Administrator
01-10-2002, 11:43 PM
[Administrator: This series of exchanges was culled from 7 pages of exchanges on the original file. Approximately three-fourths were insults and mockery to David Plaisted. The following series of exchanges was left when this and some extraneous material was removed. This is a good example of why this format is now being used for this board. ]
DAVID PLAISTED
Check out www.cs.unc.edu/~plaisted/ce/blocked.html (http://www.cs.unc.edu/~plaisted/ce/blocked.html)
for a disproof of the theory of evolution.
SCOTT PAGE
Plaisted's 'disproof' fails utterly by the same token so many other 'disproofs' fail: 1. He engages in after-the-fact probabiliuty games 2. He lacks sufficient background knowledge to catch his errors in the first place.
Nonetheless, from computer scientist Plaisted's "evolution disproof" [sic]:
"In order to get these specific 34 mutations would require roughly 10^63 trials; this could be accomplished by a population of 10^30 individuals lasting for 10^33 generations, roughly speaking, or a population of 10^33 individuals lasting for 10^30 generations, et cetera. Clearly this requires an astronomically large population or a time much longer than available,or both."
Who caught the flaw in Plaisted's reasoning?
It is in the first sentence that I quoted:
"In order to get these specific 34 mutations..."
To show how irrelevant such calculations are, try this:
Calculate the odds of you finding a specific penny on a specific corner in a specific city at a specific time on a specific day in a specific year during specific weather conditions.
The odds are staggering, yet I just found a specific penny on a specific corner etc.... this very day.
Yet statistically, working backwards, I can easily disprove it.
DAVID PLAISTED
Actually this specific issue is handled quite directly in the article and my assumptions are even somewhat too favorable to the theory of evolution.
SCOTT PAGE
It is directly handled by using the same faulty logic. Once a mutation occurs, you are handling it as though it was specified.
For example, you talk about "the right hydrogen bonding", "every one of the specified[emphasis mine] 34 sites..."
You are taking an end product and working backwards, under the erroneous assumption that that specific protein is THE one, that it is necessary as-is, etc. You write:
"Thus one can expect most mutations that change an amino acid to be deleterious...", after referring to Crow's statement regarding mutations that can be phenotypically detected (was he referring to genes inlfuencing morphology or something else?). Tell me then - which cytochrome c found in the animal kingdom is the 'good' one? that is, since the sequence of cytochrome c's vary greatley across lineages, and they all seem to work, which ones should have been removed from a population by now?
In additon, aside form the occasional reference within the text (such as the second hand quote from ReMine), you supply no bibliography and a large number of your assumptions and 'conclusions' are citationless.
Lets say that you are correct. How then can you explain 'within kind' variation in only a few thousand years? For this variation would be due to the same factors that you imply cannot account for evolution... right?
DAVID PLAISTED
I'm not sure I understand your point -- my article gives a clear justification for saying that a specific set of 34 mutations is needed. But there is a valid related point which may be what you were getting at. My article assumes that the mutation process is evaluated on the basis of being able to reach a single new protein fold. Actually there could be many folds. This is a detailed part of the argument, but anyway, as far as we know there are only a small number of folds, possibly less than 1000. Thus we are only talking about a factor of 1000. In addition, some folds will be easier to get than others; the easier ones will dominate because the harder ones will be so much less probable. On the basis of a random distribution of folds in the "mutation distance space" one would expect only a small minority of them to be the easiest ones to get. And of these, an even smaller set would be beneficial to the organism. So it does not change the argument much to assume that there is just one fold that needs to be reached.
Oh yes, in kind variation can be explained by mutations that do not affect the shape of the protein, and also by different combinations of genes, recombination, epigenetics, gene duplications, and probably other factors.
THE BARBARIAN
It appears that Plaisted has rediscovered Hoyle's Folly.
Perhaps he'd be interested in thinking about the number of genes in humans, and then the genomes of his great-great grandparents.
Using his "proof", we can show that Plaisted is so unlikely that he is statistically impossible.
So now that he has proven that he and evolution are impossible, how are we to explain those speciations, fossils, biochemical and genetic results, and one slightly off-center web site?
