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Functional Classes Of Proteins


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#1 Guest_92g_*

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Posted 06 May 2005 - 06:02 PM

This is an interesting article from Michael Behe about some experiments that demonstrate the unlikelyhood of finding function protiens through mutations.

Sauer's laboratory, in order to answer questions about protein structure that interested them, took the genes for several viral proteins, systematically took out small pieces of them (corresponding to instructions for three amino acids at a time) and inserted altered pieces back in the genes. They did this, three amino acids 'codons' at a time, for the whole length of the gene. By clever manipulation of the altered pieces they were able to screen codons for all twenty amino acids at each position of the protein. This is like trying all 26 letters of the alphabet in turn at each position of a word. The altered genes were then placed in bacteria, which read the DNA code and produced chains of amino acids from them. It turns out that bacteria quickly destroy proteins that are not folded, so Sauer's group looked for the altered proteins that were not destroyed. By determining their sequences they could tell which amino acids in a given position were compatible with producing a folded, functional protein. And what did they see?
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In some positions of the protein Sauer's group saw that a great deal of amino acid diversity could be tolerated. Up to 15 of the twenty amino acids could occur at some positions and still yield a functional, folded protein. However, at other positions in the amino acid sequence very little diversity could be tolerated. Many positions could accomodate only 3 or 4 different amino acids. Other positions had an absolute requirement for a particular amino acid; this means that if, say, a P does not appear at position 78 of a given protein the protein will not fold regardless of the proximity of the rest of the sequence to the natural protein. In terms of our sentence analogy, this is like saying that, yes, all vowels are interchangeable, but that if the last `r' is changed to any other letter, such as 's' ("Drop the anchor in one hous"), the protein sentence is no longer understandable.

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From the actual experimental results of Sauer's group it can easily be calculated that the odds of finding a folded protein are about 1 in 10 to the 65 power (6).
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It is important to realize that Sauer's and Yockey's results hold whether or not the system can replicate and is subject to Darwinian selection. The odds against finding a new functional protein structure remain astronomical in either case. This is because Darwinian selection can only discriminate based on function and, with the exception of those found in living organisms, virtually all protein sequences are functionless. An amino acid sequence can be replicated and mutated in living organisms till the cows come home and the odds are still 1 in 10&% that a new functional protein class will be produced.


Experimental Support for Regarding Functional Classes of Proteins to be Highly Isolated from Each Other

Terry

#2 Guest_Paul C. Anagnostopoulos_*

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Posted 07 May 2005 - 08:24 AM

He appears to be saying that the odds of finding any given useful protein via and undirected search are extremely low. This would be interesting if it had anything to do with reality.

~~ Paul

#3 Guest_92g_*

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Posted 07 May 2005 - 03:19 PM

I don't know,...., maybe you can elaborate a little.

Behe obviously has a different opinion than you do.

But the believer in the universal application of physical law is stuck. He must maintain, against the evidence, that different protein classes, like cytochromes and immunoglobulins, found their way by raw luck through the vast, dark sea of nonfunctional sequences to the tiny islands of function we observe experimentally. He must maintain, without any evidence, that Mesonychid gave birth over time to the whale. And why, we ask, must he maintain these positions against impossible odds and without supporting evidence? Because, he replies, I can only measure material phenomena, and therefore nothing else exists.


Terry

#4 Guest_Paul C. Anagnostopoulos_*

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Posted 07 May 2005 - 04:06 PM

Why must I maintain that proteins found their way by raw luck? Instead, I can maintain that some very simple ones formed by luck, then were selected through the dark sea of possible sequences. I could do this if I didn't have to follow the party line that evolution is nothing but chance.

~~ Paul

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Posted 07 May 2005 - 06:53 PM

Instead, I can maintain that some very simple ones formed by luck,


A person can maintain the hope that some very simple ones formed by luck, despite the evidence against it ever having happened. But even that hope requires a tremendous amount of faith, and that would be just to form a simple protien. Forget about life itself, which requires DNA, a cell structure to maintain it, the translational machinery to put the information to work, and of course the much debated information and the code(that requires a mental origin) to store it.

..... then were selected through the dark sea of possible sequences.


Behe claims that natural selection doesn't help your case.

An amino acid sequence can be replicated and mutated in living organisms till the cows come home and the odds are still 1 in 10&% that a new functional protein class will be produced.


I could do this if I didn't have to follow the party line that evolution is nothing but chance.


Selection is a filtering process. That process has an input, and that input is a random process. Consequently, the proposal of evolution via random mutation and natural selection is a random process.

Suggesting that all dogs had a common canine ancestor, and all humans had a common human ancestor, etc., etc,.etc,. is not a problem. OTH, to sugest that we all had a common microbial ancestor, well that's a different story altogether.....

