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Author
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Topic: Data, interpretation and false positive inferences
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charlie d.
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Member # 159
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posted 26. September 2003 11:10
quote:
Thats because, as I showed, it's not an overinterpretation. I think you are even misinterpreting the Axe paper (Dembski probably knows this). Douglas Axe's paper shows that it's not necessarily true that proteins can obtain a new function after the stability of the folded structure is disrupted. If the folded structure is retained, then yes, a new function is likely.
But Axe didn't look at any other function, so he could have hardly shown that, could he? On the other hand, Wang showed that transition from penicillin to cephalosporin activity is accompanied by a loss of stability (and decrease in the penicillase activity). The structural stability of the new cephalosporin-active enzyme can then be recovered by an otherwise silent mutation, Met182-->Thr (of the kind that Axe would have said are ultimately detrimental). quote:
All in all this example shows how ID can guide laboratory research.
LOL, what doesn't? The DI should add it to the list of crypto-ID research papers.
[ 26. September 2003, 11:34: Message edited by: charlie d. ]
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Nel
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Member # 614
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posted 26. September 2003 11:35
Charlie writes:
quote:
But Axe didn't look at any other function, so he could have hardly shown that, could he?
That depends on whether you can really call hydrolysis of chephalosporin a new function. Since this experiment shows that resistance to penicillin was still substantial, I don't think it has that much relevance to the Axe paper.
Charlie wrote:
quote:
On the other hand, Wang showed that transition from penicillase to chephalosporin activity is accompanied by a loss of stability (and decrease in the penicillase activity). The structural stability of the new cephalosporin-active enzyme can then be recovered by an otherwise silent mutation, Met182-->Thr (of the kind that Axe would have said are ultimately detrimental).
The possibility remains that the the stability of the unfolded state was increased. This explains why substantial pen activity was retained, such that the bacteria could still resist it.
Charlie writes:
quote:
LOL, what doesn't?
You're right, I can't think of any biological topic that wouldn't guide ID research ![[Big Grin]](biggrin.gif)
[ 26. September 2003, 11:48: Message edited by: Nelson-Alonso ]
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rafe gutman
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Member # 134
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posted 27. September 2003 14:48
nelson, most of charlie's and my utilization of the wang paper was based on this interpretation of the axe paper by dembski in his logical underpinnings of ID article, and first discussed in the lust for certainty thread:
quote:
But there is now mounting evidence of biological systems for which any slight modification does not merely destroy the system's existing function, but also destroys the possibility of any function of the system whatsoever (Axe, 2000). For such systems, neither direct nor indirect Darwinian pathways could account for them.
what the wang paper shows is that you can generate perturbations of the TEM protein, damaging the existing penicilin resistance function, but resulting in an increase in cephalosporin resistance. this directly contradicts dembski's claim.
nelson, do you consider any of the modifications of TEM made in the wang paper to possess any function whatsoever? if so, then dembski's summary is wrong.
it's as simple as that.
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Nel
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Member # 614
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posted 27. September 2003 16:46
Rafe quotes Dembski:
quote:
But there is now mounting evidence of biological systems for which any slight modification does not merely destroy the system's existing function, but also destroys the possibility of any function of the system whatsoever (Axe, 2000). For such systems, neither direct nor indirect Darwinian pathways could account for them.
Rafe writes:
quote:
what the wang paper shows is that you can generate perturbations of the TEM protein, damaging the existing penicilin resistance function, but resulting in an increase in cephalosporin resistance. this directly contradicts dembski's claim.
No, as I stated, they still retained a lot of the original activity, even the triple mutants retained much of it, enough to still resist penicilin.
Rafe wrote:
quote:
nelson, do you consider any of the modifications of TEM made in the wang paper to possess any function whatsoever? if so, then dembski's summary is wrong.
WRT the Axe paper, what matters is whether the stability of the folded structure remained, and not necessarily modifications to the active site (I think Dembski was referring to the former). The bottom line is more work should be done.
[ 27. September 2003, 17:22: Message edited by: Nelson-Alonso ]
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Pim van Meurs
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Member # 541
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posted 27. September 2003 18:46
Nelson: Thats because, as I showed, it's not an overinterpretation. I think you are even misinterpreting the Axe paper (Dembski probably knows this). Douglas Axe's paper shows that it's not necessarily true that proteins can obtain a new function after the stability of the folded structure is disrupted. If the folded structure is retained, then yes, a new function is likely.
Could you explain how this is not an overinterpretation but rather a misinterpretation? Dembski's comments seem to be quite clear and from my reading of Gross' comments and the papers in question, Axe's paper does not support what Dembski claimed it did.
Is Axe's paper still quoted as supportive of ID?
[added in edit]
It seems so
quote:
D.D. Axe, “Extreme Functional Sensitivity to Conservative Amino Acid Changes on
Enzyme Exteriors,” Journal of Molecular Biology, 301 (2000): 585–595.
This work shows that certain enzymes are extremely sensitive to perturbation. Perturbation in this case does not simply diminish existing function or alter function, but removes all
possibility of function. This implies that neo-Darwinian theory has no purchase on these
systems. Moreover, the probabilities implicit in such extreme-functional-sensitivity analyses
are precisely those needed for a design inference.
THREE FREQUENTLY ASKED QUESTIONS ABOUT INTELLIGENT DESIGN Textbook Hearing, Austin, Texas, September 10, 2003
Dembski's original email
quote:
"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." The "prevalent view" referred to here follows directly from neo-Darwinism. Axe's results are more clearly consistent with ID, though he doesn't say as much.
