Friday, January 26, 2007

Molecular Meccano

Described by some researchers as a strange form of molecular “lego” and by others as “molecular basket weaving” the beautifully shaped propeller like molecules of clathrin have a crucial role in the cell’s internal distribution network. Another description in the literature is “groovy” which I think is about right! A single clathrin complex is made up of 3 light chains together with 3 heavy chains

to form the propeller like structure called a “triskelion” meaning three-legged.
These 3 legged units can be attracted to a membrane by a variety of different molecular structures on the surface of the membrane. As they are attracted they begin to associate

and as they associate they begin to bend the membrane inwards. The structure grows to form a complete and beautiful basket or cage around a little blister of membrane which is eventually pinched off to form a separate bubble inside the membrane.
At this point the clathrin complexes can be removed and reused elsewhere.

The diagram below is adapted from here (thanks to Dr. Tony Jackson)
A Quicktime Movie is here showing the assembly of a clathrin coated vesicle. (You may have to wait a little time for it to load.)

A Flash animation of the budding off of a clathrin vesicle is available here.






86 Comments:

Blogger Tony Jackson said...

Ever since I read ‘Darwin’s Black Box’, I’ve been wondering when the ID crowd would discover clathrin-coated vesicles. Ho hum, now that the bacterial flagellum is beginning to loose some of its appeal, maybe our turn as ID poster boy has finally arrived...

Let me say up-front that I think clathrin-coated vesicles are extremely beautiful structures, yet never once have I had cause to doubt that they evolved.

Before going further, it’s worth clarifying the level of detail that it is practical to aim for here. Molecules don’t fossilise, so when dealing with these structures, some aspects of their evolutionary history can be genuinely difficult to reconstruct – especially since coated vesicles probably go back to the very origin of the eukaryotic cell. That's why Behe’s reported demand for the exact step-by-step history of all the mutations leading to the current structure is just silly (and a bit rich too, considering that his alternative is a supernatural puff of smoke). It’s as if I were to demand of a mediaeval historian that she provide me with details of every word uttered by William the Conqueror during his entire lifetime before I accept that the Battle of Hastings took place.

However, IF the clathrin-coated vesicle evolved then there should be some very clear signs of this in present structures. For starters, for any given coat protein, we expect to be able to compare their sequences from as many eukaryotic organisms as we like and fit them together into one phylogenetic tree and each of the independently derived trees should agree. It is not often appreciated how incredibly restrictive this sort of thing is. If the coated vesicle was designed, there is no a priori reason why the independently derived trees from each protein should agree with each other. Yet remarkably and within the understood errors of the technique, they do. An advocate of ID really does need to explain to me why the sequence of dolphin clathrin is more similar to the sequence of human clathrin than it is to that from say shark.

Secondly, we do not expect the proteins to have appeared from nowhere; they should each have their own distinct evolutionary history, and we should be able to infer something of this history. Indeed we can. Clathrin-coated vesicles are only one of several different classes of coat structures involved in transport. As we get more detailed structural and sequence information, it’s becoming quite clear that all these coats are evolutionarily related by a process that can be perfectly well rationalised in terms of sequential gene duplication and selection. In some case, we can even put dates to these duplication events.

Recent work has uncovered a distant similarity between these coat proteins and proteins of the nuclear pore complex. This is particularly significant, because both of these structures are involved in membrane deformation and remodelling and - importantly - it opens up new avenues of research into the very early evolution of these structures.

The individual proteins themselves also show clear evidence of evolution. On close examination clathrin for example has clearly been assembled from different and smaller ancestral proteins. For example, the so called N–terminal region (the oval at the tips of each of the three arms in the diagram), turns out to be related to a protein involved in hormone signalling, whilst the arm is related to a completely different family of proteins. That’s often how evolution works. Similar examples of ‘tinkering’ can be found for all the other coat components.

Of course none of this disproves that coated vesicles were designed, if that’s what you want to believe, fine. But then you have to explain why the Designer went to such enormous trouble to leave so many clues scattered around to make it look like they evolved. This takes us into the territory of the Victorian author Philip Gosse who claimed that God put fossils in the rocks to make it looks as if the Earth was old. His ideas were laughed off the intellectual stage even before Darwin had finished writing his big book.

6:35 pm  
Blogger Smokey said...

Tony wrote:
"An advocate of ID really does need to explain to me why the sequence of dolphin clathrin is more similar to the sequence of human clathrin than it is to that from say shark."

It'll never happen. Folks like Andrew simply lack the faith to explain all these data, so they refuse to look at them. The best you'll get in response to your question is an ignorant, comprehensive dismissal.

It must be sad to claim so much faith, while knowing in your heart that your faith is so weak that you can't open your eyes to the real world in which you live. It must be depressing for Andrew to claim to be fascinated by complexity when in reality, he is afraid to delve into it.

So, Andrew, what about clathrin even suggests design to you? There was nothing in your post to argue it.

7:41 pm  
Blogger Tony Jackson said...

Here’s something else about clathrin-coated vesicles that you won’t read about in ‘Darwin’s Black Box’.

In Andrew’s last diagram, the clathrin-coated vesicle is shown still connected via an extended neck to the membrane from which it is budding. This is the final step in the formation of the vesicle.

The helical-spring drawn around the neck represents a protein called dynamin. This protein assembles around the neck and snaps it using a fuel called GTP. Dynamin is essential in all multicellular animals, but is not used by most non-animal cells.

Recently, it’s been discovered that one class of single-celled eukaryotes called ciliates employ a similar but distinct GTP-using protein called Drp1p to do the same job as dynamin. However, the exact way Drp1p works, and the way it is targeted to the neck turn out to be different from dynamin. A phylogenetic analysis confirms that the recruitment of dynamin in animals and Drp1p in ciliates evolved independently.

This is a neat example of a well-known phenomenon called ‘convergent evolution’. In these cases, it’s the quirky lineage-specific differences in detail that give the game away.

Such things make no sense at all within an ID perspective. Unless that is, you assume the designer made the coated vesicle in a fit of absent-mindedness.


Elde NC, Morgan G, Winey M, Sperling L, Turkewitz AP: Elucidation of clathrin-mediated endocytosis in tetrahymena reveals an evolutionarily convergent recruitment of dynamin. PLoS Genet. 2005 Nov;1(5):e52

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1277907&blobtype=pdf

9:52 am  
Anonymous tempus fugit said...

tony jackson said:

That’s often how evolution works. Similar examples of ‘tinkering’ can be found for all the other coat components.

Why is evidence for 'tinkering' pro-evolution and anti-ID? 'Tinkering' after all is an engineering metaphor. What sort of notion of ID are you presupposing? Just as you would complain if we reduced all of evolution to natural selection, I think we're entitled to a better account of ID than simply the idea that the design of everything is evident simply by looking it in insolation from any larger systems of which they may be a part.

10:49 am  
Blogger Tony Jackson said...

Tempus fugit:

The word ‘tinkering’ is used here as an analogy to capture some aspects of an unfamiliar process in terms more recognizable. It was first used in this evolutionary context by the famous French molecular biologist Francois Jacob. Here’s what he said:

“Natural selection has no analogy with any aspect of human behaviour. However, if one wanted to play with a comparison, one would have to say that natural selection does not work as an engineer works. It works as a tinkerer-a tinkerer who does not know exactly what he is going to produce but uses whatever he finds around him whether it be pieces of string, fragments of wood, or old cardboards; in short it works like a tinkerer who uses everything at his disposal to produce some kind of workable object.”

So for example, many proteins appear to have been assembled piecemeal from several pre-existing sources. This process of random gene rearrangement – followed please remember by selection, can be observed directly in some cases and inferred from the examined structures of genes in other cases.

It does not of course mean that there is a literal tinkerer who randomly solders bits and pieces of different genes together and, with a shrug of the shoulder throws them out of his celestial back shed.....

Or is that what you ARE claiming?

11:49 am  
Anonymous tempus fugit said...

thanks for this, tony.

I guess that since real tinkering is what you guys in the lab do when you try to recreate evolution, it doesn't seem unreasonable to suppose there is a supernatural tinkerer as well. The alternative seems to be -- if I understand you correctly -- is there are some undisclosed self-organizing processes going on, all of which would take up many volumes that have yet to be written.

By the way, where does the Jacob quote come from?

Many thanks.

12:18 pm  
Blogger Antony Latham said...

Tony, I would be interested in more detailed comments on what the tinkering seen in proteins in phylogenetic trees actually involves. My understanding is that for such trees (classically for cytochrome c) the variations seen between different animal groups are principally mutational alterations in amino acids in the inconsequential and inactive surface regions of the molecule - not in the active regions or the highly specific regions involved in folding. I would reccommend David Swift's book 'Darwin Under the Microscope' for a good discussion of this where he shows that the most important part of the proteins remain unchanged in all these lineages. Does this not rather remove the entire argument for gradual evolution?

1:59 pm  
Blogger Tony Jackson said...

Tempus fugit: “I guess that since real tinkering is what you guys in the lab do when you try to recreate evolution, it doesn't seem unreasonable to suppose there is a supernatural tinkerer as well.”

But that as they say, is an ‘unnecessary hypothesis’, since we already have a variety of known mechanisms that can in principle explain the data.

Also, if you go down that route and still want to do science, then you have to come up with some experimental test for the presence of a supernatural designer. On a thread now far, far away I asked specifically for details of such a test and I’m still waiting….

“…The alternative seems to be -- if I understand you correctly -- is there are some undisclosed self-organizing processes going on, all of which would take up many volumes that have yet to be written.”

No, I wouldn’t say that. New genes can be generated by a process of random gene duplication and ‘exon shuffling’ in which pieces of different genes are brought together by DNA recombination. Random here means ‘not biased toward functional utility’. Then these variations are subjected to NON-RANDOM selection.

Jacob’s article was published thirty years ago in Science vol 196 page 1161 (1977). You may have to pay something if you’re not at an academic institution, I don’t know.

Antony Latham: “My understanding is that for such trees (classically for cytochrome c) the variations seen between different animal groups are principally mutational alterations in amino acids in the inconsequential and inactive surface regions of the molecule - not in the active regions or the highly specific regions involved in folding. I would reccommend David Swift's book 'Darwin Under the Microscope' for a good discussion of this where he shows that the most important part of the proteins remain unchanged in all these lineages. Does this not rather remove the entire argument for gradual evolution?”

The sequences of functionally-important sites in proteins do diverge more slowly than other regions. I don’t understand why that should “remove the entire argument for gradual evolution”.

Phylogenetic reconstructions reveal the genealogical relationship between species independently of any mechanistic theories of how this relationship evolved –that’s a separate question.

The only David Swift I'm aware of is a British comedy actor. A quick Googling suggests to me that the guy you’re probably thinking about is a Behe wanabe. Am I being unfair?

2:45 pm  
Blogger Antony Latham said...

Tony, Actually the functional core of the proteins such as cytochrome c do not change and seem to be the same in all the organisms that we look at. This is a strong argument for ID which you need to address and points entirely away from some gradual process.

The question of whether there is an evolving tree or descent with modification, is another one altogether. Many ID people would accept this. What matters is whether it happened by a very gradual process involving random mutations. The evidence in molecular biology is strongly against this. We should see, in the fauna we can look at today, evidence of gradual evolution in the core functions of proteins and we do not.

David Swift's book is available on amazon.

3:33 pm  
Blogger Andrew Rowell said...

Smokey,
I am interested in your statements about me "lacking faith" can you explain?

3:57 pm  
Blogger Tony Jackson said...

Antony Latham: “Tony, Actually the functional core of the proteins such as cytochrome c do not change and seem to be the same in all the organisms that we look at. This is a strong argument for ID which you need to address and points entirely away from some gradual process.”

I still don't see why this is an argument for ID. Natural selection can conserve as well as create.

”David Swift's book is available on amazon.”

From my admittedly cursory check on Amazon, he sure looks like a Behe wannabe to me. Life is short. Is there anything in his book that has not already been covered by Behe?

5:48 pm  
Blogger Antony Latham said...

Tony, The phylogenetic trees which Darwinists proclaim are based on variations in amino acid sequences for the non-functioning (usually external) parts of the molecules. The bits that matter - actually the parts that have specified complexity, the parts that reflect important meaningful information in the DNA, are the same in different organisms.

