    Here’s the thing: Nick knows this. He knows that Ann Gauger and Douglas Axe are actually doing research, and they aren’t doing it in a vacuum. Right or wrong, they’re consulting the work of their colleagues, they’re commenting on it, and they are – as you can see in that link I just gave, and which Ann Gauger herself gave – documenting quite a lot of what they reference in the process.

    Now, Nick throws around the lazy/dishonest charge. I ask any onlooker here: who’s lazy and dishonest? Ann Gauger, for writing up a blog entry which references the work of herself and Douglas Axe, which in turn lists dozens of references to other scientists’ work on the relevant field? Or Nick Matzke, for claiming – not only sans evidence, but in direct conflict with the actual evidence on hand – that Axe and Gauger “coudl not be bothered to do the elementary literature review” in this field?

    I’ll be waiting for your apology on this one, Nick. I mean, I know I won’t be seeing that – it’s not your MO, even when you’ve been proven dead wrong in a bold accusation. But I’ll be waiting all the same.

    I’ve got a handy reference that may help you out, however.

  6. 6
    Joe says:

    Re: BioLogic’s challenge about carbomoyl phosphate synthetase evolution.

    Here, let me google that for you:
    http://lmgtfy.com/?q=evolution…..synthetase

    In keeping with the criteria set forth by Judge Jones in Ktzmiller v Dover SB, which article, Nick, demonstrates that blind and undirected chemical processes prodiced the carbamoyl phosphate synthetase?

    Or was that just ANOTHER literature bluff?

  7. 7
    gauger says:

    Nick,

    All the evolutionary hypotheses concerning the evolution of CPS that I have seen are based on sequence and structural analysis only. No testing.

    In fact it would quite interesting to see if the hypothetical fusions and duplications that supposedly formed the first CPS in the first cells can be accomplished by purely undirected processes. A worthy experiment indeed. But until it has been shown that such a process can in fact generate an enzyme capable of channeling unstable intermediates from one active site to the next, these remain hypotheses only.

    The problem is that similarity of sequence *alone* does not establish the existence of a plausible evolutionary path.

  8. 8
    bornagain77 says:

    As Nick Matzke repeatedly makes clear on this and other sites, and as Dr. Gauger has briefly pointed out here, there is a profound disconnect between what neo-Darwinists presuppose to be true for the ability of a functional protein to easily change into other proteins of other functions and from what the laboratory work has very strongly indicated. Laboratory work indicating that such changes in functional protein sequences to other functional protein sequences are impossible. The fact of the matter is that the sequence comparisons that Nick, and other neo-Darwinists, repeatedly refer to, (as if the sequence comparisons themselves are the conclusive proof they need for the very thing they are presupposing to be true), is not supported in the least by solid empirical research. Needless to say, without a firm demonstration that proteins, any proteins at all, can actually change from one function to another different function, by a step by step gradual Darwinian process, one is not even in the field of rigorous empirical research with such careless and unsubstantiated rhetoric, but one is left completely adrift in a world of pure speculation and imagination. Clearly, such unsupported dogmatic claims, by neo-Darwinists, of the ability of functional proteins to easily change into other functional proteins, by step by step neo-Darwinian processes, is completely antagonistic to the practice of good science. It is hard to believe that neo-Darwinists can actually get away with such tripe and call it science!

    Notes:

    Nothing In Molecular Biology Is Gradual – Doug Axe PhD. – video
    http://www.metacafe.com/watch/5347797/

    “Charles Darwin said (paraphrase), ‘If anyone could find anything that could not be had through a number of slight, successive, modifications, my theory would absolutely break down.’ Well that condition has been met time and time again. Basically every gene, every protein fold. There is nothing of significance that we can show that can be had in a gradualist way. It’s a mirage. None of it happens that way. – Doug Axe PhD.

    When Theory and Experiment Collide — April 16th, 2011 by Douglas Axe
    Excerpt: Based on our experimental observations and on calculations we made using a published population model [3], we estimated that Darwin’s mechanism would need a truly staggering amount of time—a trillion trillion years or more—to accomplish the seemingly subtle change in enzyme function that we studied.
    http://www.biologicinstitute.o.....nt-collide

    Wheel of Fortune: New Work by Thornton’s Group Supports Time-Asymmetric Dollo’s Law – Michael Behe – October 5, 2011
    Excerpt: Darwinian selection will fit a protein to its current task as tightly as it can. In the process, it makes it extremely difficult to adapt to a new task or revert to an old task by random mutation plus selection.
    http://www.evolutionnews.org/2.....51621.html

    Stability effects of mutations and protein evolvability. October 2009
    Excerpt: The accepted paradigm that proteins can tolerate nearly any amino acid substitution has been replaced by the view that the deleterious effects of mutations, and especially their tendency to undermine the thermodynamic and kinetic stability of protein, is a major constraint on protein evolvability,,
    http://www.ncbi.nlm.nih.gov/pubmed/19765975

    Corticosteroid Receptors in Vertebrates: Luck or Design? – Ann Gauger – October 11, 2011
    Excerpt: if merely changing binding preferences is hard, even when you start with the right ancestral form, then converting an enzyme to a new function is completely beyond the reach of unguided evolution, no matter where you start.
    http://www.evolutionnews.org/2.....51801.html

    “Mutations are rare phenomena, and a simultaneous change of even two amino acid residues in one protein is totally unlikely. One could think, for instance, that by constantly changing amino acids one by one, it will eventually be possible to change the entire sequence substantially… These minor changes, however, are bound to eventually result in a situation in which the enzyme has ceased to perform its previous function but has not yet begun its ‘new duties’. It is at this point it will be destroyed” Maxim D. Frank-Kamenetski, Unraveling DNA, 1997, p. 72. (Professor at Brown U. Center for Advanced Biotechnology and Biomedical Engineering)

