Perhaps you saw this article from The New York Times last week. It describes some significant new findings in protein evolution:
In work published last year, Dr. Thornton reported how his group reconstructed an ancestral protein of two hormone receptors found in humans. The two, once identical, diverged along different evolutionary paths. One is now part of the stress response system; the other is involved in different biological processes, including kidney function in many animals.
In the new study, the researchers determined the exact positions of more than 2,000 atoms in the ancestral hormone receptor. The receptor existed in animals that lived more than 440 million years ago, before the last common ancestor of people and sharks. Then the researchers examined what occurred during the next 20 million years -- before another split of the evolutionary tree that led to bony fish. “That's the ancestor of you and a salmon,” Dr. Thornton said.
Alas, the paper is not currently freely available online.
The article goes on to describe how the researchers were able to pinpoint specific mutations that allowed the protein to develop different functions in different evolutionary lineages.
Of the glucocorticoid receptors that have been looked at in different species, five specific mutations are always present and distinguish them from the ancestral receptor. When the scientists introduced the five changes into the ancestral protein, they expected that it would be transformed into a glucocorticoid receptor.
Instead, the protein broke, unable to bind to any hormone.
On further investigation, the scientists found that two other mutations, which had negligible effects by themselves, strengthened some of the protein's folds so it could withstand the other five mutations. The researchers were also able to show several sequences in which the seven mutations could have occurred without the protein's functionality ever deteriorating.
Fascinating stuff! Science Daily offers further details.
The significance of this work to evolution / ID disputes is clear. The fact that proteins can get co-opted to perform novel functions is one of the major fallacies in Michael Behe's notion of irreducible complexity, a fact that has been pointed out to him many times. Behe's reply has generally been to mock such scenarios as implausible. For example, in anticipating this objection in Darwin's Black Box, Behe wrote:
For example, suppose you wanted to make a mousetrap. In your garage you might have a piece of wood from an old Popsicle stick (for the platform), a spring from an old wind-up clock, a piece of metal (for the hammer) in the form of a crowbar, a darning needle for the holding bar, and a bottle cap that you fancy to use as a catch. But these pieces couldn't form a functioning mousetrap without extensive modification, and while the modification was going on, they would be unable to work as a mousetrap. Their previous functions make them ill- suited for virtually any new role as part of a complex system. (p. 66)
This was already an absurd analogy when Behe first devised it in 1996. The present work makes it simply laughable. It has long been known that proteins can acquire novel functions through evolution, but the level of detail here is simply astounding. Courtesy of this new work, we now have a mutation by mutation account of how an important protein acquired a new function. This shows plainly that one of the major processes offered in refutation of Behe's arguments about irreducible complexity really is workable in practice.
This is how it always goes in dealing with creationists. They make grand pronouncements, based on nothing, about what is possible and what is not. Then the normal march of scientific progress shows them to be utterly wrong. When this happens, they immediately set about the task of explaining that the new work showing that X is possible in no way undermines their earlier contention that X is not possible.
So here's Behe trying to explain away this work. Here's his opening salvo:
A recent New York Times story by Kenneth Chang touted a new paper in Science by the laboratory of Joseph Thornton of the University of Oregon as refuting intelligent design. Thornton's laboratory has been interested in the evolutionary development of differences between two proteins abbreviated GR and MR. Since the two proteins are very similar, and since they bind very similar small hormone molecules, they likely developed from an ancestral gene by gene duplication and subsequent diversification. Despite Chang's story, none of that challenges intelligent design, which agrees that minor evolutionary changes can happen by random mutation and natural selection.
Sadly, there are at least two big flaws in this paragraph. The first is that “intelligent design” is not the sort of thing that makes empirical claims about what is and is not achievable by random mutation and natural selection, or any other evolutionary mechanism for that matter. Beyond some bald assertions that certain “irreducibly complex” biochemical systems could not have evolved naturally, ID offers no guidance at all on any empirical question of interest to biologists. His conclusion that the findings of Thornton and his coauthors represent minor evolutionary changes is not based on any rigorous notion of how we distinguish minor from major changes. Rather, it is based solely on Behe's need to dismiss any and all data contrary to his blinkered biological opinions.
Second, Chang did not say these findings challenged “intelligent design.” He was far more focused than that:
Supporters of intelligent design, who question evolution, have argued that mutations, occurring one by one, could not refold a protein into a new function, because the mutations would first unravel the protein into a useless, unfolded configuration.
The new study refutes that assertion, at least in this instance.
Exactly right.
Moving on, Behe offers up the following summary of what the researchers here actually did:
The gist of the new paper is that the workers reconstructed in the lab what they thought would be the ancestral protein, as well as several later evolutionary versions of it. To get to a protein mimicking modern GR, they purposely introduced several mutations to the ancestral form. The first few mutations took the protein's activity part of the way toward the modern activity. But adding several other mutations that they thought would increase the specific activity to that of modern GR unexpectedly caused the protein to lose all its ability to bind the hormones. So, after thinking awhile, the authors then went back and intentionally introduced other mutations which did not affect hormone binding, but which they hoped would strengthen a particular part of the protein. After deliberately strengthening that part, they found they could add the final mutations, the protein would retain its activity, and its activity would be much more similar to modern GR.
This is a very misleading way of putting things. Behe is keen on describing things in a way that puts maximal emphasis on the role of human design in achieving these results. But the researchers didn't just introduce several mutations. They first reconstructed the most likely form of the gene ancestral to those coding for modern GR and modern MR proteins. They did this by applying standard statistical techniques to a large sample of known variants of these genes in modern organisms. They then used known phylogenies to discover mutations that occurred during the time period in which the evolution of these genes was thought to occur. It was this process that led them to the appropriate mutations to investigate, not just some process of intelligent cogitation.