Terry

#6 Guest_Paul C. Anagnostopoulos_*

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Posted 08 May 2005 - 06:13 AM

A person can maintain the hope that some very simple ones formed by luck, despite the evidence against it ever having happened. But even that hope requires a tremendous amount of faith, and that would be just to form a simple protien. Forget about life itself, which requires DNA, a cell structure to maintain it, the translational machinery to put the information to work, and of course the much debated information and the code(that requires a mental origin) to store it.

I was simply saying that one could maintain that. One could also maintain that the first amino acid sequences formed by binding directly to something like RNA, a proposal for which there is mounting evidence.

An amino acid sequence can be replicated and mutated in living organisms till the cows come home and the odds are still 1 in 10&% that a new functional protein class will be produced.

He still doesn't seem to want to mention selection.

Selection is a filtering process. That process has an input, and that input is a random process. Consequently, the proposal of evolution via random mutation and natural selection is a random process.

No, it's not. It's a random process coupled with nonrandom selection. If you insist that a process with any random component is purely random, then playing Monopoly is a random process. And all Monte Carlo simulations are random processes. Hey, there are random components at the foundation of quantum mechanics, so the entire universe is a random process.

Suggesting that all dogs had a common canine ancestor, and all humans had a common human ancestor, etc., etc,.etc,. is not a problem. OTH, to sugest that we all had a common microbial ancestor, well that's a different story altogether.....

At what point does Dawkins's Ancestor's Tale become "a different story"?

~~ Paul

#7 Guest_92g_*

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Posted 08 May 2005 - 12:03 PM

He still doesn't seem to want to mention selection.


From the OP.

It is important to realize that Sauer's and Yockey's results hold whether or not the system can replicate and is subject to Darwinian selection. The odds against finding a new functional protein structure remain astronomical in either case. This is because Darwinian selection can only discriminate based on function and, with the exception of those found in living organisms, virtually all protein sequences are functionless


No, it's not. It's a random process coupled with nonrandom selection. If you insist that a process with any random component is purely random, then playing Monopoly is a random process.


Selection is random since the environmental factors are not deterministic. I.e. it was a matter of being at the right place at the right time, or the wrong place at the wrong time, etc....

Lets say we have a random number generator that produces integers from -10000000, to +10000000. If you select only the positives, then the outcome is still random. You've just filtered the output of the generator.

Hey, there are random components at the foundation of quantum mechanics, so the entire universe is a random process.


Some believe as much...., or should I say as little... :)

At what point does Dawkins's Ancestor's Tale become "a different story"?

You tell me. I would guess from the beginning since he believes(at least I assume he does) that all life forms decended from a common acestor.

Terry

#8 Guest_Paul C. Anagnostopoulos_*

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Posted 08 May 2005 - 05:15 PM

Perhaps you could start by quoting the entire paragraph:

It is important to realize that Sauer's and Yockey's results hold whether or not the system can replicate and is subject to Darwinian selection. The odds against finding a new functional protein structure remain astronomical in either case. This is because Darwinian selection can only discriminate based on function and, with the exception of those found in living organisms, virtually all protein sequences are functionless. An amino acid sequence can be replicated and mutated in living organisms till the cows come home and the odds are still 1 in 10&% [sic] that a new functional protein class will be produced.

So he's talking about new protein classes. Now, where is his proof that a new class of proteins cannot arise by mutation and selection? Yockey was talking about trial and error.

Selection is random since the environmental factors are not deterministic. I.e. it was a matter of being at the right place at the right time, or the wrong place at the wrong time, etc....

Again, you appear to be claiming that if a process has any stochastic elements, it is entirely random.

Lets say we have a random number generator that produces integers from -10000000, to +10000000. If you select only the positives, then the outcome is still random. You've just filtered the output of the generator.

Indeed, but if the environment is such that positive integers survive and negative die, the overall result is nonrandom.

If you insist on this line of reasoning, the entire universe is random and the inputs of some supernatural being aren't going to change that.

You tell me. I would guess from the beginning since he believes(at least I assume he does) that all life forms decended from a common acestor.

You said you had no problem with all dogs having a common ancestor. Is that as far as you're willing to go? No common ancestor of dogs and wolves, for example?

By the way, what Yockey said was:

One must conclude that no valid scientific explanation of the origin of life exists at present ... Since science has not the vaguest idea how life originated on earth, ... it would be honest to admit this to students, the agencies funding research and the public.

Behe, too, has descended into using misleading quotations to further his point.

~~ Paul

#9 Guest_92g_*

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Posted 08 May 2005 - 05:58 PM

So he's talking about new protein classes. Now, where is his proof that a new class of proteins cannot arise by mutation and selection? Yockey was talking about trial and error.

Sauer's results deomonstrate what Behe is claming.

If you insist on this line of reasoning, the entire universe is random and the inputs of some supernatural being aren't going to change that.


