The Failures of Mathematical Anti-Evolutionism

IOW “These go up to 11.” And just what does the length of the protein have to do with this?

I will repeat the question one more time: Why can the mutations necessary for these new(ish) proteins not arise one at a time? They don’t have to each be selectable. But even if they did, they would not have to occur simultaneously. Why would they?

Why do you think it implies that? One thing you do not seem to appreciate is that chloroquine would exert a strong selective pressure in favour of resistant strains. Once the drug is withdrawn, this pressure no longer exists and other variants are free to arise. It is not necessary that the resistant strain be subject to negative selection. But that is not the main problem you have here, so I just add that for your edification.

You really need to explain why you think these traits require simultaneous mutations.

Yes. If you insist it requires simultaneous mutations, please quote where this is said in the paper. Please, no more Nigel Tufnel. Give us the quote.

No, you really haven’t. You just think you have. “These go to eleven” is not an argument, sorry.

Again, support this assertion. And how deleterious is “somewhat”? Have you heard of nearly neutral theory?

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No, your claim is about protein-protein binding sites. You’re very bad at inferring content from titles and abstracts.

You’re terminally confused.

The intermittent selection, even if all patients took chloroquine, is the reason why fixation of mutant HAPLOTYPES is so rare, not mutational requirements.

And that’s overall. It just as easily could be that some of the alleles that confer chloroquine resistance have decreased fitness in the intermediate hosts irrespective of chloroquine.

[quote=“lee_merrill, post:80, topic:15042”]

The rate of chloroquine resistance is not merely a function of mutation, but of intermittent selection, recombination, epistasis, etc. Behe’s “calculation” ignores all of these important factors.

You did not read carefully. There are two MAIN paths. You are misrepresenting the bit of the paper you quoted.

[quote=“lee_merrill, post:80, topic:15042”]

No, it does not, as there is nothing that sophisticated in Behe’s book. You’ve been bamboozled. Again, high-affinity, specific binding is evolved from random variation in your immune system in only 2 weeks.

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I’ve restored part of my post that was omitted by @lee_merrill when he responded:

So you’re not going to calculate any before-the-fact probabilities of anything other than what you know evolved. All your biological system calculations are done after-the-fact, and your claims otherwise are untrue. You are bait-and-switching.

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If Behe is basing his probabilities on what evolution does then he is picking after the fact.

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Yes, that is another problem with Behe’s argument that we have not discussed at length here. This chart is from the paper entirely on which Behe based his 10-20 number1, and lists the conditions that must be met before a chloroquine resistant strain is detected in human beings:

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Behe ignores points 2-8 and pretends the frequency is accounted for entirely by factor 1. That, by itself, ought to be sufficient to sink his argument if he had one. But the other point that is easily missed is that Behe does not even have an argument. He just has a series of unrelated points, each of which is true to varying degrees, and then he magically conjures a conclusion from them. Try map out his argument and see if you disagree. In fact, I might do that myself…

1https://www.jci.org/articles/view/21682

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The longer the protein, the more unlikely it is to have an all-selectable pathway to it.

They don’t have to occur simultaneously, but if one or more of the mutations required, is non-selectable (which would seem likely, since most mutations are actually deleterious), then multiple mutations would need to occur basically simultaneously.

It’s a deduction, first a minimum of two mutations is required: “A minimum of two mutations sufficed for (low) CQ transport activity, and as few as four conferred full activity.” Then, based on the rate of occurrence of chloroquine resistance (1 in 10^20) versus atovaquone resistance (1 in 10^12) we can deduce that chloroquine resistance requires two simultaneous mutations.

Deleterious mutations are selected against, why do I need to support this assertion? And chloroquine resistance mutations disappear in a few years, which would seem to imply that these mutations are not just neutral.

WHY???

Human proteins are littered with neutral mutations that have accumulated over hundreds of millions of years. The two papers @Rumraket has linked to show how there are multiple pathways that utilize neutral mutations, so they are plentiful. Also, there are many human proteins that have known mutations to almost all non-lethal positions in the protein within the current population.

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You all are misunderstanding me, I’m saying that when you are evaluating a probability, you have to pick before-the-fact or after-the fact, regardless of whether the event has actually occurred. All the interesting probabilities are deduced by viewing the event before-the-fact, so everyone will generally focus there.

I was assuming that it is not uncommon for proteins to bind to other proteins.

I’m not sure why you emphasize haplotypes, here? And Behe’s point is that the mutant appears to be weaker, that’s a pretty plain point.

Again, Behe is not calculating, he is observing what evolution does.

“Multiple mutational pathways led to saturable CQ transport via PfCRT, but these could be separated into two main lineages.” (Summers et al.) It sounds like “separated” implies total division into two lineages.

So how do you calculate the number of possible combinations of two mutations, one neutral and one beneficial, that can result in a selectable function in a given genome?

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Proteins do not need an all selectable pathway, though. Why do you keep saying they do?

No, not if they are neutral. Which, contrary to your claim there, most of them are. Your problem is you just swallow everything Behe tells you, and he is usually wrong about what he says.