Likewise, when their initial hypothesis about the effect of the mutations did not pan out, they did not just think awhile and conjure up some new ones to try. Instead, they deduced that certain “permissive mutations” (that is, mutations whose occurrence mitigated the harmful effects of introducing the previously discussed substitutions all at once) must have occurred, and by a series of clever experiments were able to zero in on where those mutations were.
In other words, they weren't just trying out mutations willy-nilly. They were using a large data set to guide them to where the mutations had to be. This is what elevates their evolutionary hypothesis above the level of a just-so story, and gives it a solid basis in empirical fact.
But Behe is just getting warmed up:
Now, dear reader, can you guess which parts of Darwin's theory this all neglects? Of course -- both random mutation and natural selection. The workers nicely showed it is quite reasonable to think that the one ancestor protein could produce two descendants, but they didn't even try to address the question of whether it could happen by chance plus selection. Of course, getting a single amino acid mutation by chance is not a problem. But in order to have the mutation be positively selected, it has to benefit an organism. The authors (and news stories) completely ignore that -- the authors didn't measure whether duplicating the ancestral gene, and then modifying it, would benefit an organism that was used to relying on just one protein (admittedly that would be hard to do). What's more, in order to be confident that a multi-mutation scenario reconstructs a Darwinian process, all subsequent mutations have to be positively selected, too.
Of course, that final sentence is totally false. Mutations do not have to be positively selected to persist in a population. They could be neutral, or even slightly deleterious, and still persist. Such mutations might be of small consequence when they occur, but if they later combine with other mutations to produce a beneficial effect, then selection can act on the whole complex.
It is simply absurd to say that the scenario described in the paper leaves out the part about random mutation and natural selection. The mutations described by the authors are of standard types (mostly just simple substitutions), and all are known to occur randomly in great abundance. Furthermore, the authors were able to describe in great detail the effects of each of the mutations. One need only hypothesize a scenario in which those effects were beneficial (not hard to do) and you have your evolutionary scenario.
Behe demurs:
But they aren't. Although they test none of the mutations in actual organisms, the authors themselves feel that the very particular mutations they deliberately introduced, which strengthen the protein but don't affect hormone binding, would have been neutral. That makes those mutations much, much less likely to spread in a population, to be available later for when the beneficial mutations came along. In other words, the authors themselves think the scenario involves a big stroke of luck. In the New York Times Chang quotes Thornton: “'These very exquisitely adapted bodies we have represent a role of the dice,' Dr. Thornton said. 'And they could have turned out very differently.'”
Of course, Thornton said nothing about a big stroke of luck. He said merely that things could have turned out differently. And since the probability that a given neutral mutation will be present in a randomly chosen member of a population depends heavily both on the population size and the amount of time involved, Behe likewise has no basis for asserting that it is “much, much less likely” that such mutations would spread. (Incidentally, less likely than what? A slightly beneficial mutation? A strongly beneficial mutation?)
Behe tells us that this work establishes the plausibility of one ancestral protein giving rise to two descendants. But even though all of the mutations being hypothesized are very small and even though we have a good grasp on the phenotypic effects of the underlying genes, he finds it implausible that standard evolutionary mechanisms provide the explanation. Very well. What explanation does Behe prefer? Directed mutations? Divine intervention? How does an ID proponent make sense of this data? Here's Behe's answer:
Big strokes of “luck,” however, point much more to intelligent design than to Darwinism. If evolution were guided or designed to unfold in a particular way, then very improbable events would be expected to be packed into it. The bottom line is that, while the new paper is very clever work, it offers no support at all to Darwinism. If anything, the authors careful work points strongly away from randomness. If even such minor evolutionary differences as those between GR and MR are problems for chance-driven evolution, greater evolutionary difference are almost certainly beyond the edge of random evolution.
What? If the changes from the ancestral gene to the modern GR gene are part of the design of evolution, then they happened with very high probability, perhaps with certainty depending on the extent of the plan. And why, exactly, would we expect seemingly improbable events to be packed into “evolution by design?” A certain amount of chance is what you expect from a process based on randomly occurring mutations and selection in stochastically changing environments. If things are unfolding according to a plan, improbability is precisely what you do not expect to see.
Perhaps one of these days Behe will explain to us precisely what ID does, and does not, predict about nature. I'm not holding my breath.
A while back Michael Behe offered the following description of what sort of evidence he would need before accepting the naturalistic explanation over his preferred version of “God did it.” Not only would he need a step-by-step list of mutations...
...but also a detailed account of the selective pressures that would be operating, the difficulties such changes would cause for the organism, the expected time scale over which the changes would be expected to occur, the likely population sizes available in the relevant ancestral species at each step, other potential ways to solve the problem which might interfere, and much more.
It sure looks to me like the authors addressed all of these points in considerable detail. (With the exception of the population sizes, which is hardly the major sticking point here. Behe only included that one to make his list longer and more impressive.) But -- surprise! -- it still isn't enough. In fact, in Behe's world, when scientists produce a comprehensive, step-by-step, well-documented, evolutionarily feasible sequence of events through which a protein attains a novel function, it somehow ends up being evidence for design nonetheless. What a charming fellow.
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Oh well, I only have access to 8/3/2007 now, so maybe in a few weeks it will be available. Of course, that suggests that I could actually understand it all.... but then again, I'll still be heads and shoulders over Behe and the rest of his ilk.
Edit - dang, just noticed it's only the citations that I have access to. I don't think either work or school have current access. Oh well.
To simplify the attempts to convince Behe that Evolution by Natural Selection works without having to invoke God or an extraterrestrial Intelligent Designer:
Behe: it's impossible for two numbers to add up to 2.
Scientist: 1 + 1 = 2.
Behe: That in no way undermines my claim that it's impossible for two numbers to add up to 2.
Scientist: Furthermore, 0 + 2 = 2.
Behe: Okay, then, which is it? There must be an Intelligent Designer to tell us WHICH equation to use.
Scientist: Additionally, 3 + (-1) = 2.
Behe: Those are merely big strokes of "luck," and thus prove my point.
