It’s that in all the chances for malaria to develop a new binding site, none that we know of, have developed.
“This points out a particularly silly problem that underlies the entire premise of Behe’s argument in ‘The Edge’. He finds a particular observation with a certain probability, then he identifies (often wrongly, but that’s a different matter) another process that would produce a result with the same probability. He then assumes that the second accounts for the first.”
So which probabilities did you mean? I seem to have misunderstood your point.
Read again the part of my comment that you didn’t quote:
Is the conclusion drawn in that example valid? Why or why not? Just stick with this for now, and forget about trying to figure out how it applies to Behe.
But we’re not looking for “modest binding” when new protein-protein binding sites begin evolving, we’re looking for binding that elicits an adaptive response. The immune system doesn’t have to begin with modest binding, it just needs binding visible to selection. This means the strongest binders can be extremely rare compared to much weaker binders, but much weaker binders are still effective enough for selection to favor them over background affinity and provide a stepping stone towards ever stronger binding affinity.
The immune system doesn’t need to produce a well-adapted antibody in one go out of some incomprehsibly large library of variants, as it takes tiny differences in affinity for some b-cells to be favored over others.
How many antibody molecules do we need to screen to find one that selection can act on? - is a very different question from ‘How many antibody molecules do we need to screen to find one that provides moderate binding?’
As the affinity and specificity goes up, the number of molecules that meet the threshold decreases. But selection doesn’t have to begin with “moderate” binding affinity. It can begin with very weak binding affinity as long as that affinity is visible to selection.
Read this:
For starters, malaria can’t possibly “develop a new binding site,” as malaria is a disease, not an organism. One can’t coherently substitute the singular “the malaria parasite” as Behe does, either, because five different Plasmodium species cause malaria.
Please show me where Behe claims that any new binding sites are involved in chloroquine resistance, name the specific protein(s) and what they are allegedly binding to.
It looks to me like you are hopelessly confused and putting words in Behe’s mouth, Lee.
I would assume by “modest” he means visible to selection, though!
“The lesson from shape space is that, in order for the one to bind the other, we should expect to have to search through tens of millions of different mutant sequences before luckily happening upon one that would specifically stick with even modest strength, which would allow the two to spend even half of their time together. (This is likely the minimum necessary strength, enough to have a noticeable biological effect.) [11]” (The Edge of Evolution, p. 133)
“11.Most proteins are present in the cell at well below millimolar concentrations, so in order for two proteins to spend the majority of their time bound to each other, micromolar dissociation constants would be required to form even a “weak, transient” complex (Nooren, I. M., and Thornton, J. M. 2003. Structural characterisation and functional significance of transient protein-protein interactions. J. Mol. Biol. 325:991–1018). Dissociation constants on the order of micromolar seem to be required to detect interactions in yeast two-hybrid assays (Golemis, E. A., and Serebriiskii, I. 1996. Identification of protein-protein interactions. In Coligan, J. E., ed. Current protocols in protein science. Brooklyn, N.Y.: John Wiley & Sons, Inc; Estojak, J., Brent, R., and Golemis, E. A. 1995. Correlation of two-hybrid affinity data with in vitro measurements. Mol. Cell Biol. 15:5820–29).” (p. 289)
What’s missing is evidence. Where is his evidence that binding below those affinities are invisible to selection?
I could find nowhere in those references where it is substantiated that Behe’s claim that “([This] is likely the minimum necessary strength, enough to have a noticeable biological effect.)” is true, 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. It seems to me NONE of those references actually tested what dissociation constants are visible to selection.
Wow! Good that we’ve got someone here is even better informed than Behe’s best critics!
I know you don’t believe the marbles and dice are related. So what is your point? Correlation is not causation? Yeah? OK.
Hi @lee_merrill. I thought Behe was generalizing the binding site argument, not restricting it to malaria. It looks to me to be in two stages: first he deals with malaria to validate the math, then applies the math to binding sites generally (not just to malarial proteins).
What binding sites were cited in the case of malaria?
It looks to me to be sleight of hand, as you correctly noted:
What math was validated, exactly?
Which specific P. falciparum proteins (malaria is a disease caused by at least 5 different species, so it doesn’t have proteins) and which specific binding sites?
I think that Behe wants readers to think that he did that, but he really didn’t.
That’s a deduction, from “weak, transient” interactions, and “Dissociation constants on the order of micromolar seem to be required to detect interactions in yeast two-hybrid assays”.
Hi @Marty, yes, his argument involves HIV and humans and E. coli…
Well, I think he uses malaria to develop the concept of a chloroquine-complexity cluster (a CCC), and then applies this rate to the rate of development of a new protein-protein binding site.
