Dispatches from the Creation Wars

More DI Lies About Axe’s Research

I have used the analogy before comparing the ID movement to the movie Weekend at Bernie’s, where two guys drag a dead body around pretending it’s alive to keep the party going a little longer. But nowhere is that analogy more accurate than in the IDers constant flogging of the protein research of Douglas Axe, now with the Biologic Institute that the DI is funding. This work has been shredded time and and time again and shown conclusively not to support ID in the slightest, yet they keep dragging it out and propping it up with a drink in its hand, hoping no one notices the embalming fluid. and the eyes sewn shut.

Here’s a post by John West hauling it out yet again, and this time he’s enlisted Axe himself, who before now has been reluctant to claim that his previous papers actually support ID. Here is what he had to say in the past, as quoted by Barbara Forrest and Paul Gross in Creationism’s Trojan Horse:

These three statements summarize my position:

I remain open-minded with respect to the possibility that a sound argument can be made for intelligent design in biology.

I have not attempted to make such an argument in any publications.

Since I understand that Bill Dembski has referred to my work in making such an argument, I shall remain open to the possibility that my published findings may support such an inference until I have had a chance to see his argument.

Surely now that he is on the DI payroll, he has had a chance to see Dembski’s ridiculously exaggerated statement about his previous work, yet he has never corrected it or disputed it. Indeed, Casey Luskin was citing that research in just the last two weeks using the kind of language that Dembski did, with no correction from Axe despite the fact that they both work for the same company. And now Axe seems to be making a similar argument himself, one that absolutely is not supported by the results of his research. Here’s the quote from Axe that West offers:

I have in fact confirmed that these papers add to the evidence for ID. I concluded in the 2000 JMB paper that enzymatic catalysis entails “severe sequence constraints”. The more severe these constraints are, the less likely it is that they can be met by chance. So, yes, that finding is very relevant to the question of the adequacy of chance, which is very relevant to the case for design. In the 2004 paper I reported experimental data used to put a number on the rarity of sequences expected to form working enzymes. The reported figure is less than one in a trillion trillion trillion trillion trillion trillion. Again, yes, this finding does seem to call into question the adequacy of chance, and that certainly adds to the case for intelligent design.

I guess having the DI paying his salary has loosened up his ethics a bit; the fact still remains that neither of his papers provides any support at all for ID, nor are they a problem for evolution to explain. For a detailed explanation of why Axe’s research doesn’t support ID, go here and here. The 2000 JMB paper did not show “severe sequence constraints” at all. It showed quite the opposite, that you could make massive changes in the sequence of amino acids in an enzyme, knocking out 10, 20, even 30 amino acids at a time, without completely destroying the function of the enzyme. It showed that you could make 10 substitutions at a time with only a negligible effect on the enzyme’s function. And this is “severe sequence constraints”? Not even close.

Here’s a very telling fact about Axe’s research: when they had the opportunity to present the results of that work in the Kitzmiller trial, under oath, they didn’t do it. There was a great deal of questioning by the defense team about ID advocates having published articles in peer-reviewed journals. If they could have shown that some of this research actually does support ID, it would have been an enormous help to their case.

When Scott Minnich testified, he mentioned it in an offhand way as an example of ID advocates doing real research, and Richard Thompson brought it up when he cross examined Barbara Forrest, so they were clearly aware of this research. Why didn’t they have either Behe or Minnich testify about the results of that study and why it showed scientific support for ID? For one simple reason: they would have been shredded under cross examination every bit as badly as Behe got shredded over his Protein Science paper. And they knew it.

When Dembski claimed that Axe’s study showed that “any slight modification” of the protein would “not merely destroy the system’s existing function, but also destroys the possibility of any function of the system whatsoever”, he was lying. That kind of blatant distortion of the work of another scientist is enough to get you thrown out of a real professional scientific organization; at the DI, it earns you a salary. And I can tell you this for certain: had Dembski taken the witness stand, that statement would have been thrown in his face as an example of the highly dishonest PR campaign that the ID movement has engaged in about this research.