Scientist: By the way, 1.5 + 0.5 = 2.
Behe: That's microaddition, which proves my point that macroaddition is impossible.
Scientist: What do I need to show you before you'll believe that two numbers can add up to 2?
Behe: Not only would he need a step-by-step list of parameters and operations ...but also a detailed account of the arithmetical pressures that would be operating, the difficulties that changes in the parameters would cause for the equation, the expected time scale over which the equation would be expected to be solved, the likely population sizes of mathematcians available in the relevant university departments at each step, other potential ways to solve the problems which might interfere with solving the equations, and much more.
Scientist: I think I'll go teach differential equations to my dog. At least my dog is good company.
I don't know how many times I've had to refute this claim by Behe in online and other discussions with creationists; it is nice to have this solid piece of work to refer to. It would be great to have it in the TalkOrigins index!
Behe writes:
That makes those mutations much, much less likely to spread in a population, to be available later for when the beneficial mutations came along.
This is weird. Do we not know from neutral theory that neutral mutations are found widely in populations? It is common for neutral mutations to accumulate. Indeed if Behe seems to think that mutations are only likely to spread if they are beneficial then he obviously hasn't heard of Muller's ratchet, in which deleterious mutations build up over time (potentially leading to extinction of a species). It seems to me that Behe is pretty ignorant of a lot of evolutionary biology.
Great post, Jason. The more excellent research like this comes out, the more desperately you're going to hear Behe and Co. whistling past the graveyard.
You've got to wonder, does this guy realize that this is what he's going to be doing for the rest of his career? A university teacher essentially recommending ignorance and cynicism to the students he teaches.
What a disgrace.
It's also worth stating that this is kind of what you would expect from the imperfect evolutionary process, a neutral mutation here, maybe a deleterious mutation there (subsequently modified by epistatic effects to be of use). A messy process towards no particular fixed goal. So far so good. On the other hand, why would an intelligent designer work this way? Why on earth would he introduce a neutral mutation first rather than simply go along building things with nice neat helpful mutations?
Oh, I'm sorry, we're not allowed to ask these sorts of questions about the designer. My bad.
Looks like the goalposts are getting harder and harder to move.
All you people who insist that science and religion are compatible: take a good, long look at Michael Behe.
That's what happens when faith and science collide. Any argument, no matter how riduculous or factually incorrect, will be mustered to support the conclusion the 'scientist' knows is correct.
In a way, we have a lot to be grateful for. If Behe were a sophist, instead of a sincere and (in his own way) honest man, it would be a lot harder for most people to notice that his arguments are garbage.
All you people who insist that science and religion are compatible: take a good, long look at Michael Behe.
Nice strawman.
All you people who insist that science and religion are compatible: take a good, long look at Dr. Kenneth Miller and what he has accomplished professionally in his field of cell biology as well as the contributions that he has made in the fight to oppose young earth creationism, intelligent design, and to uphold and champion academically-honest science education.
1) That's not a strawman.
2) Miller never lets his science come into contact with his religion, and vice versa: he compartmentalizes.
That's what happens when faith and science collide. Any argument, no matter how ridiculous or factually incorrect, will be mustered to support the conclusion the 'scientist' knows is correct.
Rather, it's what happens when someone is certain they must collide. In that sense, Behe is a tragic example. Dembski, a farcical one.
I also don't think it is by any means clear that Behe is intellectually honest, given what he's written.
What a wierdo. He clearly grasps the science - and then uses this understanding to find a way of warping it that, while it will fool no-one with a grasp of the science, will dumbfound many of those not schooled in evolutionary biology.
What makes this so appalling is the fact this isn't mere stupidity, or delusion, but a cynically deliberate attempt to destroy science, on behalf of a barbarian agenda, for money. He knows he's lying, he knows the scientists know he's lying, yet he does it anyway, presumably because it's more lucrative to him to peddle this crap than join the ranks of ordinary scientists doing real science.
Few things make my blood boil more than religious injection into science, especially given the historical context, but I have to smile every time I see papers like this published. If anything it's an ironically redundant evolutionary cycle where quality scientific research over time forces evolutionary pressure on modern religious beliefs. Look at areas without the pressure of modern science and you'll find religious stagnation :)
I don't think the Pope of Poof (PoP) is deliberately lying in order to destroy science--he trained to become a scientist (even if he has essentially given up the calling) but he seems to be saying, like the little kid in the Santa Claus movies, "I want to believe, I want to believe, I want..." I also get the impression that he is hung up on preordained results of evolution--his collection of materials must be used to fabricate a mousetrap and nothing else.
Alas, Dr. Rosenhouse, you simply aren't giving Dr. Behe credit for the intellectual consistency in his approach.
Please change the heading: See Behe Flagellate!
What's more, in order to be confident that a multi-mutation scenario reconstructs a Darwinian process, all subsequent mutations have to be positively selected, too.
I think what ticks me off the most about press coverage of this tripe is that most journalists, in order to be "objective," choose one person to represent "each side." So, to explain evolution, they choose a prominent scientist with years of experience and loyalty to the scientific method over one's faith-based beliefs, and then on the other hand, they choose some dimwit to explain intelligent design who can selectively quote Darwin and use "big scientific words" and other useless forms of jargon to confuse the public when he/she sees fit (as if this somehow validates one's position).
The obvious problem is that the more and more journalists do this, the more credit they give the dimwits, the more these dimwits look like equals to honest scientists. Bah!
I don't care much about your view of religion, nor Behe's.
Indeed, I don't really care about other peoples' private beliefs at all, unless I have a reason to. Unless a person is a friend who wants to discuss their beliefs with me, or they are an adversary trying to justify the violation of my rights, or promote public policy I disagree with, on the grounds of their religious beliefs, it's really not my business.
I would like, however, to offer my own personal response to the above.
1) You seem to be assuming that Behe behaves the way he does because he is "religious".