A Darwinist should expect to find all sorts of stages in different organisms for the 'evolution' of these functional parts. After all each stage must have had a useful function in the Darwinan scenario and some of these should have been conserved. We do not see these stages. Does this not worry you?This is positive evidence for design. - and certainly not a 'God-of-the Gaps' argument.

6:50 pm  
Blogger Tony Jackson said...

Antony Latham: “Tony, The phylogenetic trees which Darwinists proclaim are based on variations in amino acid sequences for the non-functioning (usually external) parts of the molecules. The bits that matter - actually the parts that have specified complexity, the parts that reflect important meaningful information in the DNA, are the same in different organisms.”

I think you’re confused. Phylogenetic reconstructions are not just based on amino-acid sequences anymore (they haven’t been for some time). And none of my phylogenetics text-books ever mention ‘specified complexity’.

Come on, be honest. Have you in fact ever assembled a phylogenetic tree from sequence data? Would you know how to do it? Would you know how to interpret it? Would you know which pitfalls to look out for and know how to avoid them?

And there you go again talking about ‘Darwininsts’. I think as an experiment, next week I’m going to start calling my friends in the chemistry department ‘Daltonists’ and see how they react. Strangely, I can’t seem to find any university anywhere in the world that has a department of Darwinism. There are however, quite a few with departments of evolutionary biology or departments where evolutionary biology is taught and studied.

Of course I know why you do this. You want everybody to think evolutionary biology is more ideology than science – like Marxism or something. The irony of course is that the people who are really mixing up science with ideology (or at least with theology) are organisations like ‘Truth in Science’ - who I notice, are happily publicising your book.

10:23 pm  
Blogger Smokey said...

Antony Latham wrote:
"Tony, The phylogenetic trees which Darwinists proclaim are based on variations in amino acid sequences for the non-functioning (usually external) parts of the molecules."

You are totally, spectacularly wrong. Tony thinks that you are confused; I think you're just lying because you lack sufficient faith in your position to test it against the evidence (this is a perfect example in response to your question, Andrew).

Just to show how obvious your lie is, Antony, there are hundreds of sequence alignments published on the Web. Here's one from Tony's university:

http://www.mrc-lmb.cam.ac.uk/myosin/trees/txalign.html

Note that this includes the ENTIRE enzymatic domain, including the active site of the ATPase.

What do you have to say for yourself now, Antony?

"The bits that matter - actually the parts that have specified complexity, the parts that reflect important meaningful information in the DNA, are the same in different organisms."

You're simply lying. Look at the alignment. You also might (I know you and Andrew won't, as your faith is laughably weak) read structural biology papers that demonstrate that even after the sequence homology is undetectable over background, the functional cores of many protein families are preserved as structures.

Does your Bible have anything in it about refraining from bearing false witness as you have done here?

"A Darwinist..."

I agree with Tony. Your desperate need to label those of us who follow evidence as "Darwinists" is dishonest. What label should be used for someone like you, who simply manufactures evidence?

"This is positive evidence for design."

But your evidence doesn't even exist. You are a fraud, Antony.

2:05 am  
Blogger Antony Latham said...

Tony,
Tony said: 'I think you’re confused. Phylogenetic reconstructions are not just based on amino-acid sequences anymore (they haven’t been for some time). And none of my phylogenetics text-books ever mention ‘specified complexity’.'

I am not in least confused Tony. Just because there are other ways of doing phylogenetic trees does not invalidate the good work done on amino acid sequencing. This just happened to be the subject we were discussing. I would not expect your textbooks to mention specified complexity - rather a red herring you have thrown up there.

Tony said: 'Come on, be honest. Have you in fact ever assembled a phylogenetic tree from sequence data? Would you know how to do it? Would you know how to interpret it? Would you know which pitfalls to look out for and know how to avoid them?'

You are becoming rather defensive here of your ivory tower position in a lab - very elitist. Is noone else allowed to discuss these issues or have an opinion? I could go on about the breadth of education doctors like I have in the life sciences but won't. You won't get too many people engaging in your arguments if you have that attitude.

Tony said: 'And there you go again talking about ‘Darwininsts’. I think as an experiment, next week I’m going to start calling my friends in the chemistry department ‘Daltonists’ and see how they react. Strangely, I can’t seem to find any university anywhere in the world that has a department of Darwinism. There are however, quite a few with departments of evolutionary biology or departments where evolutionary biology is taught and studied.'

Are you saying you are actually not a Darwinist? Of course you do not go around saying you are Darwinists (though on discussions to do with ID many scientists actually do). Another red herring Im afraid.

Tony said:'Of course I know why you do this. You want everybody to think evolutionary biology is more ideology than science – like Marxism or something. The irony of course is that the people who are really mixing up science with ideology (or at least with theology) are organisations like ‘Truth in Science’ - who I notice, are happily publicising your book.'

I have immense regard for scientists and do not assume hidden ideologies. One of the people I have the highest regard for (you may be surprised) is Darwin himself...I recently bought his entire collected works and am reading them...some for the second or third time. If you ever get around to reading my book you will see this is the case.

Basically you have not answered any of the points I have made about Phylogenetics. I mentioned David Swift's book. OK - it was written a few years ago and no doubt you are on the cutting edge of developments but facts are facts. Let us argue based on facts. He goes into great detail about the actual differences between proteins in various eukaryotes, from yeasts to humans. I will quote one paragraph: "Bearing this in mind, we now turn to the phylogenetic trees that are constructed on the basis of the variations in amino acids sequence of present day proteins. The rationale behind the construction of the phylogenies is to show how the present differences between species have arisen progressively from a common ancestral sequence. But what needs to be recognised is that,even if the phylogenetic trees were valid (and there are reservations about them, noted below), they relate only to the occurrence of what are substantially neutral substitutions - the highly conserved amino acids remain unchanged (it could hardly be otherwise for conserved amino acids). So, at best, they can show only how relatively inconsequential changes might have taken place, and they certainly do not show how efficent modern proteins have developed from crude early ones."

I would like some proper discussion about this issue. May be David Swift and I and many other people are wrong, gloriously wrong. Then - at least show us where we are wrong!

10:26 am  
Blogger Tony Jackson said...

“I am not in least confused Tony. Just because there are other ways of doing phylogenetic trees does not invalidate the good work done on amino acid sequencing.”

See Smokey’s comments.

“I would not expect your textbooks to mention specified complexity”

Why not? If as you claim it’s important for the correct analysis of phylogenetic trees, shouldn’t it be at least mentioned in the text books?

“Is no one else allowed to discuss these issues or have an opinion?”

Of course you’re allowed an opinion, but to be taken seriously it has to be an informed opinion.

“I could go on about the breadth of education doctors like I have in the life sciences but won't.”

I have a vested interest in ensuring that doctors have a broad education in the life sciences, because I teach biochemistry/molecular biology to medical students.

“Are you saying you are actually not a Darwinist?”

Of course I’m not a ‘Darwinist’, I’m a biochemist/cell biologist. The theory of evolution has advanced enormously since Darwin’s day (it would be worrying if it hadn’t) and encompasses concepts that he would not easily comprehend. Biologists do not worship him as a Guru who’s every word is infallible. Rather, we remember him as the founder of a whole new field of science and for his brilliant insights. Modern biologists see further than Darwin because they are standing on his shoulders.

“One of the people I have the highest regard for (you may be surprised) is Darwin himself...I recently bought his entire collected works and am reading them...some for the second or third time.”

Good, you might learn something.

“Basically you have not answered any of the points I have made about Phylogenetics.”

I suppose because I’m still genuinely perplexed as to what you’re getting at. For example, in your first post you said:

“The question of whether there is an evolving tree or descent with modification, is another one altogether. Many ID people would accept this. What matters is whether it happened by a very gradual process involving random mutations.”

Isn’t that a bit like accepting beer, but denying brewing?

And later you say:

“We should see, in the fauna we can look at today, evidence of gradual evolution in the core functions of proteins and we do not.”

But modern flora and fauna are just that – modern. They lie at the tips of the twigs on the tree of life. Are you still stuck with a mental image of evolution as a linear progression along some great-chain-of-being thingy?

The conservation of some core regions of say cytochrome c among all eukaryotic species examined merely implies that this part of the structure was already established in the common ancestor and has been conserved ever since.

11:58 am  
Blogger Antony Latham said...

I said: “The question of whether there is an evolving tree or descent with modification, is another one altogether. Many ID people would accept this. What matters is whether it happened by a very gradual process involving random mutations.”

Tony said: "Isn’t that a bit like accepting beer, but denying brewing?"

No, it is not at all like your beer example. Behe, for example, holds pretty strongly to some form of evolution and direct reltionships between organisms - which may even be seen on an evolutionary tree. What matters (as regards the validity of ID) is whether there is any evidence that this process did or did not occur entirely without direction/design or teleology. ID theorists hold that we see evidence of such design. I am having to labour what is a fairly simple point here - it should come out clearer in my comments below.


I said: “We should see, in the fauna we can look at today, evidence of gradual evolution in the core functions of proteins and we do not.”

tony said: "But modern flora and fauna are just that – modern. They lie at the tips of the twigs on the tree of life. Are you still stuck with a mental image of evolution as a linear progression along some great-chain-of-being thingy? "

You have missed the point again. Modern evolutionary theory holds that the various taxa we have now (modern), descended from earlier ones and for many the branches must be 100's of millions of years ago (between us and yeast for example). We should therefore see at least some evidence of various stages in the core/important parts of proteins that these organisms share. The fact that the complex, informationally rich and important part of my cytochrome c is the same as that of a yeast merely points to conservation - there is no sign of change. We should be able to see at least some evidence of the unspeakably complex series of gradual changes that have, presumably, led to the cytochrome c protein. We don't. This is a huge problem for evolutionary theory. You would have to say that the proteins were all perfectly formed in our common ancestor - but that common ancestor must itself have had eons of time to have evolved such complexity - why no evidence? Why no descendants containing those pre-cursors now?

1:22 pm  
Blogger Tony Jackson said...

“ Behe, for example, holds pretty strongly to some form of evolution and direct reltionships between organisms - which may even be seen on an evolutionary tree. What matters (as regards the validity of ID) is whether there is any evidence that this process did or did not occur entirely without direction/design or teleology. ID theorists hold that we see evidence of such design.”

In ‘Darwin’s Black Box’, the nearest Behe comes to any ID theory is a bizarre bit of hand-waving quoted here from chapter 10:

“Suppose that nearly four billion years ago the designer made the first cell, already containing all of the irreducible complex biochemical systems discussed here and many others. (One can postulate that the designs for systems that were to be used later, such as blood clotting, were present but not “turned on”. In present day organisms plenty of genes are turned off for a while, sometimes for generations, to be turned on at a later time.) ….The cell containing the designed systems then was left on autopilot to reproduce, mutate, eat and be eaten, bump against rocks, and suffer the vagaries of life on earth.”

Is this what you mean by ‘evidence of design’ or a coherent, logically consistent theory of design? Come on, it’s absurd! For starters, if that were true, we’d expect humans to have plant genes in our DNA and plants to have blood-clotting genes in their DNA, but of course we don’t. As any A-level biologist should also be able to point out, genes left “turned off” for a few billion years will by now be well and truly smashed and incapable of ever being ‘reactivated’.

“Modern evolutionary theory holds that the various taxa we have now (modern), descended from earlier ones and for many the branches must be 100's of millions of years ago (between us and yeast for example). We should therefore see at least some evidence of various stages in the core/important parts of proteins that these organisms share. The fact that the complex, informationally rich and important part of my cytochrome c is the same as that of a yeast merely points to conservation - there is no sign of change.”

Within the eukaryotes, the cytochrome c is actually quite variable, with only a small patch of sequence around the haem-binding pocket that is absolutely identical at the amino-acid level between all the eukaryotes examined, and even here there are clear differences at the corresponding DNA level.

In any case, the eukaryotes are only one small branch on the total tree of life, and we can certainly extend the sequence analysis further a-field. So for example, we do indeed see other cytochrome and cytochrome-like proteins in bacterial species etc – eg. bacterial cytochromes c2, c550 and c551 proteins can all be identified and in their turn linked evolutionarily to eukaryotic cytochrome cs.

These bacterial proteins show a clear evolutionary relationship to eukaryotic cytochrome cs based on their overall tertiary structure and by now some rather limited sequence indentity. But remember, these bacteria are themselves modern organisms too. They won’t be making the ur-cytochrome if that’s what you’re after. I still really don’t get what your problem is.