Well, not exactly, if we consider the odds of chance producing life, and conclude that its not possible, then we are at the point of admitting that someone must have created it. At what level we need God to reasonably explain life as we know it is simply the place where the odds become unacceptable.

I think its clear that the odds against life arising on its own, from what ever scenario you want to suggest, are so enourmous, that even very prominent atheists are starting to admit that some God must have been involved, e.g. Antony Flew.

Now,...., Behe claims that Sauer's results also deomonstrate that the chances of proteins developing by chance that can account for darwinain evolution are also not acceptable.

So we are basically getting very close to admiting that current scientific understanding demonstrates that life as we know it must have been created in a fashion not too far from what we see today.

BTW,...,your the one with the hangup about saying that evolution is not a chance process not me.

You said you had no problem with all dogs having a common ancestor. Is that as far as you're willing to go? No common ancestor of dogs and wolves, for example?


We can take it as far as natural selection can acount for the diversity of life as we know it in probably the last 10k years. How's that????

By the way, what Yockey said was:

Behe, too, has descended into using misleading quotations to further his point.


How does this help your case????

Terry

#10 Guest_Paul C. Anagnostopoulos_*

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Posted 09 May 2005 - 08:07 AM

Sauer's results deomonstrate what Behe is claming.

How do you figure? Does a functional protein arise by random search of the sequence space?

Well, not exactly, if we consider the odds of chance producing life, and conclude that its not possible, then we are at the point of admitting that someone must have created it. At what level we need God to reasonably explain life as we know it is simply the place where the odds become unacceptable.

You're saying that a process with any stochastic element is purely random. How does God's intervention fix this problem?

BTW,...,your the one with the hangup about saying that evolution is not a chance process not me.

That's because you refuse to admit that it is not a chance process. But of course that is what creationists have to do.

We can take it as far as natural selection can acount for the diversity of life as we know it in probably the last 10k years. How's that????

Why that limitation?

How does this help your case????

Just another example of the twisting of quotes by creationists. Yockey was talking about the origin of life, not proteins.

~~ Paul

#11 Method

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Posted 09 May 2005 - 09:39 AM

There is a paper by Hayashi et al. that gets to the heart of this matter. In this experiment they replaced a part of a gene with a random sequence. After this change the infectivity of the virus dropped 6 orders of magnitude, as would be expected if a gene involved in infection was messed with. However, this virus was allowed to evolve. They did this by finding the variants with the highest infectivity, and then using that clone as the parent for the next generation. Through this process they were able to evolve a virus that had a 240 fold higher infectivity rate than the original virus. A 37-fold increase was directly tied to the inserted random sequence which had undergone mutation and selection. If random sequences are mutated and add to the fitness of a virus, why can't the same thing occur in bacteria or even humans?

Abstract:

J Mol Evol. 2003 Feb;56(2):162-8.
 
Can an arbitrary sequence evolve towards acquiring a biological function?

Hayashi Y, Sakata H, Makino Y, Urabe I, Yomo T.

Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, 565-0871, Suita City, Osaka, Japan.

To explore the possibility that an arbitrary sequence can evolve towards acquiring functional role when fused with other pre-existing protein modules, we replaced the D2 domain of the fd-tet phage genome with the soluble random polypeptide RP3-42. The replacement yielded an fd-RP defective phage that is six-order magnitude lower infectivity than the wild-type fd-tet phage. The evolvability of RP3-42 was investigated through iterative mutation and selection. Each generation consists of a maximum of ten arbitrarily chosen clones, whereby the clone with highest infectivity was selected to be the parent clone of the generation that followed. The experimental evolution attested that, from an initial single random sequence, there will be selectable variation in a property of interest and that the property in question was able to improve over several generations. fd-7, the clone with highest infectivity at the end of the experimental evolution, showed a 240-fold increase in infectivity as compared to its origin, fd-RP. Analysis by phage ELISA using anti-M13 antibody and anti-T7 antibody revealed that about 37-fold increase in the infectivity of fd-7 was attributed to the changes in the molecular property of the single polypeptide that replaced the D2 domain of the g3p protein. This study therefore exemplifies the process of a random polypeptide generating a functional role in rejuvenating the infectivity of a defective bacteriophage when fused to some preexisting protein modules, indicating that an arbitrary sequence can evolve toward acquiring a functional role. Overall, this study could herald the conception of new perspective regarding primordial polypeptides in the field of molecular evolution.



#12 ret

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Posted 14 May 2005 - 09:07 PM

[QUOTE]One could also maintain that the first amino acid sequences formed by binding directly to something like RNA, a proposal for which there is mounting evidence.[/QUOTE]

There is actually good statistical reason to doubt this. First, it has the same problems with being ordered correctly, so it doesn't really solve any problems. Second, for a single strand of RNA to replicate, there must be an identical strand of RNA nearby. To make the odds of that happening reasonable by random chance, you have to have a very large library of RNA.

