Intelligent Design proponent Michael Behe has recently taken Ken Miller to task for the latters rough handling of another ID proponent’s handling of some concepts in evolution. I don’t intend to add to the back and forth between the two (or three?) of them here. Rather, I thought I would use one of Behe’s closing remarks as an excuse to repost a (slightly-modified) Panda’s Thumb essay that pertains to one of Behe’s newer calling cards – the so-called “Edge of Evolution”.
In the last paragraph of his response to Miller, Behe says:
“It’s pertinent to remember here the central point of The Edge of Evolution. We now have data in hand that show what Darwinian processes can accomplish, and it ain’t much.”
Actually, as the following essay clearly shows, Darwinian processes can do much more than Behe suggests. Enjoy.
A few months ago I posted an essay about a remarkable example of the evolution of Irreducible Complexity from scratch, via natural, unguided mechanisms. While the reaction to this essay has been pretty muted (precious little to take note of, save for one well-hidden reference on Uncommon Descent to “No Free Lunch”, citing pages that make arguments clearly refuted in the PT essay), I had no idea that a much bigger response, or target, would emerge from the Halls of ID. This would, of course, be Mike Behe’s recently-released follow-up to “Darwin’s Black Box”, entitled “The Edge of Evolution”.
To start off with, it helps to capsulize Behe’s book. The theme of the book, indeed the very Edge of Evolution itself, is a number that Behe assigns to the probability that a protein interaction site can evolve. This number is 1 in 10^20. Behe “derives” this number from the following line of reasoning (the details have been floating around the blogosphere for a few weeks, so I’ll be brief). First, in Chapter 3, Behe discusses at some length the evolution of resistance to chloroquine in the malaria parasite Plasmodium falciparum. It has been reported that resistance to this drug involves the appearance of at least two amino acid changes. Behe argues that these need to be essentially simultaneous in appearance, and coins a term (the Chloroquine Complexity Cluster) to stand for events that involve leaps of two simultaneous mutational changes. Behe also cites a review by Nicholas White that provides an estimate of the frequency of occurrence of a “CCC” — 1 in 10^20 trials. In Chapter 7, Behe then discusses the matter of the evolution of protein binding sites. Behe reasons that the evolution of a new protein binding site will involve a modest number of amino acid changes, and that some of these changes must occur in concert; for this reason, he asserts that a single protein interaction domain is analogous in “complexity” to a CCC, and thus should be expected to occur about once in 10^20 trials. Finally, he argues that networks of more than two proteins require at least two different protein binding sites, and that selection will not act unless these changes occur simultaneously. Thus, for a trimeric complex, two sites are needed, and would be expected to occur once in 10^40 trials. In light of some general numbers (age of the universe, numbers of organisms on earth, etc.), this number would seem to lie on the other (unaccessible) side of the Edge of Evolution. This is Behe’s argument in a nutshell.
Let’s turn now to the previous PT essay. In it, we learned that the protein dubbed T-urf13 had evolved, in one fell swoop by random shuffling of the maize mitochondrial genome. We also learned some fascinating things about T-urf13. Summarizing the salient points:
T-urf13 forms heteromeric complexes in the membrane. This means that different subunits bind at least two other subunits. This means that each subunit must have at least two different protein binding sites. That’s at least two “CCC’s”.
T-urf doesn’t just form heteromers in membranes. It forms a gated ion channel. This means that each heteromeric complex must be capable of adopting at least two different conformations, of changing from one to another, and of shepherding ions through the phospholipid bilayer. This all means that the heteromers are not some non-descript clumps of polypeptide; they possess all the functionality of other, more well-known gated ion channels.
One more thing — the ion channel is gated. It binds a polyketide toxin, and the consequence is an opening of the channel. This is a third binding site. This is not another protein binding site, and I rather suppose that Behe would argue that this isn’t relevant to the Edge of Evolution. But the notion of a “CCC” derives from consideration of changes in a transporter (PfCRT) that alter the interaction with chloroquine; toxin binding by T-urf13 is quite analogous to the interaction between PfCRT and chloroquine. Thus, this third function of T-urf13 is akin to yet another “CCC”.
The bottom line — T-urf13 consists of at least three “CCCs”. Running some numbers, we can guesstimate that T-urf13 would need about 10^60 events of some sort in order to occur. Recalling Behe’s summation from p. 146:
“So let’s accept my earlier conservative estimation, and spell out some implications. The immediate, most important implication is that complexes with more than two different binding sites—ones that require three or more different kinds of proteins—are beyond the edge of evolution, past what is biologically reasonable to expect Darwinian evolution to have accomplished in all of life in all of the billion-year history of the world. The reasoning is straightforward. The odds of getting two independent things right are the multiple of the odds of getting each right by itself. So, other things being equal, the likelihood of developing two binding sites in a protein complex would be the square of the probability for getting one: a double CCC, 10^20 times 10^20, which is 10^40. There have likely been fewer than 10^40 cells in the world in the past four billion years, so the odds are against a single event of this variety in the history of life. It is biologically unreasonable.”
That makes it pretty clear — T-urf13 is a mathematical impossibility. It simply cannot exist.
Well, this is of course absurd (although the farmers whose livelihoods were devastated by Southern corn leaf blight dearly wish that Behe was correct). Indeed, it is apparent that Behe’s “line in the sand” is badly out of touch with reality. How different is it from what actually occurs? We can run some numbers of our own and compare. The amount of arable land on the earth is on the order of 200 million hectares, or about 500 million acres (I’ll do some liberal rounding to keep things simple). A really good farmer can cram 50,000 corn plants into an acre (we won’t go into what the yields would be…). A typical corn tassel may make 50 million pollen grains (OK, a superman plant, maybe, but we’re being generous here). Finally, maize has been under cultivation for less than 10,000 years. What does this add up to? If each and every arable acre on earth had been used for corn production, at the unseemingly high planting rate of 50,000 per acre, and if somewhow we could cram four plantings in per year, then this would translate to some 10^26 pollen grains in the entire history of corn production. Of course, cmsT was probably developed over a 20 year period, and probably involved a few thousand acres and 2 or 3 generations per year. Let’s say 100,000 acres and 3 generations per year, to give us a more realistic (but still generous) estimate of 10^19 pollen grains.
