Yes, but to claim he doesn’t understand what he’s asking, you need a model for questions!
So clearly… uh, god!
Somehow, don’t ask me how!
No, not the math! Anything but the math!
4 Likes
Can you cite specific examples of biological features against which any evolutionary barrier is known? If you can acknowledge that any biological features, out of ones that do actually exist in nature, could have evolved, can you name one that could not?
See, when you have a theory that consistently accurately predicts observations, it is not enough to sniff out that one question for which it doesn’t have a complete and definitive answer (and I’m not granting that any such question was actually identified) to say that therefore all of the accurate predictions the theory makes are mere ko-inky-dink. This is just like when you speak of reconciling some differences/discrepanciees, but consistently ignore any and all queries for an actual quantification of the “problem” you think you see and a demonstration that it is actually, mathematically, a problem in need of solving.
What, specifically, should have precluded a natural development of the bacterial flagellum or the blood clotting system, were it not for a designer outsmarting presumably himself?
I’m not sure why they would be emabarrassed. Sure, Bill’s prose stylings are less polished and articulate than their writing typically is. But, apart from that, his arguments are not substantively different from what they put in their books and articles. Behe has yet to retract his irreducible complexity argument despite the fact that it was addressed in the evolutionary literature over a century ago. And Michael Denton’s argument summarized below is not much dissimilar to Bill’s ignorant prattling about Venn diagrams:
Molecular equidistance is a term that was first used by Michael Denton in Evolution: A Theory in Crisis to criticise the theory of evolution. The variation in the amino acid sequence of proteins such as cytochrome C can be analyzed to provide a phylogenetic tree that matches trees provided by other taxonomic evidence. What Denton pointed out was that if the percentage difference in cytochrome C amino acid sequences was compared from one organism to other organisms, the changes could be highly uniform. For example, the difference between the amino acid sequence for the cytochrome C of a carp and those of a frog, turtle, chicken, rabbit, and horse is a very constant 13% to 14%. Similarly, the difference between the cytochrome C of a bacterium and yeast, wheat, moth, tuna, pigeon, and horse only ranges from 64% to 69%.
Denton suggested that these data undermined the notion that fish were ancestral to frogs, which were ancestral to reptiles, which were ancestral to birds and mammals. If they were, then wouldn’t the difference in cytochrome C structures be increasingly different from carp to frog, to reptile, to mammal?
So, far from being embarrassed, I think the DI would be proud of what a devoted acolyte Bill is, and how avidly he has absorbed their teachings.
If creationist apologists were capable of feeling embarrassment, wouldn’t they have thrown Ray Comfort out of their club years ago?
I was under the impression that a complete lack of shame was a requisite for membership.
3 Likes
This seems rather pedantic to me. You first declared there’s no such thing as “the beta-lactamase fold” because, you said, it’s a structural classification. But they just ARE named for the functions of proteins in actual databases.
Heck, in the CATH database that IS the full and only name for the fold(topology level in the CATH hierarchy):
https://www.cathdb.info/browse/sunburst?from_cath_id=3.40.710
Experimentally-determined protein three-dimensional structures are obtained from the Protein Data Bank and split into their consecutive polypeptide chains, where applicable. Protein domains are identified within these chains using a mixture of automatic methods and manual curation. The domains are then classified within the CATH structural hierarchy: at the Class (C) level, domains are assigned according to their secondary structure content, i.e. all alpha, all beta, a mixture of alpha and beta, or little secondary structure; at the Architecture (A) level, information on the secondary structure arrangement in three-dimensional space is used for assignment; at the Topology/fold (T) level, information on how the secondary structure elements are connected and arranged is used; assignments are made to the Homologous superfamily (H) level if there is good evidence that the domains are related by evolution, i.e. they are homologous. To browse the classification hierarchy, see CATH hierarchy.
What’s the topology/fold level called for serine beta-lactamases in the CATH database? That’s right, beta-lactamase. And nothing else.
Annoyingly there isn’t even really a fully consistent terminology on this.
Yes and for early characterized proteins those proteins in turn were usually named for the functions they were first known to perform (and the names also changed along the way, they used to be called penicillinases IIRC). Hence, the fold is named for the functions known at the time.
It’s just not clear to me why the use of the term is a mistake when, in point of fact, the name appears in widely used databases for a range of similar structures.
As for whether this is in the end a good name for the structure to hang on to, since many other functions are known for it, is hardly a fact we can blame the DI for. As much as I think they spew a lot of nonsense at the DI I’m not persuaded their use of this name for the fold is intentionally misleading, even if it ultimately might mislead someone who isn’t aware that it’s just a name and not a functional classification.