    “A problem with the evolution of proteins having new shapes is that proteins are highly constrained, and producing a functional protein from a functional protein having a significantly different shape would typically require many mutations of the gene producing the protein. All the proteins produced during this transition would not be functional, that is, they would not be beneficial to the organism, or possibly they would still have their original function but not confer any advantage to the organism. It turns out that this scenario has severe mathematical problems that call the theory of evolution into question. Unless these problems can be overcome, the theory of evolution is in trouble.”
    Problems in Protein Evolution:
    http://www.cs.unc.edu/~plaisted/ce/blocked.html

    Extreme functional sensitivity to conservative amino acid changes on enzyme exteriors – Doug Axe
    Excerpt: Contrary to the prevalent view, then, enzyme function places severe constraints on residue identities at positions showing evolutionary variability, and at exterior non-active-site positions, in particular.
    http://nsmserver2.fullerton.ed.....lution.pdf

    Darwin’s God: Post Synaptic Proteins Intolerant of Change – December 2010
    Excerpt: Not only is there scant evidence of intermediate designs leading to the known proteins, but the evidence we do have is that these proteins do not tolerate change.
    http://darwins-god.blogspot.co.....nt-of.html

    As well, the vast majority of ‘errors/mutations’ that are found to ‘naturally’ occur in protein sequences, which are ‘suppose’ to be the driving force for Darwinian evolution of phenotypes, are actually found to be ‘designed errors’. Designed errors of a ‘non-random’ nature:

    Cells Defend Themselves from Viruses, Bacteria With Armor of Protein Errors – Nov. 2009
    Excerpt: These “regulated errors” comprise a novel non-genetic mechanism by which cells can rapidly make important proteins more resistant to attack when stressed,
    http://www.sciencedaily.com/re.....134701.htm

  9. 9
    bornagain77 says:

    Here is corroborating evidence that ‘protein specific’ quantum information/entanglement resides in functional proteins:

    Coherent Intrachain energy migration at room temperature – Elisabetta Collini & Gregory Scholes – University of Toronto – Science, 323, (2009), pp. 369-73
    Excerpt: The authors conducted an experiment to observe quantum coherence dynamics in relation to energy transfer. The experiment, conducted at room temperature, examined chain conformations, such as those found in the proteins of living cells. Neighbouring molecules along the backbone of a protein chain were seen to have coherent energy transfer. Where this happens quantum decoherence (the underlying tendency to loss of coherence due to interaction with the environment) is able to be resisted, and the evolution of the system remains entangled as a single quantum state.
    http://www.scimednet.org/quant.....d-protein/

    Moreover, another fact that is completely contrary to neo-Darwinian thinking, besides ‘regulated errors’, is the fact that mathematical information is now found to reside along the entirety of a protein chain, constraining the protein chain to a specific function;

    Proteins with cruise control provide new perspective:
    “A mathematical analysis of the experiments showed that the proteins themselves acted to correct any imbalance imposed on them through artificial mutations and restored the chain to working order.”
    http://www.princeton.edu/main/...../60/95O56/

    Cruise Control permeating the whole of the protein structure??? This is an absolutely fascinating discovery. The equations of calculus involved in achieving even a simple process control loop, such as a dynamic cruise control loop, are very complex. In fact it seems readily apparent to me that highly advanced mathematical information must reside ‘transcendentally’ along the entirety of the protein structure, in order to achieve such control of the overall protein structure. This fact gives us clear evidence that there is far more functional information residing in proteins than meets the eye. Moreover this ‘oneness’ of cruise control, within the protein structure, can only be achieved through quantum computation/entanglement principles, and is inexplicable to the reductive materialistic approach of neo-Darwinism! For a sample of the equations that must be dealt with, to ‘engineer’ even a simple process control loop like cruise control for a single protein, please see this following site:

    PID controller
    A proportional–integral–derivative controller (PID controller) is a generic control loop feedback mechanism (controller) widely used in industrial control systems. A PID controller attempts to correct the error between a measured process variable and a desired setpoint by calculating and then outputting a corrective action that can adjust the process accordingly and rapidly, to keep the error minimal.
    http://en.wikipedia.org/wiki/PID_controller

    It is in realizing the staggering level of engineering that must be dealt with to achieve ‘cruise control’ for each individual protein, along the entirety of the protein structure, that it becomes apparent even Axe’s 1 in 10^77 estimate for rarity of finding specific functional proteins within sequence space is far, far too generous. In fact probabilities over various ‘specific’ configurations of material particles simply do not even apply, at all, since the ’cause’ of the non-local quantum information does not even reside within the material particles in the first place (i.e. falsification of local realism; Alain Aspect, Anton Zeilinger).