Now, this isn’t the end of things. The number of interest is the number of mitochondrial genome rearrangements — the number of shufflings that occurred to give us T-urf13. Let’s stuff 1000 mitochondria into each pollen grain, and let each of them undergo a million recombinations (people who work with corn pollen may commence to groan). This translates to about 10^28 events.
Now, recall that we are talking about, not one, but a minimum of three CCC’s. Behe says 1 in 10^60, what actually happened occurred in a total event size of less that 10^30. Obviously, Behe has badly mis-estimated the “Edge of Evolution”. Briefly stated, his “Edge of Evolution” is wrong.
I’ll close this essay by noting one source of error on Behe’s part. As I have discussed, Behe asserts that the probability associated with a “CCC” is 1 in 10^20. Where does this number come from? From footnote 16 in the first excerpt given above – White, N. J. 2004. Antimalarial drug resistance. J. Clin. Invest. 113:1084-92. Here is the actual passage from the review by White that mentions the number 10^20:
“Chloroquine resistance in P. falciparum may be multigenic and is initially conferred by mutations in a gene encoding a transporter (PfCRT) (13). In the presence of PfCRT mutations, mutations in a second transporter (PfMDR1) modulate the level of resistance in vitro, but the role of PfMDR1 mutations in determining the therapeutic response following chloroquine treatment remains unclear (13). At least one other as-yet unidentified gene is thought to be involved. 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 10^20 parasite multiplications. “
Recall that Behe equated one CCC with a double mutation, presumably based on other work showing that two point mutations in the PfCRT gene are associated with durable resistance in the parasite. But White is not talking about double mutations in PfCRT when he tosses out the number 10^20. Rather, he is speculating about the frequency of occurrence of a multigenic trait that involves two or three genes, and more (perhaps many more) than two mutations. In other words, Behe’s use of this citation to argue that the natural frequency of occurrence of a double mutation in PfCRT is 10^20 is inappropriate. This is one reason (not the only reason, but one) why Behe’s claims are so out of touch with reality.
Of course, there is more, much more. Lots and lots of combinatorial chemistry and protein structural research refutes Behe. As does the fact that every trait that Behe imagines as demanding multiple simultaneous mutations actually do not. Not only has Behe miscalculated the Edge of Evolution, he is actually pointing in entirely the wrong direction in looking for this edge. But these are issues for other essays. The example that is recalled here shows clearly that Behe’s claims are wrong.
As a postscript, two points of interest. It may have occurred to readers that the pre-emption of the Edge of Evolution by my essay is more than coincidence. But trust me — I’m not the Sal Bonpensiero of this on-going soap opera, who had secret access to Behe’s book ahead of time. (That having been said, I don’t think I’ll be taking boat rides with any ID bigwigs.)
No, what this all means is simpler. The earlier PT essay was a belated discussion related to Darwin’s Black Box, a pulling together of ideas that had been bounced around the internet for more than ten years. The fact that the previous essay is also a one-stop shopping mall of items that refutes the Edge of Evolution simply pushes home the message that the EoE is little more than a re-working of DBB. What is supposed to be revolutionary is actually just more of the same tired antievolutionary arguments.
Very interesting. Thanks for sharing.
I still struggle to understand T-urf 13. One of these days I need to figure out a good, lay explanation. This post should be one of the hottest posts on the web — one almost could believe in an intelligent design to keep this quiet, because it’s so devastating to the ID case.
So you Darwinists want this technically sophisticated stuff taught not by qualified science teachers but by unqualified parents, unqualified Sunday School teachers, and unqualified social studies teachers. You are insane.
“I still struggle to understand T-urf 13. One of these days I need to figure out a good, lay explanation.
So do I. Maybe you can take me by the hand in the comments here, so that I can adapt the essay for a wider audience. I’m more than happy to answer any question, to clarify any turgid prose.
This post should be one of the hottest posts on the web — one almost could believe in an intelligent design to keep this quiet, because it’s so devastating to the ID case.”
Spread the word! Linky linky … (or whatever they do nowadays)
The big question is:
Did these binding sites “evolve” or were they present since the protein took shape?
It appears that the membrane binding sites were always present.
And it also appears that the fungal toxin binding sites were always present.
You should probably change teh title of this post to:
“Another Hunt Strawman”.
So, Joe, are you saying that Behe would have no problems with several binding sites arising all at once, from out of thin air? Are you claiming that modest modification of pre-existing proteins is much harder than total de novo origination of a multifunctional protein?
I am pretty sure that Behe is talking about USEFUL structures.
T-URF 13 is not useful.
However it does fit in perfectly with Behe’s premise that random effects tend to damage things.
But anyway perhaps you should take it up with Behe.
Or get your premise published in a peer-reviewed journal and he will respond.
Joe G, when you claim that T-URF13 is not useful, you are in essence asserting that females are not useful. I’d love to have Behe go ahead and make the same claim. Maybe on the stand at the next “trial of the century”.
BTW, I have approached Behe about this subject. Understandably, he is unwilling, even in private correspondence, to discuss this matter.
I’m waiting for a reply to my last post. I agree with your assessment: there’s too much other stuff going on now on that thread.
While I wait for your response to Behe’s stuff, I looked around for something on Turf13.
There are strange kinds of recombination events that drive mtDNA rearrangements, and it’s not the stuff of Mendelian genetics exactly; so, I think it might be a stretch to compare Behe’s CCC and what we see in csmT.