3:27 pm  
Blogger umbjm said...

Antony: I am not in least confused Tony.

So Smokey was right--you were lying when you claimed that the functional core of proteins doesn't change.

Did you look at the link he provided? That clearly showed that you were wrong.

4:51 pm  
Blogger Antony Latham said...

Smokey: In my first comment I wrote the following....."Tony, I would be interested in more detailed comments on what the tinkering seen in proteins in phylogenetic trees actually involves. My understanding is that for such trees (classically for cytochrome c) the variations seen between different animal groups are principally mutational alterations in amino acids in the inconsequential and inactive surface regions of the molecule - not in the active regions or the highly specific regions involved in folding. I would reccommend David Swift's book 'Darwin Under the Microscope' for a good discussion of this where he shows that the most important part of the proteins remain unchanged in all these lineages. Does this not rather remove the entire argument for gradual evolution?"

I have not been lying and have used words such as 'my understanding is..' 'principally' etc. I agree that some changes have occurred in the active regions. These do seem minimal though and do not tally at all well with a gradual evolutionary history. Essentially we see conservation.

On another equally important point: can you tell us why the various phylogenetic trees constructed from amino acid, RNA sequencing etc do not agree with one another? They show very different cladistic orders and they often do not agree with the commonly understood order of evolutionary relationships.

6:19 pm  
Blogger Smokey said...

Antony wrote:

"Smokey: In my first comment I wrote the following....."Tony, I would be interested in more detailed comments on what the tinkering seen in proteins in phylogenetic trees actually involves. My understanding is..."

Antony, I wasn't responding to your first comment. I quoted and refuted your lie, quoted below.

"Tony, Actually the functional core of the proteins such as cytochrome c do not change and seem to be the same in all the organisms that we look at. This is a strong argument for ID which you need to address and points entirely away from some gradual process."

"I have not been lying and have used words such as 'my understanding is..' 'principally' etc. "

No such words appear in your lie.

"I agree that some changes have occurred in the active regions."

Then we agree that your statement was a lie.

"These do seem minimal though and do not tally at all well with a gradual evolutionary history."

In what way would you characterize the changes in the alignment I linked to as "minimal," Antony?

Out of ~1000 amino acid residues in the myosin motor domain, how many are conserved in ALL myosins?

"Essentially we see conservation."

Essentially, you are ignoring the evidence and fabricating evidence that you like better.

"On another equally important point: can you tell us why the various phylogenetic trees constructed from amino acid, RNA sequencing etc do not agree with one another?"

After allowing for systematic errors, they do agree with each other.

Why, instead of fabricating evidence, don't you point to actual evidence?

"They show very different cladistic orders..."

No, they don't, except for differences caused by systematic errors that are easily swamped by mountains of data.

"... and they often do not agree with the commonly understood order of evolutionary relationships."

Often? If this is often the case, why don't you point to a single example, Antony?

Because you are lying yet again?

8:23 pm  
Blogger Andrew Rowell said...

Smokey,

So the "lack of faith" is a lack of confidence that ID is correct... is that what you mean? We are holding on to this idea but terrified to actually confront it with reality?

9:28 pm  
Blogger Smokey said...

Andrew,

Exactly. That's why it's all blogging, spinning, and quote-mining, and no data from testing any ID hypotheses.

When I (or any other real scientist) think I have a hypothesis that I think is right, I love thinking of the best way to test it. The last thing I think of is writing a book, blogging, or publishing apologetic tomes reinterpreting other people's data.

The hypotheses that I am less interested in testing are the ones I have less faith in, with one exception--I am more interested in overturning dogma. That's why the ID/creationist babbling about conservatism is so dishonest and disgusting.

If I apply those criteria to the ID movement, including those with credentials, it is utterly clear that you have no real faith.

Like a series of tributaries! Emilio thought, and felt once more the visceral thrill of trying to disprove a hypothesis he knew was robust.
Mary Doria Russell, Children of God

While the science in this quote is linguistics, this thrill is the same across all science. Because ID isn't science, you can't point to a single person on Earth who is trying to disprove (testing) an ID hypothesis.

10:25 pm  
Blogger Andrew Rowell said...

Smokey,

Time will show with regards to ID research.

What do you think of Kuhn's work? Do you consider it complete rubbish?

10:42 pm  
Blogger Smokey said...

Andrew,

I'm glad to see that you didn't bother challenging anything I wrote. Does that mean that you agree with me?

As for your reply, time HAS ALREADY shown. There's simply nothing to ID, not even real faith. No one is even planning to test an ID hypothesis.

It's not because it's impossible--heck, I've tested one of Dembski's most fundamental assumptions in the process of identifying the function of a single protein, and found it to be rubbish.

What does Kuhn have to do with the absence of faith in the ID movement, other than an attempt to change the subject?

Why do you think you so obviously shy away from engaging in any real discussion here?

10:56 pm  
Blogger Antony Latham said...

Smokey and Andrew: Just to show that your position on phylogenetics is not held by some of the major players in the field, here is a quote from Carl Woese: "No consistent organismal phylogeny has emerged from the many individual protein phylogenies so far produced. Phylogenetic incongruities can be seen everywhere in the universl tree, from its root to the major branchings within and among the various taxa to the makeup of the primary groupings themselves." Woese, Carl. 1998. The Universal Ancestor. Proceedings of the National Academy of Sciences USA. 95: 6854-6859

Woese you will agree is an acknowledged leader in this field. In my book I also mention the fact that he finds the phylogenetic tree of life to be "rootless" based on RNA sequences. This accords well with at least an initial intelligent input to the construction of life.

Andrew said "In any case, the eukaryotes are only one small branch on the total tree of life,..."

I am rather amazed that you think they are a small branch when all the rest are bacteria.

Anyway - going back to the conserved functional part of cytochrome c: I assume you know that Human cytochrome C works in yeast that has its own native Cytochrome C gene deleted - even though yeast cytochrome C differs from that of humans over 40% of the protein. (Tanaka et al 1988). In fact only just over one third of the 104 amino acids in cytochrome C are apparently needed for its function. 37 of the 104 have been found at equivalent positions in every cytochrome c that has been ever sequenced. In other words - I am correct in saying that the core part is the same in every organism. These 37 identically positioned amino acids must have come (in neo-Darwinian terms) from a very long history of pre-cursors. We should have some evidence of this in some of the modern organisms but we do not.

11:07 pm  
Blogger Smokey said...

Antony:

1) Carl Woese wrote that in 1998. What proportion of total sequence data has been produced since he wrote that? It's both lame and dishonest to quote-mine and implicitly claim that nothing has happened in 9 years.

2) "In my book I also mention the fact that he finds the phylogenetic tree of life to be "rootless" based on RNA sequences. This accords well with at least an initial intelligent input to the construction of life."

You're desperately cherry-picking. You're being completely, utterly dishonest when you limit consideration to RNA when you consider that protein sequences do a far better job of getting you to the roots. In fact, I cited a paper that used this to draw conclusions about the the common ancestor of eukaryotes in the other thread. Andrew, of course, ignored it.

3) "Anyway - going back to the conserved functional part of cytochrome c: I assume you know that Human cytochrome C works in yeast that has its own native Cytochrome C gene deleted - even though yeast cytochrome C differs from that of humans over 40% of the protein."

Yes. There are hundreds of cases in which human transgenes rescue mouse mutants, too.

"In fact only just over one third of the 104 amino acids in cytochrome C are apparently needed for its function."

You're simply lying again. If you deleted the 2/3 that aren't conserved, you'd have no function whatsoever. YOU CAN'T DRAW ACCURATE CONCLUSIONS ABOUT WHAT IS NEEDED FROM SEQUENCE ALIGNMENTS--YOU HAVE TO DO EXPERIMENTS. Does the shouting help get across this essential point?

"37 of the 104 have been found at equivalent positions in every cytochrome c that has been ever sequenced."

I know. But are those positions consecutive in the protein, Antony? By what logic did you conflate conservation with necessity? The logic of someone so lazy that he won't do anything empirically?

"In other words - I am correct in saying that the core part is the same in every organism."

No, you're just redefining "functional core" in nonfunctional terms because I called you on your blatant lie. It would take deletion experiments to define any real functional core, not sequence alignments. Have you even bothered to look for them before making your expansive claim? How can you claim anything about function when you haven't measured function?

"These 37 identically positioned amino acids must have come (in neo-Darwinian terms) from a very long history of pre-cursors. We should have some evidence of this in some of the modern organisms but we do not."

Another spectacular lie! We have loads of evidence. There's a huge superfamily of related proteins:

http://expasy.org/prosite/PDOC00169

And here's an alignment showing that some residues are conserved, but their positions clearly aren't:

http://expasy.org/cgi-bin/aligner?psa=PS51007&color=1

I eagerly await your use of the "No True Scotsman" fallacy, 'cause that's all you have left.

Antony, here's how I know you are lying: I have directly tested the assumption that conservation of certain residues necessarily means that those residues are necessary for function. It is utterly false.

You, OTOH, lack the faith in your hypothesis to do anything empirically. So you quote-mine, cherry-pick, redefine critical terms, and lie instead.

12:09 am  
Anonymous Anonymous said...

Smokey, thanks for link to aligned myosin sequences at http://www.mrc-lmb.cam.ac.uk/myosin/trees/txalign.html; but link on this page to the unrooted phylogenetic tree doesn't seem to work. Do you have another link to it?

1:03 am  
Blogger Smokey said...

Try clicking the links on this page:

http://www.mrc-lmb.cam.ac.uk/myosin/trees/trees.html

1:55 am  
Blogger Tony Jackson said...

Antony Latham: “Andrew said "In any case, the eukaryotes are only one small branch on the total tree of life,...". I am rather amazed that you think they are a small branch when all the rest are bacteria.”

I said that, not Andrew. I think your comment is highly revealing as to your true understanding of biology. See this and feel suitably humble:

http://itol.embl.de/itol.cgi

“On another equally important point: can you tell us why the various phylogenetic trees constructed from amino acid, RNA sequencing etc do not agree with one another?”

Do you understand the concept of the error bar?

By the way, I notice you still haven’t answered the questions I posed earlier:

1) Have you in fact ever assembled a phylogenetic tree from sequence data?

2) Would you know how to do it?

3) Would you know how to interpret it?

4) Would you know what pitfalls to look out for and know how to avoid them?

I’m betting the answers to those questions are: no, no, no and……no.

7:13 am  
Blogger Antony Latham said...

Smokey, It is becoming a bit tedious going over this again. We have agreed that the facts are that 37 of the amino acids in cytochrome c are ALWAYS in position and are the same in every organism. These are the ones that make it cytochrome c and are responsible for the folding, haem position etc. I never said that such core amino acids had to be in a continuous sequence. Of course there are others in between. It is about time you admitted all this - as I said at the beginning, the core functional amino acids do not change. It is very rich to say that this is a lie.

You are wrong on another point - rRNA is used by researchers at the top of their field for the analysis of the deepest roots of the 'universal tree' (which is indeed found to be rootless).

Sorry Tony: if you still think the eukaryotes (everything other than prokaryotes and Archaea)are a small side branch then I am very perplexed to put it mildly.

As for your last 4 questions Tony: I do not have the privilege of working in a biochemists research lab but I defend my right to argue about these issues despite that. Otherwise us lesser mortals have to sit passively as we are fed the 'truth'. The fact that many ID proponents are doing just as much serious front line lab work should make you cautious about flagging this up again - do you not think?

9:24 am  
Blogger Tony Jackson said...

“Sorry Tony: if you still think the eukaryotes (everything other than prokaryotes and Archaea)are a small side branch then I am very perplexed to put it mildly.”

So did you go to that website I recommended? Here it is again:

http://itol.embl.de/itol.cgi

And that doesn’t even mention viruses, a vast and still largely unexplored area of phylogenetics.

“As for your last 4 questions Tony: I do not have the privilege of working in a biochemists research lab but I defend my right to argue about these issues despite that. Otherwise us lesser mortals have to sit passively as we are fed the 'truth'.”

No one is stopping you saying whatever you like about evolution – your published book is proof enough of that. But…..if we are going to discuss, say phylogenetics constructively, then you really are going to have to bite the bullet, read some of the papers and learn at least enough of the technical details that you can understand the arguments we’re making. As it is, I get a queasy feeling that you don’t know what you’re talking about and an even queasier feeling that you don’t care that you don’t know what you’re talking about.