2 Likes
This seems rather pedantic to me. How do you know that they weren’t just abbreviating “beta-lactamase/transpeptidase-like”?
I am pointing out that adopting their rhetoric is deceptive because neither they nor you have the slightest idea whether or not any particular mutation affects folding.
Stability is not a proxy for function, your earlier attempt to defend their deception.
Activity, whether crudely or carefully measured, does not tell us about folding, your current attempt to defend their deception.
Because Axe wasn’t measuring structure in any way. Even if he had measured activity, he wouldn’t have been measuring folding or any other aspect of structure.
So… you are seriously claiming that naming conventions have anything to do with whether Axe knew (or cared) about whether “any particular mutation affects folding”???
@Rumraket is right, and I would say obviously so. The naming convention is not where the deception of the DI lies. I am sure they are happy to see how it contributes to their misinformation. But that’s life in a world where religious commitment hobbles minds and wrecks integrity.
2 Likes
Because they use the term DD-peptidase/beta-lactamase at the homologous superfamily level of the hierarchy, instead of the topology/fold level.
Thank you for pointing that out, though I literally made that same point myself so go figure…
I must repeat my request for you to stop assigning views to me I do not hold. I recall explicitly telling you to do this both in another thread, and in a private message. Do you find this within your capacity?
Shall we now also go over, again, how you personally having characterized the effect of a small handful of mutations to α-tropomyosin and found 8 stabilizing rather than destabilizing, doesn’t actually allow you to extract a general trend for the stability-effects of mutations on protein structure, and that such a trend can only be extracted by sampling more broadly both from different species and different types of proteins?
That’s sort of like if someone says “the average mutation is deleterious” and you say “but on this gene I studied we found 8 that were beneficial.”
Fucking LOL dude…
1 Like
No, I am pointing out that using “fold” or “folding” helps in the DI’s deception, because folds are structural classifications, regardless of naming. Laypeople don’t know this and see this beta-lactamase as having a unique “functional fold,” the only one that has beta-lactamase activity (@Rumraket pointed out the falsehood of this) and has no different activities (the additional falsehood I am pointing out).
I agree and didn’t claim it was. The deception is using structural terms to pretend to have something profound to say about structure with slapdash experiments that don’t even come close.
3 Likes
You fried my irony meter there.
Let’s. Just to be clear, I didn’t do it personally. I supervised the postdoc and students who did the hands-on work.
I didn’t. I was very clear about that in the very thread you linked to above:
LOL. Was that not clear, Mikkel?
I cited our work because finding 8 of 8 disease-causing mutations increasing stability was unremarkable.
Active-site changes that decrease function pretty consistently increase stability. We’ve known this for a very long time. One old example:
https://www.pnas.org/doi/epdf/10.1073/pnas.92.2.452
For large collections of hypomorphic alleles (for example G6PD, because deficiency protects against malaria), there appear to be groupings with differing relationships between stability and function:
https://www.cell.com/cell-reports/fulltext/S2211-1247(17)30246-2
And it’s not limited to mutations. You can do a control PCR reaction to measure the activity vs. stability of Taq DNApol at different temperatures in an afternoon. Stabilizing the most abundant family of proteins in your body, the collagens, by glycation caused by excess glucose causes enormous human suffering in people with diabetes.
Your responses are getting pitiful, seriously.
Saying it’s 50/50 is to say what the trend is: In your opinion the trend is 50/50.
But it isn’t 50/50 (the average mutation is actually destabilizing on protein structure as empirical studies designed to get at the tendency shows), and your supervision of your postdocs and students finding 8 stabilizing mutations in alpha-tropomyosin doesn’t show that it’s 50/50.
You finding cases where mutations (to active sites, for example) are stabilizing is a textbook example of cherrypicking. Proteins are more than their active sites.
There are studies that do the work no single or collection of cherrypicked studies do. Attempt to get a distribution of effects. They find that it’s a gaussian, with the mean substantially in the destabilizing. I cite some of them in that thread, there are others that show the same.
Why do I have to explain this? You should not need me to explain this. What the fork is going on?
On another note, what the hell blew up your irony meter? You are the one constantly assigning views to me I don’t hold, I haven’t assigned one to you. Accusing me of adopting conflations, buying into or defending positions that I have never supported either inadvertently nor explicitly.
You can’t be serious.
You appear to have a strong tendency to misrepresent qualified statements as not qualified. What drives this?