There are these factors associated with mtDNA inheritance that may make us pause a bit:
(1) it happens cytoplasmically
(2) it involves mostly recombinant effects
(3) it’s effect, in the case of csmT, can be reversed via nuclear DNA products
(4) plasmid-type rearrangments can’t be ruled out [this is certainl the case for csm-S]
(5) lastly, let’s not forget that the result of these rearrangements is ‘deleterious’; that is, the male pollen are rendered sterile.
I was next door and noticed your comment. I was particularly interested in your assertion that TURF-13 is ‘deleterious’ because the male pollen is rendered sterile. Why would you say that? If the male pollen is sterile in a hermaphroditic plant, that makes it a female. We have numerous examples of plant species which are gynodioecious, that is, maintain populations with both hermaphroditic and female plants (many of which use CMS to produce teh females, just like TURF-13). Charles Darwin studied gynodiecious plants in his 1877 book “Different Forms of Fowers on Plants of the Same Species”. He wondered why females would persist in these species, and began evaluating the characteristics of the two types. He found that the female plants had consistently higher seed yields than the hermaphrodites. Other researchers have found this to be so as well, so, in terms of fitness, cytoplasmic male sterility is not deleterious. Another thing to keep in mind is, gynodioecious species can benefit from female plants because they can outcross, whereas the hermaphrodites primarily self-fertilize.
Thanks for bringing this discussion over here.
Before I discuss the specifics about mutations in PfCRT, I need for you to clarify how you can take this statement of White’s:
and insist that the “as-yet unidentified gene” is that which encodes PMDR1. Anyone who reads this paragraph will see immediately that White is proposing the existence of a third gene, unidentified to this point. PfMDR1 is identified and its role in chloroquine resistance understood (at least to a point). It is beyond me how one can read this and claim that the “as-yet unidentified gene” codes for PfMDR1. I’m fairly certain White does not mean this.
PaV, on the UD boards, you asked:
Um, PaV, Behe’s entire argument focuses on the development of resistance to chloroquine in the malaria parasite. The quote you think rescues Behe from my criticisms here has to do with resistance to an entirely different drug. Behe’s magic number, 10^20, has nothing to do with resistance to sulfadoxine-pyrimethamine (that’s what SP stands for in your quote).
Regardless, let’s look at the entire paragraph you are snipping from. I believe that, the disconnect between SP and Behe’s magic number aside, it is clear that other issues beyond the mere frequency of occurrence of the triple mutation you cite come into play here. Since Behe cares only about frequency of occurrence, it is obvious that SP resistance (mentioned by Behe only in passing, and not in the context of mutation, protein evolution, or any of the other aspects of the Edge of Eovlution) is not going to rescue Behe.
Here’s the whole paragraph:
Getting to the rest of your comment:
Behe was talking about the frequency of occurrence of a new functional site on a protein, and did not distinguish between any of the myriad of possible ways that DNA may change.
Rather than put words in Behe’s mouth, why don’t you ask him about this subject. You’re both UD contributors, and I would expect that he won’t avoid a question from you (as he has from me).
So? Are you claiming that Behe would call organellar genomes out of bounds?
So? Are you claiming that recombinational genome shuffling, that in fact samples very limited protein sequence space, is in some way special when it comes to the origination of totally new functional proteins? If so, what is your evidence?
Also, are you suggesting that Behe would make similar claims? if so, what is his evidence?
So? Do you know the mechanism of restorers? How can this be in any way relevant to Behe’s Edge of Evolution?
So? Is Behe’s argument being reduced to a special case that is so contrived as to be irrelevant to virtually all of biology? Do you think Behe would make the distinctions that you are trying to? Could you ask Behe for us?
Yeah, females are evolutionary dead ends.
What is your point, PaV?
I can’t highlight anything you’ve written. What’s up?
“Anyone who reads this paragraph will see immediately that White is proposing the existence of a third gene, unidentified to this point.”
Let’s say you’re right about this, what does this then have to do with the “initial” CQ resistance which is the object of Behe’s CCC?
White brings up the issue of PfDMR1 mutations because SP and Verapamil both reverse the “initial” CQ resistance. So, if you have a malarial strain that has become resistant to CQ, SP or Veparamil can both be used against that strain. I’m sure this is good news for medical doctors and those treating malaria throughout the world. But, genetically, this is NOT the “initial” response to CQ by a malarial strain, the situation that Behe addresses in his book and in his use of the CCC. Further, notice that White says that the PfDMR1 mutations affects the “in vitro” situation, not the “in vivo” situation to which White applies his 1 in 10^20 calculation. White ends his sentence saying that “the role of PfDMR1 mutations in determining the therapeutic response following chlorquine resistance is unclear. Then in the next sentence White says that “[a]t least one other gene is thought to be involved.” Involved in what? It seems certain he means “involved” in the “therapeutic response.” Finally, White states very directly that “chlorquine resistance in P. falciparum . . . is initially conferred by mutations in a gene encoding a transporter (PfCRT).” When White makes his 1 in 10^20 calculation, it is based on these PfCRT mutations, and NOTHING ELSE. There’s no mention whatsoever of SP, Veparamil, or “in vitro” findings. You might not like that, but unless, and until, White tells us that his calculation is based on more than those two PfCRT mutations, it is inutile to postulate that “more” than the PfCRT gene is involved in “initial” CQ resistance.
In your second post, you say:
“The quote you think rescues Behe from my criticisms has to do with resistance to an entirely different drug. Behe’s magic number, 10^20, has nothing to do with resistance to sulfadoxamine-pyrimethemine . . .”
Remarkably, you’ve missed the entire point I was making. The paragraph that you’ve taken this quote from begins this way:
Yet, White talks about “single point mutations” having an in vivo probability of 1 in 10^12.