Out of context quote-mining can only get you so far. It doesn’t cut any ice with most practicing scientists.

I’m not being elitists or snooty here. I’m making an absolutely central point. Smokey, myself and others have put in quite a bit of effort (not just here, but on other threads as well) to point you and your friends in the right direction and even given you references to papers and websites that illustrate some of the themes we are talking about. Now read them!

“The fact that many ID proponents are doing just as much serious front line lab work should make you cautious about flagging this up again - do you not think?”

Didn’t we have this argument somewhere else in another lifetime? I don’t believe there is any serious ‘front line lab work’ in ID.

10:48 am  
Blogger Tony Jackson said...

Oh and by the way, your claim that you can’t do phylogenetics because you don’t work in a biochemistry lab is silly. These days, all you need is a computer and access to the web (although a nice chair and a cup of coffee also helps).

Start here:

http://paup.csit.fsu.edu/

11:14 am  
Blogger Antony Latham said...

Tony said:So did you go to that website I recommended?

Yes I did. Noone is arguing against the fact that single celled organisms have vast numbers of species. If that is the criteria for big or small branch then fine. I was (and I think most would agree) referring to the fact that eukaryotes constitute the only 'branch' that has complex multicellular creatures and plants - including you and I. It is therefore 'big' in complexity and diversity. All this in any case seems a red herring. I do not wish to score points for the sake of it.

Tony said: "No one is stopping you saying whatever you like about evolution – your published book is proof enough of that. But…..if we are going to discuss, say phylogenetics constructively, then you really are going to have to bite the bullet, read some of the papers and learn at least enough of the technical details that you can understand the arguments we’re making. As it is, I get a queasy feeling that you don’t know what you’re talking about and an even queasier feeling that you don’t care that you don’t know what you’re talking about."

I do not know as much as you about biochemistry - obviously. I depend on people like you to provide the facts and I read them. In this context show me one thing I have said so far which is actually in error. We have established (at last) that cytochrome c does indeed have a core group of amino acids which constitutes an active essential and totally unchanging part which is in every organism ever looked at. You and smokey refuted this but now remain silent about it....

12:11 pm  
Blogger Smokey said...

Andrew,

Let's dissect Antony's evasive responses and see how they all flow from his dishonesty and his lack of faith.

Antony wrote:
"Smokey, It is becoming a bit tedious going over this again. We have agreed that the facts are that 37 of the amino acids in cytochrome c are ALWAYS in position and are the same in every organism."

Andrew, what Antony is desperately avoiding is the fact that whether those proteins were designed or evolved, the sequences in nature are optimized ones, not the minimal ones necessary for function. Making any claim about a functional core requires functional assays, not sequence alignments. Remember that above, I pointed out that I personally have tested this assumption. If Antony was an inquisitive person with any confidence in his opinion, he would ask for the data instead of ignoring my response and reasserting his false claim.

"These are the ones that make it cytochrome c and are responsible for the folding, haem position etc."

So, Antony, there are two obvious predictions for you to avoid checking against reality:
1) mutating any of these residues will abolish cytochrome c function.
2) no members of the family with fewer conserved residues will rescue a cytochrome c mutant.

So, Antony, what odds will you give me that both of these predictions can be demolished, and how much money will you bet? This is a test of faith.

Andrew, there are multiple papers that show Antony's claim to be a lie. Note that he isn't citing any functional data to support his claims about function. He will continue to assert his lie, he will avoid asking for the papers that show his claim to be false, and he won't put up his money, all because he has no faith in his position.

"I never said that such core amino acids had to be in a continuous sequence. Of course there are others in between."

Then those amino acid RESIDUES (not amino acids) are part of a functional core, too. Determining the functional core requires functional assays. Do you know of any functional data relevant to your claim? I do! ;-)

"It is about time you admitted all this - as I said at the beginning, the core functional amino acids do not change."

It's time you admitted that they can easily be changed experimentally, meaning that they are not essential parts of a functional core.

"It is very rich to say that this is a lie."

I do say it is a lie. You are an incredibly dishonest man who lacks faith in his claims. That's why you make claims about functional cores of proteins while refusing to look at the functional data.

Andrew: someone with faith and interest would first want to see the data. Antony is driven by ego.

"You are wrong on another point - rRNA is used by researchers at the top of their field for the analysis of the deepest roots of the 'universal tree' (which is indeed found to be rootless)."

Antony, your claim is almost a decade old. You are profoundly ignorant, and you are afraid to lose your ignorance.

"As for your last 4 questions Tony: I do not have the privilege of working in a biochemists research lab but I defend my right to argue about these issues despite that."

But you don't argue the issues from the data. Quotes aren't data, and in your heart, you know it.

"Otherwise us lesser mortals have to sit passively as we are fed the 'truth'."

Then why won't you do some alignments for yourself? Are you afraid of what you might find?

"The fact that many ID proponents are doing just as much serious front line lab work should make you cautious about flagging this up again - do you not think?"

Antony, NO ID proponents are doing ANY work to test any ID hypotheses. They, like you, are afraid to test their wishful thinking against reality.


Tony wrote:
"But…..if we are going to discuss, say phylogenetics constructively, then you really are going to have to bite the bullet, read some of the papers and learn at least enough of the technical details that you can understand the arguments we’re making. As it is, I get a queasy feeling that you don’t know what you’re talking about and an even queasier feeling that you don’t care that you don’t know what you’re talking about."

See, Andrew? As Tony notes, Antony is afraid to look at the data for himself.

"I do not know as much as you about biochemistry - obviously. I depend on people like you to provide the facts and I read them."

No, Antony, you ignore the facts. Every time you have been challenged to support your claims with facts, you resort to subterfuge like quote-mining and redefinition of obvious terms like "functional."

You have no faith, so you are afraid of the facts.

"In this context show me one thing I have said so far which is actually in error. We have established (at last) that cytochrome c does indeed have a core group of amino acids which constitutes an active essential and totally unchanging part which is in every organism ever looked at."

Indeed. But your lie is that these amino acid residues (they are no longer amino acids) are required as part of a functional core. Multiple, published functional assays of mutants at these completely conserved residues show that you are lying.

"You and smokey refuted this but now remain silent about it...."

You are delusional, Antony. We are the ones citing data, you are the one afraid of data. Why didn't you answer Tony's question about whether you have ever bothered to do a sequence alignment for yourself?

4:53 pm  
Blogger Tony Jackson said...

“No one is arguing against the fact that single celled organisms have vast numbers of species. If that is the criteria for big or small branch then fine. I was (and I think most would agree) referring to the fact that eukaryotes constitute the only 'branch' that has complex multicellular creatures and plants - including you and I. It is therefore 'big' in complexity and diversity.”

OK, but that’s not always a relevant criteria when it comes to phylogenetic considerations. Anyway, don’t bacteria themselves also have some pretty spiffy and amazingly complex things? Like, er....flagella.

“In this context show me one thing I have said so far which is actually in error.”

Where do we start? See posts from Smokey and umbjm.

“We have established (at last) that cytochrome c does indeed have a core group of amino acids which constitutes an active essential and totally unchanging part which is in every organism ever looked at.”

Re-read Smokey’s posts Carefully.

5:05 pm  
Blogger Antony Latham said...

Smokey and Tony:

Going back to those 37 constant amino acid residues: you suggest they are not essential for function but just the most optimal (they must be either essential or optimal in evolutionary terms for them to be so consistently conserved) Fine - they are the optimal ones. Optimal for what? For the function of the molecule of course. Whatever way you look at it they are functional, as I have been saying all along...why is this a problem?

It is still a sensible question to ask - why or how did these residues become so optimally organised from the earliest times - with no evidence of present organisms containing other arrangements on the presumably long and tortuous path of gradual evolution of cytochrome c?

Smokey said: "Antony, NO ID proponents are doing ANY work to test any ID hypotheses. They, like you, are afraid to test their wishful thinking against reality".

Really? How about Dean Kenyon - Professor Emeritus of biology at San Francisco State University...or Scott Minnich of University of Idaho. Very sweeping statement you made there.

10:02 pm  
Blogger Andrew Rowell said...

David Swift on Molecular Phylogenies.

It may help at this point to have a few notes from David Swift's book:

He gives the diagram of a most parsimonious tree for Cyt C and says "it shows clear similarities to traditional morphologu based phylogenies. This parallel between molecular and morhological phylogenies was seen as strong supporting evidence of the evolutionary process. Not only did these early rsults strengthen the acceptance of Neo-Darwinism, it also indicated that the new findings from molecular biochemistry would be entirely consistent with it."

He then gives a diagram of the phylogeny of the globins and talks about the idea of a molecular clock with different proteins changing at different speeds over time- histone H4 being slow and fibrinopeptides being very fast.

The next section then goes on to discuss the neutral theory and briefly describes the confirming evidence for it and the arguments between neutralists and selectionists over the last two decades.

Swift then goes on to argue that as more sequence data has become available they began to cast doubt upon the early interpretations.

A phylogenetic tree does not really tell us very much about the origin of the function of the proteins concerned.
An important point that Swift makes is that the phylogenies of these similar proteins are constructed on the basis of their differences. These differences occur in positions of the protein which tend towards neutrality in their effects on normal function. Thus the phylogenies may be a useful guide to how these proteins have changed over time they do not help a great deal in terms of explaining how the original useful function arose in the first place.

He argues that with many proteins there are large numbers of amino acid positions in the protein which require a particular amino acid or which only allow a very small subset of amino acids to be present for biological function. He suggests that this indicates that when a protein first appear on the scene as a functional selectable entity it has the function that we are aware of today and has reached somewhere within the outer constraints for that particular proteins activity.

The problems of phylogenetic trees.

The rates of amino acid substitution vary considerably in different proteins. Some workers have concluded that the molecular clock ticks so erratically that it is of no value.
Swift references Baba et al and Joysey to confirm that a parsimonious tree based soley on the degree of similarity between sequences differed so much from a conventional phylogeny that other explanations had to be added to overcome the anomalies. In the end scientists end up looking for ways to make the molecular data fit the morphological data.

Different proteins produce different phylogenetic trees.
A number of real oddities have been found in these kind of studies – (cyt-c in Arabidopsis)

There is the difficulty of using raw differences between sequences to assess relatedness as the number of changes will not have followed a direct route.

Studies on the rubisco protein in plants suggest that even with closely related group the differences are just toggling between a number of possible positions and do not give reliable results.

The relationship between the testicular cyt c and the somatic cyt –c is problematic.

10:11 pm  
Blogger Andrew Rowell said...

Tony,
Just out of interest have you got Michael Denton's book- "Evolution a Theory in Crisis"? If so I would be interested in your comments on chapter 12.

10:18 pm  
Blogger Smokey said...

Antony wrote:
"Going back to those 37 constant amino acid residues: you suggest they are not essential for function..."

Suggest? Hell, I KNOW they aren't. That took me about 30 seconds to figure out. Does that give you a general idea about the superficiality of your approach?

"... but just the most optimal (they must be either essential or optimal in evolutionary terms for them to be so consistently conserved) Fine - they are the optimal ones."

Good! We agree that you lied when you labeled them as essential.

"Optimal for what? For the function of the molecule of course."

Why "of course," Antony? Because someone as ignorant as you says so?

Why couldn't they be optimized for completely different reasons--BEFORE translation?

"Whatever way you look at it they are functional, as I have been saying all along...why is this a problem?"

Because you lied about a simple, factual matter, and now you're peddling additional fabrications to salvage your dignity.

"It is still a sensible question to ask - why or how did these residues become so optimally organised from the earliest times -"

We don't know that they did. We only have sequences from organisms that live now.

"... with no evidence of present organisms containing other arrangements on the presumably long and tortuous path of gradual evolution of cytochrome c?"

You forgot your other lie, Antony. There is a huge family of related proteins. I pointed you to an alignment that you ignored, because you lack real faith in your position.

"Really?"

Really.

"How about Dean Kenyon - Professor Emeritus of biology at San Francisco State University"

Not testing any ID hypotheses.

"...or Scott Minnich of University of Idaho."

Not testing any ID hypotheses. Have you read any publications from either of them?

