There are two types of living cells that we know of on earth-
1. Prokaryotic cells:
1. Prokaryotic cells:
2. Eukaryotic cells [from the greek word karyon meaning nut or kernel – prokaryotic meaning “before a kernel” and eukaryotic meaning “with a true kernel” – the kernel being the nucleus of the cell.]
Eukaryotic cells not only have a “kernel” the nucleus but they have a goodly number of other internal compartments inside the cell too.
There is the complex structure of the onion like “endoplasmic reticulum” around the nucleus, there is the “golgi apparatus” looking like a pile of plates ready for a feast, there are the mitochondia looking like sausages out of some crazy sausage machineand there are the lysozymes- the waste recycling plants of the cell.
These different compartments each have their special function inside the eukaryotic cell.
The problems of transport are therefore much more complicated in the eukaryotic cell than they are in the prokaryotic cell.
It is these traffic problems that Behe mentions in chapter 5 – (From here to there) of “Darwin’s black box”
He first uses two analogies to explain the problem he is seeking to elucidate.
1. The delivery of urgently needed vaccine to an area of the country where there is an outbreak of a highly infectious viral disease. If the correct vaccine arrives at the correct location then lives can be saved- if not lives will be lost. Behe then imagines a film director making a film called “epidemic” in which the vaccine labels get muddled – This situation is similar to the situation inside a cell he argues when the transport system breaks down- death is the result.
2. He then imagines a robotic space ship exploring space with its battery crusher compartment, its library, its master machines and so on- This imaginary space probe is then compared to a cell
He then asks…. Is this analogy real?
This is illustrated using a protein he calls “garbigase.” A temporary copy of the relevant section of data from the DNA library is made- the messenger molecule. This messenger molecule passes to a nuclear pore- a tiny little door in the wall of the kernel. Proteins in the pore recognise the molecule in a process analogous to a challenge of identity with a secret password being given and the pore opens. In the cytoplasm a master machine the “ribosome” begin the process of converting the linear coded data into a 3D machine- in a process which biochemists have aptly named “translation” to make part of a brand new gleaming machine.
Diagram of translation:
Diagrams of a ribosome:
The first part of the machine to be made is a special combination code which quickly and neatly sticks to a code “hood” (signal recognition particle) causing the translation process to pause. The hooded new machine then locates a docking site in the surface of the onion. The docking process un-pauses the translation process and the newly made full length machine – a baby garbigase molecule - is fed into the inside of the onion compartment. As it passes into this new compartment the special code sequence to gain its safe entry is clipped off and a large carbohydrate molecule is bolted onto it.
Special proteins then cause a bubble of the onion wall to form and this pinches off into a separate little bubble containing molecules of the new garbagase protein. This little package then moves to another compartment called the Golgi apparatus and joins with the wall of this new compartment.
This kind of process happens two more times as the enzyme passes through several compartments of the Golgi apparatus. Another carbohydrate group is added to the enzyme and this is then trimmed by another enzyme leaving an special code MI-6 molecule.
In the final compartment of the golgi apparatus 3 blade propellor proteins snap together in a patch forming a bubble making cage. Within this bubble there is a MI-6 checker protein that binds to MI-6 pulling it into the bubble before it buds off. On the outside of the bubble is a tiny rabbit-SNARE protein that binds only to a tiny rabbit- proteins on the surface of the final compartment to which this little bubble is journeying.
Once the final docking process has completed further special membrane fusing proteins join the bubble to the wall of the waste disposal compartment so that it becomes part of it emptying its contents into its final destination.
15 comments:
Andrew: Apologies for not responding to your email, our server has been down (a contractor cut through a main cable – not much intelligent design there).
Now I see you’ve posted on protein and membrane traffic, so I’ll expand on what I was going to say to you about ‘irreducible complexity’ here. I’ve mentioned some of these thoughts before, but they bear repeating and I’ve added further examples from Chapter 5 of ‘Darwin’s Black Box’ to make it relevant to this post.
If you did want to investigate ‘irreducible complexity’ as a research topic, the obvious way to do it is by doing gene-knockouts and seeing what happens. But if you knock-out a gene, it’s well-known that the effect is context-dependent. That’s my really important take-home message and it’s precisely what Behe conveniently omits to mention. So for example, knocking out a particular gene might well inactivate a system and be lethal in a whole animal but not do so in a cell, or it could be lethal in one particular mouse strain but not another and so forth. I’ve previously given the example of clathrin in different yeast strains and lymphocytes, but there are lots of others cases.