So, White is saying this: (1) since the “in vivo” probablity of making an a.a. substitution (i.e., a ‘single point mutation) is 1 in 10^12, AND, since 10^13 malarial parasites are produced in a single malarial infection, then resistance to certain drugs which involve only a ‘single’ a.a. substitution/genetic event on the part of P. falciparum would be quite prevalent; (2) the ‘calculated’ probability of CQ resistance is 1 in 10^20. Therefore, this MUST involve more than a ‘single genetic event’. And this “may” mean that another gene is involved. (Or, it may simply be limited to the ‘two’ a.a. substitions at positions 76 and 220 that P.falciparum, in fact, develops.)
Now White does say another gene “may” be involved, but, at the time of his 10^20 calculation, this wasn’t known (I don’t know if anything has come out since 2004 on this, do you?). Let’s assume that another gene was involved, and that it, too, needed two a.a. substitutions for CQ resistance to develop. We now have 4 a.a. substitutions arising in 10^20 replications. What mammal species ever had that many replications in its entire history? This is still paltry. And, in fact, in response to what Ian Musgrave wrote about HIV’s vpu, Behe refined his Table 1 or 2, whichever it was, to reflect 4 a.a. as the “edge of evolution”.
This is like the man who says that the football that came flying out of Giant Stadium couldn’t possibly have been thrown by Ellen de Generes because Ellen de Generes can only throw a footbal twenty feet; to which you then respond, “Your entire logic is wrong. In fact, Ellen de Generes can throw the football 40 feet.” I don’t really see how 4 a.a. now solves a situation where maybe a twenty a.a. substitutions are needed for realistic evolutionary progress to take place. Remember that Behe says that most protein binding blocks involve at least 10 proteins, and that this represents a minimum for biochemical processes. It’s easy to disrupt a process; but much harder to ‘build’ one from scratch.
Concerning Turf13, I wrote:
its effects, in the case of csm-T, can be reversed by nuclear DNA products
To which you respond:
“So? Do you know the mechanism of the restorers? How can this be in any way relevant to Behe’s Edge of Evolution?”
Have you thought this phenomena through yet? If nuclear DNA can reverse what are essentially recombinant events, then this is NOT a random event. Hence, we are forced to ask if the mitochondrial recombinant events are ‘random’ in the first place?
Behe deals with random genetic events. And, he deals with “progressive” evolution, which, despite what you and Dave Wisker write, is, in the case of male “sterility” a ‘regressive’, not a ‘progressive’ event. I suppose that Darwinists would say that male sterility renders a male more “fit” to be a eunoch. Sorry, but most males aren’t interested in being eunochs.
Thus, isn’t this just a case of comparing apples to oranges?
From what we know, that which happens between the malarial parasite and anti-malarial drugs is classically a case of NS at work. How the mitochondria came about, how its recombinant events occur, and how they’re reversed, is NOT clearly a case of NS at work. We, indeed, don’t know with certainty how the mitochondria arose. We can’t do an experiment where this thesis can be tested. So we can’t therefore claim that it was a case of NS at work. This is simply begging the question.
I dunno. The blockquote, b, i tags all work for me.
I don’t run wordpress, I just use it.
No, White is not saying this. You, PaV, like Behe, are putting words in White’s mouth.
The figure 10^20 is mentioned only in the context of the origination of a multigenic trait, one component of which is PfCRT. The honest and accurate statement that Behe (and other antievolutionists) should be making is that this figure represents a possible limit for the occurrence of this particular multiple mutation, and that the figure should be revised in the light of more work on PfMDR1 and the unidentified third component of the durable resistance White is discussing.
But we’re not gonna see that, are we?
About nuclear restorers:
Um, nuclear restorers do not reverse the recombinations that give rise to cms-associated genes. They encode other proteins that mediate the rather specific breakdown of the RNAs encoded by cms-associated genes.
Curiously, PaV, in bringing this subject up, you give us yet other examples of violation of Behe’s rule. Nuclear restorers are RNA-binding proteins that have changed to acquire new specificities. In other words, more “CCC’s”. More things that Behe asserts cannot possibly arise in nature (or at the hands of breeders, for that matter).
The disconnect between Behe and reality is indeed stunning.
No matter how you phrase it, PaV, you are claiming that femaleness is a dead-end, regressive trait. I can’t wait for Behe to make that claim on the witness stand (or in a truly open forum, where he can be challenged).
As for “progressive” traits, here is what Behe says:
In case you haven’t been paying attention, PaV, the essay we are commenting about explains how T-urf13 is a coherent, complex system in every sense that Behe laid out in DBB.
Beyond that, this niggling about “progressive” and “regressive” makes no biological sense. To illustrate, I extend a challenge to you, PaV. Your task is to identify a “coherent, complex system” whose origination, biosynthesis, and/or function is not directly impacted by “regressive” activities. (In case this is unclear, the challenge is to identify systems that are not impacted by ubiquitin and/or microRNAs/siRNAs.)
This whole “progressive/regressive” ploy is a cheap attempt to define away a problem instead of actually addressing it. In other words, it’s sophistry, not science.
Arthur, you wrote:
“The honest and accurate statement that Behe . . . should be making is that this figure represents a possible limit for the occurence of this particular malarial mutation, and that the figure should be revised in the light of more work on the PfDMR1 and the unidentified third component of the durable resistance White is discussing.”