    Here is corroborating evidence that ‘protein specific’ quantum information/entanglement resides in functional proteins and DNA:

    Coherent Intrachain energy migration at room temperature – Elisabetta Collini & Gregory Scholes – University of Toronto – Science, 323, (2009), pp. 369-73
    Excerpt: The authors conducted an experiment to observe quantum coherence dynamics in relation to energy transfer. The experiment, conducted at room temperature, examined chain conformations, such as those found in the proteins of living cells. Neighbouring molecules along the backbone of a protein chain were seen to have coherent energy transfer. Where this happens quantum decoherence (the underlying tendency to loss of coherence due to interaction with the environment) is able to be resisted, and the evolution of the system remains entangled as a single quantum state.
    http://www.scimednet.org/quant.....d-protein/

    Quantum Information/Entanglement In DNA – short video
    http://www.metacafe.com/watch/5936605/

    In fact since quantum entanglement/information falsified reductive materialism/local realism in the first place (Alain Aspect; Anton Zeilinger) then finding quantum entanglement/information to be ‘protein specific’ is absolutely shattering to any rational hope that materialists had in whatever slim probabilities there were for specific functional protein sequences, since a ‘transcendent’, ‘non-local’, cause must be supplied which is specific to each unique protein structure. Reductive materialism, which is the basis of neo-Darwinian thought, is simply at a complete loss to supply such a ‘non-local’ transcendent cause, whereas Theism has always postulated a transcendent ‘non-local’ cause for life!

    Though the authors of the ‘cruise control’ paper tried to put a evolution friendly spin on the ‘cruise control’ evidence, for finding such a highly advanced ‘Process Control Loop’ at such a base molecular level, (before natural selection even has a chance to select for any morphological novelty that a protein may have from ‘random’ mutations), the fact is that this strict limit to the variability of a protein, imposed by the quantum information of a protein to the protein’s specific function, is very much to be expected from a Intelligent Design/Genetic Entropy viewpoint, and this finding is in fact a very constraining thing to the amount of variation we should reasonably expect from any specific protein in the first place!

    As well, needless to say, the overall implications of finding non-local quantum information in life on a massive scale are staggering to put it mildly!!!

    Quantum Entangled Consciousness – Life After Death – Stuart Hameroff – video
    http://vimeo.com/39982578

    Quantum no-hiding theorem experimentally confirmed for first time
    Excerpt: In the classical world, information can be copied and deleted at will. In the quantum world, however, the conservation of quantum information means that information cannot be created nor destroyed. This concept stems from two fundamental theorems of quantum mechanics: the no-cloning theorem and the no-deleting theorem. A third and related theorem, called the no-hiding theorem, addresses information loss in the quantum world. According to the no-hiding theorem, if information is missing from one system (which may happen when the system interacts with the environment), then the information is simply residing somewhere else in the Universe;
    http://www.physorg.com/news/20.....tally.html

    Does Quantum Biology Support A Quantum Soul? – Stuart Hameroff – video (notes in description)
    http://vimeo.com/29895068

    Music and verse

    Carrie Underwood – Temporary Home
    http://www.youtube.com/watch?v=LraOiHUltak

    Matthew 6:19-21
    “Do not store up for yourselves treasures on earth, where moth and rust destroy, and where thieves break in and steal. But store up for yourselves treasures in heaven, where moth and rust do not destroy, and where thieves do not break in and steal. For where your treasure is, there your heart will be also.

  10. 10
    Jonin says:

    One of the most disappointing discovery in my recent insights on the evolutionary thinking, especially about the “hard” and “heavy” science that support it, was that almost the strongest argument in support for it is relied on comparisons.

    Genetic sequences comparisons, body plans comparisons, bones comparisons, phenotype comparisons.

    That’s really sad…

    I thought there were lots of scientific “wonders” in the “backstage” of one of the most followed theory of the last two centuries but, reading, for example, in Lodish’s “Molecular cell biology” – by the way an excellent book that, at the very least, doesn’t mention all the “iconographic” stuff like finches, moths, archaeopterix, etc – all those speculations and conjectures just because “..sequences analysis demonstrate the evolution..” of “this” or “that” made me extremely unsatisfied..

    I can really imagine the disappoint of YOU guys when I read comment like the one above by Nick Matzke..

    But the thing that truly impressed me in this case is the “tons” of scientific poofs that a guy like him should “use” to criticize Gauger’s and Axe’s excellent work, instead of pointing out [only] to [the same] mere comparisons pubblications..

    http://en.wikipedia.org/wiki/Nick_Matzke

    “..the former Public Information Project Director at the National Center for Science Education (NCSE)..”

    Ooops, I really didn’t know…:(

  11. 11
    Jonin says:

    “…the “tons” of scientific poofs ..”

    Sorry, I meant to write “proofs”, even if in the mistake there’s an hidden onomatopoeic meaning that…;)

  12. 12
    Genomicus says:

    In “Intricate Co-ordination”(Biologic Perspectives,, April 30, 3012), Biologic Institute senior scientist Ann Gauger…

    Just thought I’d point out that we’re not one thousand years in the future 😉

  13. 13
    Genomicus says:

    I won’t add my own thoughts to the origin of carbamoyl phosphate synthetase yet, but here are a couple of papers that are worth looking into:

    “Evolutionary relationships of the carbamoylphosphate synthetase genes,” 1995 (Journal of Molecular Evolution).

    Key points from this paper:

    1. Gram-negative CPS consists of two subunits, while in eukaryotes the two subunits have fused.

    2. The two kinase subdomains of CPS may have arisen through gene duplication of an ancient gene.

    3. The exon-intron organization of these two subdomains prompted the authors to suggest that the ancient exons encoded ~19 amino acid residues.

    Next, a paper from 1996 published in Molecular Biology and Evolution, “Phylogenetic analysis of carbamoylphosphate synthetase genes: complex evolutionary history includes an internal duplication within a gene which can root the tree of life.”

    The key point:

    We confirm that internal similarity within the synthetase domain of CPS is the result of an ancient gene duplication that preceded the divergence of the Bacteria, Archaea, and Eukarya, and use this internal duplication in phylogenetic tree construction to root the tree of life. Our analysis indicates with high confidence that this archaeal sequence is more closely related to those of Eukarya than to those of Bacteria. In addition to this ancient duplication which created the synthetase domain, our phylogenetic analysis reveals a complex history of further gene duplications, fusions, and other events which have played an integral part in the evolution of CPS.