Isn’t it time to bury this corpse, guys? All it’s doing is stinking up the place.

Comments

  1. #1 Jim Anderson
    January 11, 2007

    According to your second backstory link, Axe was already a DI fellow, with the DI partially funding his research, when he claimed neutrality.

    That could even be more evidence that the DI has been pressuring and pressuring Axe to “get with the program.” Even when he was “with it” at first, he wouldn’t commit.

  2. #2 J-Dog
    January 11, 2007

    Ed – Don’t be a spoilsport! It gives me, and I am sure others, immense enjoyment to see you shred Luskin, Dembski and DI arguments on a regular basis. Was it Voltaire that said if the devil did not exist, we would have to invent him? Watching you and the other SB’rs kick some DI butt is always fun. Don’t tell them to bury the body, pull it into the spotlight!

  3. #3 Daniel Morgan
    January 11, 2007

    I was very interested in assessing the methodology used in the paper to support this huge probability calculation. As I suspected, it seems to do nothing but point out that a bad assumption went into a theory regarding the constraints upon mutation. He points out at the end of the section [I bolded] that the bad assumption is that each mutation will have functional selection, and instead, neutral drift accumulation occurs, and is then selected for with some integral (final function-aiding) mutation.

    What he found is that once a protein’s sequence has been streamlined and “co-optimised” to some function, it is difficult to cause neutral mutations from that point, with respect to the function presently held. However, this is obviously idiotic if one tries to argue against this mechanism being the way in which proteins acquire new functions.

    The paper is quite reasonable, and this figure he cited on the DiscoInst’s blog about the “trillion trillion trillion” has nothing to do with disconfirming evolution, nor confirming ID.

    In addition to active sites, enzymes depend upon protein scaffolds with suitable structural properties. If an appropriate pattern of hydrophobic and polar residues were the only sequence requirement for such scaffolds (the binary-code hypothesis, [Kamtekar et al 1993]), then we would expect roughly half of the 20 amino acid residues to be suitable at every position. This would mean that there are 10171 suitable amino acid specifications for the exterior of TEM-1 β-lactamase. A much lower figure can be obtained by applying the assumption of context independence to the collection of acceptable substitutions reported by Huang and co-workers (henceforth, the Huang set; [Huang et al 1996]). Thus, multiplying the number of residues in the Huang set (including wild-type) at all 171 exterior non-active-site positions gives 10110 acceptable specifications. By way of illustration, the ratio of these two numbers (10110:10171) is similar to the ratio of the volumes of an iodine nucleus and the moon. It is clear that even when context independence is presumed, the data indicate that the binary-code hypothesis greatly underestimates the extent to which function constrains sequence.
    The assumption of context independence also leads to a vast underestimate, though. Comparison of blaMY and blaBG to bla{MY} and bla{BG} (Table 1) shows that substitutions from the conservative set used here are significantly less disruptive than many substitutions in the Huang set. As a consequence, we would expect function typically to be lost well before 30 exterior substitutions from the Huang set could be combined. Inspection of the Huang set shows the average (geometric mean) number of acceptable substitutions at exterior positions to be 3.4. If the TEM-1 enzyme could tolerate 15 such substitutions in any combination, this would amount to about 1029 acceptable exterior specifications [3.415×171!/(15! 156!)=1029]. A different calculation, where it is assumed there is a single alternative to the wild-type residue at each exterior position such that up to 30 of these alternatives can be introduced in any combination, gives a higher estimate of 1033 acceptable specifications [171!/(30! 141!)=1033]. This higher figure compares to the figure obtained assuming context independence (10110) as the volume of an electron compares to the volume of a sphere with a radius equal to the mean Earth-Sun distance.
    With exterior constraints being so severe, how is it that mutant studies often find greater tolerance at exterior positions? The catastrophic effect referred to above suggests an answer. When TEM-1 substitution groups are combined (Table 1), the resulting relative hydrolysis activities are always lower than the product of the relative activities for the various groups. One likely explanation for this co-operative functional disruption is that it results from progressive loss of stability of the native fold. If most individual substitutions are mildly destabilising, several may be introduced without catastrophic loss of stability and function. As a consequence, studies using small numbers of substitutions typically would not detect the corresponding minor disruption…
    The fact that the amino acid differences between two closely related β-lactamase enzymes clearly are not functionally inconsequential might seem to contradict the notion that homologues are connected by a path of neutral substitutions. However, the neutral theory claims neither that most possible substitutions nor that most possible paths between close homologues are selectively neutral. It claims, rather, that the actual historical paths consist primarily of substitutions that each were neutral in their own context.
    The findings of this work can be accommodated within the framework of the neutral theory by postulating that substitutions initially having no significant effect become invested with functional importance as further substitutions accumulate.