I don’t think you’re disputing White’s figure of 1 in 10^20. That’s not a problem. I pointed out in the last post, to which you were responding, that a “single genetic event” has a probability of occurring of 1 in 10^12. [“The single point mutations in the gene encoding cytochrome b (cytB), which confer atovaquone resistance, or in the gene encoding dihydrofolate reductase (dhfr), which confer pyrimethamine resistance, have a per-parasite probability of arising de novo of approximately 1 in 10^12 parasite multiplications.”] I don’t think you would dispute this either. Now, when White states this: “As the probability of multigenic resistance arising is the product of the individual component probabilities, this is a significantly rarer event. P. falciparum parasites from Southeast Asia have been shown to have an increased propensity to develop drug resistance,” then, obviously, he’s expecting something more than the 1 in 10^12, and he’s very likely saying that in the case of CQ, with its associated 1 in 10^20 rate of occurrence, “more” than one gene is involved. His mention of the PfDMR1 gene in this context suggests this. Nonetheless, the 1 in 10^20 probability is (1)”in vivo”, not “in vitro”, and therefore the “in vitro” effects of SP and VP on the PfDMR1 gene are only “possibly” involved, and (2) White says that “it is thought”, not “it is known”, that an “as-yet unidentified gene is involved.”
Isn’t the really “honest” answer this: CQ resistance, which is known to involve two critical a.a. substitutions in the PfCRT gene, has an “in vivo” probability of arising of 1 in 10^20. But an “as-yet unidentified gene may be involved”, and so the total number of a.a. substitutions involved in CQ resistance “may” be higher?
And, of course, as I put it in the post you’re responding to, let’s be generous. Let’s say, definitely, that another gene is involved, making the 1 in 10^20 probability correspond to 4 a.a. substitutions. Again, 1 in 10^20 replications is more than the total number of any mammal species that has ever existed. How does this make any real difference when it comes to the “limits” of evolution?
Arthur, in your next post, you wrote:
“Curiously, Pav, in bringing this subject up, you give us yet other violations of Behe’s rule. Nuclear restorers are RNA-binding proteins that have changed to acquire new specificities. In other words, more CCC’s. More things that Behe says cannot possibly arise in nature (and at the hands of breeders, for that matter).”
I’m obviously no expert in ‘csm’, nor do I have any desire to become one. In what little I’ve read since you’re last post, it seems that what happens in male sterility is the mutation of a particular mitochondrial protein through various recombinant events, resulting in mitochondrial death, which in turn cause the death of the male pollen cells. Now you may not want to talk about “progressive” versus “regressive” mutational events, but when the mitochondria ‘mutates’ in such a way as to be lethal, I don’t consider this progress.
The nuclear restorer then comes along and cuts off the transcription of the very protein that befire caused the mitochondria to ‘die’, and so, male fertility is now restored since the pollen no longer die.
So, what are we looking at? We’re looking at a protein that goes haywire, and which is then ‘cut off at the pass’ by nuclear DNA. The only “new” function is a lethal function. Is this how “progressive” evolution takes place, through the rise of lethal functions?
Here’s your task. Demonstrate how a “coherent, complex, system” came into existence through random events.
What’s more remarkable, that an organism loses its use of eyesight, or the origination of eyesight? I think you can see that there’s a real big difference between “progressive” and “regressive” events.
I think we just happen to see the same things in very, very different ways. I don’t think there’s much of a disagreement about ‘facts’, it’s the interpretation that is fundamentally different. On this, it’s hard to see how either of us is going to convince the other. Pace.
Three replies in one comment:
PaV, why do you ignore PfMDR1? That was also mentioned in the paragraph Behe misrepresents, and it is not the unidentified gene mentioned by White.
So you reject the notion (well-established) that cell death is an important and positive contributor to the development of new tissues, limbs, and organs.
We’ll add this to the list of well-established facts that you choose to ignore, or re-write, or wish away.
We’re not talking about loss of eyesight. We are talking about the evolutionary transitions between different modes of sexual reproduction.
Well, PaV, when your interpretations cause you to equate females with eunuchs, when they lead you to the conclusion that femaleness is a regressive condition and an evolutionary dead end, when they evoke statements to the effect that the well-established mechanisms that contribute to numerous aspects of animal development are regressive and not positive contributors to the animals survival and well-being, then I would agree that there is little hope for you. It does amaze me, though, that your defense of Behe as if his books are sacred scripture will bring such incredible statements from your keyboard.
Comments en passum:
Two reasons: (1) PfDMR1 involves treatment with either SP or VP. We’re talking about CQ resistance. If you introduce another drug therapy, and another gene becomes involved, why would you find that surprising? (2) this is an in vitro, not an in vivo effect. (I’ve now said this three times)
In all of this, the only really important aspect to me is the accumulation of “information” through evolutionary means. In this regard, the mitochondrial route of transitioning from male to female maize involves only the “loss of information” on the part of the mitochondria, to the point that it becomes lethal. The “restoration” of maleness involves a “reduction” in the defective information that this “evolved” (in your opinion) mitochondria produces, rendering this “evolved” mitochondria less lethal.
(1) When femaleness in maize is brought about by the loss of maleness, then we’re seeing something in the plant kingdom that we don’t normally see happening in the animal world. In the animal world, the loss of maleness would be equivalent to something like what being made a eunoch is. This is only outrageous in your mind, but not outside of it.
(2) Where did I say that femaleness is a “regressive condition”? This is you putting words into my mouth. I did say this is an example of “regressive” evolution. Why? Because, again, I only see a ‘loss’ of information, not the generation of new information. To me, this is what is critical in understanding biological reality: how is new information brough about. We live, after all, in the “Information Age”. This is what I’m always looking for. Let’s face it, even in the case of the CCC in the PfCRT gene, this is basically a dimunition of function–but it does solve the threat of CQ.
(3) As to loss of function and its ‘regressive’ aspect: tell me, do you need blueprints for tearing down the outside of a wall so that a new bedroom can be added? Do you catch my drift?
Before I respons, let me point out that I still cannot copy and paste text from your post–which makes this repartee entirely to tedious. So, I’ll just leave off with this last statement.