DAVID PLAISTED
I see your point, but to me this does not appear to be related to my article. Maybe if you could explain it more clearly? The possible protein folds appear to be determined by the laws of physics and the question is how they could be generated by evolution. Another thing people may not realize is that all the cytochrome C etc in different organisms has the same shape. What my article is concerned with is not the detailed amino acid sequences, which have an element of randomness, apparently, and to which your argument might apply, but their shape.
THE BARBARIAN
Suppose a series of new enzymes evolves to catalyze a potential food substrate in a species of bacteria. The new enzymes obey the laws of physics in their folding. Why would we expect it to be any different?
Another thing people may not realize is that all the cytochrome C etc in different organisms has the same shape. What my article is concerned with is not the detailed amino acid sequences, which have an element of randomness, apparently, and to which your argument might apply, but their shape.
David, cytochrome c has the same shape in all organisms, because it has the same activity in all organisms. It is essential in glycolosis. The shape of the molecule is dictated by its activity. While some minor folding can be different, cytochrome c would lose its effectiveness if the active sites were different.
DAVID PLAISTED
David, cytochrome c has the same shape in all organisms, because it has the same activity in all organisms….
The problem is that the protein folds are separated by many mutations, to our best knowledge. In between is a wasteland of reduced fitness. Evolution always climbs the fitness landscape, or at least does not descend it. Therefore it cannot cross from one peak to another. The mechanism proposed to get around this has to do with "useless genes" and this is the subject of my paper. Typical beneficial mutations (if there are such) just change an amino acid and this requires only one mutation, so it does not require evolution to cross a fitness valley.
Harmful mutations tend to be eliminated from the population and beneficial ones tend to be retained, as well as some of the neutral ones. It is possible that harmful mutations could accumulate and render a population or individual less fit temporarily. However this will eventually result in a higher death rate for the population. Anyway, this has all been treated in population genetics studies and formal models have been developed to describe what happens. What we have to deal with is the probability of evolution behaving in a certain way and the probability of crossing a wide fitness valley is very low.
THE BARBARIAN
The problem is that the protein folds are separated by many mutations, to our best knowledge.
But where in the biochemical phylogeny of cytochrome c, are there many mutations? How many mutations do you think there can be in a molecule that size? Why do you suppose that there are some constant regions that rarely or never are changed?
In between is a wasteland of reduced fitness.
Show me. Between which two forms is there this "wasteland", and how do you know that?
Evolution always climbs the fitness landscape, or at least does not descend it. Therefore it cannot cross from one peak to another.
First, since all cytochrome c seems to have about the same ability to catalyze reactions, there seems to be no "fitness peak" with regard to the existing variations. Second, you are very wrong in thinking that a population cannot descend from a fitness peak. Indeed, you seem to be assuming that "fitness peaks" are a constant, and do not move about themselves. This they also do. A nice description of the process could be found in most introductory texts on evolution.
Changes in cytochrome c happen to be "just one amino acid". And there is no evidence whatever that such change involves a trek across a fitness valley, even if such "valleys" were a constant.
DAVID PLAISTED
There's a miscommunication here. Differences between cytochrome C in different organisms do not involve a change of shape. Thus there is no fitness valley to cross. The problem is how evolution could generate proteins having new shapes. This would involve many mutations to change from one shape to another and in between the protein would be useless. You should read the paper for details.
THE BARBARIAN
Dave, would you be interested in some research that shows proteins being changed to entirely new functions?
One way that the "fitness valley" can be avoided, is by duplicate genes. One of several to many copies can be modified, while the rest serve their original function. In this way, there is no "fitness valley".
But we know for a fact that useful new proteins can evolve, because we have seen it happen. So, we end up wondering whether we should go with the "new proteins are impossible" theory or the reality that they do evolve.
RUFUS ATTICUS
Evolution always climbs the fitness landscape, or at least does not descend it. Therefore it cannot cross from one peak to another.
You are 100% wrong. You seem to be using Wright's work without reading the entire volume. Populations can and do shift between "adaptive peaks" by genetic drift. Evolution is not all about positive selection. Selection does not always climb the hill either. I have personal experience with a frequency-dependent selection model in which the fitness of a population can decrease from natural selection alone. I hope you will fix your argument to take this into account.