    I also find it interesting that his calculations about toleration of 15 and 30 mutations shows a searchspace with 1029 or 1033 “acceptable specifications” for RM/NS, yet this is considered evidence of ID via “severe constraints”, which rule out chance? And, keep in mind that this is all in reference to the maintenance of some original function, not in reference to generation of new function.

    Perhaps I’m just misunderstanding the paper, but I don’t think I am.

  4. #4 Ed Brayton
    January 11, 2007

    No, you’re reading it right Daniel. That’s why I’m just baffled by how they can claim that there are “severe sequence constraints” on the function of this enzyme. He changed out 10 amino acids at a time with little effect on the original function and had to change out 40 amino acids at a time before destroying that original function. And he never even checked for any alternative function (though as Matt Inlay notes in the link above, other researchers have done so and found that there are other functions for the altered enzyme). It is simply a lie to claim that this research found that “any slight modification” destroyed “all possibility of any function.” If you made that claim in a grad school paper, you would get a failing grade for crying out loud.

  5. #5 Dave S.
    January 11, 2007

    Maybe he’s using Dembski’s own definition of ‘intelligence’, which would seem to include natural selection.

  6. #6 Jeremiah
    January 11, 2007
    
    Lets see:
    
    
    1:1,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
    000,000,000,000,000
    
    Is still a chance.
    
    The fact that it happened doesn't in one bit support ID or contradict evolution.
    
  7. #7 Henry
    January 11, 2007

    Let me give my take on Axe’s research, his arguments, and where I think he goes wrong.

    In 1996, Douglas Axe authored a paper examining the tolerance to substitutions of the hydrophobic cores of certain enzymes. (http://www.pnas.org/cgi/content/abstract/93/11/5590)
    He states that “[i]f some measure of exquisite, native-like core packing is necessary for enzymatic function, this would constitute a significant obstacle to the development of novel enzymes, either by design or by natural or experimental evolution.” However, Axe found that the there were no very rigid requirements (other than the hydrophobic requirement) for sequence specificity in constructing the core of a particular enzyme. He states in his paper:

    “Thus, the results presented here demonstrate that mere
    hydrophobicity is nearly sufficient as a criterion for the construction of a barnase core that provides adequate structural integrity for enzymatic function in vivo….That the requirements for attainment of a functional core are relatively lax has important implications for protein evolution. The considerable optimization power of biological
    selection (13-15) requires a pre-existing structure exhibiting a phenotypically significant level of activity. The presence or absence of such starting structures is, therefore, critical in determining the evolutionary course of any system undergoing replication with random mutation. If protein folds required unique core sequences for function, starting structures for evolutionary optimization of noncore residues would be profoundly rare: for a 13-residue core, only 1 in 2013 (_1017) random sequences would qualify. Relative to this, the core permissiveness demonstrated here amounts to an increase by 12 orders of magnitude in the prevalence of starting structures.”

    Thus Axe has produced research that has actually supported evolutionary biology.

