So much for deleterious intermediate sequences somehow preventing the evolution of new, more, or better functions.
Recombination is blind to the fitness-effects of the result, and intragenic recombination can still result in the combination of mutants which are individually neutral or beneficial, but together show reciprocal sign epistasis. The frequency with which recombinations are deleterious is lower than the frequency with which mutations are deleterious, but theyâre still ârandomâ with respect to their effect on fitness. So a large number of variants are still generated through recombination, and selection occurs between them.
Yup. Recombination that is random with respect to fitness is how we get the antibody binding site repertoire, too. Itâs a major source of variation for evolution.
Possibly. At the very least, it would almost certainly not be due to evolution.
So letâs try put Beheâs argument into the form of a syllogism:
If any CCC mutations occurred in the course of the evolution of the human species, then human evolution would have required Intelligent Design at some point.
Conclusion: Human evolution required Intelligent Design at some point.
Do you think that is a valid argument? Or is there a step or two missing?
Casey Luskin, a rather stupid and dishonest ID propagandist with no training in biology, is hardly a reliable source to cite. As it happens, Behe eventually admitted that Vpu represents a new functional protein complex that evolved in HIV, so this is a dead issue.
Good Lord.
Please pay attention. I am going to speak as slowly and clearly as I can:
Now, please repeat that back so I know you were paying attention this time.
You know this, or should: Because CR is a more complex adaptation, requiring more mutations, some of which have to occur in a specific order. But none of which must occur simultaneously.
And you know whatâs really frustrating? We can keep talking about this for as long as I have the patience, probably with you never understanding and accepting. And the thing is, this does not even support Beheâs argument at all. Chloroquine resistance is entirely unnecessary to illustrate what Behe is trying to argue. There probably is some trait that would require four simultaneous mutations that is rarely if ever seen. No one would deny this. But by bringing up malaria and harping endlessly on it, Behe gets to engender long and complicated debates the quickly exceed the already weak grasp of biology that most of his sycophantic followers possess, and they end up thinking âBoy, thatâs a lot of complex stuff they are talking about. I donât understand any of it, but so long as scientists are arguing with Behe, Behe must have some point.â
I donât think this is accidental. Beheâs goal is not to convince scientists or scientifically informed people. His goal it to convince you. And look how well that is working.
You have not shown this. The prevalence of CR in a population not exposed to chloroquine has been observed to only go down from 85% to 13% in eight years. Now, I am no population geneticist, but some people here are, so Iâd really love to see you show them the math that indicates this must be due to strong negative selection.
âThese go up to 11.â
I am beginning to strongly suspect you are utterly incapable of understanding what we are talking about, and we are all wasting our time.
However, you do serve the useful purpose to illustrating how Beheâs scientifically inept propaganda can convince people unable to or uninterested in understanding the science, not to mention basic logic, that demonstrates that Beheâs argument is just hot garbage.
Itâs good evidence they donât have a functional fold, though.
Sure, but Axe generalizes to the prevalence of functional folds in general, so he gets a general estimate of functional proteins.
But protein chimeras are not simulations of typical evolution.
âHe went on to screen a library of 1.65 million different hybrid genes created (using a molecular biology protocol called ITCHY) from what was essentially random fragments of existing genes, to see whether one of these millions of new hybrid genes could perform a function that could compensate for one of the 107 different dysfunctional mutant genes.â
But what is the probability that two severed gene parts will find each other and recreate one of the original genes? 1 in 1.65 million, so itâs not surprising if a functional gene appears on this order of magnitude.
âInterestingly the self-rescue is not a fully intact version of the original knocked out gene, being partially constituted of a smaller fragment from it, but is nevertheless able to carry out its function, at least while fused to a fragment of another gene.â
So this is a gene fragment that still operates, when connected to another fragment, not so surprising, and also not a good exploration of protein sequence space.
But there are examples Behe lists beyond the edge of evolution: âWith the criterion of two protein-protein binding sites, we can quickly see why stupendously complex structures such as the cilium, the flagellum, and the machinery that builds them are beyond Darwinian evolution. The flagellum has dozens of protein parts that specifically bind to each other; the cilium has hundreds. The IFT particle itself has sixteen proteins; even complex A, the smaller subset of IFT, has half a dozen protein parts, enormously beyond the reach of Darwinian processes. In fact, drawing the edge of evolution at complexes of three different kinds of cellular proteins means that the great majority of functional cellular features are across that line, not just the most intricate ones that command our attention such as the cilium and flagellum. Most proteins in the cell work as teams of a half dozen or more.â (The Edge of Evolution, p. 146)
I just canât map out the path by which they evolved, because the claim is that they were designed.
Four mutations of the 5 or 6 mutations required would be deleterious, and I recommend reading Beheâs argument before discarding it.