2) You seem to be assuming that all other "religion" is highly similar to Behe's presumed "religion".
3) You are ignoring the example of Ken Miller and many others who do valuable scientific work despite publicly professing membership in an organized religion.
Last, but not least -
4) Because science is intentionally more or less objective, I can judge other peoples' grasp of scientific subjects. If someone tells me that they don't "believe in evolution", I know that they are ignorant of that branch of science. On the other hand, I cannot fairly judge another person's subjective personal beliefs. Therefore, if someone accepts mainstream science, and tells me that for them, it is compatible with their particular religion, I simply take them at their word.
Less likely than God, apparently. But he'll never say it out loud.
Not only that, but this is done selectively.
There can be no question that the media, or much of it, has attempted to create the impression that "ID" is some kind of legitimate "alternate" view being promoted by "visionary mavericks". Fortunately, nobody cared very much, and things are improving now.
My guess is that the media did/does this because ID/creationism is perceived as being sheltered under the umbrella of the "conservative movement". (For example, only the Republican presidential candidates were asked if they "believed in evolution", and three volunteered that they did not, to little or no media criticism.)
Jason, big thumbs up to this article and I would like to second the suggestion that this should be included in the T.O archive somewhere.
Strangely, I got to thinking about protein stability last week, inspired by:
(1) having made a big pro-evolution rant about how so many mutations have no effect due to degeneracy, or a minor effect since hydrophilic and hydrophobic amino acids of similar strength tend to cluster around similar genetic spellings and
(2) watching the BOINC screensavers (apart from the SETI one) that I have running... I can't remember if it's Rosetta or Predictor, sitting there trying to find good or valid energy conformations or somesuch...
Some bits of the proteins can flap around wildly, some seem stuck, and many "jiggle" in-between. I know I'm likely looking at just possible conformations as opposed to actual jiggling, but that's the way proteins ought to behave in real life, and it got me to thinking that perhaps a lot of proteins only spend a certain amount of time in a 'usable' conformation, and that this could be stabilized and destabilized by changes in the amino acids, giving different rates of catalysis... and a rate of catalysis, well, can be good, bad, or neither. Or, it could merely be dictated by fit. Or both. Either way, stabilization would be key.
It's of interest to me in a way because I gain no effect from caffeine, sedatives or analgesics (and fortunately almost never need them). Significant mutation somewhere, I'm sure, but is it positive? Negative?
It's like learning computers in the 80's, and then having geeks become cool and eminently employable ;) So many mutations are shoulder shrug-worthy until they're put to the test in a different environment.
It's damnably neat to see researchers finding things like the protein stabilization allowing other changes. This is the ultimate putting our money where our mouth is, and is one giant slap in the face to Behe's EoE book which asserts (by all I've heard about it) that changes by natural selection are impossible because two or more of the "right" mutations have to happen at the same time.
We now have a 1-step-at-a-time path that's functional all the way through, and it was indicated by what's in Nature, not just poking in our own plan.
it seems to me that Behe will never change his rhetoric - evidence will not convince him - he'll just spin a bunch of "sciency" sounding words around his BELIEF that goddidit.
reminds me of a Star Trek writer inventing a gadget to fill a plot hole and using "sciency" sounding jargon-babble to decribe it. - "rerouute the plasma streams through the dilithium crystals and interlace the tachyonic fields - we should get an extra .05 warp factor"
all crap
Behe has evolved slightly, though. His argument has mutated from
"It can't happen, irreducibly complex you see".
to
"Well, okay, there's a series of mutations whereby it could, but I'll bet it didn't".
Somehow this reminds me of SJ Gould's illustration of the progress of the drunk with the wall on one side of the path and the road on the other.
The probabilistic progression does work; we are all intermediate forms!
Ancient Geologist
His argument has mutated from
"It can't happen, irreducibly complex you see".
to
"Well, okay, there's a series of mutations whereby it could, but I'll bet it didn't".
Call me crazy, but I personally suspect that he'll sneak the goalposts back to the former position as soon as he finds himself facing an audience which is either sympathetic or just unlikely to have read about the study from this article.
That's what happens when faith and science collide.
Yeah, but when faith and science are both guided by sensible and observant drivers, who stay sober and keep their eyes on the other vehicles, they don't collide.
Also, Behe seems to have made the additional mistake of trying to drive both vehicles at once, and, like that upper-class twit in the Monty Python show, ended up running over himself.
"... [W]hen their initial hypothesis about the effect of the mutations did not pan out, they ..."
A. [followed the materialist evilutionist paradigm and] deduced that certain "permissive mutations" ... must have occurred, and by a series of clever experiments were able to zero in on where those mutations were.
.. OR ..
B. viewed the outcome through the lens of the Intelligent Design paradigm and declared it was impossible for evolution to do it, and thus concluded that an intelligent designer must have done it. (Then, having gone as far as humans could go in this particular area, they took up the study of some other question.)
Which paradigm has increased our understanding of nature?
What's more, in order to be confident that a multi-mutation scenario reconstructs a Darwinian process, all subsequent mutations have to be positively selected, too.
It's nitpicky, but couldn't Behe argue that neutral mutations, genetic drift, etc., is not "Darwinian"?
Does ID involve anything other than bitching about modern biology? My own, positive suggestion for ID research: sequence the salamander genome.
"in Behe's world, when scientists produce a comprehensive, step-by-step, well-documented, evolutionarily feasible sequence of events through which a protein attains a novel function, it somehow ends up being evidence for design nonetheless. "
Well, of course. This sort of co-option tactic has been around a long time. I first saw it laid out ex[plicitly in veterinarian Randy Wysong's book "The Creation Controversey", which, if I remember correctly, came out in 1976. In this pulp fiction, Wysong appears to have believed that 'life' had been created in a lab somewhere (he provided no citations), but blew off any notion that this somehow supported evolution. He declared that because it took place in a lab, the experimenters had added 'the magical ingredient KNOW-HOW' (caps in original), thus producing evidence for purposeful creation, not naturalistic processes.