MR BEN
This is where you make your fundamental mistake in your reasoning: The probability of evolution producing a particular pattern is not simply the naive number of permutations of that pattern, it is the cumulative probability of a mutation at each stage producing a better protein.
By your reverse probability reconing, I should not exist, as the probability of my parent meeting each other, falling in love, conceiving me, not to mention the specific random genes that I am made of, are astronomically huge.
But probability can only be worked in the forward direction. How probable is it that somebody 'like' myself would be born. Quite probable actually.
By the same token, applying probability forward on your 34 genes.. we can se that at any given stage (from 1 to 34), the probability that the odd beneficial mutation would come along to advance the utility of the sequence and eventually produce something 'like' the final result is quite high. That doesn't mean that if we did it again, we'd get the same 34 pairs. That would be very very unlikely (just like the chances of a genetic twin brother of myself being conceived by my parents), but we easily get another protein 20-40 that would do more or less the same thing.
So, you must ask yourself.. what are the chances that any mutation on a given genome in any protein will produce a better adapted individual. The answer is small, but large enough to happen all the time by chance.
DAVID PLAISTED
To Barbarian: Yes, I believe proteins can assume new functions by mutations. But this does not create proteins of new shapes.
But I would be interested in your examples anyway.
You say that the fitness valley problem can be avoided by duplicate genes. Yes, this is a very good observation and it is exactly this possibility that my article discusses in detail.
To RufusAtticus: All my argument assumes is that mutations that are harmful are eliminated from a population. It could happen that genetic drift would even make a whole population decrease in fitness since harmful mutations might spread to the whole population before they were eliminated. But this would require a small population and a very high probability of harmful mutation, it seems to me. Actually one can even have error catastrophe if the mutation rate is too high and the whole population could die out. In that case of course one would not have proteins of new shapes evolving either so it would not affect my argument. The question is how proteins of new shapes could evolve. But your frequency-dependent selection model sounds interesting -- is it in the literature anywhere or is there some way I can learn more about it?
To Mr. Ben: I believe I answered your objection in an earlier reply.
THE BARBARIAN
Yes, I believe proteins can assume new functions by mutations. But this does not create proteins of new shapes.
That would have to happen, if it had a new function. Maybe not a large change, but a change. What keeps that from accumulating small changes? We also know that happens.
But I would be interested in your examples anyway.
"Evolution on a Petri Dish : The evolved B-galactosidase system as a model for studying acquisitive evolution in the lab", Barry G Hall, Evolutionary Biology (1982) #15, pg 85-150.
RUFUSATTICUS
Rich Meagher has done some work on the evolution of the actin gene complex in plants. The genetic phylogenies indicate multiple gene duplication events with sequental diversifications. All gene families are basically formed the same way.
Molecular evidence from comparing the "same" gene from multiple species indicates that not every residue evolves at the same rate. Concerved regions, like active sites, don't evolve much. Initial evolution of the protein has basically optimized it. Protein evolution can also occur because of evironmental shifts. The old protein no longer functions "optimally" (but still functions), so some mutants can arise that are more fit than the old one.
You also need to remember that "less fit" is not equivilent with harmful.
But your frequency-dependent selection model sounds interesting -- is it in the literature anywhere or is there some way I can learn more about it?
The work that I am directly a part of is in preperation. (My advisor is in NZ now writing it up.) It is based on some earlier work by her. I can't recall off hand if she fleshed out the possible trajectories in that paper but here is the PubMed reference. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2341034&dopt=Abstract
I honestly don't know of any additional FDS models that show the same effect, but I suspect they exist. You might want to try a literature search.
DAVID PLAISTED
Can a different selection model help protein evolution? I can't see how it could. Someone referred to "frequency based selection" and it took a while for that to sink in. The idea is that some mutations may be preferred based on their frequency, if for example individuals preferred mates that were unusual in some way. But I've thought about this and can't think of any reasonable selection model that would materially help the evolution of new protein shapes.