I don’t consider Behe’s books as sacred scripture. But what about you? Is the “Origins” sacred to you? How is it that a book that is so wrong about so many fundamental expectations on the theory is still even talked about? Wrong about the age of the earth. Wrong about the fossil record. Wrong, in great part, about sterility. Wrong about how inheritance works. And so forth. But there are ways in which Darwin was correct. But as a theologian said of Darwin and Wallace’s presentation at the Linnean Society in 1858: “In what is correct, nothing is new. In what is new, nothing is correct.”
But that’s not the point here. Behe published his book two years ago. Who has effectively debunked it? No one. You have NS at its fiercest with P. falciparum vying with chlorquine. And with 10^20 replications, what do we find? Two a.a. substitutions. We’re basically NOT seeing NS working. We’re seeing an effect brough about by completely random events–neutral evolution, if you will. But, as we can see, neutral evolution doesn’t get you far. I just can’t see here any kind of robust system of informational change. And I think it is only via informational mechanisms that evolution can take place. Pace.
Not true. And I don’t see how you can possibly get this from the paragraph Behe misrepresents.
Well, if you recall, we are talking about Behe’s pronouncements. As far as I can tell, whenever Behe makes claims about “information”, he is speaking about proteins. And, as the example under discussion shows, new information that far exceeds Behe’s “limit” can and does arise via random natural processes.
How can the addition of a new irreducibly complex gated ion channel be considered to be a loss of information?
How can the evolution of a new RNA-binding specificity be considered a “loss of information”?
As far as I can tell, PaV, you’re just making up new terms and shifting goalposts madly, all to avoid the obvious implications.
The fact is, the core of Darwin’s theory – all life shares a common ancestry, and all life evolved via descent with modification, with natural selection acting on the variability that arises randomly – is correct. After all these years, these central themes remain intact.
(Well, I guess we can add genetic drift to natural selection as a means to fix random variation in living things, but you know what I am getting at.)
Yeah, right. No Behe supporter has even come close to refuting the essay under discussion here. Heck, Behe hisself refuses to address this case (or others that I have discussed).
You must wonder – why won’t Behe engage a biochemist in discussion on this matter? I know why – it’s because he’s wrong and he knows it. He isn’t about to let a peer rain on his gravy train.
Wrong. As has been shown repeatedly. Why do you insist on ignoring White’s own words?
Surely you jest. NS is not the reason that resistance spreads through populations of the parasite?
Hmm.. are you suggesting that NS is the source, the driving force that causes mutation?
I am pretty sure that other of my essays on this blog, as well as other examples from discussion boards, would lead you to contradict yourself. (Heck, you’ve done that with T-URF13, with your incredible statements regarding the modes of sexual reproduction in plants.) That’s because you have a model of evolution and a perception of information that are both out of touch with biological reality.
The concept of genetic drift and neutral variation was actually not lost on Darwin, as this passage clearly illustrates:
Arthur, if we can’t get the facts straight, how can we ever hope to reach some kind of reasonable conclusion? In response to my saying that PfDMR1 should be ignored because it involves the use of VP or SP, you say, “Not true.” Really?
In a 2007 ‘minireview’, (http://www3.interscience.wiley.com/cgi-bin/fulltext/118546650/PDFSTART) John Hyde writes:
If PfCRT is named after its resistance to chloroquine, and, if the “key” a.a. change is at one site, why are you going on about PfMDR1? Hyde, in the same article, also tells us that MDR stands for “multi drug resistance”, which means that though it might develop resistance to CQ, it also develops resistance to other drugs and, hence its resistance cannot be considered CQ specific.
As to T-URF13, here’s some quotes from an article:
Isn’t it clear that T-URF13 very likely involves a “loss-of-fucntion” scenario, and, hence, shouldn’t be viewed as an evolutionary “development”?
Sorry, a ‘blockquote’ got cut out and the two quotes run together. There’s a little bit of my writing between the two longer quotes.
I fixed the blockquotes (I think).
Not even close and you don’t get tell me what I am claiming.
T-URF 13 is so useful they stopped using that strain due its suscepitibility to fungal toxins.
Also Darwinian processes didn’t have anything to do with its “evolution”.
But again you have been told this and will continue to ignore it.
I understand his position- you haven’t even demonstrated an understanding of his claims.
I looked up the Levings, 1993 paper that PaV referred to:
“Furthermore, cross-linking studies show that URF13 exists as monomers, dimers, trimers,
and other oligomeric structures in the membrane. A relationship between CMS and the structure of URF13 in the membrane, however, remains unclear.”
1. Are we sure that URF13 must exist as an oligomer in order to produce CMS?
2. Does URF13 function as a gated channel, absent the pathotoxins?
Also, from this paper,
“Mitochondrial genomes are models for recombination dynamics. There are hundreds of copies per cell, and, as such, they can undergo a wide range of recombination events through direct and indirect repeats. Hence, mitochondrial DNA is essentially a polyploid genome, sustaining deletions and duplications, with little consequence to the general viability of the organism.”
This sounds similar to the part of the immune system that produces anti-bodies. If so, then mitochondrial genomes would not be representative of nuclear evolution.
Thanks for stopping by. As far as your questions are concerned:
1. I am not sure we know for sure the answer to that question. I would guess than the answer is yes, but that’s just a guess based on my expectations for how an ion channel might assemble in a membrane.
2. The pathotoxin is the “key” that opens the gate. So the protein is still a gated ion channel, just closed.
(3) Plant mitochondrial genomes certainly have features that stand them apart from nuclear genomes. But I am not sure I would rule out all relevance. In the instance of interest here, for example, we can take home the message that genome shuffling, in organelle or nucleus (or bacterial genome), has the potential to generate completely new functional proteins.
Art…I mean Prof. Hunt…I mean….darn it! Now that I know you’re a professor, I feel I should be addressing you as Prof. Hunt. Do your students know that you like sports? Could that ruin your reputation?