    So what is so different about the 2000 Axe paper? Well, as Ed has pointed out, Axe found that when you change roughly 20% of exterior residues, you will have complete loss of function. So what does this imply in the way that base substitution can explore local areas of polypeptide space? Axe states the following:

    “The results reported here indicate that the true picture is very different. In the hybrid experiment, a set of sequences that are direct intermediates between the two parent b-lactamase sequences was produced. All of these hybrid sequences, in other words, lie on conceptual paths by which one parent sequence is transformed into the other with a minimum number of substitutions. The fact that they all lack biologically significant function means that the points representing these intermediate sequences in a seascape picture are below sea level. Since all of the direct paths from the TEM-1 enzyme to the P. mirabilis enzyme that were sampled dip below sea level, it is reasonable to conclude that a substantial majority of the possible direct paths do likewise. These two natural
    enzymes would therefore be best pictured as points on different quasi-islands (dry peaks largely surrounded by water). There must be a dry path connecting these quasi-islands via others if they are descendants of a single enzyme, and there may also be direct connecting paths, but from an aerial view, much more water than land separates them. The two enzymes are different designs in the
    important sense that their smallest corresponding parts, their aligned residues, are not freely interchangeable.”

    In other words, Axe is stating that when two homologues (sharing 50% identity) are hybridized, there are intermediate points at which the hybrids suffer complete loss of function. If you have to change a significant number of exterior residues (say, 1 in 5) in order to mutate from homologue A to homologue B, as per Axe, then more than likely the intermediate paths dip below ‘sea-level’ in regard to protein topology, which means that at some point in the accumulation of neutral mutations, the intermediates will lose the functional identity of protein A before it can assume the selective advantage of the functional identity of protein B. The implication is that the parent enzymes have to share a closer similarity than 50% in order to be considered as evolutionary related to one another and descended from a common ancestor enzyme. Axe attempts to put some limit on the necessary similarity of the parent enzymes:

    “It appears that the same could be said of an even more similar pair of enzymes. The b-lactamase hybrids described here are inactive despite being shuffled along only a third of the total chain length. This implies that most hybrids shuffled along their entire lengths would lack activity even
    if the parent sequences shared somewhat more than 50% sequence identity. An analysis of intermediate sequences between two 85 %-identical ribonucleases (Serrano et al., 1993) suggests that all hybrids are active at this level of similarity. Somewhere between these levels then, in the neighbourhood of two-thirds identity, lies a boundary below
    which differences between homologues can be expected to have functional importance. A group of homologues like the Class A b-lactamases is therefore viewed more accurately as a quasi-archipelago(a group of quasi-islands interconnected by narrow land bridges) than as a summit (Figure 5)…”

    Axe is estimating that the parent enzymes have to be 2/3 identical in order to be able to successfully accumulate enough neutral mutations to be able to find another functional homologue in polypeptide space. Therefore, if protein A is 85% similar to a hypothetically functional (but not yet evolved) protein B, protein A can explore local polypeptide space without losing function to find protein B by the cumulative action of base substitution. However, if protein B is 50% similar to A, then, as per Axe, mutations cannot accumulate in A to produce B, since the boundary for cumulative mutations exploring polypeptide space without loss of function has a boundary at 2/3 sequence identity.

    Now, having made Axe’s argument, here is what I am confused about. No one to my knowledge is arguing that neutral base substitution is the only method of exploring protein space. In fact, there is a whole apparatus of methods to explore protein space, from exon shuffling, insertions, deletions, recombination, etc. Take, for example, this paper (http://www.pnas.org/cgi/content/full/96/6/2591#B1) In it the authors state:

    “The exponential complexity of protein space limits evolution by means of DNA base substitution alone and remains a major challenge to many quantitative treatments of evolution. Random assembly and base substitution are ideally suited for searching local regions of polypeptide space, as demonstrated experimentally by the isolation of large numbers of stable structures from random encoded peptide libraries (1-3) and the rapid improvement of function seen in molecular evolutions of synthetic antibodies (4-6). //However, in vitro homologous recombination experiments, termed DNA shuffling, have already demonstrated the limitations of protein evolution by means of base substitution alone (7-11). Indeed, a complete hierarchy of natural mutational events composed of rearrangements, deletions, horizontal transfers (12), transpositions (13), and other nonhomologous juxtapositions, in addition to base substitution and homologous recombination, is required for the rapid generation of protein diversity.//”

    In other words, we have to look at the heirarchy of mechanisms in order to get a good picture of protein evolution, not just base substitution. This is what Axe has not taken into account.