I think the largest misunderstanding has to do with protein folding. People really need to understand more about protein structure. I'll try to give some basics here. Proteins are composed of sequences of amino acids (the primary structure). Some parts of this sequence fold into regular structures called alpha helices and beta sheet (secondary structure), typically about half of a protein. Alpha helices are spirals and beta sheets are parallel or antiparallel and more or less straight. The rest of the protein is irregular. Then these structures fold together into some geometrical configuration called the tertiary structure, which is what I am concerned about. This has to do with how two alpha helices may rest against each other and so on. This tertiary structure can be called a "fold," though I'm not sure that is the exact use of this term. Now, the question is how new folds can arise. Less than a thousand folds are known and it is suspected that not many more can exist. (Another way of counting says about 10,000 but I think it means something else -- anyway the number is small). Each fold has restrictions on what kind of amino acid can appear at what position -- not just for the protein to be beneficial but simply for the fold to form. For example hydrophobic residues (amino acids) typically appear on the inside of a protein and other amino acids typically appear on the outside, but at least one amino acid can appear either place. Each fold has tight restrictions of this nature. If one replaces an amino acid by a similar one, the fold will probably not change, and this is the kind of changes in the different versions of cytochrome c. However, a random sequence of amino acids is highly unlikely to have the right kind of amino acids for _any_ fold and will become a useless glob that will probably react in harmful ways.
The question is where the folds came from since there are too many for all of them to have been present in the first reproducing system (it would be far too complex). Different folds are separated by many mutations -- to our knowledge, at least 70 percent of the amino acids have to change to change to another fold. As one travels an optimal sequence of mutations between folds, here is what happens: First the original fold becomes more and more unstable. Then the protein will not fold at all and will be a useless glob. Then the new fold will begin to form but will be highly unstable. Eventually the new fold will form and be stable. But even then there is no guarantee that it will benefit the organism. All the proteins on this path will be less useful than the original one, but the new fold may be just as useful. So how could evolution create a new fold? The duplicate gene idea is OK except the problem is that in the process of crossing from one fold to another, many other mutations will also occur that will randomize the rest of the protein and so at the end with very high probability one will have basically a random protein that will not form the desired fold anyway. And it will probably have many harmful added reactions. The details are in the paper and as far as I can see it is completely rigorous and refutes the theory of evolution. But if there is a mistake somewhere, no one in this discussion has pointed it out yet.
Thanks for your input, anyway. It has helped me to see where the argument can be misunderstood.
RUFUSATTICUS
If you really want to work the bugs out of your idea, why are you not consulting experts in protein folding and evolutionary biology?
MESK
I think the largest misunderstanding has to do with protein folding. People really need to understand more about protein structure. I'll try to give some basics here.
<snip explanation of protein folding>
This tertiary structure can be called a "fold," though I'm not sure that is the exact use of this term.
The two terms mean similar things, but are not precisely equivalent. The term "fold" has a broader meaning than "tertiary structure". Two proteins can have the same basic fold, but differ in the precise spatial arrangement of their structural elements (that is, their tertiary structure).
Now, the question is how new folds can arise. Less than a thousand folds are known and it is suspected that not many more can exist. (Another way of counting says about 10,000 but I think it means something else -- anyway the number is small).
The total number depends on how rigorously you define the term "fold", and the precise methods used to evaluate the data. Some estimates are based on the protein structures currently available from online databases, while others used theoretical calculations.
I did a quick Google search on the subject and found this site, which you might find useful:
Protein Origami: Exploring the world of protein folds http://www.cbs.umn.edu/class/fall2000/mimp/8006/review00/FOLDS.HTML
Each fold has restrictions on what kind of amino acid can appear at what position -- not just for the protein to be beneficial but simply for the fold to form. For example hydrophobic residues (amino acids) typically appear on the inside of a protein and other amino acids typically appear on the outside, but at least one amino acid can appear either place. Each fold has tight restrictions of this nature. If one replaces an amino acid by a similar one, the fold will probably not change, and this is the kind of changes in the different versions of cytochrome c.
That's true. Many amino acid differences between cytochrome c proteins are conservative (that is, the two amino acids are chemically similar), and these differences generally don't change the overall fold of the protein. For instance, the cytochrome c of humans and that of the protozoon Tetrahymena have the same basic fold, despite possessing less than 50% amino acid identity.
But don't be fooled into thinking that this means that the structure is somehow "protected" from amino acid changes. Many proteins possess certain residues which are absolutely crucial for correct folding, so that even a conservative change at these sites can change the overall fold of the protein. A similar effect can be achieved by multiple mutations at several different sites.