Although in a sense, we all ‘know what he means’ when Behe talks about ‘irreducible complexity’, the above considerations mean that in practice it’s surprisingly hard to demonstrate it rigorously for a given system in all cases. For example, in chapter 5 of ‘Darwin’s Black Box’, Behe talks about I-cell disease. This is a tragic inherited disease in which patients develop severe mental retardation and die very young. As Behe correctly points out, this disease is caused by a mutation that interferes with the mechanism required to target lysosomal enzymes (the lysosome is labelled in your diagram). Neurones are particularly sensitive to this mutation and die, because their lysosomes no longer work properly. To Behe’s mind this is an example of ‘irreducible complexity’. But again, context is everything. It turns out that other cells and tissues are surprisingly unaffected by this mutation. Lymphocytes from these patients have normally functioning lysosomes. Presumably there must be alternative trafficking routes in these cells.
Don’t think of the secretory pathway as a rigid linear highway. There is generally more than one way to get from A to B within the secretory pathway. If you want an analogy think in terms of motorways, A roads and B roads. If the M11 is closed, it’s not literally impossible to drive from Cambridge to London – although it might take longer.
Now I’m sure that if you knocked out enough components from a pathway then you would destroy it, but what does that prove? As I think I said earlier, another of Behe’s fallacies is to think that removing a protein component from some subcellular system in a modern organism recreates the ancestral structure, but that’s just wrong.
I work on clathrin-coated vesicles, specialised structures involved in transporting proteins between some of the intracellular compartments shown in your diagram. Now another point that is completely missed by Behe is one that was picked up by Smokey when talking about bacterial flagella. Smokey pointed out that there is no such thing as THE bacterial flagellum. Similarly, there is no such thing as THE clathrin-coated vesicle. Although there are many underlying similarities between coated vesicles from different species – certainly enough to justify the study of different model organisms to identify common principles - there are also quite a few species-specific and tissue-specific differences. Some proteins are essential for coated vesicle function in one species, but not so in another. For example, in mammals two proteins called amphiphysin and dynamin are both required to produce a free vesicle, but amphiphysin is not needed to do that job in fruitflies and dynamin is not needed for this job in Trypanosomes. There are lots of similar examples. This sort of thing is well known to workers in the field, and just goes to show how biologically naïve Behe really is.
My other disagreement with Behe is over his misuse of the machine analogy. It captures some important aspects of the structure, but not all. By claiming that ‘molecular machines’ are just like mousetraps, I think Behe takes the analogy too far, and that promotes misunderstanding. I previously gave the example of the Ypt1p secretion mutant in yeast to illustrate why this can be misleading.
In summary then, I reckon that ‘irreducible complexity’ is a slippery and not very helpful concept for scientists to use in their day-to-day thinking and experiments. That’s probably why more than ten years after his book was published I can only find three references to Behe’s ‘irreducible complexity’ in a PubMed search of the scientific literature (and all of those references were hostile). As an added aside, it’s worth considering what possible use ‘irreducible complexity’ would be to a medical researcher trying to really understand I-cell disease.
I’ll post more on clathrin and targeting signals later. Right now, I have to go and mark some essays.
By the way, if any body wants a list of references to the primary literature on targeting and evolutionary inferences thereof, let me know and I’ll put something together.
Tony,
A list of references would be great especially focusing on material available on the web.
Is there anything like a good review of the evolution of intracellular transport. I cannot find much on the web but I have only spent an hour or so looking. Talk origins does not seem to have done an article responding to Behe's chapter... maybe you should write one Tony :-)
Andrew,
As someone who works in the field of intracellular transport, let me explain a few things to you.
1) Behe's description is laughably simplistic. It's not even an undergraduate's understanding of the complexity.
2) Behe's analogy "the vaccine labels get muddled" describes the normal state of compartmental labels. He wants you to think that it's digital like DNA, when in fact, the labels are entirely fuzzy and partially redundant. For example, many of the "bubbles" go the wrong way as well as the right way.
3) It's also not IC, because of the redundancy. Most homozygous null mutations in the "labeling" components--Rabs, SNAPs, SNAREs, etc.--aren't lethal.
