Yes, in all of the malarial parasite’s responses to various drugs and human mutations, no new protein-protein binding sites have developed.
- We don’t actually know that.
- You understood the previous explanations for why that supposed fact(presuming it is one) is of no significance, right? That a new protein-protein interaction presumably hasn’t evolved in response to antibiotics, in the Plasmodium parasite, does not at all support the claim that such PPIs are difficult to evolve, since that is just as well explained by such PPIs simply not contributing to alleviating the antibiotic problem.
2 Likes
Those are the very claims I am asking how are substantiated in the references given. You can’t then say they are “deductions” from themselves. That would just make them pure question begging assertions.
Are you here saying you also couldn’t find any support in the references given, for those claims?
1 Like
What assay did you run to determine that? Did you publish these findings somewhere?
3 Likes
What’s the evidence that Behe has looked? Why have you stopped quoting him?
I am arguing against Behe’s claim that the evolution of chloroquine resistance requires at least two simultaneous mutations, as well as against the reasoning he uses to reach this conclusion.
This is a thing Behe has said.
So, sorry, your accusation is false.
1 Like
Maybe I was distracted by the marbles and dice.
At the time Behe wrote, it was commonly understood that K76T and A220S were the most common pair of mutations in PfCRT. https://www.cell.com/molecular-cell/pdf/S1097-2765(05)00077-8.pdf see the table on the third page of the pdf. Then six years later, Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa - PubMed in the abstract they are still considered the key markers .
Are you suggesting that has changed? There are some other variants, but I don’t know the distribution.
Well, if there were new protein-protein interactions, there are people more than eager to make them known! And PPIs are fundamental building blocks, so their absence in the face of evolutionary pressure is worthy of notice. But Behe grants that such can develop (e.g. the sickle mutation in humans), and he puts the edge at two PPIs. And then there’s VPU in the HIV virus, in response to antivirals, which shows that they can develop.
No, I mean deductions from the papers, which show the level at which weak, transient interactions occur, or interactions at all.
You still seem to be distracted by something, and are missing the point.
There was never any evidence that these mutations had to occur simultaneously.
Behe’s entire argument is based on the belief that they do.
When the pathways by which resistance evolved was worked out in detail, it was confirmed that no simultaneous mutations were required.
Amazingly, Behe claimed this as vindication of his claim that simultaneous mutations were required. And, equally amazingly, his minions have simply accepted this as true. Can you kindly explain why you still believe he was right when he was so clearly wrong?
1 Like
That does not support Behe’s claim that simultaneous mutations are required.
Being key markers does not mean that they had to occur simultaneously.
No, Behe is still wrong and is still misrepresenting the data and literature.
1 Like
That would require that they themselves have detected them, wouldn’t it? You are really trying to extract a lot of mileage out of this “someone would have told us” line.
You’re assuming both their absence (which you haven’t shown, and you’ve no idea what kind of work is required to detect if a novel one has evolved in some parasite somewhere), and you’re assuming that they should have developed in response to the chloroquine antibiotic seemingly in some almost axiomatic belief that they should be able to solve any problem.
No, the papers don’t show that. The papers detail practical methods for detecting and characterizing protein-protein interactions in vitro and in vivo. They do not in any way show “the level at which weak, transient interactions occur, or interactions at all” in the cell. And they most definitely don’t show at what level such interactions are visible to selection. They just don’t. That is not in those papers.
Behe is obviously pulling a bs literature bluff, citing papers that don’t support the claims he is making because the claims he’s making are not being tested in those papers.
And I am asking for evidence that the claims being made, that " *[This] is likely the minimum necessary strength, enough to have a noticeable biological effect." where [This] is that protein and ligand spend half of their time together, or that micromolar dissociation constants are required to be visible to selection.
We’ve now come full circle around to me, again, asking for substantiation of claims that aren’t being substantiated. And you’re just repeating the claims. Do the actual facts matter to you at all?
Edit: Incidentally it is easy to find papers that show that millimolar dissociation constants are highly biologically significant:
Sure there is, in the rate of chloroquine resistance arising, in about 1 in 10^20 organisms, versus atovaquone resistance arising in about 1 in 10^12 organisms.