Behe's latest 'this is really evidence for ID' schtick is just the latest in this sickeningly disingenuous line of creationist "reasoning."
Raging Bee wrote:
And then went on to claim that it was "just a flesh wound," inviting the scientists to come back so he could bite their kneecaps off. (Yes, I know I've mixed 'em up. Who cares?)
Seriously, it astounds me how bullet-proof these guys think their arguments are; every argument from them is "heads I win, tails you lose." Though we point it out it 'til we're blue in the face, they just REFUSE to admit that they've been caught at what amounts to cheating. My only question is, at what point does this cross the line and go from just gobsmacking dishonesty over to disassociative insanity?
~David D.G.
ngong asks, "couldn't Behe argue that neutral mutations, genetic drift, etc., is not "Darwinian"?"
Well, sure he could-- but another of the creationists' favorite arguments is claiming "Darwinism" is a religion that "Darwinists" believe in regardless of the evidence. If Behe admits that modern evolutionary theory contains a lot of stuff Darwin never thought of, he'd have to give up that argument. And the last thing the IDers are willing to do is to give up a logical-sounding argument just on the flimsy excuse that it's dead flat wrong.
Several versions of a protein which may exist in creatures today have differing gene implementations.
One can compare the gene sequences in all existing creatures and identify "conserved" regions.
One can then experiment by playing with the "non conserved" regions, and watching what happens.
It stands to reason that unless one is dealing with a very narrow sequence of events such that something only like pigeon hole principle can be applied to rule out other routes, it's pure presumption to say that one knows when and where and how as the researchers of this paper assert. It seems distressing their claims are swallowed uncritically merely because it is anti-Behe.
There have always been functional intermediates for slightly modified forms of proteins. There have been "compensatory mutations" found in CQR malarial strains (even I could recognize them when I compared amino acid sequences of the PfCRT protein and it's ancestors in various malarial strains). This is no big deal, and Behe is very aware of them...
But finding a few viable intermediates does not imply radical new functionality can be synthesized. A GR is still a GR. There may be intermediate forms between one viable GR to another viable GR, but they are stil GRs. It may be that the intermediate form from one GR to another needs a couple compensating mutations in advance to prevent break down as it transforms to another kind of GR. If so, the story is even WORSE or at best neutral for Darwinian evolution as it highlights the fragility of the system. If mutation X needs 2 preceding mutations such as Y and Z to make X, possible, one is faced with more difficulty, not less. If mutaion A and B, make any of mutation C,D,E,F,G possible withouth being lethal, it only states the obvious of what we already know, namely, there are several possible ways to implement a working gene for the same kind of protein.
The problem then is determining the functional space of solutions in the space of all possible sequences, and no one on Earth knows the exact answer to that. Behe circumvents the difficulty by exploring situations where binding site specificity is needed by definition. Behe took Sean Carroll to task when Carroll appealed to the ease of creating binding sites in the lab. Behe rightly pointed out the downside of such easily obtained non-specific protein binding: the proteins will partner with all sorts of agents to form highly undersirable interactions. Thus Behe thoroughly humiliated Sean Carroll's argument.
Moreover, folding is not the only criteria by which protein effectiveness is measured, not even binding site specificity, but there are other considerations such as Protein Dark Energy.
It appears the authors of the paper in question haven't even begun to touch on the issues of protein dark energy, and it may be, when they consider protein dark energy problems, their presumptions of the viability of protein intermediates will collapse!
So in sum, the research does not overturn what Behe claims, and the research may have overstated its convicion on the viability of intermediate states on some pre-mature assumptions as to what will really work in an organismal context verus some computer simulation or lab experiment where proteins are examined in isolation.
Hey, Jason,
You're going to need to set up one of those UV bug zappers. The site is starting to attract Sal-skeeters.
"So in sum, the research does not overturn what Behe claims, and the research may have overstated its convicion [sic] on the viability of intermediate states on some pre-mature assumptions as to what will really work in an organismal context verus [sic] some computer simulation or lab experiment where proteins are examined in isolation."
So many hypotheses to test, so little time! Let's hurry to the DI research labs and get to work!
No? You mean blogging <=> actual bench research? Silly research scientists need to learn how to work smart, not hard.
And are we all forgetting about Protein Dark Matter? Amino-axions are the key!
"But finding a few viable intermediates does not imply radical new functionality can be synthesized. A GR is still a GR. There may be intermediate forms between one viable GR to another viable GR, but they are stil GRs. It may be that the intermediate form from one GR to another needs a couple compensating mutations in advance to prevent break down as it transforms to another kind of GR."
And that's it for this weeks episode of "As the Goalposts Move". Tune in next week to find out whether Sal Cordova claims that all lab research amounts to "intelligent design" and therefore can never, ever demonstrate evolution.
My earlier link to Protein Dark Energy failed. Here it is:
Protein Dark Energy
"It appears the authors of the paper in question haven't even begun to touch on the issues of protein dark energy, and it may be, when they consider protein dark energy problems, their presumptions of the viability of protein intermediates will collapse!"
So please explain again how "protein dark energy" figures into this. Sure it is a cool-sounding phrase, but how specifically does it nullify the authors' conclusions?
Could you also identify any relevant papers that you have published on the physical chemistry of protein-ligand binding specificity? I can't seem to find them in PubMed.