If you disagree with me, your rebuttal would be of the form:

1) The ID hypothesis X makes prediction Y.
2) Joe Blow tested prediction Y, and produced the following data...

Real scientists produce data from tests of their own hypotheses.

"Very sweeping statement you made there."

Yes, and it is true, unlike your sweeping lies.

-------

Andrew Rowell said...
"David Swift on Molecular Phylogenies."

Why resort to authority, Andrew? Do you lack the faith to look at the data for yourself?

Wait! Is David Swift an authority on anything relevant here?

"Swift then goes on to argue that as more sequence data has become available they began to cast doubt upon the early interpretations."

That's nice and fuzzy. What about the data, Andrew?

"A phylogenetic tree does not really tell us very much about the origin of the function of the proteins concerned."

Actually, it does, particularly when we find that a protein of unknown function is related to proteins of known function.

"An important point that Swift makes is that the phylogenies of these similar proteins are constructed on the basis of their differences."

Yes. What is the significance of this, Andrew? Why is that an important point? How can one produce a phylogeny without differences?

"These differences occur in positions of the protein which tend towards neutrality in their effects on normal function."

NO. This is Antony's lie that we just dispensed with.

"He argues that with many proteins there are large numbers of amino acid positions in the protein which require a particular amino acid..."

And without actual data, such arguments are meaningless.

"He suggests that this indicates that when a protein first appear on the scene as a functional selectable entity it has the function that we are aware of today and has reached somewhere within the outer constraints for that particular proteins activity."

That's total BS, demonstrated experimentally, of course. Tony has already pointed this out.

"Different proteins produce different phylogenetic trees. A number of real oddities have been found in these kind of studies – (cyt-c in Arabidopsis)"

Yes, we know. We know that there are systematic errors that will produce this. We overcome them by using many different protein sequences.

"The relationship between the testicular cyt c and the somatic cyt –c is problematic."

Why, Andrew?

11:05 pm  
Blogger Smokey said...

Andrew,

Analyze Antony's strategy here. First, he lies:

"We should have some evidence of this in some of the modern organisms but we do not."

Then, I point out his lie:
"Another spectacular lie! We have loads of evidence. There's a huge superfamily of related proteins:

Then, I point him to the data:
"http://expasy.org/prosite/PDOC00169

"And here's an alignment showing that some residues are conserved, but their positions clearly aren't:

"http://expasy.org/cgi-bin/aligner?psa=PS51007&color=1"

What does Antony do, Andrew? He simply repeats his lie in a later post, hoping you won't notice:
"... with no evidence of present organisms containing other arrangements on the presumably long and tortuous path of gradual evolution of cytochrome c?"

Now, "no evidence" is a very sweeping claim that requires looking for evidence before making it. Yet, when I point Antony to evidence, he makes no attempt whatsoever to address it. He just repeats his lie, because he simply has no real faith.

What sort of Christian bears false witness like this?

11:13 pm  
Blogger Antony Latham said...

smokey: here is a recent paper from Scott Minnich. Please read it carefully

http://www.discovery.org/scripts/viewDB/index.php?command=view&id=2181

You challenge with:

1) The ID hypothesis X makes prediction Y.
2) Joe Blow tested prediction Y, and produced the following data...


1/ the Id hypothesis is that if we study the bacterial flagellum we should not see any function for it if any of the constituents are lost.

2/ In this paper he shows that loss of just one constituent in the system leads to loss of others. There is no function unless all constituents are in place.

By the way in the discussion he also challenges the idea that co-option of the T3SS is an evolutionary pathway to the flagellum. Phylogenetic analyses of gene sequences shows that Type 3 secretory systems are most likely derived secondarily from fully formed flagella.

Smokey: Your blustering and frankly abusive tone does little for your credibility as an objective scientist. Can you calm down a bit??

Yes I have looked at the other 'related' proteins to cytochrome c. This is like looking at similar bits of various complex machines - most cars for instance have varieties of computer chips and micro circuits - all a bit different. Cars are designed.

cytochrome c - despite all your protestations has got identifiable minimal numbers of amino acid residues (37) which are in all organisms containing this vital protein. Have you worked out the chances of such numbers of precisely placed residues occuring randomly? Remember,in evolutionary theory, they had to be organised randomly at each step before natural selection could work.

I challenge you and Tony to show me a clear and theoretically feasable evolutionary history of any protein - from the first replicating molecules to a fully fledged enzyme. Obviously this had to happen in a very short geological time because we now have evidence for photo-synthetic bacteria from 3.8 billions years ago....more or less the time when asteroid collision and conditions had become possible for life.

10:13 am  
Blogger Andrew Rowell said...

Smokey,
Do you agree with the following summaries?

1. We agree that for a particular protein with a particular function there are areas of the amino acid sequnce which are tightly conserved accross many different organisms.

2. We agree that these conserved areas are often those associated with the business part of the molecule and its overall structure eg. folding etc.

3. We agree also that there are gene families where the usual explanation is that a gene duplication event has taken place in the past and the two copies have diverged so that they have a related but different function. The common example here is the globin family. The bridge between different sub families requires the substitution of one set of conserved amino acid sequences for another.

10:17 am  
Blogger Andrew Rowell said...

Smokey,
I said:
"A phylogenetic tree does not really tell us very much about the origin of the function of the proteins concerned."

You said:
Actually, it does, particularly when we find that a protein of unknown function is related to proteins of known function.

Sure the similarity of conserved regions is useful in pointing to possible functions... but that is not what I was talking about.

Knowing what its function is does not tell us how the function arose.

10:25 am  
Blogger Andrew Rowell said...

Smokey,
You said:
"We know that there are systematic errors that will produce this. We overcome them by using many different protein sequences."

Are you saying that simply using large numbers of sequences solves all the problems of these anomalies?

10:29 am  
Blogger Andrew Rowell said...

Smokey,
You said:
"It's not because it's impossible--heck, I've tested one of Dembski's most fundamental assumptions in the process of identifying the function of a single protein, and found it to be rubbish."

I am interested Smokey...can you give me some more details?

11:41 am  
Blogger Tony Jackson said...

Andrew. Whoa, slow down, some of us work for a living and can't stay at the computer all day.

I've just got time for one thing at the moment:

"Tony, Just out of interest have you got Michael Denton's book- "Evolution a Theory in Crisis"? If so I would be interested in your comments on chapter 12."

Michael Denton eh? It's been a while since I heard that name - twenty years in fact since I read "evolution, a theory in crisis". No I don't have a copy of his book with me and frankly I don't want to waste time trying to find one, so I'm working from memory here. But I do recall a gloriously dopey example of misunderstanding from his book concerning the interpretation of cytochrome c phyologenetic trees. As I remember, Denton was shocked to discover that the number of amino-acid differences between say the yeast and human cytochrome c and between the yeast and fish cytochrome c was approximately the same. According to Denton this disproves evolution.

Let’s make something positive out of this: Andrew and Antony, for your homework tonight, in no more than one paragraph, please explain where Denton went wrong.

You can communicate with each other, and you are allowed to use any textbooks or web-based material you like.

Extra marks will be given for clear and concise answers.

Off-topic waffling will be severely penalised.

I’m serious. I’m giving this problem to my first year students this afternoon. Let’s see if you can beat Cambridge’s brightest.

11:58 am  
Blogger Smokey said...

Antony wrote:
"smokey: here is a recent paper from Scott Minnich. Please read it carefully..."

I did. It's not a paper. It's a Web page. The PDF at the link contains ZERO data relevant to any ID hypothesis.

"1/ the Id hypothesis is that if we study the bacterial flagellum we should not see any function for it if any of the constituents are lost."

You're lying again. The ID hypothesis is that IF this is the case, then the flagellum could not have evolved.

Secondly, all that is required to falsify the condition of "any" is the loss of a SINGLE constituent does not result in loss of function. If you had the courage to look at data, you'd know that this is true for many of the components of the eubacterial flagellum (you're so shallow that you don't know that bacteria have nonhomologous flagella, not a single type).

"2/ In this paper he shows that loss of just one constituent in the system leads to loss of others. "

So what? Other papers show that loss of just one constitutent has no significant effect. One has to test all to test a hypothesis that refers to "any."

"There is no function unless all constituents are in place."

You're a pathological liar, Antony. Would you like me to point you to the many papers that prove it?

I hypothesize that you wouldn't.

"By the way in the discussion he also challenges the idea that co-option of the T3SS is an evolutionary pathway to the flagellum."

By the way, that idea was challenged long ago.

"Phylogenetic analyses of gene sequences shows that Type 3 secretory systems are most likely derived secondarily from fully formed flagella."

Which unequivocally proves that the eubacterial flagellum is not IC, because components are missing and the remaining components have a different function.

"Smokey: Your blustering and frankly abusive tone does little for your credibility as an objective scientist. Can you calm down a bit??"

Why, Antony? Lying is second nature to you. It's obvious that you know that you are lying, as you simply reiterate your lies when challenged.

"Yes I have looked at the other 'related' proteins to cytochrome c."

Then you were lying when you claimed, "...with no evidence of present organisms containing other arrangements..."

"This is like looking at similar bits of various complex machines - most cars for instance have varieties of computer chips and micro circuits - all a bit different. Cars are designed."

I already knew that. What I also know is that the components of cars don't fit into nested hierarchies like the components of living things do. Your analogy is fraudulent.

"cytochrome c - despite all your protestations has got identifiable minimal numbers of amino acid residues (37) which are in all organisms containing this vital protein."

I protested your lie in claiming that the 37 residues were ESSENTIAL. Have you considered remedial English classes?

"Have you worked out the chances of such numbers of precisely placed residues occuring randomly?"

No, because it's irrelevant. They came to be in those positions by a decidedly nonrandom process.

"Remember,in evolutionary theory, they had to be organised randomly at each step before natural selection could work."

You're lying again, because you are assuming that your lie -- that these are ESSENTIAL for function -- is true.

Nothing but lies, Antony. How can you call yourself a Christian when you can't resist bearing false witness?

"I challenge you and Tony to show me a clear and theoretically feasable evolutionary history of any protein - from the first replicating molecules to a fully fledged enzyme."

Nylonase:
http://www.nmsr.org/nylon.htm
http://www.talkorigins.org/origins/postmonth/apr04.html

In return, please tell me the names of your parents, and explain how you know that they are your parents--I want your complete history, including the date and time of your alleged parents' copulation, the date of fertilization, and the position of the ovum along your alleged mother's oviduct.

Then, you need to give me a complete history of the design of the eubacterial flagellum, as well as the other bacterial flagella. From the beginning.

5:20 pm  
Blogger Smokey said...

Andrew wrote:
"Smokey,
Do you agree with the following summaries?

1. We agree that for a particular protein with a particular function there are areas of the amino acid sequnce which are tightly conserved accross many different organisms."

Yes. Do you agree that inferring from sequence alignments that the conserved residues are essential for the particular function is invalid, and that claiming this inference as a fact is a lie?

"2. We agree that these conserved areas are often those associated with the business part of the molecule and its overall structure eg. folding etc."

Often, but not always.

"3. We agree also that there are gene families where the usual explanation is that a gene duplication event has taken place in the past and the two copies have diverged so that they have a related but different function."

Yes. Do we agree that IDers and creationists have no explanation for this phenomenon, as well as the fact that the sort of partially-overlapping functions this evolutionary mechanism produces are NEVER observed in any objects known to be designed?

"Sure the similarity of conserved regions is useful in pointing to possible functions... but that is not what I was talking about."

It's not only useful in pointing to possible functions, but also in the origin of those functions, which is exactly what you were talking about.

"Knowing what its function is does not tell us how the function arose."

I didn't claim that. I claimed that the relationships do tell us something about how the function arose.

"Are you saying that simply using large numbers of sequences solves all the problems of these anomalies?"

Yes, large numbers of sequences for different genes for the organism one is attempting to classify. Do you agree that quoting from a 9-year-old paper in an effort to rebut a statement about the statement of molecular phylogeny today constitutes a blatantly dishonest evasion?

"I am interested Smokey...can you give me some more details?"

I am willing to, but under conditions (it would require a lot of effort and explanation):

1) You quote and directly respond to every point I have made in this comment thread.

2) You correct your gross misrepresentation of my explanation as to why Behe's demand is a red herring:
http://idintheuk.blogspot.com/2007/01/possible-pathways-for-evolution-of_27.html


3) You address my accurate analogy for intracellular transport in the same thread.
If you disagree with it, you must cite data from the primary literature that support Behe's sophomoric analogy.