2. Anyway, back to the subject. Cornelius Hunter seems to think that the URF13 complex functioned as a gated channel, prior to the pathotoxin key. But I can’t find any literature that even suggests that. Do you know of any?
3. Maybe we can’t rule out all relevance of mutations in mitochondrial genomes for understanding evolution of nuclear genomes, but now the burden of proof seems to shift to you to show how relevant it is.
Well now I’m damned curious about the function of URF13, regardless of whose side it helps. An article that speculates about it:
Click to access cms.pdf
“Another possible mode of action of URF13 is by the same mechanism that results
disease sensitivity–that is, an anther-specific compound interacts with URF13 to
permeabilize the inner mitochondrial membrane. This anther specific compound would
have similar properties to T-toxins and methomyl, but must be limited to the anther so
that other cells function normally. However, the anther specific compound has not yet
been isolated–though some evidence it exists. For example in trangenic tobacco, even
when URF13 was targeted to the mitochondrial membrane, the plants failed to show male
sterility, possibly due to the absence of the factor to cause the pore formation.“
Bilbo, if you start calling me Prof, I’ll ban you 🙂 .
Yeah, everyone knows I like sports. A long time ago, I gave a talk at Mich State. Instead of taking me out to eat in the evening, my hosts got me into the student section at an MSU basketball game. It was perfect hospitality.
I believe that you are doing fine on your own when it comes to how T-urf13 may be working during pollen development. As far as the relevance of this to nuclear genes, I guess we need to keep our eye on the prize. This example shows that random sequence rearrangements can yield functional proteins with a relatively high frequency. While nuclear genomes may not be so promiscuous at the gymnastics we see in plant mitochondria, they bring to the table other, equally versatile modes for scrambling genetic information – things like exon shuffling, recombination, “creation” of transcribed sequences, etc. The lesson of T-urf13 is that any mode of “deck shuffling” may lead to new proteins.
I would also note that T-urf13 is directly applicable to bacterial genomes, and that what we have seen in corn is a likely explanation for the origins of at least some of the ORFans that so captivate people like Paul Nelson.
Some more questions:
1. Does the heteromeric arrangement of URF13 proteins necessarily mean that there are at least two binding sites? I found an article that suggested that they were binding at the same subunit. I can reference it later.
2. Behe argues that foreign proteins can bind more readily to cellular proteins than other cellular proteins can. I can reference this later, also. So he would reject the pathotoxin binding as either being part of an IC system, or as being a second or third binding site.
3. So minus some other evidence, we may have only one binding site for URF13.
About your latest questions:
1. There is no way that a protein that has a single self-interaction site can form a multimer larger than a dimer. You can see this by taking a bunch of, say, ping pong balls and putting a single dot (representing the single binding site) on each of them. If you do so and try to arrange them such that the dots on each ball touch each other, you will see that the only arrangement that is possible is a dimer. To get higher-order multimers, you need at least two sites on each ball.
2. Behe is just plain wrong when it comes to his assertions about “foreign” vs. “cellular” proteins. Heck, his claims would effectively rule out half or more of all gene regulatory mechanisms. (Google search term – E3 ubiquitin ligase.) As for the suggestion that pathotoxin binding is not really part of an IC system, you need to recall that Behe wrote an entire book around an analogous small molecule-protein interaction (between antimalarials and their target). You also need to recall that, in DBB, Behe explicitly included the key to a gated ion channel as part of the IC system. IOW, if Behe were to argue as you do, he would be contradicting his own claims.
3. No, there are at least three “CCC’s” in T-urf13. As my responses to 1 and 2 indicate.
1. I guess I’m not clear on the meaning of “binding-site” as used by Behe. If it means the place where two proteins bind to each other, then URF13 has one binding-site: the place where URF13 binds to its copy. If it means the place on a particular protein that allows it to bind to another protein, then URF13 has two binding sites. I suspect that Behe means the first definition. For example, he rules out sickle hemoglobin as being able to bind to itsef as an example of two binding-sites. Though later he talks about sickle hemoglobin being able to develop the ability to bind to itself because: (a) 90% of the blood cell is made up of it, allowing more frequent contact; and (b) because hemoglobin is symmetrical (p.150 of EoE). So maybe he’s equivocating. I’m not sure. One of those many questions I’d like to ask him about someday.
So temporarily at least, for the sake of argument, I’m willing to assume that URF13 has two binding-sites.
I’m not yet willing to grant the third binding-site. I tried googling E3 ubiuitin ligase, but I didn’t understand it. I think you’re point is that some regulatory proteins need to bind to a more general class of cellular proteins, or they won’t work. OK, but wouldn’t that be the exception to the rule? Behe’s argument that foreign proteins will more readily bind to cellular proteins still sounds pretty strong. Interestingly, Behe never discusses in detail how foreign proteins evolve to bind to other proteins. As far as I can recall, all of EoE involves cases of organisms breaking their own machinery so that foreign proteins or organisms can’t work.
So I’m not granting the third binding-site…yet.
As to the gated ion channel: Here’s where I think it would help if we knew how the URF13 oligomers worked to cause CMS (assuming that was their selective function). Are they gated ion channels that are activated by cellular proteins and allow the contents of the mitochondria to leak out, causing CMS somehow? If so, then we certainly have a very sophisticated system, IC or not. I think Behe might argue that it isn’t IC, since the gate and the channel are the same protein (or its copies). Still, I think the sophistication of the system would be a stiff challenge to his claims.
But what if the URF13 monomers and oligomers cause CMS not by being a gated ion channel, but some other way, such as acting as a plug that slows down mitochondrial activity? And there are no cellular proteins that interact with the URF13 oligomer to open a channel? In that case, there is no sophisticated system, IC or not.