And no, there wouldn't be a single review of the "evolution of intracellular transport," because the subject is too complex to fit in a single paper. There aren't even any single reviews of the MECHANISMS of intracellular transport, because that is too complex as well.
Behe is misleading you.
Hello Smokey,
Thanks for your comments.
Behe makes the point that in the Mol Biol of the Cell there is no attempt to describes the evolution of an intracellular transport system despite the chapter being a very long chapter.
Behe says this "A search of the professional literature and textbooks shows that no one has ever proposed a detailed route by which such a system could have come to be."
Are you saying that this is false?
Are you saying that this was false when Behe said it?
Are you saying that Behe must have known that it was false when he said it?
I accept that it is more important to begin with to work out how the system works than to work out how is arose.
BTW Tony...
You may want to hold fire on your clathrin comments because I have a post on clathrin vesicles in development which may be more directly relevant.
Andrew wrote:
"Thanks for your comments."
You're welcome.
"Behe makes the point that in the Mol Biol of the Cell there is no attempt to describes the evolution of an intracellular transport system despite the chapter being a very long chapter."
How is that a point? How do you define "an intracellular transport system," BTW? It's not a term used in the field.
"Behe says this "A search of the professional literature and textbooks shows that no one has ever proposed a detailed route by which such a system could have come to be.
"Are you saying that this is false?"
I'm saying that it's a red herring. A "detailed route" would fill dozens-to-hundreds of textbooks.
It's a red herring because there are plenty of papers that describe and discuss the evolution of the families of COMPONENTS of these systems. These are enormous gene families with partially-overlapping functions, which makes no sense in design terms. IOW, one never sees this sort of complexity in designed machines.
For example, here are four papers (three available on the Web) on the evolution of one of the families of molecular motors that play critical roles in these systems (some null mutants are lethal), but are omitted in Behe's sophomoric description:
http://www.mrc-lmb.cam.ac.uk/myosin/Review/Reviewframeset.html
http://www.pnas.org/cgi/content/full/103/10/3498
(this is just a more general discussion of the one below)
http://www.pnas.org/cgi/content/full/103/10/3681
But this is the best one, if you can get Nature:
Richards, T. A. & Cavalier-Smith, T. (2005) Nature 436, 1113–1118.
"Are you saying that this was false when Behe said it?"
No, it's more subtle than that. I'm saying that it is spectacularly irrelevant. The idea that such a description would fit into a single textbook or paper is preposterous.
"Are you saying that Behe must have known that it was false when he said it?"
I'm about 99% sure that Behe must have known that it was a red herring when he wrote it, and he used it to deceive his audience. It sure worked on you!
"I accept that it is more important to begin with to work out how the system works than to work out how is arose."
Good, but they aren't separate questions, which is another way in which Behe's rhetoric is both dishonest and deceptive. Behe wants you to conclude that because there is no complete, detailed description of an entire system available, that this somehow means that no one is actually working on the evolution of such systems.
For example, when you eat a meal and your pancreas secretes insulin, the insulin binds to receptors on your fat cells (adipocytes), causing them to rapidly move a glucose transporter (GLUT4) from the inside of the cell to the surface of the cell. People in the field estimate that 1000 of your ~30000 proteins are involved in the signaling and response during this single, five-minute process. It is an incredibly important subject of research because it is the process that is defective in ALL Type 2 diabetics.
1) Do you predict that any single paper anywhere would ever attempt to describe the entire mechanism? If so, how could a meaningfully detailed description fit in a single paper?
2) If the mechanism of the process is that complex, wouldn't any detailed description of the evolution of that process be much, much more complex?
Do you see how Behe is deceiving you by setting his goalposts (an American football metaphor) at his requirement for a detailed description of the entire system?
Do you see the incredible irony in the fact that those who claim that biological complexity argues for design underestimate the magnitude of the complexity by at least two orders of magnitude?
Finally, something to chew on: it's not the existence of complexity or the magnitude of complexity that is relevant here, but the NATURE of the complexity, something the Behe avoids like the plague.
For a frightening glimpse into this complexity, check out these attempts (about half of them relate to aspects of intracellular transport) to summarize parts of these mechanisms:
http://tinyurl.com/2knccb
Andrew, you’re out gunned here...