Paul Gross responds
Yehouda Harpaz responds
More recently Dembski strengthened the claim
quote:
But there is now mounting evidence of biological systems for which any slight modification does not merely destroy the system's existing function, but also destroys the possibility of any function of the system whatsoever (Axe, 2000). For such systems, neither direct nor indirect Darwinian pathways could account for them.
Source
Destroy the possibility of any function
[ 27. September 2003, 18:54: Message edited by: Pim van Meurs ]
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Nel
Member
Member # 614
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posted 27. September 2003 19:25
Pim,
See my previous posts.
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Pim van Meurs
Member
Member # 541
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posted 27. September 2003 21:25
I looked at your previous post and failed to find any relevant answers to my questions. What am I missing?
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Nel
Member
Member # 614
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posted 28. September 2003 22:52
Pim,
From your post it's obvious that you don't seem to understand any of my points. You should ask specific questions if you don't understand my posts. I'm not going to take up bandwidth by repeating myself.
[ 28. September 2003, 23:14: Message edited by: Nelson-Alonso ]
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Rex Kerr
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Member # 632
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posted 29. September 2003 04:44
Nelson has already granted that proteins can take on new functions "if the folded structure is retained". And the Wang paper demonstrates just such an event.
So it's not clear to me what you're still discussing!
If Dembksi maintains that there are systems where any slight modification destroys the possibility of any fuction of the system whatsoever, then the Wang paper clearly demonstrates that TEM is not one of these systems, as Nelson has apparently already agreed.
But if Dembksi made a mistake (and, being human, he's allowed) and overstated the case, then the Wang result just serves to highlight that the Axe result didn't really demonstrate the conclusion that no function could be retained; it just gave some hints that the system was rather delicate.
As Nelson said, "The bottom line is more work should be done."
[ 29. September 2003, 04:44: Message edited by: Rex Kerr ]
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Pim van Meurs
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Member # 541
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posted 29. September 2003 12:54
Dear Nelson,
you stated 'see my previous posting', I looked and failed to see any relevance. Perhaps Nelson would like to make an attempt at clarification of his points? Perhaps a few paragraphs tying together his ideas especially in light of my posting and his one-liner response?
That more work needs to be done?
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Nel
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Member # 614
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posted 29. September 2003 18:01
Rex writes:
quote:
Nelson has already granted that proteins can take on new functions "if the folded structure is retained". And the Wang paper demonstrates just such an event.
But the Axe paper does not.
Rex writes:
quote:
If Dembksi maintains that there are systems where any slight modification destroys the possibility of any fuction of the system whatsoever, then the Wang paper clearly demonstrates that TEM is not one of these systems, as Nelson has apparently already agreed.
Dembski was referring to the Axe paper, and how any slight modification to non-active site of a protein would not only cause the function to cease, but a new function is unlikely. In the Axe paper, the folded structure was destabilized, and so function was lost. In the Wang paper, there was still substantial pen activity such that resistance to pen was still possible. One possibility is that the stability of the unfolded structure was increased.
[ 29. September 2003, 18:13: Message edited by: Nelson-Alonso ]
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rafe gutman
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Member # 134
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posted 29. September 2003 19:05
nelson,
a. how many amino acid substitutions can you make to a protein so that the changes are considered "slight"?
b. were all of the mutations made by axe non-functional?
[ 29. September 2003, 19:07: Message edited by: rafe gutman ]
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Nel
Member
Member # 614
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posted 29. September 2003 19:11
Rafe thats discussed in the Axe paper:
quote:
First, highly conservative replacements of exterior residues, none of which would cause significant functional disruption alone, are combined until roughly one in five have been changed. This is found to cause complete loss of function in vivo for two unrelated monomeric enzymes: barnase (a bacterial RNase) and TEM-1 b-lactamase. Second, a set of hybrid sequences is
constructed from the 50 %-identical TEM-1 and Proteus mirabilis b-lactamases.These hybrids match the TEM-1 sequence except for a region
at the C-terminal end, where they are random composites of the two
parents. All of these hybrids are biologically inactive.
[ 29. September 2003, 19:14: Message edited by: Nelson-Alonso ]
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charlie d.
Member
Member # 159
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posted 29. September 2003 19:29
quote:
Dembski was referring to the Axe paper, and how any slight modification to non-active site of a protein would not only cause the function to cease, but a new function is unlikely.
Based on what? Wishful thinking?
Axe tested only one function, and all his conclusions can only be related to that function. Thus, he could say his mutants lost activity on some antibiotics, but he couldn't say whether those same mutants might be able to exert some other function he has not tested for (indeed, Axe does not make this mistake in his paper). The fact that Wang shows that a protein can lose >99% of its original function, and much of its stability, and still work very well at something else, makes this possibility tangible (regardless of how much of the original function was maintained, Nelson: ask yourself whether you know how many new substitutions can the anti-cephalosporin enzyme now tolerate, before its function is lost and yet another function is found. This just shows how proteins can "hop" through fitness "valleys".)
I don't know how many more times I have to repeat this very trivial fact. It's so obvious.
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Nel
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Member # 614
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posted 29. September 2003 19:40
Charlie:
quote:
The fact that Wang shows that a protein can lose >99% of its original function, and much of its stability, and still work very well at something else, makes this possibility tangible (regardless of how much of the original function was maintained,
Only because it was able to retain the original pen activity. You pretty much reworded your original argument while still ignoring my response to it.
[ 29. September 2003, 19:42: Message edited by: Nelson-Alonso ]
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