"of the major fallacies" should read "one of the major flaws"
Jason:
Question: If Dr. Thornton's research shows how "proteins can acquire novel functions through evolution," such that "we now have a mutation by mutation account of how an important protein acquired a new function," and this shows the power of an evolutionary mechanism, is this not an equally interesting study showing the limitations of such a mechanism (pay attention to the last line, which states that proteins cannot evolve through a route of folded, which equals functional, intermediates):
Exploring the conformational properties of the sequence space between two proteins with different folds: An experimental study
Author(s): Blanco FJ, Angrand I, Serrano L
Source: JOURNAL OF MOLECULAR BIOLOGY 285 (2): 741-753 JAN 15 1999
Document Type: Article
Language: English
Cited References: 52 Times Cited: 19
Abstract: We have examined the conformational properties of 27 polypeptides whose sequences are hybrids of two natural protein domains with 8% sequence identity and different structures. One of the natural sequences (spectrin SH3 domain) was progressively mutated to get closer to the other sequence (protein G B1 domain), with the only constraint of maintaining the residues at the hydrophobic core. Only two of the mutants are folded, each of them having a large sequence identity with one of the two natural proteins. The rest of the mutants display a wide range of structural properties, but they lack a well-defined three-dimensional structure, a result that is not recognized by computational tools commonly used to evaluate the reliability of structural models. Interestingly, some of the mutants exhibit cooperative thermal denaturation curves and a signal in the near-ultraviolet circular dichroism spectra, both typical features of folded proteins. However, they do not have a well-dispersed nuclear magnetic resonance spectrum indicative of a defined tertiary structure. The results obtained here show that both the hydrophobic core residues and the surface residues are important in determining the structure of the proteins, and suggest that the appearance of a completely new fold from an existing one is unlikely to occur by evolution through a route of folded intermediate sequences. ////
...they just REFUSE to admit that they've been caught at what amounts to cheating.
That's basically how they pretend to "win" an argument: they simply smile and say, "None of what you said convinces me of anything, therefore you're wrong." Forget drugs -- this sort of simpleminded religious faith is the ultimate escape from reality.
Sal: care to tell us how "protein dark energy" is relevant to ANY point you're trying to make? Oh, and while you're at it, would you care to explain how my arguments resemble an (alleged) incident of surgical mutilation of innocent children? If that's too tough, you can just apologize for making such a comparison (see Comment #155717), and be done with it.
One more thing: that article on "protein dark energy" needs an editor. Entropy is not "a type of energy."
Pfft. "Protein dark energy" my eye. Based on a reading of the article Sal linked to, it's nothing more than the random thermal energy that manifests itself as motion and vibration of the molecule, like Brownian motion. Every molecule has it.
The main thrust of the work is to show that entropy changes are important in protein binding. This is not surprising; chemists have known for about 200 years that entropy can be a predictor of spontaneous processes.
Sal, why is it that you and your ID/creationist cohorts look at every new publication and tout it as being a problem for evolution? Is it because you have no research programs of your own, so the best you can do is misinterpret real scientists' findings?
Quoth Raging Bee: "Entropy is not "a type of energy.""
It is for creationists, who also think atheism is a religion, not playing softball is a sport and not collecting stamps is a hobby.
Here's a really minor question that's been bugging me: How did Sal, in his original post, manage to get the phrase "Protein Dark Energy" into blue, non-underlined text, and not have it link to ANYTHING?
He later said the link "failed," and gave us a real link. But a "failed" link normally means an incorrect or invalid URL; in this case, no attempt was made to create any sort of hypertext link. When I right-clicked the text, it did not give me any information about a link to anything, as I get when I right-clicked the actual link.
I suspect Sal merely made the text blue, thinking we would just meekly accept that he had a source and not actually try to read the article. Then he realized he'd forgotten to underline the text as well, thus blowing his oh-so-clever ruse, and he then had to give us a real link.
That's my theory anyway, at least until I hear a better one.
Bee, there's a specific way that you can screw up the html for a link such that the scienceblogs comment engine for some reason renders it in the link color but not as a link. I've done this a couple times by accident, and I once figured out exactly what it is you have to type to make it happen, but now I don't remember how to replicate it. I do remember it was a relatively easy mistake to make.
Okayl, I've been told elsewhere that you can do that by using the "a" tag and forgetting the "href=..." bit. So it could have been an honest mistake. But with Sal, one never knows -- faking a link really isn't much lower than prividing a real link to an article that has nothing to do with any point Sal was trying to make. Tossing out references to other scientists and publications, falsely asserting that they prove his case, and hoping his readers don't have the time to look anything up themselves, is another signature tactic of Sal's.
Why didin't Sal link to the Nature article his link cites? Wait...I can think of a reason...it has little to do with what he's saying.
I get what he is trying to say. He is trying to imply that protein-ligand bonding involves more than simple structure. Well, duh. Protein-ligand bonding involves chemistry. As opposed to simple building blocks that fit together schematically there are certain chemical (eg. electron density, thermodynamic, etc.) considerations involved in determing the free energies that give us expected versus unexpected results. The paper states a method, a rather convincing method in my opinion, to determine the free energy contribution from the molecular motion (eg the wiggle waggle of the bonds) using NMR, and it addresses a consideration for drug research.
Does anyone get Sal's link between his defense of Behe and his citation?
Does anyone get Sal's link between his defense of Behe and his citation?
Same as every time Sal posts: the link is, his citation halted criticisms of Behe, because instead of discussing Behe or anything related to Behe we're now discussing Sal.
Robby:
is this not an equally interesting study showing the limitations of such a mechanism (pay attention to the last line, which states that proteins cannot evolve through a route of folded, which equals functional, intermediates):
So, I am really not qualified to discuss the technical issues here, and I don't have access to either the Blanco et al article you mention or the new Nature article the NYT story is about. But I think there are certain conclusions we can draw with just the text we have here.
What specifically your quote says is that the Blanco research "suggest[s]" that "the appearance of a completely new fold from an existing one is unlikely to occur by evolution through a route of folded intermediate sequences".
Note that this suggestion is not ruling out the production of new protein function by evolution, only one particular sequence of events by which that evolution is likely to happen: a sequence whereby one fold in a protein becomes another by a series of stepwise mutations (by context it appears only point mutations were considered?), at each step of which the protein continues to fold correctly.