1 in 10^40 organisms.
I think it was the same binding site, though:
" How could single amino acid changes have caused an entirely new function to evolve? Residue 33 does not contact the ligand, and residue 36 makes only a minor and apparently nonspecific contact to Pins at one end of the binding site (Figure 7âfigure supplement 1). Overall, the residues that compose the Pins-binding surface are almost entirely conserved from Anc-gkdup to Anc-GK1PID (Figures 5B, 7A,B), and the backbone structure of the binding lobe is almost identical between the crystal structures of extant GKPIDs, gk apo-enzymes, and a gk apo-enzyme containing mutation S36P (Figure 7B, see also ref. Johnston, et al., 2011). Thus, the Pins binding surface appears to have been present, even before the interaction with Pins itself evolved."
But I donât think a fibril is what should be called a general, higher-order structure.
If new protein-protein binding sites are just one mutation away, in general, then such new sites would gum up the working of the cell.
But one mutation away from binding is not a compromise, itâs immediate.
No, it isnât, because enzymatic activity is a continuous function, not a binary one. Do you understand that?
Itâs not valid because his method was not designed to measure that. The detection of two clones of ~10^8 that have measurable beta-lactamase activity in unimmunized mice disproves Axeâs extrapolation utterly and completely.
If Axe thought it was valid, why hasnât he done any more experiments to follow up in the last 18 years?
Itâs not a valid criterion, because Behe misrepresents the evidence, despite cherry-picking a few cases himself.
Then you should be able to map out the path by which they were designed.
I donât, but then I read papers by assessing the data, not looking for a little bit of text that I can pretend supports my position.
Everyone in the biz does, though.
How do you think that inherited early-onset Alzheimer disease works, Lee? How does inherited prion disease work? Donât they involve single-residue substitutions?
No, it isnât. Axe has no idea whether the mutated proteins are capable of some other function, all he knows is they donât give sufficient resistance to allow the bacteria to grow under the concentration of antibiotic present in the agar.
So the protein might have lost the beta-lactamase fold, that doesnât mean it has no fold, and it definitely doesnât mean itâs nonfunctional. Those conclusions simply canât be extracted from that experiment.
No, he doesnât. He writes words intended to make you believe that his experiment can be generalized in this way, but nothing in his experiment can logically support that conclusion. It is obviously false, since we know of proteins with functions at much higher frequencies in sequence space, and we know of sequences too short to form protein folds that nevertheless are capable of performing functions that enhance reproductive fitness.
So amino acid sequences donât need to be so large that they can fold to be able to function, and many protein functions are known to occur at much higher frequencies in sequence space than the serine beta-lactamase fold.
Yes they are.
They occur spontaneously all the time. Theyâre just one result of how mutations can occur and result in novel functional genes. Whether by deletions that bring together two other pieces, copy and insertion into an already existin gene, transposition or what have you. Hereâs an example:
Several other examples are mentioned in the discussion of that paper.
Youâre confused. Nobody says it has to produce one of the original genes. The point is that combining pieces of different existing genes can produce new genes with new functions. As happened here.
There were other genes with functions produced than that partial self-rescue, which did not involve fragments from the knocked out gene. Which is explained in that article already.
No, it doesnât âstill operateâ. If the fragment of the protein alone was able to function and compensate for the function that was knocked out in the deletion strain, then the protein the fragment is derived from would rescue the deletion strain already, and thereâd be no need for the novel fusion protein.
So itâs obviously only when the fragments of two different proteins are together and forms novel fusion protein that this combination makes them able to perform a new function either of them were individually incapable of before. Thus this chimeric protein really is a novel functional protein.
Itâs a fantastic exploration of protein sequence space. So fantastic that one needs only screen through approximately 330-thousand such random fusion proteins to find one that can rescue a deletion strain, as opposed to having to screen 1077 sequences to find a new functional protein.
Amazingly every single assertion you made in that post is factually incorrect.
Kids, @lee_merill is what happens when you read pro-ID and creationist literature (which is actually just a form of religious apologetics) to get your science education rather than taking a real biology education. You end up with a completely false view of biochemistry, molecular biology, and evolution, and you end up spewing demonstrable falsehoods ad nauseam seemingly with no shame or care.
I just want to say I love that post of yours. Rather than deal with the facts or try to engage in some critical thinking youâre reduced to repetitions of the same vacuous and contra-factual assertions.
Go see if you can find some Demons. Stop trying to argue about biochemistry.
No, they are beyond Beheâs edge if and only if the changes are necessarily required to be simultaneous. It is the necessity of simultaneity that needs to be demonstrated, which Behe has not done.