    My own thoughts on this may follow if I can cook up the time.

  14. 14
    NickMatzke_UD says:

    Nick,

    All the evolutionary hypotheses concerning the evolution of CPS that I have seen are based on sequence and structural analysis only. No testing.

    In fact it would quite interesting to see if the hypothetical fusions and duplications that supposedly formed the first CPS in the first cells can be accomplished by purely undirected processes. A worthy experiment indeed. But until it has been shown that such a process can in fact generate an enzyme capable of channeling unstable intermediates from one active site to the next, these remain hypotheses only.

    The problem is that similarity of sequence *alone* does not establish the existence of a plausible evolutionary path.

    Ann,

    Why didn’t you even bother to mention these in your post on the DI website and the BioLogic website? How was that responsible communication with the public?

    Furthermore, the blanket dismissal of phylogenetic evidence just doesn’t wash. Literally hundreds of thousands of scientists use phylogenetic analysis every single day. That’s how the evolution of the flu virus is traced. That’s how we figure out if the HIV in person A came from person B. That’s how we identify unknown microbes, viruses, illegallly imported animal products, etc. There are hundreds, probably thousands, of publications just on the statistics involved in estimating phylogenetic trees, and testing the validity of the methods in various ways.

    Making a statement such as the one you make just shows you don’t know what you are talking about, and the scientific community need not take you seriously.

  15. 15
    NickMatzke_UD says:

    Adorable claim. Just one problem: it’s not only false, it’s demonstrably false. And in this case, all that’s necessary to do is to show the very work Ann cites, in that exact article and not only read it, but look at the references.

    None of which are any of the articles on the EVOLUTION of CPS, which I was able to find with a simple google search, but which Gauger and her fans were pretending didn’t exist.

    Here’s the thing: Nick knows this. He knows that Ann Gauger and Douglas Axe are actually doing research, and they aren’t doing it in a vacuum. Right or wrong, they’re consulting the work of their colleagues, they’re commenting on it, and they are – as you can see in that link I just gave, and which Ann Gauger herself gave – documenting quite a lot of what they reference in the process.

    Now, Nick throws around the lazy/dishonest charge. I ask any onlooker here: who’s lazy and dishonest? Ann Gauger, for writing up a blog entry which references the work of herself and Douglas Axe, which in turn lists dozens of references to other scientists’ work on the relevant field? Or Nick Matzke, for claiming – not only sans evidence, but in direct conflict with the actual evidence on hand – that Axe and Gauger “coudl not be bothered to do the elementary literature review” in this field?

    The title of this thread is “A Biologic Institute Challenge to Darwinism”. And yet, the issuers of the challenge didn’t even bother to do the simplest, most basic first step on the question of the evolution of a system, namely looking up the literature on the evolution of this system.

    Amongst other extremely relevant things that such a literature search would have revealed would be the fact that there are lots of variants on the CPS and related systems, and some of the relatives have some of the parts and some of the functions. This disproves the argument which the ID people put forward, which was the claim that this system had to have come together all at once. Ain’t so, because there are pieces of the system existing and functioning right now, despite being “partial”.

    ID rebuttal 101, really.

  16. 16
    Joe says:

    Nick,

    Phylogenetic analysis does not provide evidence for any mechanism- an undergrad understands that.

    Also not all evolution has to be Darwinian. Using the standard set by Judge Jones,which article, Nick, demonstrates that blind and undirected chemical processes prodiced the carbamoyl phosphate synthetase?

    Or was that just ANOTHER literature bluff?

  17. 17
    Joe says:

    Nick Matzke, the great equivocator:

    The title of this thread is “A Biologic Institute Challenge to Darwinism”. And yet, the issuers of the challenge didn’t even bother to do the simplest, most basic first step on the question of the evolution of a system, namely looking up the literature on the evolution of this system.

    Using the standard set by Judge Jones, which article, Nick, demonstrates that blind and undirected chemical processes prodiced the carbamoyl phosphate synthetase?

  18. 18
    nullasalus says:

    Nick,

    None of which are any of the articles on the EVOLUTION of CPS, which I was able to find with a simple google search, but which Gauger and her fans were pretending didn’t exist.

    A complete lie on your part.

    Nowhere does Gauger or the DI pretend that no one has been discussing CPS evolution. The challenge given was this: “How does a neo-Darwinian process evolve an enzyme like this? Even if enzymes that carried out the various partial reactions could have evolved separately, the coordination and combining of those domains into one huge enzyme is a feat of engineering beyond anything we can do.”

    Nowhere – not anywhere in the article – is it stated by Gauger that this is completely ignored by neo-darwinist. And it’s no surprise why it’s not stated: because that’s not necessary. They’re stating what the challenge is, and that the challenge remains to be met. Period.

    You don’t deny this. Instead you manufacture a strawman and proceed to shoot it down. It’s dishonest, Nick. Walk it back.

    Amongst other extremely relevant things that such a literature search would have revealed would be the fact that there are lots of variants on the CPS and related systems, and some of the relatives have some of the parts and some of the functions.

    Irrelevant for the claim in question. Why do you persist in answering charges Gauger didn’t make, or calling her out for saying things she did not say?

    The fact that you have to put words in Gauger’s mouth in order to answer her here says a lot.

    This disproves the argument which the ID people put forward, which was the claim that this system had to have come together all at once.

