I See Red (not quite protein-protein binding)
There is a wonderful article in todays issue of Nature on bioluminescent organisms in the deep seas. We like to think of the deep seas as dark, since virtually no light filters into the abyssal depths from above. However, the deep sea abounds with bioluminescence, bacteria and sea life of all sorts glow gently in the depths, enough to seriously hamper the Antares deep sea neutrino telescope that is searching for the flashes of light the represent the rare interactions of neutrinos with other matter (subscription required).
As fascinating as bioluminescence is in its own right, the article links to an amazing paper. One that puts yet another dent (if that is possible) in Dr. Behe’s key thesis; that multi-amino acid binding sites are difficult to evolve. But how does the ability of a fish to see red refute a central argument of Dr. Behe’s “Edge of Evolution”
In the abyssal depths, most fish (and other organisms) are sensitive to blue light, as red light is heavily absorbed by the depth of water overhead. In fact, most are blind to red light, a fact that marine biologists use to observe deep sea denizens unobtrusively, by illuminating the study area in red light. However, some organisms have evolved to take advantage of this red blindness. Some species of befanged dragon fish have developed red bioluminescence, which allows them to see, but remain unseen, in the dark depths.
One of these dragonfish species is even more remarkable, in that it has no red sensing pigment itself, but uses bacteriochlorophyll to harvest the red light. Chlorophyll is the pigment plants and many bacteria use to capture light for photosynthesis. How dragonfish acquire this chlorophyll is not clear at the moment.
Right now you are scratching your heads and saying, “Alright, that’s pretty amazing, but how does dragonfish seeing with chlorophyll have any bearing on Behe’s claim that protein-protein binding sites are hard to evolve?”
Proteins bind to each other by matching up knobs and depressions on the proteins surfaces, in much the same way that a key fits into a lock. It is a bit more complicated to be sure, as well as matching shapes, the amino acids that makeup the proteins surface cam be neutral, charged or oily, and these properties have to match as well. Also, both the lock and the key are “floppy” as proteins are flexible and can (and do) move and flex so that what you think are not complementary shapes can flex into shapes that bind. Nonetheless, the lock and key analogy is helpful to visualize proteins binding to each other.
Now, where does chlorophyll fit in? The above lock and key model is also valid for binding of small molecules. Everything I said about protein-protein binding applies exactly to protein-small molecule binding. Small molecules have to fit the shape, charge and “oilyness” of the protein “lock” too,
Dr. Behe claims that at least 3 or more amino acids must be mutated simultaneously before a partner protein can bind to another protein with high affinity (and a selectable activity). The same should hold for small molecules as well, if Dr. Behe's assumptions are true, as most bind to proteins in special pockets to three or more specific amino acids. So, if Dr. Behe’s claims are true, then we would expect it vanishingly unlikely for any random small molecule to bind with reasonable affinity to a protein and result in a selectable activity. This is where chlorophyll comes in.
Chlorophyll is a copper magnesium containing molecule[1] that is similar to the iron containing heme molecule; the oxygen-binding component of haemoglobin. When red cells break down, there release their heme. Free heme is mildy toxic, and the body has fairly efficient ways of getting rid of it. You can also imagine that there is selection against heme binding for those proteins that don’t actually use it (such as haemoglobin and other enzymes that use iron as a catalyst), clamping a mildly toxic compound to the outside of a protein is not a good survival plan. So one would expect that the surfaces of non-heme proteins would be under selection pressure to avoid binding heme like molecules like chlorophyll. Wouldn’t you?
To determine how chlorophyll works as a visual pigment, researchers injected mice with a water soluble metabolite of chlorophyll (see the free online paper ). Remember, chlorophyll is a plant pigment that is alien to the tissues of vertebrates. This molecule was not only selectively taken up by the eye, but was concentrated almost exclusively in the retina, in the pigment layer.
And that’s not all; the injected mice were now able to respond to red light! The chlorophyll metabolite was acting as a visual pigment, harvesting light and passing the energy on to the visual pigments of native mouse photoreceptor cells.