I may be misunderstanding you, but you seem to be presenting this other study as if it somehow refutes, or places restrictions on the findings of, the research described in the NYT article. But from the NYT article:
As I understand what is being described here, this new study explicitly addresses and shows one way around the kind of roadblock described by the first study, that of nonfolding intermediate sequences. The story is unclear on exactly how it does address it-- I am unsure on whether they are saying that the protein did unfold and then refold, or if they are saying that the "contextual" mutations mentioned changed which variants of the proteins would tend to correctly fold in the environment where the protein was found. It would be nice to get some clarification from someone with more familiarity with this subject. But it does seem clear from what we have here, assuming the second study was valid and the NYT reporter described it correctly, that the second study was developed with results of the kind found by the first study specifically in mind, and offers one way of showing how evolution can work even in the presence of the first study's findings.
So, one study manually walks through a certain way of stepping mutations to turn one protein into another, and concludes that evolution would not have been able to walk the path taken by experiment; another study manually steps through a set of mutations between proteins in a different way, and concludes that evolution well could have taken that path. These findings do not call evolution into question, but rather allow us to understand which ways evolutionary processes do and do not behave in a practical setting.
Re: "Question: If Dr. Thornton's research shows how "proteins can acquire novel functions through evolution," such that "we now have a mutation by mutation account of how an important protein acquired a new function," and this shows the power of an evolutionary mechanism, is this not an equally interesting study showing the limitations of such a mechanism (pay attention to the last line, which states that proteins cannot evolve through a route of folded, which equals functional, intermediates):"
I'm guessing this is intended to be a quote-mine to refute the results of the Science paper. However if you read this paper (not just the abstract), you will find that it describes a specific transition that may or may not be plausible. The authors of the JMB are looking at the possibility of recreating a transition between proteins of similar size that have different topologies or folds. There is no strong evidence that they are even related to a common ancestral protein, given that their sequence identity is only 8% (you can get that easily with two completely unrelated proteins). The authors sampled the sequence space between these two protein domains a limited number of times (27 trials) and failed to find stable intermediates. This is an interesting result, but it may not be that informative because it is quite possible that there is no series of sequence changes between these unrelated proteins that is stable--why should this necessarily be the case? [Google Maps can't give you road directions between Chicago and Honolulu either.] There is also the possibility that the experimenters did not sufficiently search the sequence space--27 is not a large number.
However if you want evidence that it is possible to find intermediate paths between distantly related proteins with different folds, this has been studied by M. Cordes using bacteriophage Cro proteins that have somewhat different topologies (all-alpha vs. alpha + beta folds) but a relatively low degree of identity (25%). See: Biochemistry. 2006 Sep 5;45(35):10542-53. Sequence analysis, molecular genetic, and biophysical studies identified an "ambivalent" peptide sequence--incorporating stabilizing interactions specific to the two different forms of the Cro protein--that could fold as either a pair of alpha-helices *or* a beta-hairpin. If it replaced the corresponding segment in the all alpha-helical Cro protein this intermediate sequence formed a stable pair of alpha helices. If it were incorporated as part of the alpha + beta Cro protein, it formed a beta-hairpin.
Another important point to note is that even mutant forms of proteins, which do not have a stable fold, can persist at high levels in cells due to the intervention of molecular chaperones (e.g. some mutant forms of the tumor suppressor protein p53). In some cases, these chaperones may even be able to restore activity of the mutant protein (J Biol Chem. 2007 Jul 31; [Epub ahead of print]). Susan Lindquist has also made the point that chaperones such as Hsp90 act as a kind of a "buffer" against genetic variations that would otherwise be deleterious. This suggests that chaperones make it possible for random genetic variation to explore a large portion of sequence space than would otherwise be possible (Nature 396, 336-342 (26 November 1998).
JEH:
No, I was not quote mining Blanco in order to refute the results of Dr. Thornton. Rather, I was juxtaposing Thornton's work next to Blanco's, and asking the very legitimate question, why does Jason Rosenhouse get very excited about results that comport with standard evolutionary theory, but is not nearly as ecstatic in reporting results that constrict and limit the same theory. Now, you correctly report that Blanco's results indicated that in the two chosen protein domains tested, the group found no stable intermediates between the two domains. Certainly if they had found stable intermediates this would have elicited great deal of excitement and would have been said to have vindicated the ease at which evolution can take one fold to another by a route of functional intermediates; but since they did not you say, /of course/ we do not expect to find intermediates between these very different protein folds since there is no evidence that they are related.
I suppose, jeh, that you will find Doug Axe's research /very/ interesting, since he did essentially the same test on protein homologues that are supposed to have shared an evolutionary ancestor, and derived the same conclusions. In his 2000 paper he states:
"The results reported here indicate that the true picture is very different. In the hybrid experiment, a set of sequences that are direct intermediates between the two parent b-lactamase sequences was produced. All of these hybrid sequences, in other words, lie on conceptual paths by which one parent sequence is transformed into the other with a minimum number of substitutions. The fact that they all lack biologically significant function means that the points representing these intermediate sequences in a seascape picture are below sea level. Since all of the direct paths from the TEM-1 enzyme to the P. mirabilis enzyme that were sampled dip below sea level, it is reasonable to conclude that a substantial majority of the possible direct paths do likewise. These two natural
enzymes would therefore be best pictured as points on different quasi-islands (dry peaks largely surrounded by water). There must be a dry path connecting these quasi-islands via others if they are descendants of a single enzyme, and there may also be direct connecting paths, but from an aerial view, much more water than land separates them. The two enzymes are different designs in the
important sense that their smallest corresponding parts, their aligned residues, are not freely interchangeable."
So what Axe did was hybridize two homologues (sharing 50% identity), and he noted that there are intermediate points at which the hybrids suffer complete loss of function. So to derive one homologue from another, according to Axe, one has to go through a an intermediate path that dips below 'sea level' of functional protein topology. Intersting stuff.