    First, even if your claims were true, it’s not an argument being put forward by Ann Gauger in the article quoted. Why are you trying to change the subject, Nick? Why is it that all of your arguments given here against Gauger involve responding to things she has not said? Isn’t that rather dishonest?

    Second, even if precursors or variants on the CPS parts are seen in relatives – and whether those are ‘relatives’ would be a whole other subject – that still doesn’t speak against the claim Gauger is making here: whether neo-Darwinian processes are sufficient to explain what is seen. It’s not an argument against evolution, full stop, that Ann is giving. It’s an argument against neo-Darwinian processes.

    Nick, ID critics burn their own credibility when they make baseless charges of what they criticize, and criticize their opponents for saying things they have not said.

  19. 19
    nullasalus says:

    By the way, Nick claims that ‘none of which are articles on the EVOLUTION of CPS’, in the multitude of references given in the very research paper Ann Gauger’s post is about.

    Here’s just one of those cited works: The Generation of New Protein Functions by the Combination of Domains. During evolution, many new proteins have been formed by the process of gene duplication and combination. The genes involved in this process usually code for whole domains. Small proteins contain one domain; medium and large proteins contain two or more domains. We have compared homologous domains that occur in both one-domain proteins and multidomain proteins. We have determined (1) how the functions of the individual domains in the multidomain proteins combine to produce their overall functions and (2) the extent to which these functions are similar to those in the one-domain homologs. We describe how domain combinations increase the specificity of enzymes; act as links between domains that have functional roles; regulate activity; combine within one chain functions that can act either independently, in concert or in new contexts; and provide the structural framework for the evolution of entirely new functions.

    Would you look at that. A discussion of the proposed evolutionary origins of new protein functions. Sounds an awful lot like that ‘basic literature review’ Nick claims the Biologic Institute never does. In fact, it seems to go above and beyond the mere google scholarship Nick subscribes to.

    One would almost get the impression his claim here was blankly dishonest. But why would Nick fib about something like this?

  20. 20
    NickMatzke_UD says:

    Would you look at that. A discussion of the proposed evolutionary origins of new protein functions. Sounds an awful lot like that ‘basic literature review’ Nick claims the Biologic Institute never does.

    null,

    These aren’t about CPS, which is what the challenge was about.

  21. 21
    NickMatzke_UD says:

    Nowhere – not anywhere in the article – is it stated by Gauger that this is completely ignored by neo-darwinist. And it’s no surprise why it’s not stated: because that’s not necessary. They’re stating what the challenge is, and that the challenge remains to be met. Period.

    That’s precisely like posting a “challenge to Darwinism” which said “How did birds evolve?”, without noting that there are relevant fossils, papers, etc.

    You don’t get to issue a challenge, when you have done no work or writing on a topic, and your opposition has multiple peer-reviewed publications addressing said topic. Well, obviously you physically can do it, it’s a free country, but to anyone in science you look moronic doing it.

    Best case for your position: You guys issued a challenge. I answered it with reference to the literature. Your only hope is to address and rebut the literature, in detail. Otherwise there is no reason to take you seriously at all. I’m not going to do your investigative work for you.

  22. 22
    NickMatzke_UD says:

    Phylogenetic analysis does not provide evidence for any mechanism- an undergrad understands that.

    Not true. Descent with modification is the mechanism, and it is basically proven when phylogenetic analysis indicates strong statistical tree signal in the data. Within the broad mechanism of descent with modification, we have mechanisms of modification, namely mutations and the population genetic mechanisms which spread mutations in the population, such as drift and selection. These are all extremely well-studied mechanisms whose existence is not at all in doubt. And the sequence substitution models used in phylogenetics nowadays actually explicitly take the different relative probability of different sorts of mutations into account. And these sequence substitution models are also tested as standard parts of phylogenetic analysis.

    So, basically, you don’t know what a well-informed undergraduate would know about this topic.

  23. 23
    nullasalus says:

    Nick,

    These aren’t about CPS, which is what the challenge was about.

    No, CPS was used as an example. The challenge was as followed: “For more information about the challenge to Darwinism presented by protein folds, go here.” With ‘here’ being a link to the paper I’ve been talking about. CPS was featured as an instance of this challenge. By the way, regarding precursors? The very article also says this: “Even if enzymes that carried out the various partial reactions could have evolved separately, the coordination and combining of those domains into one huge enzyme is a feat of engineering beyond anything we can do.”

    And what’s the paper called? “The Case Against a Darwinian Origin of Protein Folds”.

    The ‘basic literature review’ was done, and anyone who bothered to actually read the article – as well as the linked research – would realize as much.

    Nick, ID critics who make false claims about ID, ID research, and ID proponents aren’t going to convince people who notice these things and pay attention. Until ID critics start to be honest about what their opponents are saying, and certainly what research they’re engaging in, they’re not going to convince any skeptics who are actually paying attention.

  24. 24
    nullasalus says:

    Nick,

    Best case for your position: You guys issued a challenge. I answered it with reference to the literature. Your only hope is to address and rebut the literature, in detail. Otherwise there is no reason to take you seriously at all. I’m not going to do your investigative work for you.

    “You guys”? I’m not even an ID proponent! But I believe in accurately representing the claims of people I’m criticizing, and it’s clearly to anyone who actually reads the article and the linked research that you’re not doing so.

    You couldn’t even represent the challenge accurately. You made up what Ann was claiming in the article and the research, and you ignored the cites in the article. The fact that you’re not admitting this and refuse to walk back your claims undercuts your entire position here.