In order to transfer energy to the visual pigment protein, the chlorophyll must bind to it. Now, the diagram above shows the bacterial protein that normally binds chlorophyll, and the visual pigment protein. You can see immediately that they are very different proteins (one is like a clamshell, the other a tube, and the visual pigment, rhodopsin, is not a heme binding protein). The coordinating amino acids that bind chlorophyll in the bacterial protein (or the plant protein for that matter) are absent in the visual pigment protein, so it’s not a case of chlorophyll binding to a similar molecule and doing what it did before.
So, in the absence of any mutations, a small molecule that needs to bind to multiple amino acids of a protein in a distinct orientation to work, can bind to a completely different protein, unrelated to its normal binding partner in a species that never normally sees this small molecule in its tissues and provide a selectable function, right off the bat.
That is astounding. According to Dr. Behe’s arguments (which apply equally well to small molecule-protein interactions as to protein-protein interactions), this sort of interaction is vanishingly unlikely. Yet we see it. This shows once again that Dr. Behe’s arguments about binding and selectability are fatally flawed.
It’s enough to make an ID supporter see red.
[1] Yeah, major dimness attack, I could even see the magnesium ion in my own diagram!
40 Comments
Dave Thomas · 22 November 2007
Great post, Ian!
Irreducibly complex pigments have made Behe Blush Before (in principle, anyway).
Cheers & salutations, Dave
djlactin · 22 November 2007
trivial-error nazi mode again:
Chlorophyll does not contain copper, as you state; it contains Magnesium (as shown in your illustration).
Otherwise, a fascinating post. Light-trapping pigment from a completely different branch of the tree, preferentially sequestered in the retina! Whood'a thunk it?
Nigel D · 22 November 2007
Ian, the binding doesn't seem all that unlikely, since rhodopsin contains the cofactor retinal, which has a similar hydrophobicity to the long hydrocarbon tail of chlorophyll. What is astounding is that the absorption of light by chlorophyll can bring about the same conformational change in rhodopsin as does retinal when it isomerises in response to light absorption. This conformational change then triggers the signalling cascade that initiates a nerve impulse.
In a similar vein, proteins can form quite specific interactions with other proteins that do not encounter each other in their normal environments. A good example of this is when a (recombinant) mammalian protein is expressed in bacteria. Occasionally, a host cell protein will co-purify with the recombinant protein. Sometimes, the interaction between the bacterial protein and the mammalian one is so strong that it becomes a significant challenge to purify the recombinant protein without the bacterial protein associated with it.
In these cases, although I am not sure how much work has been done to look into these interactions (we do not have a very good library where I work), the interaction is so persistent that it almost has to be specific binding. Thus, this is a case of two random proteins forming a specific interaction with one another due simply to their individual surface chemistries, without the requirement for any mutations at all.
So, while you make the point that proteins need to adapt to avoid binding small molecules that would confer a disadvantage to the function of the protein, there are also examples of proteins that need to be adapted to avoid binding to other proteins where the interaction would be disadvantageous. Which makes Behe's incredulity of specific protein-protein interactions all the more ludicrous.
Hmmm, reading that back I'm not sure I've been very clear, but I hope the core point gets across.
Dan Gaston · 22 November 2007
Quite true Nigel. One interesting aspect of protein evolution that is, of course, always overlooked by the ID/Creationist crowd is that in terms of binding, and even enzymatic reactions, proteins pretty much always carry out spurious side reactions/bindings to greater or lesser extents depending on concentrations of protein/binding partners/substrates, etc. One thing that we are quite certain has happened in many cases is where we can look at a protein family that has evolved through gene duplication and divergence. The common ancestor was more flexible and loose, carrying out many reactions with some specificity. As duplicates accumulate then individual duplicates, through mutation and selection, are refined for individual reactions, binding conformations, etc.
Of course this is coupled with other methods of duplication and divergence schemes were new functions are evolved in their entirity. Evolution isn't always about gaining enw complexity but in many cases about reducing interactions and reactions and refining one of many strategies.
Stephen Wells · 22 November 2007
That's really astonishing- I would never have expected immediate function like that.
Cue creationist claims of front-loading in 3...2....1....
wright · 22 November 2007
Absolutely amazing. This makes me wonder about life on other worlds, perhaps on some of the gas giant moons or Mars. If life on this planet is driven to explore such extremes, then surely evolution must be no less relentless elsewhere in the universe.
So if we find life beyond Earth, we should expect it to display a similar (allowing for differences in its home environment) depth and breadth of diversity, function and adaptation.