4) You perform Tony's homework assignment.

5) You explain why Antony does not ask for details in the same situation.

6) You do all of this without any attempts to change the subject.

You see, Andrew, as a scientist, I set up conditions so that my hypothesis about your motivation can be falsified.

6:25 pm  
Blogger Tony Jackson said...

Antony Latham:
"I challenge you and Tony to show me a clear and theoretically feasable evolutionary history of any protein - from the first replicating molecules to a fully fledged enzyme."

Bloody hell Antony, you don't ask for much do you? Why don't you re-read my very first post on this thread and take on board my mediaeval historian analogy.

7:47 pm  
Blogger Tony Jackson said...

Andrew: "A number of real oddities have been found in these kind of studies – (cyt-c in Arabidopsis)"

Andrew, I'm genuinely curious about this claim about Arabidopsis cytochrome c, because I've found it on several creationist websites and I also gather that it's mentioned in David Swift's book. Can you tell me where does this claim come from and why exactly does it cause problems for evolution?

7:57 pm  
Blogger Andrew Rowell said...

Smokey,
You asked:
"Do you agree that inferring from sequence alignments that the conserved residues are essential for the particular function is invalid, and that claiming this inference as a fact is a lie?"

If it was not true I would call someone who maintained that it was - mistaken. I would tend to be very cautious indeed about the use of the word "lie". In my opinion you would need to do some protein engineering and check for the function. However tight conservation I would say is a good clue which bits are functionally more important.

10:15 pm  
Blogger Andrew Rowell said...

Smokey,
"2. We agree that these conserved areas are often those associated with the business part of the molecule and its overall structure eg. folding etc." Often, but not always."

Are you saying that some positions show strong conservation which can be changed without in any way affecting function?

10:16 pm  
Blogger Andrew Rowell said...

Smokey,
"2. We agree that these conserved areas are often those associated with the business part of the molecule and its overall structure eg. folding etc." Often, but not always."

Are you saying that some positions show strong conservation which can be changed without in any way affecting function?

10:17 pm  
Blogger Andrew Rowell said...

Smokey,
"Do we agree that IDers and creationists have no explanation for this phenomenon, as well as the fact that the sort of partially-overlapping functions this evolutionary mechanism produces are NEVER observed in any objects known to be designed? "

Many IDers would agree that evolution is the correct explanation of this phenomenon. I think Behe would.

I think concluding that this never happens with human design is too sweeping- has someone done an exhaustive study?

10:20 pm  
Blogger Andrew Rowell said...

Smokey,
"It's not only useful in pointing to possible functions, but also in the origin of those functions, which is exactly what you were talking about."

Can you give an example?

10:22 pm  
Blogger Andrew Rowell said...

Smokey,
"Do you agree that quoting from a 9-year-old paper in an effort to rebut a statement about the statement of molecular phylogeny today constitutes a blatantly dishonest evasion?"

No not necessarily. Not all papers writen 9plus years ago are out of date entirely now. It depends on the statement and the progress that has been made in improving the methodology.

10:25 pm  
Blogger Andrew Rowell said...

Tony,

This is the paragraph about Arabidopsis:

It was therefore, somewhat disconcerting to find that the amino acid sequence of its cyt c was significantly more like that of yeast than of most other higher plants; and the situation is even more enigmatic because other features of the A. thaliana cyt c gene such as the control regions and intron structure and codon usage are typical of higher plants.

10:58 pm  
Blogger Smokey said...

Andrew wrote:
"If it was not true I would call someone who maintained that it was - mistaken."

That won't work with Antony. Besides, he has continued to assert it more than once, without offering a shred of supporting data, so characterizing it as a lie was perfectly accurate.

"I would tend to be very cautious indeed about the use of the word "lie"."

Why? It is a false statement made with intent to deceive. It takes less than 30 seconds to find papers in which invariant residues of cyt c were mutated without eliminating function. Surely you must agree that Antony is implicitly claiming to be knowledgable about the relevant primary literature.

"In my opinion you would need to do some protein engineering and check for the function."

Exactly. It's long been done, and Antony's claim is utterly false. If he's merely mistaken, why didn't he offer it as a reason for repeating his false claim?

"However tight conservation I would say is a good clue which bits are functionally more important."

More important, yes. Essential, no way.

"Are you saying that some positions show strong conservation which can be changed without in any way affecting function?"

Yes! Would you mind conveying this simple, important point to Antony for me?

"Many IDers would agree that evolution is the correct explanation of this phenomenon. I think Behe would."

But would you? And how do you explain the total absence of discussion of the nature of this complexity in ID and creationist tomes?

"I think concluding that this never happens with human design is too sweeping- has someone done an exhaustive study?"

No. Is one needed? Is partially-overlapping function (of different components) something you would ever consider in designing anything?

"Can you give an example?"

G proteins.

"No not necessarily. Not all papers writen 9plus years ago are out of date entirely now."

Ah, but you are eliding the issue of quoting instead of citing data. And you were doing so well up to this point?

"It depends on the statement and the progress that has been made in improving the methodology."

That was why I asked Antony a question, which he didn't answer, which is consistent with an egotistical motivation and/or dishonesty.

You quoted:
"It was therefore, somewhat disconcerting to find that the amino acid sequence of its cyt c was significantly more like that of yeast than of most other higher plants..."

But one's discomfort can be quickly relieved by running other Arabadopsis genes against the database. It's entire genome has been sequenced since those words were written! Again, we PREDICT that any tree based on a single gene will have misclassification because of systematic errors; for example, a mutation and reversion (2 mutations) will be scored as no change.

12:04 am  
Blogger Tony Jackson said...

I’ve been thinking about David Swift’s claim that the cytochrome c sequence from the thale cress, Arabidopsis thaliana is closer to fungi cytochrome c than other plants. His insinuation is that trees are unreliable and the whole practice of constructing them is a waste of time.

There’s something about this claim that doesn’t smell right, so I decided to check the facts. Here’s what I’ve found:

The sequence of the whole Arabidopsis genome was published just over six years ago and anyone with access to a computer and the web can explore it. I found two Arabidopsis cytochrome c genes, one on chromosome 1 and the other on chromosome 4. They share 93.8% sequence identity at the amino-acid level.

I took each of these sequences and compared them to other cytochromes c. Guess what? They both cluster quite sensibly with other plant sequences. For example, the chromosome 1 cytochrome c is 98.2% identical to the rape protein, 96.4% identical to pumpkin and so on. You get similar numbers with the chromosome 4 sequence. The claim that Arabidopsis cytochrome c is grossly discordant is false.

Where did David Swift get his story? My first thought was that he just made it up, but to be fair, it’s a specific claim, and that suggests he really did read it somewhere. I think the source of the confusion is this paper:

Kemmerer, EC, Lei, M and Wu, R: structure and molecular evolutionary analysis of a plant cytochrome c gene: surprising implications for Arabidopsis thaliana. Journal of Molecular Evolution. Vol 32, 227-237 (1991).

These people were the first to attempt the cloning and sequencing of any plant cytochrome c at a time when this sort of thing was still quite difficult. They reported a strange result in which their claimed Arabidopsis cytochrome c was indeed much more closely related to yeast than expected.

I took Kemmerer’s sequence (both DNA and protein) and ran it against the Arabidopsis genome sequence. I can’t find it! Admittedly I haven’t had time to do this in an exhaustive way, with relaxed parameters etc, but it’s not looking good. I don’t think it’s there.

Let me hazard a guess as to what’s probably going on:

1) Back in 1991, I think Kemmerer et al made a mistake and instead of cloning Arabidopsis cytochrome c, got the gene from some weird fungus (there are indications from reading the materials and methods of their paper that this is a strong possibility).

2) They then over-interpreted their results.

3) Along came the creationists who speed-read just the paper’s summary and merrily announced another nail in Darwin’s coffin.

David Swift’s claims were published in his book “Evolution Under the Microscope”, which is mentioned approvingly by the ‘Truth in Science’ crowd as a cutting-edge example of British ID research.

Note, this book was published in 2002 - almost two years after the Arabidopsis genome sequence was finished. At any time since the end of 2000, Swift could easily have checked the facts as I have done. It doesn’t even take very long – I did most of this work in my lunch-break.

Smokey: There are still some aspects of this story that puzzle me. I’d appreciate your take, and given the way the story is being amplified on creationist web-sites I think the implications go further than just this blog. If you’re interested, drop me a line. My email address is on the Cambridge biochemistry department web site.

2:47 pm  
Blogger Antony Latham said...

Smokey, I hope you are not still too angry. You seem to think that anyone in my position is a deceiver and fraud. I have not tried to deceive - (and in fact at no time said in my comments that those 37 residues were 'essential') - we are talking past each other. Can we leave that particular issue?

You have made reference to my faith being weak. I just want to say that my faith does not depend at all on whether ID is correct or not. That is not the issue for me personally.

Scott Minnich's paper is published. It just happens to be on that web site. Have you clicked on the PDF link to see it?

I am intrigued with the nylonase being made from a frameshift mutation. I am impressed - will have to look into this more. However you did not answer my question which was how did proteins get to be made in the first cells. For the nylonase the apparatus of DNA, transcription and ribosomes etc were already in place. I am not looking for an account of every step - that is impossible - but I have never heard any good theoretical evolutionary explanation of how the chemicals on the early earth ended up as cells producing proteins. This is a crucial issue. Even if there was an RNA world to begin with (itself having huge problems)- the DNA needs a host of enzymes before it can itself work. (proof reading, polymerase etc). And how about the cell wall? This is not just ignorance - it is genuinely a massive logical problem to see it happening undirected.

8:10 pm  
Blogger Smokey said...

Tony wrote:
"Smokey: There are still some aspects of this story that puzzle me. I’d appreciate your take, and given the way the story is being amplified on creationist web-sites I think the implications go further than just this blog."

Tony, this is just SOP for these fraudsters.
-------
Antony Latham said...
"Smokey, I hope you are not still too angry."

Antony, at no time have I been angry. Your dishonesty is perfectly predictable, and I enjoy calling you on it, as you become even more dishonest in doing so.

"You seem to think that anyone in my position is a deceiver and fraud."

Where have I said such a thing?

"I have not tried to deceive - (and in fact at no time said in my comments that those 37 residues were 'essential')..."

You're lying yet again, Antony. You wrote:
"We have established (at last) that cytochrome c does indeed have a core group of amino acids which constitutes an active ESSENTIAL and totally unchanging part which is in every organism ever looked at."

"cytochrome c - despite all your protestations has got identifiable minimal numbers of amino acid residues (37) which are in all organisms containing this vital protein. Have you worked out the chances of such numbers of precisely placed residues occuring randomly? Remember,in evolutionary theory, THEY HAD TO BE organised randomly at each step before natural selection could work."


The first includes (caps mine) the word that you claimed never to have used, the second claims that they are essential without using the word.

"... - we are talking past each other. Can we leave that particular issue?"

Why? It's a perfect one for demonstrating your shallow, dishonest approach.

"Scott Minnich's paper is published. It just happens to be on that web site. Have you clicked on the PDF link to see it?"

Yes, and if you were able to read with any competence, you would have realized that I commented directly on it. I noted that it contained no data derived from a test of an ID hypothesis.

And since you're fond of arguments from authority, Mike Behe admitted under oath that I am right and you are wrong.

"I am intrigued with the nylonase being made from a frameshift mutation. I am impressed - will have to look into this more."

I doubt it. I suspect you will only see what you want to see.

"However you did not answer my question which was how did proteins get to be made in the first cells."

It was a stupid question, because no one knows the answer; we only have hypotheses, not theories. It also brings out your core dishonesty, as MET has nothing to do with the origins of life. This was about you changing the subject because I was calling you on your blatant lies and ignorance.

BTW, you didn't answer Tony's simple and relevant questions, either: "Have you in fact ever assembled a phylogenetic tree from sequence data? Would you know how to do it? Would you know how to interpret it? Would you know which pitfalls to look out for and know how to avoid them?" Those are relevant questions to ask of someone who claims to understand so much from cyt c alignments.

"...I have never heard any good theoretical evolutionary explanation of how the chemicals on the early earth ended up as cells producing proteins."

That's because by definition, evolutionary explanations start with living things.