  25. 25
    gauger says:

    I’ll respond in detail later on our Facebook page and web page about why domain fusions and duplications are not trivial things, and why I therefore do not take sequence or structural similarity as proof of origin. Proteins are not built of lego blocks, with interchangeable parts. But those of you who have read Doug’s article already know that.

    Thanks to those who have emphasized what I actually said in the original blog. As has been noted, I alluded to the proposed evolutionary history in my final sentence, then said that any assembly of the whole was the problem. And it still is.

  26. 26

    “Here, let me google that for you:”

    Oh, goodie, another literature bluff from Matzke, this time courtesy of a Google search.

    Nick, some of us are literally exhausted by your constant tossing out of literature that is either irrelevant to the question at hand or doesn’t actually say what you claim it does. Then you add the absurd “Gee, if only the ID guys had read the literature” nonsense.

    It is old. It is tiring. Stop it.

  27. 27
    NickMatzke_UD says:

    I’ll respond in detail later on our Facebook page and web page about why domain fusions and duplications are not trivial things

    Domain fusions and duplications are such incredibly standard and well-accepted concepts in molecular biology that there are literally government-funded databases specifically devoted to cataloging them. Bioinformatics would basically not work if you forbid these concepts. Molecular biology would be crippled, since you could never take experiment X and extrapolate the structure etc. to difficult-to-experiment-on system Y with the same domain structure. Gimme a break.

  28. 28
    gauger says:

    One more comment, and then I’ll sign off. I do not discount all phylogenetic analysis. It is most useful for close-in things, like tracing the evolution of flu strains or HIV, where changes are recent. What I question is whether or not wholesale recombination of protein domains can make new, complex functions by unguided means. How hard are such fusions to accomplish? Has anyone attempted to address that question? Doug and I are addressing it.

    It should also be noted that I do not exclude the possibility that CPS actually was the product of such a fusion. But could it have happened by an undirected process? How fine-tuned would the two halves have to be to make the new enzyme come together at all, let alone function?

    These are questions worth asking.

  29. 29
    bornagain77 says:

    Nick states:

    Domain fusions and duplications are such incredibly standard and well-accepted concepts in molecular biology that there are literally government-funded databases specifically devoted to cataloging them.

    “well-accepted concept” does not equate to true concept! Moreover Tax Payer funding of Darwinian evolution, (by a majority of Tax Payers who do not even believe Darwinian evolution), does not equate to Darwinian evolution being true either!

    I don’t know the average number of protein-protein binding sites required to accomplish a new domain-domain fusion event, but I do know Dr. Behe has done research in the area of protein-protein binding, which is required in a domain-domain fusion event, that severely questions the efficacy of blind processes to do as such;

    “The likelihood of developing two binding sites in a protein complex would be the square of the probability of developing one: a double CCC (chloroquine complexity cluster), 10^20 times 10^20, which is 10^40. There have likely been fewer than 10^40 cells in the entire world in the past 4 billion years, so the odds are against a single event of this variety (just 2 binding sites being generated by accident) in the history of life. It is biologically unreasonable.”
    Michael J. Behe PhD. (from page 146 of his book “Edge of Evolution”)

    Despite this severe limit, the preliminary evidence we have, indicates there is, surprisingly, a ‘rather low’ conservation of Domain-Domain Interactions occurring in the Protein-Protein interactions between different species:

    A Top-Down Approach to Infer and Compare Domain-Domain Interactions across Eight Model Organisms
    Excerpt: Knowledge of specific domain-domain interactions (DDIs) is essential to understand the functional significance of protein interaction networks. Despite the availability of an enormous amount of data on protein-protein interactions (PPIs), very little is known about specific DDIs occurring in them.,,, Our results show that only 23% of these DDIs are conserved in at least two species and only 3.8% in at least 4 species, indicating a rather low conservation across species.,,,
    http://www.plosone.org/article.....ne.0005096

    Behe’s work also bleeds over into Nick’s ‘duplication’ claim, for the fact is that neo-Darwinists simply don’t have any empirical evidence to support their assertion that novel proteins arise from duplication events:

    Michael Behe, The Edge of Evolution, pg. 162 Swine Flu, Viruses, and the Edge of Evolution
    “Indeed, the work on malaria and AIDS demonstrates that after all possible unintelligent processes in the cell–both ones we’ve discovered so far and ones we haven’t–at best extremely limited benefit, since no such process was able to do much of anything. It’s critical to notice that no artificial limitations were placed on the kinds of mutations or processes the microorganisms could undergo in nature. Nothing–neither point mutation, deletion, insertion, gene duplication, transposition, genome duplication, self-organization nor any other process yet undiscovered–was of much use.”
    http://www.evolutionnews.org/2....._edge.html

    Is gene duplication a viable explanation for the origination of biological information and complexity? – December 2010 –
    Excerpt: The totality of the evidence reveals that, although duplication can and does facilitate important adaptations by tinkering with existing compounds, molecular evolution is nonetheless constrained in each and every case. Therefore, although the process of gene duplication and subsequent random mutation has certainly contributed to the size and diversity of the genome, it is alone insufficient in explaining the origination of the highly complex information pertinent to the essential functioning of living organisms. © 2010 Wiley Periodicals, Inc. Complexity, 2011
    http://onlinelibrary.wiley.com.....5/abstract