That does not mean that two simultaneous mutations are required. They could be sequential over several generations.
4 Likes
The human genome encodes thousands of proteins that are crucial for life. These proteins function by interacting with a variety of targets, including other proteins, nucleic acids, carbohydrates, lipids, metabolites, small molecules and metals, etc. For more than a century, researchers have attempted to understand the nature of these protein–ligand interactions and how they regulate cellular events. Although the current scientific literature contains thousands of articles devoted to protein–ligand interactions (e.g. searching PubMed with the term protein interactions yields > 250 000 articles), the majority of these studies focus on high-affinity complexes (typically with a K D < 10−6 m) that are readily detectable and therefore amenable to a variety of techniques for analysis. When an interaction is weak or very weak (e.g. K D > 10−4 m), many conventional approaches fail or become unreliable. Thus, compared to the large database of the tight protein–ligand complexes, information about weak protein–ligand complexes is still scarce, and few of these have been thoroughly investigated or structurally characterized. Indeed, a significant bias still exists toward treating weak protein–ligand interactions as nonspecific and physiologically irrelevant. Such a bias mainly stems from considering the mean concentration of a particular protein in the cell, which typically lies in the nanomolar to micromolar range. At such concentrations, weak interactions are expected to have no consequence.
This simple view, however, is fundamentally flawed. Certain subcellular compartments are significantly enriched in certain proteins; thus, their local concentration can be high, as is the case for proteins involved in the assembly of focal adhesions, actin filaments or proteins assembling into viral capsids [1, 2]. Indeed, in these scenarios, ultra-weak protein–ligand interactions become biologically important. Other examples of low-affinity complexes are those formed transiently by proteins involved in electron transfer or multi-enzyme complexes [3, 4]. The transient nature and low stability of such noncovalent assemblies is such that, in vitro, the complexes usually dissociate, rendering detailed structural studies by most common techniques (e.g. X-ray crystallography) challenging. Because of these problems, weak interactions have, until now, received comparatively little attention, despite the fact that weak and transient complexes are extremely important with respect to the regulation of biochemical pathways, allosteric regulation and signaling cascades in cells. There are many other examples where weak interactions play crucial roles, often providing effective mechanisms for the cell to quickly respond to temporary stimuli. For a complete elucidation of life processes, it appears necessary to investigate both strong and weak protein–ligand interactions.
1 Like
You understand that repeating this doesn’t make it more valid, right?
2 Likes
Correct. There are many cases in which binding must be relatively weak to be physiologically reversible.
1 Like
I’m sitting here a bit shocked at what I think I’m reading. Somebody help me out. Are you all saying that Behe claims these multiple mutations have to occur in the same generation? If you read the book it’s obvious he doesn’t mean that.
Quoting from the book, “…Darwinian processes. The necessary preconditions are all there: tiny, incremental steps—amino acid by amino acid…” You guys are claiming he doesn’t know this?
Is this just a misunderstanding of the word “simultaneous”? Simultaneous in his context only means they have to be there “at the same time.”
As @lee_merrill quotes, Behe points out that resistance to atovaquone requires one mutation and arises in about 1E-12 plasmodia, and CQR (from the historical data) arises about 1E-20 plasmodia. So obviously he is not claiming the multiple mutations are in the same generation (that would be 1E-24). But they have to be there simultaneously.
Where are you guys getting that he claims multiple specific mutations must arise in one generation?
To the best of my knowledge, anywhere that probabilities are presented claiming that some combination of mutations is highly unlikely as an argument against evolution, the probabilities presented are a product of independent and simultaneous random events. This is true of Behe, Dembski, and countless other ID supporters down to my most recent discussion with @lee_merrill. The calculation of this sort of probability for non-simultaneous events is never considered.
Even Dembski, who must understand the correct calculation (he has an MS in statistics), uses the probability for simultaneous independent random events.
This all goes back to Rosenhouse’s criticisms of mathematical anti-evolutionism.
I would like to note this is the topic which originally interested me in the ID/evolution debate (c.2004). I do not object to people believing in a divine creator. I very much object to people using bad math to claim creation as scientific fact.
8 Likes