  8. #8 Les Lane
    January 11, 2007

    As I suspected, it seems to do nothing but point out that a bad assumption went into a theory regarding the constraints upon mutation.

    This is hardly surprising. The whole of ID rests on making bad assumptions. To achieve success, ID must obscure these assumptions. From their perspective this is a case of insufficient obscurantism.

  9. #9 Tyrannosaurus
    January 11, 2007

    According to Axe base substitution is the “only” recognized method to go from parent protein A to hypothetical B. The constraint implicit is not just the percentage of initial similarity between parent A and hypothetical B expressed as 2/3 similarity but to the method explored namely substitution. If he were a graduate student his advisor would have a fit!!!!! For example the most obvious question to the student “Is there any other mechanism(s) to effect changes in polypeptide chains? Name a few and comment?

  10. #10 Dave Carlson
    January 11, 2007

    Okay, I realize this is off-topic, but I couldn’t not bring it up here. According to ATBC (I’m in a bit of hurry, and I don’t have a link handy; somebody please correct my omission when you have a chance), this is the latest from Dembski at UD:

    If I ever became the president of a university (per impossibile), I would dissolve the biology department and divide the faculty with tenure that I couldn’t get rid of into two new departments: those who know engineering and how it applies to biological systems would be assigned to the new “Department of Biological Engineering”; the rest, and that includes the evolutionists, would be consigned to the new “Department of Nature Appreciation” (didn’t Darwin think of himself as a naturalist?).

    Voltaire would be proud.

  11. #11 Daniel Morgan
    January 11, 2007

    Henry,

    “[i]f some measure of exquisite, native-like core packing is necessary for enzymatic function, this would constitute a significant obstacle to the development of novel enzymes, either by design or by natural or experimental evolution.” However, Axe found that the there were no very rigid requirements (other than the hydrophobic requirement) for sequence specificity in constructing the core of a particular enzyme.

    And he seems to have simply re-confirmed that argument with more evidence in the newer paper — he points out that more selective flexibility [a larger searchspace] exists than can be accounted for by something like a hydrophobic model.

    Axe is estimating that the parent enzymes have to be 2/3 identical in order to be able to successfully accumulate enough neutral mutations to be able to find another functional homologue in polypeptide space. Therefore, if protein A is 85% similar to a hypothetically functional (but not yet evolved) protein B, protein A can explore local polypeptide space without losing function to find protein B by the cumulative action of base substitution.

    And, if A is the result of a gene duplication, then it has no selection pressure whatsoever, and is free to move towards a new protein with a new function through [nearly] infinite space.

    In other words, we have to look at the heirarchy of mechanisms in order to get a good picture of protein evolution, not just base substitution. This is what Axe has not taken into account.

    Good point. All he seems to have given evidence of is that proteins which have already been optimized to some present function cannot have their flexibility in maintaining function explained solely by selectable base substitutions.

    Hardly “evidence for ID”. Again, can someone explain just what ID is such that some sort of evluation of Axe’s statement can be made? Is he saying that this is evidence that common descent is impossible? Is he saying that homologous proteins have all been created ex nihilo? What is he saying? Evidence for “design” = ? in this case?

  12. #12 Henry
    January 11, 2007

    Daniel:

    You are right that gene duplication and divergence is one of the many mechanisms to generate diversity in protein folds. We must remember, however, to put this in context of many other mechanisms. No specific mechanism is efficient enough in and of itself to navigate through protein space, but collectively many different mechanisms can. If one only considers gene duplication and divergence, for example, Axe could point to his 2004 paper where he demonstrated that protein folds are rare in sequence space, and thus /random/ drift would be unlikely to hit upon any fold that is biologically useful. In this light, consider the paper, “Rapid evolution in conformational space: A study of loop regions in a ubiquitous GTP binding domain” (http://www.proteinscience.org/cgi/content/full/13/3/608)