    Evolution by Gene Duplication Falsified – December 2010
    Excerpt: The various postduplication mechanisms entailing random mutations and recombinations considered were observed to tweak, tinker, copy, cut, divide, and shuffle existing genetic information around, but fell short of generating genuinely distinct and entirely novel functionality. Contrary to Darwin’s view of the plasticity of biological features, successive modification and selection in genes does indeed appear to have real and inherent limits: it can serve to alter the sequence, size, and function of a gene to an extent, but this almost always amounts to a variation on the same theme—as with RNASE1B in colobine monkeys. The conservation of all-important motifs within gene families, such as the homeobox or the MADS-box motif, attests to the fact that gene duplication results in the copying and preservation of biological information, and not its transformation as something original.
    http://www.creationsafaris.com.....#20110103a

    The Limits of Complex Adaptation: An Analysis Based on a Simple Model of Structured Bacterial Populations Douglas D. Axe*
    Excerpt: In particular, I use an explicit model of a structured bacterial population, similar to the island model of Maruyama and Kimura, to examine the limits on complex adaptations during the evolution of paralogous genes—genes related by duplication of an ancestral gene. Although substantial functional innovation is thought to be possible within paralogous families, the tight limits on the value of d found here (d ? 2 for the maladaptive case, and d ? 6 for the neutral case) mean that the mutational jumps in this process cannot have been very large.
    http://bio-complexity.org/ojs/.....O-C.2010.4

    An Insurmountable Problem for Darwinian Evolution – Gene Duplication – And Minor Transformation of Protein Function – podcast – May 2011
    http://intelligentdesign.podom.....1_43-07_00

    Nick also claims

    Bioinformatics would basically not work if you forbid these concepts.

    No it does not Nick! Disallowing the unsubstantiated neo-Darwinian conjectures of blind processes to generate unfathomed levels of integrated complexity means that neo-Darwinian evolution will not work as the overriding framework. Science, bioinformatics (the gathering of biological information about different species), will continue on unimpeded, and in fact, the ‘cataloging of information’ will, once freed from the having to force fit everything into a false neo-Darwinian framework, will finally be able to be cataloged into the correct ‘top-down’ genetic entropy framework i.e. ‘top down’ sub-speciation! Until this gross miscarriage of science is corrected, it is very sad to see that atheists fight tooth and nail in courts and legislatures for the right to brain wash our children in public schools with this pseudo-scientific garbage!

    Music and Verse:

    Newsboys – God’s Not Dead
    http://www.godtube.com/watch/?v=FMF12FNU

    Romans 1:20-23
    For since the creation of the world God’s invisible qualities—his eternal power and divine nature—have been clearly seen, being understood from what has been made, so that people are without excuse.
    For although they knew God, they neither glorified him as God nor gave thanks to him, but their thinking became futile and their foolish hearts were darkened. Although they claimed to be wise, they became fools and exchanged the glory of the immortal God for images made to look like a mortal human being and birds and animals and reptiles.

  30. 30
    Joe says:

    Nick matzke- equivocator:

    Descent with modification is the mechanism,

    Descent with modification is a design mechanism as far as you know.

    What descent with modification does not say is whetjher or not teh modification was by design or just an accumulation of genetic accidents.

    IOW Nick, once again you prove to be nothing but an equivocator.

    That’s right, Nick actually believes that ID is anti evolution. Ignorance doesn’t help you, Nick.

  31. 31
    Joe says:

    Domain fusions and duplications are such incredibly standard and well-accepted concepts in molecular biology…

    And what is the evidence they are blind and undirected processes as opposed to design processes? Or are you still stuck in equivocation mode?

  32. 32
    Jonin says:

    Directly from Doug Axe’s work, just in the bottom of the abstract, back from 2000..

    And we’re talking about a pr article on “J. Mol. Biol.” and not from a “creationist” journal, as probably NM would define “Bio-Complexity”..

    “Extreme Functional Sensitivity to Conservative
    Amino Acid Changes on Enzyme Exteriors”

    “..Contrary to the prevalent view, then, enzyme function places ***severe constraints*** on residue identities at positions showing evolutionary variability, and at ***exterior non-active-site positions***, in particular.

    Homologues sharing less than about two-thirds sequence identity should probably be viewed as ***distinct designs*** with their own sets of optimising features.”

    And in the article:

    “..The fact that conservative replacement
    of only a fifth of the exterior residues causes
    near total loss of activity in both enzymes shows
    that function actually places very tight constraints on amino acid identities at exterior positions..”

    I really would like to know which part of the supposed and simplier “ancestral” enzyme would have “fused” with others parts as to form the actual CPS..Maybe exactly at the “exterior non-active-site positions”?

  33. 33
    NickMatzke_UD says:

    One more comment, and then I’ll sign off. I do not discount all phylogenetic analysis. It is most useful for close-in things, like tracing the evolution of flu strains or HIV, where changes are recent. What I question is whether or not wholesale recombination of protein domains can make new, complex functions by unguided means. How hard are such fusions to accomplish? Has anyone attempted to address that question? Doug and I are addressing it.

    Exactly identical methods, literally the same programs and statistics, are used for both. You can’t just assert that it is legit to accept the results in one case and arbitrarily reject the results in another case. It’s as arbitrary as when young-earth creationists accept carbon-dating back to 6,000 years ago, but arbitrarily reject the result when the same method returns a result of say 25,000 years.

  34. 34
    NickMatzke_UD says:

    I don’t know the average number of protein-protein binding sites required to accomplish a new domain-domain fusion event

    Um…one. That’s what a “protein-protein binding site” does, bind two proteins.

    Or actually, zero, if the two domains are linked covalently by being made part of the same gene, resulting in one big amino acid chain.