"And how about the cell wall?"

What about it? We don't have cell walls at all, Antony. Only plant cells do.

"This is not just ignorance..."

No, it is rank dishonesty and arrogance as well.

9:41 pm  
Blogger Tony Jackson said...

Smokey, Yeah…It’s an endless game of ‘whack-a-mole’.

Except the ‘Arabidopsis-cytochrome-c-disproves-evolution’ meme is a rare case where the origin of the whole misunderstanding can apparently be uncovered and traced back in detail for everyone to see. I’m thinking it would make a good exhibit in a rogues’ gallery on somewhere like Talk Origins or Pandas Thumb.

Andrew, Antony,

Have you done your homework yet? It’s been over 24 hours.

All my students got the right answer in a heartbeat.

The question I posed is absolutely central to the proper interpretation of phylogenetic trees derived from sequence data. In literacy terms, it’s roughly equivalent to the question “can you read?”

It’s also a good indication of whether it’s worth hanging around here.

8:05 am  
Blogger Andrew Rowell said...

Tony,

I did ask for an extension to the deadline. I am planning to do both your and Smokey's homework but it might take me a while!

Andrew

9:12 am  
Anonymous Hrafn said...

Andrew:

Unless I'm very much mistaken, the mistake that Denton made has already been discussed in an earlier thread (where the same mistake was made by some researchers, and the resulting evolutionary 'anomaly' was made much of by Creationists).

2:22 pm  
Blogger Andrew Rowell said...

Hrafn,

I cannot find it and I think I would have remembered if this had been discussed here before.

3:14 pm  
Blogger Smokey said...

Andrew wrote:
"I did ask for an extension to the deadline. I am planning to do both your and Smokey's homework but it might take me a while!"

I don't see why. It's not that hard.

5:09 pm  
Anonymous Hrafn said...

Andrew:

Denton's name did not come up on that thread, but the circumstances seem very similar to the one Tony recounted on this thread.

5:30 pm  
Blogger Tony Jackson said...

Hi hrafn...

Shhh! I want Andrew to figure it out for himself :-) !

5:39 pm  
Blogger Antony Latham said...

Smokey I said:"However you did not answer my question which was how did proteins get to be made in the first cells."

You said: "It was a stupid question, because no one knows the answer; we only have hypotheses, not theories. It also brings out your core dishonesty, as MET has nothing to do with the origins of life. This was about you changing the subject because I was calling you on your blatant lies and ignorance."

Look - if you want to confine the discussion to the situation post the first complex cells then you are simply evading what is one of the most important issues in debating ID. You must address the problem of how the first cells and therefore proteins arose. There are some very sound arguments for intelligent input into the formation of life - which includes your beloved proteins. You cannot side step these issues.

Have you read Paul Davies book 'The Fifth Miracle'? (it now has a different name I think). Very good indeed on the problem of supplying meaningful/syntactic information into DNA. This is the nub of the problem - though there are many others.

And then there is the cell membrane - which contains at least 50 proteins and must transport ions efficiently among many other jobs....what did the first replicating DNA (now we ARE talking evolution) do without the membrane? You need DNA to construct a membrane and you need a membrane for all the apparatus to function. A basic chicken and egg conundrum.

6:29 pm  
Blogger Smokey said...

Antony wrote:
"Look - if you want to confine the discussion to the situation post the first complex cells..."

I want to confine the discussion to your blatant lie--your repeated claims that conservation of a residue means that it is essential for function. This is falsifiable in 30 seconds (literally). In your post before this one, you lied again, denying that you ever used the word "essential." I quoted you telling the lie twice, once using the word and once without.

"... then you are simply evading what is one of the most important issues in debating ID."

If I followed your lead, my tactic would be to start with a lie and reassert it every time the lie was pointed out, then try to change the subject. Unlike you, I am an honest person.

"You must address the problem of how the first cells and therefore proteins arose."

1) No, I don't, and
2) Why would cells necessarily come before proteins?

"There are some very sound arguments for intelligent input into the formation of life - which includes your beloved proteins."

No, there aren't, as your pathological lying demonstrates.

"Have you read Paul Davies book 'The Fifth Miracle'? (it now has a different name I think)."

No, I read the primary literature. Have you read ANY of the relevant primary literature, Antony?

"Very good indeed on the problem of supplying meaningful/syntactic information into DNA."

Does it include any new data?

"... You need DNA to construct a membrane..."

Why? Because a guy who lies through his teeth says so?

7:16 pm  
Blogger Antony Latham said...

Smokey you said:"I want to confine the discussion to your blatant lie--your repeated claims that conservation of a residue means that it is essential for function. This is falsifiable in 30 seconds (literally). In your post before this one, you lied again, denying that you ever used the word "essential." I quoted you telling the lie twice, once using the word and once without."

I admit that I did after all say essential. My sincere apologies for getting this wrong. Not intentional - but I doubt if you will believe that Smokey. That there is such extreme conservation of those residues across all creatures is still a point for discussion but you do not want to go down that line.

Yes I have read some of the primary literature about the origin of life - I have already mentioned Woese but there are quite a few others. I feel you do not want to discuss it so this may well be my last message unless someone else takes up the thread. And it is a nice day outside so I better get going - (before the Scotland V England match of course.)

11:03 am  
Blogger Smokey said...

Antony wrote:
"I admit that I did after all say essential. My sincere apologies for getting this wrong."

I'm impressed by your honesty.

But don't you repeat this falsehood in your book? If so, how will you apologize to your readers?

And since you got it so wrong, what does that in turn do to the conclusion that depended on this false assumption? What does it do to every argument Dembski has ever made in his books, for example?

"Not intentional - but I doubt if you will believe that Smokey."

I have an open mind and I am all ears. If your use of the term "essential" was not intentional, what term did you intend to use? What point were you intending to make?

"That there is such extreme conservation of those residues across all creatures is still a point for discussion but you do not want to go down that line."

Ah, but I do! Wanna bet?

"Yes I have read some of the primary literature about the origin of life - I have already mentioned Woese but there are quite a few others."

Antony, I'm sorry, but I don't believe you for several reasons, including:
1) You didn't "mention" Woese, you quote-mined his paper, a dishonest practice. Scientists cite data.
2) The paper from which you quote-mined is not part of the primary literature, because the primary literature is the stuff that has new data in it. Why don't you, as a physician, know this?
3) You offered a quote from 1998 as though it somehow contradicted all the data gathered between 1998 and 2007.

9:22 pm  
Anonymous Hrafn said...

Tony:

It seems unlikely that Andrew is going to work it out, even with hints.

3:54 am  
Blogger Smokey said...

I tend to agree. It's interesting that Antony never responded to Tony's challenge.

6:01 pm  
Blogger Antony Latham said...

I have just re-read (after many years) Ch.12 from Denton's book in which he discusses the phylogenetic trees constructed from amino-acid sequences in proteins. At the severe risk of being hammered by you biochemists, I will give you some thoughts.

He shows that when we look at the percent sequence differences for cytochrome c between different organisms we see a clear pattern. The percent difference between the bacterium Rhodospirillum rubrum C2 and all other classes of organisms is astonishingly the same - around 65%. This includes comparisons with yeasts, plants, insects, reptiles, birds and mammals.

Moving up the taxonomic tree, the percent differences between yeasts and all 'higher' organisms is around 45% very constantly, insects and higher animals around 25% etc.

And so we do not see any obvious correlation between sequence differences and degree of morphological difference...(otherwise we would expect yeasts to differ less from bacteria than humans do).

The easy way to explain this is to say that mutations have occured in organisms over time at a steady rate in neutral amino acid residues - and so we simply see a reflection of time since the common divergence of all of us from bacteria. It seems impossible to explain it by selective forces - because we would surely expect some correspondence between sequence changes and morphology (which,as I said above, we do not - even 'living fossils' seem to have the same percent of changes over time).

The main, and I think most powerful, argument he puts against this simple explanation is to do with the enormously different generation times that different organisms have. For example - in the insects: cicadas have a generation time of 17 years while fruit flies have one of about 2 weeks. Yet despite the far greater chances of mutations/unit time being highest in fruit flies, we see exactly the same divergence. Likewise, in mammals the rodents reproduce with very short generation times compared to elephants or humans - yet we see exactly the same percent divergence from each other and from the bacteria.

Denton puts all this much better than I - but I would like to find out if your solution (which you say you got in minutes)can explain the pattern we see, given the enormous differences in generation time between organisms.

11:11 pm  
Blogger Tony Jackson said...

Isn’t Google amazing? Here’s the quotation that I remember from Denton’s book from all those years ago. He’s talking about the fact that when comparing the amino acid sequence of cytochrome c of a bacterium with such widely diverse eukaryotes as yeast, human, horse, etc, all of these have more-or-less the same percentage difference with the bacterium. Denton is troubled by this fact as he apparently seems to think that that an organism such as a horse should have diverged more than the yeast.

"The fact that all the individual species must be stationed at the extreme periphery of such logic [evolutionary] trees merely emphasize the fact that the order of nature betrays no hint of natural evolutionary sequential arrangements, revealing species to be related as sisters or cousins but never as ancestors and descendants as is required by evolution."

Denton has made the classic mistake of confusing modern organisms as ancestors. Interestingly, I found another creationist, Christian Schwabe, writing five or so years after Denton who made the same mistake.

Here’s a site where the Denton/Schwabe misunderstanding is explained in more detail that I care to go into:

http://home.planet.nl/~gkorthof/korthof56.htm

(scroll down to ‘The Schwabe-Denton interpretation of cytochrome-c differences’).

To be fair, the generation time argument is a bit more sophisticated and was occasionally brought up by legitimate workers in the early days of sequencing. However, mutation rates are more strictly based on changes per cell division and not generation time. Over vast swathes of evolutionary time, the molecular clock ticks remarkably regularly, but it is a stochastic clock.

Serious scientists have thought about these things seriously. You can even get a simple summary from some of the professionals that do this sort of thing for a living eg:

http://sandwalk.blogspot.com/2006/12/michael-denton-and-molecular-clocks.html

If you too want to understand the issues seriously, please, please, don’t read Denton (or Behe).

9:35 am  
Blogger Tony Jackson said...

By the way Antony,

Since you didn't actually answer my original homework question, but merely replied with more questions of your own. It's an ' F ' for fail I'm afraid...

10:45 am  
Blogger Tony Jackson said...

Sorry to belabour the point, but if there is anybody out there who is still confused over Denton's dumb mistake, here is a very good explanation of the fallacy:

http://members.cox.net/ardipithecus/evol/lies/lie011.html

1:13 pm  
Blogger Smokey said...

Antony wrote:
"I have just re-read (after many years) Ch.12 from Denton's book..."

You're just showing your fear of the primary literature. In your heart, you know that you don't know what you are talking about.

"...At the severe risk of being hammered by you biochemists, I will give you some thoughts."

They aren't your thoughts, Antony. You're just regurgitating Denton's gross misrepresentations of MET, as explained in the links Tony offered. I hypothesize that you know that you're intellectually incapable of looking at actual data and thinking independent thoughts about them without someone to guide you. Do you agree?

"...The percent difference between the bacterium Rhodospirillum rubrum C2 and all other classes of organisms is astonishingly the same - around 65%. This includes comparisons with yeasts, plants, insects, reptiles, birds and mammals."

That's what is predicted by common ancestry.

"Moving up the taxonomic tree,..."

There is no "moving up." A more accurate metaphor is a bush in which time starts at the center and the surface is the present. You're only looking at the present.

"And so we do not see any obvious correlation between sequence differences and degree of morphological difference..."

Why should we? Cyt c has nothing to do with morphology.

"...(otherwise we would expect yeasts to differ less from bacteria than humans do). "

No, we don't. Of course, unlike you and Denton, we actually understand evolutionary theory.

"...so we simply see a reflection of time since the common divergence of all of us from bacteria."

Why would the common ancestor of humans and bacteria be a bacterium?

"It seems impossible to explain it by selective forces..."

Indeed it does, because it is most easily explained by drift, which is an important part of MET, but never mentioned by Darwin. This is why your babbling about Darwin, "Darwinists," and "Darwinism" illustrates intellectual shallowness.

"Denton puts all this much better than I -..."

But it's still just as wrong.

"... but I would like to find out if your solution (which you say you got in minutes)..."