I think Andrew has painted things with a huge brush, which is not always the best way to enhance understanding. So instead, I’ll focus on just one specific problem to illustrate yet again why I don’t rate Behe.
This problem concerns the way proteins are targeted to the mitochondria. These organelles (again, they’re shown in your diagram) are responsible for supplying a major fraction of the cell’s energy needs. They are distantly descended from free-living bacteria that began a symbiotic relationship with an early eukaryote. As part of that evolutionary history, mitochondria still retain a small genome which encodes a few of the proteins required by the organelle. However, over evolutionary time there has been a general drift towards more and more mitochondrial genes being transplanted to the nucleus.
Mitochondrial proteins produced from such nuclear genes somehow have to get to their correct organelle. How do they do that? It turns out that such proteins contain, right at the start of their amino acid sequence, a so called ‘targeting signal’ made of about the first ten or so amino acids and which docks with import machinery in the mitochondrion.
A mitochondrial gene newly transplanted into the nuclear genome must acquire this signal or it risks turning into a pseudogene. So how easy is it to acquire a functioning targeting signal? Some years ago a clever experiment was performed to find out. It’s a neat example of how our intuitive ‘gut feelings’ about these issues can lead us badly off-course. The scientists took a gene for a mitochondrial protein, then replaced its normal targeting signal with random DNA sequences sized to encode between about ten and thirty amino acids. They then determined what fraction of these random sequences acted as functioning mitochondrial targeting signals for the protein.
What do you think the answer was? One in ten million? Or some other Dembski number perhaps? Actually, they got a remarkable 3 to 5%! Subsequent work with more truly random and uniformly-length sequences increased this estimate still further. Evidently, it’s almost ridiculously easy to evolve working targeting signals.
One more point is worth making here. Because the results were so striking and the way the experiment was conducted was so elegant, this work is rather well known in the field. It was published in 1987 – almost ten years before Behe wrote his book. Yet he tells us with a straight face that no experiments have been done to address the evolutionary origins of protein traffic!
Baker A and Schatz G: Sequences from a prokaryotic genome or the mouse dihydrofolate reductase gene can restore the import of a truncated precursor protein into yeast mitochondria. Proc Natl Acad Sci U S A. (1987) 10: 3117-21.
Lemire BD, Fankhauser C, Baker A and Schatz G: The mitochondrial targeting function of randomly generated peptide sequences correlates with predicted helical amphiphilicity. J. Biol. Chem. (1989) 264: 20206-20215
And see also: Kaiser CA, Preuss D, Grisafi P, Botstein D: Many random sequences functionally replace the secretion signal sequence of yeast invertase. Science (1987) 235:312-317
(This paper reports a similar experimental design in which random sequences were used to replace the signal that targets proteins to the endoplasmic reticulum – see diagram above. This time an incredible 20% of such sequences worked!)
Tony wrote:
"Yet he tells us with a straight face that no experiments have been done to address the evolutionary origins of protein traffic!"
That's what he wants his audience to conclude, but he is sneaky enough not to use such a blatant lie.
Andrew concluded this because Behe pointed out that no one has "proposed a detailed route" for a whole system (which would take many shelves full of books to produce), that the parts aren't being addressed.
For me, Behe's use of misdirection demonstrates his intent to deceive his audience.
"BTW Tony...
You may want to hold fire on your clathrin comments because I have a post on clathrin vesicles in development which may be more directly relevant."
Andrew, I'm genuinely curious. Why on earth do you do this? You are pushing a very, very, very big boulder up a very, very, very steep hill for no sensible purpose.
And frankly, it's getting painful to watch.
Tony,
I am fascinated by the elegance of biochemistry and particular by the complexities of these systems. I am convinced that the belief in abiogenesis purely by unintelligent mechanisms is crazy. I am amazed that biochemists can look at all this complex circuitry and control and still rule out the possibility of any design.
It is so complex that you need a PhD and 10 years research to properly understand a small part of it....but on the other hand it is so simple that chance plus time can build it without so much as breaking into a sweat!
smokey said:
Do you see the incredible irony in the fact that those who claim that biological complexity argues for design underestimate the magnitude of the complexity by at least two orders of magnitude?