Dave Thomas · 22 November 2007
hoary puccoon · 22 November 2007
How come we don't all have chlorophyll in our visual systems already? It seems that it would have been useful during the cretaceous, when mammals were sneaking around in the dark to avoid the dinosaurs.
Of course, if evolution has to proceed by individual, viable steps, it makes sense that a chemical that's never been found in the vertebrate line would not suddenly appear. But if evolution is under the control of an Intelligent Designer, why wouldn't he have done something useful, like give us night vision, instead of harrassing us with chloroquinine-resistant malaria?
SteveF · 22 November 2007
Not entirely on topic, but a couple of interesting upcoming papers concerning proteins and evolution:
http://www.biomedcentral.com/content/pdf/1752-0509-1-49.pdf
http://www.biomedcentral.com/content/pdf/1472-6807-7-79.pdf
Bruce Thompson GQ · 22 November 2007
Olorin · 22 November 2007
hoary puccoon said: "How come we don’t all have chlorophyll in our visual systems already?"
IANAB, and my question is, where do the deep-sea fish encounter chlorophyll? (Probably differently from rabbits, who, as everyone knows, don't wear glasses because they eat all the carrots on their plates.) Before you can bind to something, you have to obtain it in a form that you can use.
Even though binding may be easy, the alarm bells go off when Ian says: "Remember, chlorophyll is a plant pigment that is alien to the tissues of vertebrates. This molecule was not only selectively taken up by the eye, but was concentrated almost exclusively in the retina, in the pigment layer." I can visualize an IDer crowing: "Look! A perfect example of a design event! Gthe designerod put the chrolophyll in the fish for the express purpose of giving them night-vision goggles. QED."
Nigel D · 22 November 2007
jeh · 22 November 2007
"If the Designer is Popeye ..."
I yam what I yam, and that's all that I yam. ; }
Bruce Thompson GQ · 22 November 2007
hoary puccoon · 22 November 2007
I don't know about the Popeye hypothesis, Bruce. While the absence of canned spinach during the cretaceous era is a plausible explanation for why we don't have chlorophyll in our eyeballs, your whole approach seems MUCH too rational for Intelligent Design.
Ian Musgrave · 22 November 2007
Bruce Thompson GQ · 22 November 2007
Gerard Harbison · 22 November 2007
You don't need specific binding to rhodopsin. This is probably excitonic energy transfer; it happens over quite a long distance; as long as the chlorins partition into the rod cell membrane, which is plausible, they probably can do the transfer.
It's an interesting paper, but it doesn't prove what you want it to prove: i.e. specific chlorin-rhodopsin interaction.
Nigel D · 23 November 2007
Bruce Thompson GQ · 23 November 2007
Ian Musgrave · 23 November 2007
Nigel D · 24 November 2007
Curses, I misread a part of Gerard's comment. I was taking it as specific binding to the protein (but not necessarily in the same pocket as retinal), not as partitioning into the membrane. Of course, Ian is correct in his responses there.
If the chlorin binds to the protein in any kind of specific or preferential way (and thus becomes concentrated within the same regions of the body and of the cells in those tissues) then nonspecific electron transfer may indeed play a role. Otherwise, it could not initiate the visual transduction cascade.
Thus, either the chlorin is binding specifically to the protein but is effecting nonspecific electron transfer to bring about the conformational change in the protein, or the chlorin is genuinely mimicking the role of retinal, and is bringing about a specific conformational change in the proetin in response to absorption of a photon of red light. Cool!
Gerard Harbison · 24 November 2007
Gerard Harbison · 24 November 2007
snaxalotl · 25 November 2007
re: copper
perhaps you were thinking of vegetables cooked in copper kettles, where the magnesium atom is replaced by copper and the green color is more resistant to fading in low ph
shiftlessbum · 26 November 2007
The link provided to the paper is dead (at least to me). Can someone post the citation in conventional format? thanks,
Alveno Kondyles · 29 November 2007
You guys are taking Behe's words out of context. He excluded external proteins in his argument. They fall under a different category from the edge of evolution. For Darwinism to be true any advancement would have to take place without the help of other organisms. Symbiotic relationships always help the argument for design. Your illustrations aren’t 3D therefore only hint at the complexity of shape space, and in matching up proteins for binding. When two organisms come together for a purpose then it’s design. Some of you guys are just discussing minutiae, and not contributing to the larger discussion.