    In commenting on Blanco’s results (someone who Steve Meyer is fond of citing), the authors of this paper state:

    “The generation of radically novel protein folds during evolution is often seen to be problematic. In this text, the term “fold” will refer to the backbone trajectory of a domain. It is unclear how a protein with one fold could evolve into a different fold without going through unstable and nonfunctional intermediates that would be subject to purifying selection (Blanco et al. 1999)….Considering the number of constraints involved in the folding of a protein domain, //a drift in sequence space of a gene is unlikely to produce a useful gene product: This process would have to rely on the neutral evolution of pseudogenes for extended periods while remaining free of nonsense mutations. This is an improbable scenario at best (Blanco et al. 1999).// Likewise, other processes can lead to novel protein architecture, such as: (1) circular permutation, (2) invasion/withdrawal of -strands have been reported (Grishin 2001) or (3) in ambiguously folding regions that can be used as a pivot for the spontaneous generation of new folds. However, the sequential and successful repetition of these events to generate novel protein architectures seems to be unlikely. Although such events clearly have occurred as isolated cases, it is unclear whether such sequences of improbable events have occurred with sufficient frequency to account for the diversity of known folds in proteins.”

    Of course, just because neutral evolution in pseudogenes may be an inefficient process in itself, that does not stop the authors from investigating other mechanisms:

    “It is unwise to reject an explanation solely on the basis of its apparent unlikeliness. Such arguments have been made to discount the possibility of the evolutionary origin of complex biological structures such as the vertebrate eye; yet, most rational biologists accept that it must have happened. Specifically, in this case, there is no way to determine the frequency of unsuccessful trial protein fold because selection rapidly culls these from view. Thus, in principle, the limited diversity (~4000 in the PDB database on May 20, 2003) of distinct protein folds possibly could be explained by a combination of spontaneous sequence changes and larger recombination/permutation events yielding into a structural drift from an initial to a final fold. Although a probabilistic argument on its own is insufficient to invalidate this model, further improvements to our understanding of the mechanism of emergence of new protein folds can be made if an alternative and intuitively more probable hypothesis could be validated by observations.

    We propose that rapid evolutionary change in loops has the potential to generate novel architectures by exploring the conformational space independently from the core protein to which they are attached. If few contacts exist between a loop and the protein’s core, these loop sites can evolve independently while “hitchhiking” on the expression of their “host” protein. The mechanism of protein fold evolution proposed herein does not assume improbable structural rearrangements within the constrained sites of a protein. Rather, it holds that sites in sequences can be inserted/deleted/substituted in a stepwise fashion while merely playing a peripheral role to biological function. This appears to be the case in the highly variable regions of the conserved GTP binding domain.”

    I think that Axe has authored several very good research papers, and has demonstrated that there are specific boundaries to several modes of evolution considered exclusively by themselves. He fails, however, to consider these mechanisms in concert with one another, and this is the main question at hand.

  13. #13 Gerard Harbison
    January 11, 2007

    Building on Daniel’s point about similarity, in fact 15% difference is often enough to create a functional and entirely different enzyme. The polyketide synthase gene family is a beautiful example. In the bacilli, the entire ~ 12 step biosynthetic pathway for each of three antibiotics is performed by a cluster that contains around a couple of dozen genes, all of which are apparently derived by duplication of a single ancestral gene. There are pairs of proteins in these pathways family that perform entirely different steps of the synthesis but are better than 80% identical.

    Nice recent paper
    http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1482889

    And in particular look at the sequence identities in table 2.

  14. #14 Ed Brayton
    January 11, 2007

    That is one of the many problems with this paper, it assumes that existing function is the only possible function. But as Gerard notes, there are often homologous proteins that differ by only a few amino acids that perform distinct functions, sometimes complementary and sometimes completely different. This is true, for example, of the entire blood clotting cascade. Axe did not bother to test for other possible functions, despite Dembski’s absurd claim that “any slight modification” destroyed “any possibility of any function whatsoever.”