    Look, folks, it’s not like this is rocket science. Enzymatic pathways can and do function with a bunch of separate enzymes floating around, processing intermediates. Diffusion of products is so fast that this can often work just fine even with all of the enzymes unconnected and free in solution. But, sometimes, an advantage had be had by physically attaching two enzymes to each other, which raises the local concentration of the substrate. One way to do this is domain fusion, where two enzymes or enzyme domains are stuck together in the same gene, through exon shuffling or a similar process. (There are thousands of known examples of this.) Tighter cooperative mechanisms can evolve later. Just pretending that none of this is known won’t get you anywhere with real
    scientists who are familiar with the facts.

  35. 35
    bornagain77 says:

    Nick you claim

    ‘Um…one. That’s what a “protein-protein binding site” does, bind two proteins.

    OKie dokie, Though Nick looking at the picture it sure doesn’t look like one:

    http://media.tumblr.com/tumblr.....r7pr3y.jpg

    But anyway let’s presuppose that you are right, that it only takes one protein-protein binding site to join two domains into a novel enzyme. A enzyme that just so happens to catalyze a reaction for the cell that the cells we currently observe are now dependent on (whew that’s a lot of leeway granted just to satisfy your atheistic premise Nick!) but anyways,,,, how hard is to get just one protein-protein binding site?:

    Viral-Binding Protein Design Makes the Case for Intelligent Design Sick! (as in cool) – Fazale Rana – June 2011
    Excerpt: When considering this study, it is remarkable to note how much effort it took to design a protein that binds to a specific location on the hemagglutinin molecule. As biochemists Bryan Der and Brian Kuhlman point out while commenting on this work, the design of these proteins required:
    “…cutting-edge software developed by ~20 groups worldwide and 100,000 hours of highly parallel computing time. It also involved using a technique known as yeast display to screen candidate proteins and select those with high binding affinities, as well as x-ray crystallography to validate designs.2”
    If it takes this much work and intellectual input to create a single protein from scratch, is it really reasonable to think that undirected evolutionary processes could accomplish this task routinely?
    In other words, the researchers from the University of Washington and The Scripps Institute have unwittingly provided empirical evidence that the high-precision interactions required for PPIs requires intelligent agency to arise. Sick!
    http://www.reasons.org/viral-b.....-sick-cool

    Nick it just ain’t looking good for your dogmatic atheism buddy!

    further notes:

    Without enzyme, biological reaction essential to life takes 2.3 billion years: UNC study:
    In 1995, Wolfenden reported that without a particular enzyme, a biological transformation he deemed “absolutely essential” in creating the building blocks of DNA and RNA would take 78 million years.“Now we’ve found a reaction that – again, in the absence of an enzyme – is almost 30 times slower than that,” Wolfenden said. “Its half-life – the time it takes for half the substance to be consumed – is 2.3 billion years, about half the age of the Earth. Enzymes can make that reaction happen in milliseconds.”
    http://www.med.unc.edu/www/new.....-unc-study

    “Phosphatase speeds up reactions vital for cell signalling by 10^21 times. Allows essential reactions to take place in a hundreth of a second; without it, it would take a trillion years!” Jonathan Sarfati
    http://www.pnas.org/content/100/10/5607.abstract

    Dang that ole neo-Darwinian magic just knows no bounds Nick!

  36. 36
    kairosfocus says:

    Joe (& Dr Matzke):

    Pardon, but descent with some degree or other of modification is a RESULT (observed or inferred), not a dynamic that drives change.

    The Darwinian mechanism is more or less:

    Chance variation + differential reproductive success –> descent with modification

    The debate is over the degree of modification that is possible or reasonable on the accessible gamut of resources. (Observe that modern YEC thinkers seem to think roughly the level of the family is a reasonable upper limit, and view this as a designed mechanism of adaptation that confers robustness to life forms. Leading design thinkers include people who hold to views all the way up to universal common descent.)

    KF

    PS: Joe the requested thread is up.

  37. 37
    NickMatzke_UD says:

    I’m not a Dr. yet, I don’t know where that started.

  38. 38
    Genomicus says:

    I’m not a Dr. yet, I don’t know where that started.

    Oops. And I’ve called you that many times…

  39. 39
    Genomicus says:

    bornagain:

    Nick also claims:

    Bioinformatics would basically not work if you forbid these concepts.

    No it does not Nick! Disallowing the unsubstantiated neo-Darwinian conjectures of blind processes to generate unfathomed levels of integrated complexity means that neo-Darwinian evolution will not work as the overriding framework. Science, bioinformatics (the gathering of biological information about different species), will continue on unimpeded, and in fact, the ‘cataloging of information’ will, once freed from the having to force fit everything into a false neo-Darwinian framework, will finally be able to be cataloged into the correct ‘top-down’ genetic entropy framework i.e. ‘top down’ sub-speciation!

    Umm, except that Nick Matzke’s comment was regarding domain fusions and duplications, and you cannot at all deny that these things happen through non-teleological mechanisms. Gene duplication is well-documented and well understood. Tandem repeat slippage during replication, gene conversion, etc., can cause gene duplications. And when it comes to protein fusions, sometimes all you need is the mutation of a stop codon such that it is converted to any one of the amino acids found in life.

  40. 40
    bornagain77 says:

    I did not deny gene duplication. In fact I referenced several articles showing severe limits to the gene duplication scenario. Thus once again we have wide open, unrestrained, conjectures for how all the diversity in proteins/genes came about without any solid empirical basis for such extrapolation! i.e. pseudoscience!!!

  41. 41
    Mung says:

    Nick Matzke. Doctor of Disinformation.

    There. You’re a Dr. now.

  42. 42
    kairosfocus says:

    NM: Pardon, I saw others speak of you as Dr and so I followed. Hope you succeed soon with the diss and the defense viva. KF

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