“Basically 50/50” in opposite directions is not a trend. 70/30 in opposite directions is not a trend, either.
Why did you omit “basically”?
5 years later, we don’t have encyclopedic knowledge.
Really? What kind of proteins? All? Average ones, or only a particular type? It’s literally there in the first word of the Introduction.
What do we know about the biophysical process by which that particular type of protein folds?
Again, you employ a blatant straw man fallacy. My pointing out that 8 for 8 is unremarkable is not a claim that it demonstrates “50/50.” How could it? What did I write in the discussion of that paper? Did you forget that they also had opposite effects on contractility?
Your pretending that a study explicitly limited to a specific structural subset of proteins is universal isn’t cherrypicking?
IMO, the best we’ve got to reflect what’s going on in vivo are the collections of GOF and hypomorphic alleles. As @swamidass noted, P53 mutations are about 50/50, and I notice that you completely ignored the G6PD ones. Why?
No. The reality is that no study can do all that work. All of them are limited in some way. The in vitro ones are necessarily highly biased in favor of those proteins that are easier to purify. Guess what kind those are?
Collections of hypomorphic and GOF mutants are not limited in that way.
In what type of proteins? A specific type, no?
In what type of proteins? IDPs? What’s the antecedent of “it,” precisely and literally?
Not for surface residues, for which the mean was basically 0. You are missing so much by trying to win arguments with this lame cherrypicking. You can’t even see it in the data you are presenting!
I don’t know of any that are comprehensive. Certainly none you cited were.
Because you’re not explaining anything. You appear to be arguing for the sake of arguing, particularly obvious from your repeated straw men.
See above.
All of which I think is fine to point out, which you can do without accusing me of buying into any of their crap. You can simply add clarification and we wouldn’t have entered into this mutual argument to begin with.
I do not appear to have such a tendency at all, but in this case I ignored it because it’s obviously irrelevant and a simple thought-experiment can reveal how.
Consider that if your “basically 50/50” encompasses 70/30 or 65/35 then it’s essentially a worthless statement to say 50/50 because you can really just claim anything goes when you said “basically”. Where is the cut-off? How far does “basically” extend here?
But contextually it becomes all the more clear that your 50/50 didn’t, in point of fact, encompass 70/30 or anything like it. You erected your “basically 50/50” as a response to me merely saying that the trend is towards destabilizing on average, so as to contradict and correct me. At that point I had not even said what I thought the true distribution was like, so it’s rather mysterious why you would consider 50/50 to be a contradiction or correction of me saying it is skewed towards destabilizing, if in fact your “basically 50/50” can encompass a 70/30, which would be skewed towards destabilizing.
So please John, let’s not pretend we are so stupid we aren’t aware what you’re doing. You’re obviously bs’ing to save face now.
A statement of a ratio, or relative frequency, is not to make a statement about a trend? What is this humpty-dumpty approach to discussion? Seriously!
Making a statement about the relative frequency is to make a claim about what the trend is. The extreme desperation on display here looking for a way out of this where you save face is unbecoming.
Be an adult. Admit you were wrong, admit you misrepresented me, admit you didn’t know what the ratios were, and then just move on.
But you haven’t supported that here or 5 years ago.
“On average” of what, specifically? All known proteins, or a handful of small, globular proteins that are easy to express and purify?
But now you claim to know, but you are dodging questions about the evidence.
My position is that the true distribution is not known.
Who is “we,” here?
Speaking of awareness, have you ever purified a non-tagged protein?
Says the guy who wrote that I was trying to
??? Really? Where did I do that?
The point is that no one knows what the ratios are. Every study is biased in sample selection in some way. I stated that pretty clearly. What is interesting is that you are claiming:
But you haven’t replied to a single question about the studies you cited relevant to their generalization. Did you read the papers you cited?
So I might be wrong, but that would depend on whether the papers you cited were about:
-
Only small, globular proteins that are easy to purify. How would their stability be biased relative to the “true” distribution for all proteins?
-
Proteins with toxic substrates and nontoxic products. How would that skew stability?
-
A protein that any molecular biologist knows is so stable that it functions outside the bacteria that produce it?
So? The Mexican link you provided didn’t work.
What enormous evidence supports this claim?
I would argue that this claim is a result of methodological naturalism and the resulting inference to common descent of all life.
Random mutation and natural selection is being used to explain how the differences occurred base on inferring that whales are reproductively related to land mammals.
The reasoning is a by product of a limitation in the scientific method.