So the editors of the Journal of Molecular Biology let one slip? âEstimating the Prevalence of Protein Sequences Adopting Functional Enzyme Foldsâ is the published title. And I think itâs safe to say the protein probably lost the beta-lactamase fold, and that it definitely lost a function. And testing for any possible function would be prohibitive. Axe writes:
âThe focus, then, will be on mode of catalysis rather than rate. The justification for this is that there is a clear connection between active-site formation and protein folding, in that active sites generally require the local positioning of multiple side-chains that are dispersed in the sequence. Something akin to tertiary structure, however crude, must therefore emerge in working form before natural selection can begin the process of refining a new fold. By assessing the difficulty of achieving the sort of structure needed to form a working active site, we therefore gain insight into a critical step in the emergence of new protein folds.â
But Axe is after the average, any outliers would be taken into account, certainly, and do you have the references? And similar studies have been done that produce similar averages, so it seems to have some confirmation: âThis is a difficult problem to approach experimentally, however, and no clear picture has yet emerged. A number of studies have suggested that functional sequences are not extraordinarily rare,1., 2., 3., 4., 5. while others have suggested that they are.6., 7., 8., 9.â
Thatâs fine, but they are not typical of evolution, is the point.
And Iâm not saying that, please re-read my statement more carefully.
Certainly, but Iâm saying the partial self-rescue functions are not that surprising to occur.
Isnât that what he called a partial self-rescue? Those are just disregarded. But he writes âInterestingly the self-rescue is not a fully intact version of the original knocked out gene, being partially constituted of a smaller fragment from it, but is nevertheless able to carry out its function, at least while fused to a fragment of another gene.â I take this to mean the fragment is able to carry out its function, while fused to another fragment, which other fragment presumably does not participate in the function.
Then it should be modeled on what evolution actually does, using a typical spectrum of mutations.
Well, itâs disputed, and I have disputed each of your points! Itâs called having a discussion.
We need âCCC mutations would be required in the evolution of humans.â
All rightâŚ
But simultaneous mutations are deduced from the mutation rate, for one, and from the fact that the mutations appear to be singly deleterious, i.e. they disappear in the absence of chloroquine.
A more parsimonious explanation is that the mutations are deleterious, and thus must occur together.
âThe prevalence of the chloroquine-resistant pfcrt genotype decreased from 85% in 1992 to 13% in 2000. In 2001, chloroquine cleared 100% of 63 asymptomatic P. falciparum infectionsâŚâ
So it apparently disappeared completely in 1 year, letâs not leave that part out. Now Iâm not a population geneticist either, but there does seem to be an indication here of negative selection.
Behe has not demonstrated the existence of such mutations in humans. Nor has he demonstrated the existence of double CCC mutations in any organism whatsoever
Bit of a problem for his argument, donât you think?
Show your math.
I will repeat: The prevalence of CR only went down from 85% to 13% in eight years.
Is that consistent with strong negative selection?
You seriously think eight years is not enough time, in an organism with such a short reproduction cycle, for an additional mutation to occur as the initial mutations hang around at a frequency of somewhere between 13% and 85%?
Think, man.
No, not more parsimonious. Just the one you want to be true.
Again, we do not need to speculate about this. Summers research as shown how CR evolves. It does not require simultaneous mutations. Period.
LOL! That is not what it says.
You are becoming more ridiculous by the moment.
Now, donât tell me youâve never seen This Is Spinal Tap.
A competent scientist does not extrapolate to a global claim from a single case and then never bother to follow up. A more reasonable hypothesis is that it is in his financial interest to deny the reality of this.
No, itâs a fact. Behe himself has admitted it in the case of HIV, remember?
So why would you demand a path for evolution?
It demonstrates that you are completely wrong.
They certainly did.
Axe didnât bother to measure enzymatic activity. Thereâs even a commercial kit available. Or maybe he did and didnât like the results?
And the paperâs use of âfoldâ is even worse, because âfoldâ is a structural, not a functional, term.
The beta-lactamase activity in the paper I linked to is in the context of the immunoglobulin fold, which is shared by hundreds of non-immunoglobulin proteins.
Certainly not and yes.
So we agree that Beheâs approach is wrong, since he only considers one type of mutation instead of the whole spectrum. Progress!
Repeating your falsehoods is not disputing, Nigel.
So why do you view Behe as credible on any other evidence? And why does his credibility vanish in your eyes when it comes to common descent of humans and other apes?
Ignoring the intermittent selection.
If it takes 8 years for the allele frequency to decrease, thatâs not exactly deleterious.
A sample of 63 cases is not sufficient to conclude complete disappearance. I suspect that even you know that.
Youâre not a statistician, virologist, geneticist, or biochemist, either, but youâre claiming to understand all of those fields better than the professionals here. Why is that?