[QUOTE]If you insist that a process with any random component is purely random, then playing Monopoly is a random process.[/QOUTE]

I think he was trying to say that you can't select what hasn't been made yet. Selection cannot solve this problem, because the problem is before selection occurs. If no creature is ever born with the mutation, the mutation won't just pop out of nowhere so that it can be selected. That is probably what Behe was trying to say as well.

[QUOTE]If you insist on this line of reasoning, the entire universe is random and the inputs of some supernatural being aren't going to change that.[/QUOTE]

That's not really true, because you can't really show that the universe is random. If there is a God, as we maintain, that has absolute control over anything that He can invoke at any given time, then the universe is not necessarily random. Also, if He created it, it cannot be random, because He created it with all future events in mind. In all honesty, you have to admit that this means that the universe isn't random in this scenario (which is reality, by the way).

[QUOTE]We can take it as far as natural selection can acount for the diversity of life as we know it in probably the last 10k years. How's that????[/QUOTE]

I don't know that we need to limit it that much. I have yet to see any reasonable evidence to say that the Earth would have to be that old, in the Bible or in nature. If you are relying solely on the genealogies in the Bible, it should be stated that they weren't listed completely. The style at the time was not to list everyone in the ancestral line, and the purpose of the Bible did not demand that they do so. In fact, it can be shown from the Bible that not all of the genealogies were complete. Even from a young earth perspective, the earth could be older than 10,000 years.

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Posted 15 May 2005 - 07:16 AM

There is actually good statistical reason to doubt this. First, it has the same problems with being ordered correctly, so it doesn't really solve any problems. Second, for a single strand of RNA to replicate, there must be an identical strand of RNA nearby. To make the odds of that happening reasonable by random chance, you have to have a very large library of RNA.

What problem with being ordered correctly? Vasopressin consists of about 10 amino acids, if I recall correctly. I can obtain that with a mere 20^10 random experiments, and that's assuming that the amino acids have to be completely specific.

I think he was trying to say that you can't select what hasn't been made yet. Selection cannot solve this problem, because the problem is before selection occurs. If no creature is ever born with the mutation, the mutation won't just pop out of nowhere so that it can be selected. That is probably what Behe was trying to say as well.

Fine, then say that mutation is a random process (which is probably false). But don't say "the proposal of evolution via random mutation and natural selection is a random process."

That's not really true, because you can't really show that the universe is random. If there is a God, as we maintain, that has absolute control over anything that He can invoke at any given time, then the universe is not necessarily random. Also, if He created it, it cannot be random, because He created it with all future events in mind. In all honesty, you have to admit that this means that the universe isn't random in this scenario (which is reality, by the way).

I didn't say that the universe is entirely random. I said that 92g's idea that any random factor make a process entirely random implies that the universe is entirely random.

~~ Paul

#14 ret

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Posted 21 May 2005 - 10:02 PM

Fine, then say that mutation is a random process (which is probably false).


I don't suppose you have some reason to think it's false?

Vasopressin consists of about 10 amino acids, if I recall correctly.


We're not talking about a single protein, we're talking about an entire genetic code for a living creature. The most liberal estimates I have seen (by evolutionists) for the genetic code of the first organism was 100,000 base pairs long, with 10,000 amino acids and 100 functional proteins. Even if it is simpler to get a protein that you need, it doesn't matter if you only get one. Also, I didn't say anything about the amino acids being ordered correctly, I was speaking of RNA. RNA codons would have to be the exactly correct groups of three for each amino acid they are coding for, meaning that the odds are tripled for each amino acid, and for the protein as a whole because of it. And that's just one problem with the RNA theory.

I didn't say that the universe is entirely random. I said that 92g's idea that any random factor make a process entirely random implies that the universe is entirely random.


I was trying to explain to you that he wasn't trying to say that (I think). You just weren't understanding the way he was wording it. The selection part of the process isn't random, meaning that the entire process isn't random. The results, however, cannot include something that was excluded as a possibility in the beginning. In other words: you can't select something that doesn't exist.

#15 Modulous

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Posted 22 May 2005 - 03:21 AM


Fine, then say that mutation is a random process (which is probably false).

I don't suppose you have some reason to think it's false?

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Do a google search for mutation hotspots. I think that is what he may be referring to.

#16 ret

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Posted 29 May 2005 - 12:29 PM

Do a google search for mutation hotspots. I think that is what he may be referring to.


Thanks, Modulous. Paul, if this is what you meant, I'm afraid that doesn't cut it. Even if the small minority of mutations are not random, the majority of them are. Unless you have evidence to the contrary, which I would be happy to see, I am forced to retain my view that I stated earlier.

If this isn't what you meant, then please reference what you did mean.




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