Antony, you are incredibly dense. I didn't offer a "solution" to Denton's gross misrepresentation, I called you on your lie when you claimed that conservation of aa residues allowed one to conclude that they were essential for function. Denton uses this same lie, of course.

Again, here's the lie in formal form:

1) If aa residues are universally conserved, then they are essential for function.
2) 37 of the residues of cyt c are conserved.
3) Therefore, those 37 are essential for function.

Now, think carefully (Denton won't help you). What empirical evidence (some of which is MORE THAN TWENTY YEARS OLD!) would directly and absolutely falsify the claim that 37 of the cyt c residues are essential for function?

What search terms would a responsible, competent scientist enter into PubMed to look for data that would falsify this claim?

I'll help you start: the first one is "cytochrome c"!

So, to recap:
1) You falsely presented a hypothesis (conserved aa residues are essential for function) as fact;
2) The hypothesis can be shown to be spectacularly wrong by searching the primary literature;
3) You now claim that your claim was not intentional, but you have yet to explain your actual intent;
4) You now bring up entirely different issues, based on gross misunderstanding of the same data, as though they are relevant.

Let's see if you can get something from this: conservation of residues does NOT mean that they must essential for function. The data show this, even for the specific case from which you were trying to fallaciously generalize.

An honest, sincere person who was merely mistaken would show an interest in the actual data, yet you have none. The only rational explanation that I can see is that in your heart, you know that you are wrong, and you have no real faith that you are right.

4:34 pm  
Blogger Antony Latham said...

Smokey said "You're just showing your fear of the primary literature. In your heart, you know that you don't know what you are talking about."


This is quite sad Smokey. You should really get a grip on things - this comment of mine was simply to say I had read the chapter we were discussing!

I said:"...The percent difference between the bacterium Rhodospirillum rubrum C2 and all other classes of organisms is astonishingly the same - around 65%. This includes comparisons with yeasts, plants, insects, reptiles, birds and mammals."

You said: "That's what is predicted by common ancestry."

Of course it is - that is obvious. Read on!

I said: "Moving up the taxonomic tree,..."

You said: "There is no "moving up." A more accurate metaphor is a bush in which time starts at the center and the surface is the present. You're only looking at the present."

A cladogram is the way I look at it and is the best way to see the 'evolutionary relationships - and in a cladogram we do indeed move up with time. Of course what we see now is the present! Wrong again!

You said: "Why would the common ancestor of humans and bacteria be a bacterium?"

The first cells were bacteria. Basic micro-palaeontology.

I said: ""It seems impossible to explain it by selective forces..."

You said: "Indeed it does, because it is most easily explained by drift, which is an important part of MET, but never mentioned by Darwin. This is why your babbling about Darwin, "Darwinists," and "Darwinism" illustrates intellectual shallowness."

You really are getting carried away here. I am agreeing with this...and indeed if you bothered to read Denton and the entirety of what I wrote you would see that he agrees with drift as the most likely modern evolutionary explanation - he then brings up the major major problem of differing generation times - which you studiously avoid. Tony has given some references which at least address this problem of generation time variation - basically dismissing it. That is fine - at least they address it. It seems too easy to dismiss to me. To get such precise sequence variation across the board from the bacterium is remarkable - given the very different generation times in different groups - even with the fact, pointed out, that it is cell divisions which count (they too vary greatly).

In your beligerance you have not even begun to address the issue which I brought up in my comment.

Thank you Tony for the references - I will check them out when I can get time.

6:49 pm  
Blogger Tony Jackson said...

Antony “To get such precise sequence variation across the board from the bacterium is remarkable - given the very different generation times in different groups - even with the fact, pointed out, that it is cell divisions which count (they too vary greatly).”

Well what are you getting at? The ‘clock-like’ nature of molecular sequence divergence between species is well established. The neutral theory, and more recently the nearly-neutral theory provide a rationale for this ‘remarkable’ phenomenon (incidentally, the near-neutral theory can also explain the relative insensitivity of the clock to variations in generation time between lineages). No miracles or Deus ex machina needed.

So how does ID explain these observations? Isn’t that the critical question?

10:14 pm  
Blogger Smokey said...

Antony wrote:
"This is quite sad Smokey. You should really get a grip on things - this comment of mine was simply to say I had read the chapter we were discussing!"

We weren't discussing a chapter of anything. We were discussing your false assertion that conservation of aa residues means that they are essential for function.

"...is astonishingly the same - around 65%. This includes comparisons with yeasts, plants, insects, reptiles, birds and mammals."

I said: "That's what is predicted by common ancestry."

"Of course it is - that is obvious. Read on!"

How can it be both obvious and astonishing at the same time, Antony?

Antony said: "Moving up the taxonomic tree,..."

I said: "There is no "moving up." A more accurate metaphor is a bush in which time starts at the center and the surface is the present. You're only looking at the present."

"A cladogram is the way I look at it and is the best way to see the 'evolutionary relationships -..."

You're looking at it the wrong way. Please drop the attempts to present yourself as an original thinker.

"... and in a cladogram we do indeed move up with time."

This is why it's wrong. Bacteria have been evolving for as long as humans have.

"The first cells were bacteria. Basic micro-palaeontology."

No one knows what the first cells were, Antony.

"..and indeed if you bothered to read Denton and the entirety of what I wrote..."

Why should I bother to read Denton? He doesn't understand these trees at all.

"... you would see that he agrees with drift as the most likely modern evolutionary explanation - he then brings up the major major problem of differing generation times - which you studiously avoid."

Uh, Antony, do all organisms in each lineage have the same generation time? If not, there's no reason to hold up the generation time of the species from which you have a sequence as something immutable throughout the lineage.

"Tony has given some references which at least address this problem of generation time variation - basically dismissing it. That is fine - at least they address it. It seems too easy to dismiss to me."

Why do you dismiss any discussion of the effect of your false claim on your book?

Why don't you explain how your false claim was unintentional?

10:50 pm  
Blogger Antony Latham said...

Smokey you said:"We weren't discussing a chapter of anything. We were discussing your false assertion that conservation of aa residues means that they are essential for function."

If you look at the original comment by Andrew about chapter 12 of Denton's book you will see that Tony then challenges us to say where Denton went wrong in this chapter. That is the context and why I was commenting on that chapter.

You said: "How can it be both obvious and astonishing at the same time, Antony?"

Where is your sense of wonder Smokey?

I said ""A cladogram is the way I look at it and is the best way to see the 'evolutionary relationships -..."

You said: "You're looking at it the wrong way. Please drop the attempts to present yourself as an original thinker."

Sorry Smokey - a bush metaphor is fairly useless and is almost never used in describing relationships. Cladograms are much better.

You said: "Why do you dismiss any discussion of the effect of your false claim on your book?"

None of these arguments are in my book. I don't mention cytochrome c or conservation of residues or Denton's ideas on sequences. Please get your facts right. I joined this discussion because it interested me now.

You pretend to comment on Denton without reading him. You seem not to understand that he already knows all the standard answers which you have given. The fact that he throws in the valid point about generation times is simply a very interesting point - not to be dismissed lightly. The fact is that the Cicadas have less chance of mutating per unit time than fruit flies and they have been around a very long time in evolutionary history. We should see this reflected in different sequence variation but we seem not to. I find this interesting.

As the comments are degenerating rapidly into point scoring I may well leave it here ...I think I said that before.

11:33 pm  
Blogger Smokey said...

Antony wrote:
If you look at the original comment by Andrew about chapter 12 of Denton's book you will see that Tony then challenges us to say where Denton went wrong in this chapter. That is the context and why I was commenting on that chapter."

Sorry, Antony, but you're wrong again. That came AFTER you started making your false claim about conservation meaning necessity for function. You still haven't explained how your claim was not intentional, nor have you expressed a bit of interest in the data that falsify your claim.

"Where is your sense of wonder Smokey?"

It's right there, triggered by biology. I mean the data, not books of apologetics that misrepresent the data.

Where is your sense of wonder, Antony? Tony asked, "Come on, be honest. Have you in fact ever assembled a phylogenetic tree from sequence data? Would you know how to do it? Would you know how to interpret it? Would you know which pitfalls to look out for and know how to avoid them? " and you did nothing but offer the false claim that you would have to be in a biochemistry lab. What are you afraid of? All the sequences and tools are available on the Web, but you are afraid to look at the data. Where's YOUR sense of wonder again? All I see is cowardice: hiding behind quote-mining and making lame excuses for not looking at the data.

"Sorry Smokey - a bush metaphor is fairly useless and is almost never used in describing relationships."

This is hysterically funny, coming from someone who has never looked at the data nor described it. I already pointed you to a bush diagram; thanks for tacitly admitting that you were afraid to look at it. Here are two for you to run away from:

http://www.pnas.org/cgi/content/full/103/10/3681/F1

http://www.mrc-lmb.cam.ac.uk/myosin/trees/gifs/tree.jpg

Now, if you are correct in claiming that bushes are "almost never used," how is it that I can find them used twice in a single field--myosins?

"Cladograms are much better."

How would you know? You claim that you must be in a biochemistry lab to graphic representations of sequence relationships. You confuse a theoretical paper with the primary literature.

"None of these arguments are in my book."

Page 25 of your book doesn't contain the sleazy straw man claim, "...the problems seem insoluble on a PURELY RANDOM materialistic basis." ???

Tell me, Antony, what exactly is random about natural selection, much less PURELY random? That bit of dishonesty is in the same vein as the lie you introduced above:

"cytochrome c - despite all your protestations has got identifiable minimal numbers of amino acid residues (37) which are in all organisms containing this vital protein. Have you worked out the chances of such numbers of precisely placed residues occuring randomly? Remember,in evolutionary theory, they had to be organised randomly at each step before natural selection could work."

"I don't mention cytochrome c or conservation of residues or Denton's ideas on sequences."

See the quote of you above.

"Please get your facts right. I joined this discussion because it interested me now."

Facts are data. You are afraid of data. You lie about the data in your book, blatantly:
"To keep this in perspective we also need to realise that we share 60% of our genome with the humble banana"

This is an incredibly idiotic lie. What sort of scholar would confuse whole-genome identities with coding-region (only 1-2% of the genome) identities?

"You pretend to comment on Denton without reading him."

I'm commenting on what you called your own thoughts. Are you now claiming that you don't have any original ones?

You comment on genomic identities without realizing that you are two orders of magnitude off in your claims. You are just a dilettante.

12:18 am  
Blogger Tony Jackson said...

“If you look at the original comment by Andrew about chapter 12 of Denton's book you will see that Tony then challenges us to say where Denton went wrong in this chapter. That is the context and why I was commenting on that chapter.”

And you didn’t answer the question did you? I asked the question for a very good reason. Denton’s error reveals a gross misunderstanding of the most basic concept in the field. An error so large that one would be justified in not taking anything Denton says about sequence alignments seriously. I wanted to see if you too were at least capable of spotting the same error. Apparently not.

“The fact that he throws in the valid point about generation times is simply a very interesting point - not to be dismissed lightly.”

But I’m not sure it is a valid point. Certainly not in the way you want it to be as a death-blow to evolution. As I noted, this and similar issues have been discussed seriously in the past and the general consensus is that Denton is grossly overstating the problem. I gave a couple of reasons why, and I also linked to an article on Larry Moran’s blog where he too gives a few more reasons why.

I think I spot a pattern here. You scour books written by sympathetic ID or creationist sources to find supposed anomalies that you fancy pose ‘problems for Darwinism’. Even when there is a kernel of truth in the factoid you uncover, you generally have no real understanding of the issues or the proper biological context in which to place it. More often than not the supposed facts you latch onto (eg ‘irreducible complexity’) don’t have any grounding in biological reality at all.

“Where is your sense of wonder Smokey?”

I speak for myself here, although I suspect Smokey would agree. My sense of wonder is enormously enhanced by knowing a bit about the structures I study, how they work and how they came to be. How could this not be the case?

“When we no longer look at an organic being as a savage looks at a ship, as something wholly beyond his comprehension; when we regard every production of nature as one which has had a long history; when we contemplate every complex structure and instinct as the summing up of many contrivances, each useful to the possessor, in the same way as any great mechanical invention is the summing up of the labour, the experience, the reason, and even the blunders of numerous workmen; when we thus view each organic being, how far more interesting -- I speak from experience -- does the study of natural history become!”

Charles Darwin

11:05 am  

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