  15. #15 Guts
    January 11, 2007

    In other words, we have to look at the heirarchy of mechanisms in order to get a good picture of protein evolution, not just base substitution. This is what Axe has not taken into account.

    I think you’ve made an excellent point here by the way. But one implication of this is that evolution is far more complex than a run of the mill Darwinist once thought.

  16. #16 Guts
    January 11, 2007

    Brayton:

    Axe did not bother to test for other possible functions, despite Dembski’s absurd claim that “any slight modification” destroyed “any possibility of any function whatsoever.”

    Actually, in a sense, Axe showed this in figure 5, most substitutions were destabilizing. By the way, nothing about Axe’s research has been “shredded” , I’m not sure why you would say that. Wang’s research which came out shortly after virtually confirmed Axe’s paper.

    J Mol Biol 2002 Jun 28;320(1):85-95
    Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs.
    Wang X, Minasov G, Shoichet BK.

  17. #17 Ed Brayton
    January 11, 2007

    The research has not been shredded; it is a perfectly routine study of its kind. The absurd claims about how it allegedly supports ID have been shredded.

  18. #18 Shygetz
    January 12, 2007

    But one implication of this is that evolution is far more complex than a run of the mill Darwinist once thought.

    Yes, it is more complex than a “run of the mill Darwinist” would think. However, evolutionary biologists have known for quite some time that evolutionary biology is more complex than Darwin published (which is why calling them Darwinists is as silly as calling a physicist Bohring).

    Actually, in a sense, Axe showed this in figure 5, most substitutions were destabilizing.

    Figure 5 in the 2000 Axe paper did no such thing. In fact, it is not a diagram of protein stability at all; it is an attempted visualization of antibiotic resistance presumably conferred by different protein mutants. Completely different from stability. Axe did not address the possibility of alternative function at all.

    The Wang paper you cited actually does examine this possibility, and finds that there are trade-offs; loss of activity versus the ancestral target actually corresponds will the gain of activity versus the selected target, indicating that changes in environmental selective pressures can also serve as a bridge from one functional sequence to its homolog (i.e. you can mutate from a funcional penicillin lactamase to a functional cephalosporin lactamase back to a functional penicillin lactamase). They also make some measurements of protein thermal stability (which Axe did not) and found that some mutations lower stability, and others increase it (surprise, surprise).

    Axe’s data seem to be fine, and the work seems to be well done. His conclusions stem from invalid assumptions and overreach his data (which is not uncommon, and somewhat forgivable).

  19. #19 Guts
    January 12, 2007

    Henry:

    They also make some measurements of protein thermal stability (which Axe did not) and found that some mutations lower stability, and others increase it (surprise, surprise).

    Actually if you compare figure 6 in Wang’s paper with figure 5 in Axe’s paper, you’ll see that they came to the same conclusion, most substitutions were destabilizing. The same substituion that stabilized the protein kept comming up, which means that substitutions that have this ability are probably few and far between.

    Brayton:

    The research has not been shredded; it is a perfectly routine study of its kind. The absurd claims about how it allegedly supports ID have been shredded.

    I think it does. The exterior positions of the protein was supposed to be floppy, you were supposed to be able to change all 171 positions.

  20. #20 John
    January 12, 2007

    Wow, Guts, how dishonest can you get?

    Ed quoted Dembski’s lie:
    Axe did not bother to test for other possible functions, despite Dembski’s absurd claim that “any slight modification” destroyed “any possibility of any function whatsoever.”

    And Guts tried to defend it with another lie and some misdirection:
    Actually, in a sense, Axe showed this in figure 5, most substitutions were destabilizing.

    As Shygetz pointed out, Figure 5 has absolutely nothing to do with stability. Axe’s paper does not support Dembski’s lie because Axe never looked for “any function whatsoever,” he only looked for the original function. Therefore, your attempt to defend Dembski’s lie fails miserably.

    By the way, nothing about Axe’s research has been “shredded” , I’m not sure why you would say that.