Major logic fail. Even if the Summers paper didn’t actually tell you why CR arises infrequently as it does, your reasoning would still be invalid. There are any number of reasons that a particular trait might arise infrequently besides a requirement for simultaneous mutations. But as it happens, the paper actually tells you why the resistant strain is less frequent than might be expected. Note the bolded sentence:

Mutations in the chloroquine resistance transporter (PfCRT) are the primary determinant of chloroquine (CQ) resistance in the malaria parasite Plasmodium falciparum . A number of distinct PfCRT haplotypes, containing between 4 and 10 mutations, have given rise to CQ resistance in different parts of the world. Here we present a detailed molecular analysis of the number of mutations (and the order of addition) required to confer CQ transport activity upon the PfCRT as well as a kinetic characterization of diverse forms of PfCRT. We measured the ability of more than 100 variants of PfCRT to transport CQ when expressed at the surface of Xenopus laevis oocytes. Multiple mutational pathways led to saturable CQ transport via PfCRT, but these could be separated into two main lineages. Moreover, the attainment of full activity followed a rigid process in which mutations had to be added in a specific order to avoid reductions in CQ transport activity. A minimum of two mutations sufficed for (low) CQ transport activity, and as few as four conferred full activity. The finding that diverse PfCRT variants are all limited in their capacity to transport CQ suggests that resistance could be overcome by reoptimizing the CQ dosage.

Got it? The mutations had to be added in a specific order, but were still added one at a time. The astonishing thing is that it says right there that Behe is wrong, yet he and his gullible sycophants actually thought this paper vindicated him! I find that very strange, and very sad. Don’t you?

Jeez, you really don’t read very carefully. Go look at what I actually asked, then see if you can come up with an answer.

"In a few YEARS??!!! " And you honestly think drift alone is not capable of removing a variant that is not subject to selection either way in an organism that reproduces as rapidly as C. falciparum in a matter of a “few YEARS?”

This is the problem: You really have no understanding of the bare basics of this subject, so you are vulnerable to Behe’s underhanded efforts to bamboozle you with his BS because he is saying something you want to be true. I actually feel sorry for you, because then you come onto a forum like this and embarrass yourself.

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Sorry, I should have said “deleterious” instead of “non-selectable”.

No, Behe observes what evolution did, this includes all the factors. But the following statement, specifically for chloroquine resistance, seems clear: " Resistance to chloroquine in P. falciparum has arisen spontaneously less than ten times in the past fifty years (14). This suggests that the per-parasite probability of developing resistance de novo is on the order of 1 in 1020 parasite multiplications."

  • Chloroquine resistance occurs in about 1 in 10^20 organisms, requiring two singly-deleterious mutations
  • We’ll call a CCC a chloroquine-complexity cluster, an event requiring two singly-deleterious mutations.
  • A double-CCC (an event requiring two CCCs) is beyond the edge of evolution.
  • Based on considerations from shape space, a new protein-protein binding site would need several singly-deleterious mutations, or a CCC.
  • So two such binding sites would be a double-CCC, beyond the edge of evolution.

No, your non sequitur does not become true by your repeating it. Behe ignores all but one and misrepresents himself as in agreement with White.

There’s noting about simultaneous mutations in there. What is clear is the list in the same paper that Behe ignores.

BTW, Faizal asked you to map out Behe’s argument, not just reiterate his assertions.

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He has made zero observations. He has used textual misattributions to claim that it’s all about mutation.

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Another “These go to 11.” If he took all the factors into account, then how does what he concludes about chloroquine resistant apply to every other trait in every other organism, where completelhy different factors are at play?

Objectively wrong, as you should know by now. Why are you repeating a falsehood?

Sure, call it whatever you want. Call it “Rumplestiltskin” if that’s what you want to do."

OK, sure. Lots of things are beyond the “edge of evolution.” No one expects the malaria bug to evolve the ability to do differential calculus while playing the banjo.

Codswallop. How does this follow from what preceded it, even if what preceded was true (which it isn’t)?

More codswallop.

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To be fair, I actually think @lee_merrill did map out Behe’s “argument”, such as it is.

It really does seem to be a series of assertions, most of them outright contradicted by empirical evidence, with no logical connection from one to the next.

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Let’s drill down on this a bit more. Here, again, is that table from White’s article.

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As I understand it, Behe’s argument is based on the premise that the factors that have determined the frequency with which CR has evolved in malaria can be extrapolated to any other organism, such that any other trait of the same “complexity” would require as many reproductive cycles to arise. So let’s see how those factors apply to the species H. sapiens.

Factors 1 and 2 are not problematic, and are trivially true. Obviously, the mutation(s) responsible for the novel trait will have to first arise in a single individual before spreading to the rest of the population. And the degree to which it is subject to negative selection (which is what Behe is alluding to in #2) will affect how fast, and whether, it would spread.

With #3. however, we start to encounter some problems. He refers to the “number of parasites in the human host that are exposed to the drugs.” Human beings are not parasites living in another host, and we are not all being exposed to a pharmaceutical agent designed to kill us.

I also fail to see how #4 would apply to us. Again, we are not all being exposed to some drug that is intended to kill us, so its concentration and pharmacokinetic properties have no bearing on whether a particular genetic trait will arise and be fixed in our species.

Without belabouring the point, the same problems exist for the remaining points in that list. They all pertain specifically and exclusively to a parasitic organism residing in a host that is being treated with a pharmaceutical designed to kill the parasite. I hopefully need not explain to you that this does not apply to more than a very small portion of the organisms that have inhabited the earth. In fact, it does not apply to any organism prior to the last half of the 20th century, when antibiotic drugs were first developed.

So I really do not see how Behe is justified in using a figure that applies to the malaria parasite as one that applies equally well to every other living thing. Could you clarify?

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The only possible combination that results in a selectable function would be both mutations–if I’m understanding you correctly.

That’s not what I am asking.

There are 3 billion bases in the haploid human genome. How many combinations of two mutations within those 3 billion bases will produce a beneficial change? How would you do that calculation, and how would you do the same for any given genome?

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