Henry J · 30 November 2007
Alveno Kondyles · 1 December 2007
What aspect of evolutionary theory implies that species never help each other? Creatures helping each other is not an example of evolution. Evolution is creatures changing into something else thru random genetic mutations. Natural selection is more closely related to living things helping each other to survive. A bird finding a bee nest, and screams so that the badger can find the nest to eat its honey. Animals helping man to plow his fields, track his prey, or guard his camp etc. These examples may help the creature to survive, but are independent of evolution. Natural selection could play a role in evolution if there were really some major changes occurring in the cells, but there isn’t. That is one of the points that Behe’s book makes. Observing Malaria, HIV, and E. Coli for almost 50 years, shows that even though they have had numerous genetic mutations, none of mutations have changed them. Accurate predictions can be made about evolution, and whether it has had any effect at all on life, because of the massive populations of the three organisms, and their mutation rates. Time therefore is irrelevant. The HIV virus genetic thumbprint is so small, that any mutations to that, would have a more significant impact on it evolving into something else, then some creature with millions, or billions of genes.
Henry J · 1 December 2007
Alveno Kondyles · 2 December 2007
You really need to read BeHe's latest book so I don't have to answer every question myself. Again he shows that there is no change occurring in creatures. This is the scientific evidence, from studies done with Malaria, HIV, and E.Coli. When some one speaks of evolution it entails the dogma of all life coming from a single cell organism, or from a rock, or from the vacuum of space, whatever was here before the big bag. They also believe that the Big Bang is a product of evolution. Evolution is both a political movement, and a religious movement, that's why its adherents fight so ardently in the face of impossible odds. Something doesn't come from nothing. Also the creation of the universe shows fine tuning, without which there would be no life on earth. Taking small incremental steps, one mutation at a time in order to evolve life is impossible. It takes a completed created cell to make another complete created cell. ATP needs to be contributed to the ATP creating process, in order to make more ATP. Where did the first ATPs come from before the cell made ATP? Where did the info in DNA come from? etc.
ben · 2 December 2007
Richard Simons · 2 December 2007
Henry J · 2 December 2007
Nigel D · 4 December 2007
Nigel D · 4 December 2007
Nigel D · 4 December 2007
Alveno, one more point:
In what way do any of your comments address Ian's post, in which he describes a counter-example that demonstrates that what Behe claims in EoE to be impossible really does occur?
One counter-example is all that is required to refute a claim of impossibility, but there are others.
Alveno Kondyles · 5 December 2007
Before the beginning there was nothing. There was not even the vacuum of space, since space didn't even exist. Then all the mass, and energy that would ever exist spontaneously came from the nothing. Billions of years went by. Then the earth took form. Initially it was inorganic. Then spontaneously organic life came out of the rocks, minerals,water etc. That happened about 4 billion years ago. Gradually one nucleotide,one amino acid, one mutation at a time, life evolved. Until all the life that you now see came to be, including humans with billions of genes, and over 80,000 distinguishable proteins. Lets go in reverse. Human from bacteria via a googol of intermediate creatures, bacteria from inorganic elements, inorganic elements from Big Bang, and Big Bang from nothing.Therefore man came from a single cell organism via inorganic via Big Bang via Nothing. Man via Nothing.
I hope that I clarified for Nigel what I meant from the statement that "man came from a rock". Life spontaneously coming from nothing is exactly what evolutionist believe? Right? I believe that something can not come from nothing! Therefore I must believe that a causative intelligent agent created everything. It's only logical. One other thing. If everyone that Nigel trusts to feed him accurate info is as bias as he is, then Nigel better read the books himself. I read some comments about Coyne's review of Behe's book. I went to The University of Chicago web site to read his review myself. I now know that some comments were accurate, and some were in error.
[edited to fix bad html IFN]
gadfly: · 17 December 2007
I'm not convinved that the difference between a small molecule and a big one isn't valid. It is a lot easier to stick a small piece of paper to a refrigerator with magnet, for instance, that a large pad. Maybe the chrlorophyll molecule isn;t really bound at all, just weakly attracted. To disprove Behe, you would have to find a three amino acid binding site on a protein that developes quickly.
Ian Musgrave · 17 December 2007