    It would be more correct to say that Dembski’s lies and Axe’s revision of the significance of his data have been thoroughly shredded.

    Wang’s research which came out shortly after virtually confirmed Axe’s paper.”

    Papers are made up of data and interpretation. Axe’s data and interpretation in his paper are consistent with those of the Wang et al. paper. The latter paper, however, beautifully illustrates Dembski’s lie as well as it shows that reducing one function easily results in increasing other functions, which is predicted to occur frequently by MET. This also contradicts Axe’s revised interpretation.

    Guts, how do you fit the Wang et al. paper into an ID hypothesis, assuming you have a hypothesis?

  21. #21 Guts
    January 12, 2007

    Sorry I called Shygetz Henry by accident.

  22. #22 Guts
    January 12, 2007

    As Shygetz pointed out, Figure 5 has absolutely nothing to do with stability.

    The seascape representation shows what Axe concludes about proteins and biological function, I never said it actually showed data about stability, I’m simply pointing out what Axe concluded about the substitutions.

    The latter paper, however, beautifully illustrates Dembski’s lie as well as it shows that reducing one function easily results in increasing other functions, which is predicted to occur frequently by MET.

    Figure 1b in the Wang paper shows that it already had this function, it’s not a new function.

  23. #23 Henry
    January 12, 2007

    Guts:

    I think that we all agree that Dembski severely misrepresented Axe’s results. This is not in question. Axe was able to perturb many amino acids without loss of its original function, contrary to what Dembski has suggested. (If Dembski did understand the results, as I suspect he did, he should have taken care to accurately report them.) If Dembski were to fairly represent Axe’s results, he should have stated that they placed a limit on sequence identity that any two enzymes must have maintained if they were the result of evolution by base pair substitution exploring local sequence space while maintaing /original/ function. What is far more interesting is Axe’s comments about his paper. Axe is completely correct that his paper has placed a limit on chance in producing new protein structures. Chance–as in neutral drift on exterior residues exclusively. He did not review, however, how a whole apparatus of evolutionary change could discover new protein folds by mechanisms other than neutral drift.

    It is true that Axe’s results in no way contradicts intelligent design and does put constraints on neutral evolution (as in what residues are likely to vary and the extent that they can vary as a result of neutral evolution). BUT THIS DOES NOT YIELD A POSITIVE CASE FOR ID. IT DOES NOT EVEN INVALIDATE THE CURRENT EVOLUTIONARY CONCEPTION OF HOW NEW PROTEIN FOLDS ARISE–SINCE IT DID NOT CONSIDER ALL THE MECHANISMS INVOLVED. Axe’s results are appreciated, but they must not be overextended. Heck, if the DI continues to sponsor Axe’s research, all power to them. But Axe’s results must not be misconstrued as implying something that they have not demonstrated.

  24. #24 John
    January 13, 2007

    Guts tried a falsehood and straw man:

    “I never said it [Figure 5]actually showed data about stability…”

    You wrote, “you’ll see that they came to the same conclusion, most substitutions were destabilizing.” You also wrote, “Actually, in a sense, Axe showed this in figure 5, most substitutions were destabilizing.”

    If you twice claim that figures showed that most substitutions were destablilizing, you’re making an explicit claim about stability.

    I wrote, “The latter paper, however, beautifully illustrates Dembski’s lie as well as it shows that reducing one function easily results in increasing other functions, which is predicted to occur frequently by MET.”

    Guts’s straw man:
    “Figure 1b in the Wang paper shows that it already had this function, it’s not a new function.”

    I never claimed that it was a new function. I claimed that it increased other activities.

    Thanks for such a succinct demonstration of the mendacity at the heart of ID.

  25. #25 Daniel Morgan
    January 14, 2007

    Perhaps someone could invite Axe himself to appear here in the comments section and answer for us how his paper supports ID-creationism. That would be fun. [evil grin]

  26. #26 Guts
    February 13, 2007

    John I have no idea what you’re talking about. There is a difference between a figure showing a table of values concerning stability and a representation thereof.

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