I've been following this discussion, which in its own way is fascinating but leaves me rather puzzled. I have a hard time telling the difference between what an evolutionary and an ID position would look like in terms of the research being discussed. The only thing that seems to be clear is Behe has not adequately represented the state of knowledge in intracellular transport. But the word 'evolution' here seems to have little meaning here except as a synonym for 'process' or maybe even 'procedure' (which you cause the evolution to happen through an intervention). So does 'evolution' have any particular meaning in the context, or is it just a metaphor?
Andrew wrote:
"I am fascinated by the elegance of biochemistry and particular by the complexities of these systems."
You've got to be kidding. If you are fascinated by the complexities, why did you stop at Behe's sophomoric description? You aren't interested at all.
"I am convinced that the belief in abiogenesis purely by unintelligent mechanisms is crazy."
What's crazy is your conflation of cell biology with biochemistry and abiogenesis.
"I am amazed that biochemists can look at all this complex circuitry and control and still rule out the possibility of any design."
This is cell biology, not biochemistry. And yes, if you have the guts and faith to actually look at the complexity, the NATURE of it has never been seen in a designed object. But you're afraid. You lack real faith.
"It is so complex that you need a PhD and 10 years research to properly understand a small part of it..."
Baloney. No one claimed that. It is so complex that it can't be described in a single paper, or even in a single book, but people without PhDs understand this all the time.
Did you read the papers I pointed you to, or were you afraid of anything but Behe's predigested twaddle?
"...but on the other hand it is so simple that chance plus time can build it without so much as breaking into a sweat!"
Careful, Andrew, you're regurgitating the standard lie. It's not not chance + time, it's (chance + SELECTION) x time.
Why do creationists always leave out selection? Is it because they are stupid, or because they are dishonest, or both?
"I've been following this discussion, which in its own way is fascinating but leaves me rather puzzled. I have a hard time telling the difference between what an evolutionary and an ID position would look like in terms of the research being discussed."
Then you need to read the papers. The evolutionary position produces hypotheses that can be tested to produce data. The ID position produces...nothing but quote-mining.
"The only thing that seems to be clear is Behe has not adequately represented the state of knowledge in intracellular transport..."
But is that clear to Andrew?
"So does 'evolution' have any particular meaning in the context, or is it just a metaphor?"
It has a great deal of meaning, if you look at the phylogeny papers. It makes clear predictions about which mechanisms and which components will be found in different organisms and cell types, for example.
ID (the movement) predicts nothing. An ID hypothesis can predict many things, but its proponents lack sufficient faith in it to subject any hypothesis to any real test.
Smokey: ".. These are enormous gene families with partially-overlapping functions, which makes no sense in design terms. IOW, one never sees this sort of complexity in designed machines."
This is correct, and an important point that deserves to be better appreciated. The process of sequential gene duplication and gradual divergence leads naturally to an interesting property that, if you want to go for savvy PR-friendly buzzwords, you could call ‘redundant complexity’.
This makes biological systems quite different in character to man-made machines. A particularly clear example that’s relevant here is a large gene family called Rab. I mentioned them briefly a few posts ago in the context of the evolution of their regulators REP and GDI. Rabs control the efficiency with which transport vesicles attach to their target membranes. Although different Rabs have distinct preferences, these are not always absolute. There is an inherent ‘fuzziness’ in some aspects of their specificity. This of course can make it very frustrating if you’re trying to untangle their function, but it arises naturally out of the evolutionary process itself. There really is nothing quite like this in human-designed machines
Tony wrote:
"This is correct, and an important point that deserves to be better appreciated. "
Thanks. But how do we get Andrew to appreciate this incredibly important point, when he falsely claims to be fascinated by complexity, but refuses to explore the complexity beyond data-free apologetics like Behe's?
How do we get people (who clearly have so little faith in their position that they are afraid to examine any real data) to look at the data BEFORE reaching an irreversible conclusion?
Smokey: “But how do we get Andrew to appreciate this incredibly important point, when he falsely claims to be fascinated by complexity, but refuses to explore the complexity beyond data-free apologetics like Behe's? How do we get people (who clearly have so little faith in their position that they are afraid to examine any real data) to look at the data BEFORE reaching an irreversible conclusion?”
I don’t know the answer to that question. I do think that ignoring this issue is not an option anymore. As I think I said on a previous thread, I’ve stayed around because I want people who come here, and who may be vaguely sympathetic to ID without knowing much biology to at least get our side of the story.
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