As one biologist reported on at evolutionnews.org
"Chang has misrepresented what the paper in fact demonstrates. This paper says nothing about how one protein fold might evolve into another fold with a different 3-dimensional structure. Rather, it describes one hypothetical set of changes that might convert the mineralocorticoid receptor (MR) to a glucocorticoid-specific receptor (GR). To change MR to GR does not require anything like unraveling the fold. The protein backbone still follows the same course, and the vast majority of its amino acids are unaltered. In fact the "evolved" MR started out able to bind to both hormones, as Ortland et al acknowledge in their paper, so relatively few changes were able to boost recognition of cortisol in preference to aldosterone. Even then, most changes they tested were non-functional, and in at least one case, required a second mutation to restore activity.
Thornton overstates his case also. He has shown a possible, but by no means easy route (see Edge of Evolution) to convert MR to GR. But in terms of functional shifts, this is minor. It's not even close to explaining how really new functions and structures arise."
"... why does Jason Rosenhouse get very excited about results that comport with standard evolutionary theory, but is not nearly as ecstatic in reporting results that constrict and limit the same theory."
Perhaps because he may be familiar with a larger body of literature than those few papers often cited by IDers as refuting evolution by natural selection. For every one paper that may appear to be puzzling (at least at first), there are thousands of others that provide abundant evidence of evolution by natural selection
So let's me honest here--you are an advocate of intelligent design, no? I don't have a problem with that per se, but I do have a problem when individuals say they are for open inquiry and critical thinking, but then immediately dismiss the bulk of the evidence that goes against their preconceived notions (which if they are being honest, have their origins in their religious beliefs).
Re: "As one biologist reported on at evolutionnews.org"
This is a dead give away. Isn't this the Discovery Institute web site?--the Fox News of science web sites--always fair and balanced!
It's so odd that the "biologist" at this site would be critical of the Science paper's conclusions.
"Thornton overstates his case also. He has shown a possible, but by no means easy route (see Edge of Evolution) ..."
What is this book you speak of, "Edge of Evolution?" Oh, you mean the book by that Micheal Behe guy--I think I've heard something about it on the web. That's the guy that favorably accepted comparison to Einstein on the John Stewart show.
"I suppose, jeh, that you will find Doug Axe's research /very/ interesting, ..."
Is it surprising that Doug Axe's work is cited? Isn't he on the Discovery Institute payroll? Sounds like someone has an axe to grind.
If Axe is right, it should be almost impossible to evolve a new protein fold by natural selection. How then was it possible for researchers to evolve and refine via in vitro selection, a non-biological ATP-binding proteins with a well-defined structure as described in the Smith et al. paper, "Structural Insights into the Evolution of a Non-Biological Protein: Importance of Surface Residues in Protein Fold Optimization" published at PLOS One? This not a designed protein, it is an evolved protein--the end result of random chance.
I think the unnamed biologist is right in that this does not represent a radically new protein fold evolving. But that was not Behe's original claim! He wanted new functions and step-by-step accounts of mutations, and he got that. If he meant new protein folds, why not say so from the start?
As for the claim, "It's not even close to explaining how really new functions and structures arise.", please note that this was only the first step-by-step account of the evolution of two enzymes from an ancestral sequence. Would the ID people be so kind as to signify what would qualify as "really new", instead of moving the goalposts each time evidence for evolution comes in?
It would also be nice if they were a bit more explicit in what they think happened. Did a designer intervene every time a new protein fold appeared? I'd be a bit careful about predicting that:
Evolution of protein fold in the presence of functional constraints
"The discovery of chameleon sequences that can adopt alternative secondary structures in the same protein, thus affecting its composition, has already shaken the presumed invariance of protein fold [...]. Recent structures revealed even more remarkable examples of large-scale fold variations, altering the protein architecture and topology."
The "failed link" has the Anchor On (angle bracket, a, close angle bracket) and Anchor Off (angle bracket, slash, a, close angle bracket) codes but nothing else.
For example, suppose you wanted to make a mousetrap. In your garage you might have a piece of wood from an old Popsicle stick . . ., a spring from an old wind-up clock, a piece of metal . . . in the form of a crowbar, a darning needle for the holding bar, and a bottle cap that you fancy to use as a catch. But these pieces couldn't form a functioning mousetrap without extensive modification . . .
Biological amateur here, but didn't he just outline the process of evolution? Parts have functions, and become modified to have other functions.
and while the modification was going on, they would be unable to work as a mousetrap.
Maybe not as a mousetrap, but as something else, perhaps? A piece of wood, a darning needle, and a spring might make a dandy weapon for spearing prey, and be on the way to being a trap for prey.
Their previous functions make them ill- suited for virtually any new role as part of a complex system.
Finally, isn't this just arguement by assertion?
Shortened Post:
Science: See, Behe? What you said was wrong.
Behe: No it's not! (Moves Goalposts)
Behe is an absolute master of linguistic misdirection. He is a perfect example of how an ideological blind spot can lead a very intelligent man to say jaw-droppingly stupid things.
"I think science promotes methods of inquiry that are hostile to the tenets of many faiths (such as sola scriptura)?
Can you define sola Scriptura for me? I think you may be taking it to mean that Christians only get their information from the Bible, which is not actually what the doctrine is. Is this how you are defining it?
Also, can someone point me to a thread on this blog, where interpretation of evidence according to one's worldview is discussed? I think that would be a helpful thread for many of us, as it seems that the word "science" is being used to refer to conclusions based solely on evidence when science must be interpreted by a thinking individual with a worldview bias. Thanks.
"Also, can someone point me to a thread on this blog, where interpretation of evidence according to one's worldview is discussed? I think that would be a helpful thread for many of us, as it seems that the word "science" is being used to refer to conclusions based solely on evidence when science must be interpreted by a thinking individual with a worldview bias. Thanks."
OK, you first--so what's YOUR worldview bias?
merisn
gumrks