Now even if the URF13 oligomers aren’t originally a gated ion channel, don’t the pathotoxins make them into one? Yes. Does that mean we now have a sophisticated system, IC or not? I think we’re at least back to the foreign protein debate, here. But possibly more. I think Behe’s point was that IC systems were difficult to evolve within an organism. I think his idea was that IC systems provide a selective advantage for the host organism, but were difficult to evolve. The idea of a foreign organism being able to take advantage of the machinery of the host organism, or that by providing one of its own parts a foreign organism turns the host organism’s parts into a (IC) machine doesn’t seem to be what Behe was referring to. Is that relevant? Wouldn’t the probability calculations still be the same? What are the odds of a foreign protein turning the URF13 oligomer into a gated ion channel? Isn’t that what Behe needs to account for? Maybe. I’m not sure. But we still have Behe’s foreign protein exclusion.
So I’m not granting sophisticated machinery, IC or not…yet.
I’m having a tough time with the notion that a protein with a single self interaction site must be limited to dimer formation at most. I see the ping pong ball analogy – and how stearic hindrance would force this result. But what if the protein had a side chain with the interaction site on it. I’m certainly not a protein chemist, but I’ve seen cartoon images of membrane proteins with carboxy terminals that stick out of the membrane (usually for signal transduction purposes) and for all the world could be mistaken for an octopus’ leg. So lets put our recognition signal out there on the arm… so now the core of the protein body won’t provide a block to the approach of more than one other similar molecule.
Now if the recognition signal has a complementarity aspect to it (like DNA where bases on one strand have to be matched by their complement on the opposite strand) then perhaps we’re still stuck to the dimer limitation. But in proteins the amino acid motifs that allow for attractions and chain interactions are not always complementary. While I don’t have a specific motif that I can point to that would serve my point I can imagine it possible to have a sequence that would interact with another motif slightly down the chain. Imagine a hand recognizing the wrist on a second arm. If the ‘hand’ at the end of one protein arm attaches to the ‘wrist’ of another protein then the hand on the second is free to attach to the wrist of a third protein (now we have a trimer) and if these theoretical arms are long enough to avoid the stearic hindrance from the core of the protein this process could continue to build a tetramer or even larger group.
Too far fetched? I did Google E3 ubiquitin ligase and took a look at Li and Zhang’s review in Cell Division 2009, 4:2… and they talk about a destruction box motif RxxLxxxxN/D/E that is a recognition factor. True this particular example is not for recognition between two homologous proteins (though different APCs may actually target each other for destruction, but thats another issue). My only point here is that with such a long motif it seems to me that a hand and wrist type analogy seems as plausible as the ping pong ball model.
If I were Art, I think I would respond to the hand/wrist analogy as follows: The hand is one interaction site, the wrist is a second interaction site. My question would be, does a binding site mean the same thing as an interaction site (in which case there are two binding-sites), or does it mean the place where two intereaction sites interact (in which case there is one binding-site)? And which one did Behe mean?
I’m sort of thinking that I have confused you such that you are thinking about E3’s in the same context as polyketide binding. I apologize if that is the case.
My point in referring to E3’s is best made in responding to another of your comments:
!! Exception to the rule??!! If anything, E3-target binding is the rule. There are many hundreds or thousands of different E3’s in a eukaryotic cell.
As for Behe’s argument, I would point out that Behe offers precisely zero evidence to support his assertion. In contrast, antibodies, E3’s, defense-related receptors in plants, and likely many other examples tell us that protein-protein interactions involving nothing but cellular components are quite evolvable.
Clem, I think I can see your point. But I don’t think it really pertains to Behe’s argument, nor to the refutation we are discussing here. Behe considers an interaction site to be one that involves a very small number of amino acids (perhaps as few as two). As Bilbo points out, you have described a case involving more than one site.
As for Bilbo’s last question, it doesn’t really matter what Behe would try to claim in order to avoid the insult I have made to his ideas. If he is going to try and argue that a single interaction site can simultaneously bind (in identical fashion) two additional subunits, the he is in essence enlarging the site to encompass much more than a single “CCC”. Which in turn renders his revised definition subject to the same argument (and refutation) that I have been making.
Just so we don’t lose sight of things, remember that Behe is claiming that more than one “CCC” is beyond the grasp of natural genetic “forces”.
Bilbo, you said:
That’s what work done with the protein in yeast and E. coli tells us.
A long time ago on the ISCID boards, Jed Macosko made the statement that single polypeptides can be IC. I would love to hear Macosko and Behe duke it out over this point.
Also, if Behe is going to be claiming that a single polypeptide cannot be IC, then he is going to have a hard time with the bacterial and mammalian fatty acid synthesizing systems.
At first blush I don’t see an immediate application of my hand/wrist junction to this debate with Behe either. But so long as I’m playing with a hypothetical protein (for I have no experimentally verified protein system to point to) why can’t one (or possibly two) amino acid changes in a sequence modify the protein chain in a manner that it begins to recognize a piece of its own sequence up or down the chain… a piece of already existing sequence – thus requiring only one (or possibly two) mutations and not actually generating a second site de novo?
Similarly one might hypothesize a deletion – in phase (3, 6, 9 bases) – so that a sequence of amino acid(s) is cut from the protein resulting in bringing a few formerly separated aa residues closer together and generating a sequence that acts to recognize a cite up or downstream on the protein backbone as described above? This deletion would be one event.
Likewise an in phase insertion could create the same phenomenon. So with three potential “single event” mechanisms to create the hand/wrist protein cite(s) it seems there is actually a better chance for this to occur (hypothetically).
Just a thought.
Happy Holidays all!
thankful i came across your page
This is so stupid. No one knows if blind and mindless processes did it. And THAT is the question. There isn’t any evidence that T urf 13 arose via blind and mindless processes. ID says that organisms were designed to evolve and recombination is a designed process