However, a random sequence of amino acids is highly unlikely to have the right kind of amino acids for _any_ fold and will become a useless glob that will probably react in harmful ways.
Sure, but evolution does not produce "random" proteins. It builds on pre-existing proteins that already possess defined tertiary structures. Changes in these proteins do not generally produce "useless globs", but can simply rearrange the preformed structural elements to generate different folds.
The question is where the folds came from since there are too many for all of them to have been present in the first reproducing system (it would be far too complex). Different folds are separated by many mutations -- to our knowledge, at least 70 percent of the amino acids have to change to change to another fold.
Well, not always. In general, proteins with greater than 30% sequence identity are likely to have the same basic fold. However, it is often possible to change a protein from one fold into another by altering only a few important residues.
As our understanding of the forces governing protein structure grows, researchers in the field of "protein engineering" are discovering precisely which amino acids need to be changed to produce specific changes in protein structure. This can include changes from one protein fold to an entirely different one.
[ January 10, 2002: Message edited by: Administrator ]
DAVID PLAISTED
Check out www.cs.unc.edu/~plaisted/ce/blocked.html (http://www.cs.unc.edu/~plaisted/ce/blocked.html)
for a disproof of the theory of evolution.
SCOTT PAGE
Plaisted's 'disproof' fails utterly by the same token so many other 'disproofs' fail: 1. He engages in after-the-fact probabiliuty games 2. He lacks sufficient background knowledge to catch his errors in the first place.
Nonetheless, from computer scientist Plaisted's "evolution disproof" [sic]:
"In order to get these specific 34 mutations would require roughly 10^63 trials; this could be accomplished by a population of 10^30 individuals lasting for 10^33 generations, roughly speaking, or a population of 10^33 individuals lasting for 10^30 generations, et cetera. Clearly this requires an astronomically large population or a time much longer than available,or both."
Who caught the flaw in Plaisted's reasoning?
It is in the first sentence that I quoted:
"In order to get these specific 34 mutations..."
To show how irrelevant such calculations are, try this:
Calculate the odds of you finding a specific penny on a specific corner in a specific city at a specific time on a specific day in a specific year during specific weather conditions.
The odds are staggering, yet I just found a specific penny on a specific corner etc.... this very day.
Yet statistically, working backwards, I can easily disprove it.
DAVID PLAISTED
Actually this specific issue is handled quite directly in the article and my assumptions are even somewhat too favorable to the theory of evolution.
SCOTT PAGE
It is directly handled by using the same faulty logic. Once a mutation occurs, you are handling it as though it was specified.
For example, you talk about "the right hydrogen bonding", "every one of the specified[emphasis mine] 34 sites..."
You are taking an end product and working backwards, under the erroneous assumption that that specific protein is THE one, that it is necessary as-is, etc. You write:
"Thus one can expect most mutations that change an amino acid to be deleterious...", after referring to Crow's statement regarding mutations that can be phenotypically detected (was he referring to genes inlfuencing morphology or something else?). Tell me then - which cytochrome c found in the animal kingdom is the 'good' one? that is, since the sequence of cytochrome c's vary greatley across lineages, and they all seem to work, which ones should have been removed from a population by now?
In additon, aside form the occasional reference within the text (such as the second hand quote from ReMine), you supply no bibliography and a large number of your assumptions and 'conclusions' are citationless.
Lets say that you are correct. How then can you explain 'within kind' variation in only a few thousand years? For this variation would be due to the same factors that you imply cannot account for evolution... right?
DAVID PLAISTED
I'm not sure I understand your point -- my article gives a clear justification for saying that a specific set of 34 mutations is needed. But there is a valid related point which may be what you were getting at. My article assumes that the mutation process is evaluated on the basis of being able to reach a single new protein fold. Actually there could be many folds. This is a detailed part of the argument, but anyway, as far as we know there are only a small number of folds, possibly less than 1000. Thus we are only talking about a factor of 1000. In addition, some folds will be easier to get than others; the easier ones will dominate because the harder ones will be so much less probable. On the basis of a random distribution of folds in the "mutation distance space" one would expect only a small minority of them to be the easiest ones to get. And of these, an even smaller set would be beneficial to the organism. So it does not change the argument much to assume that there is just one fold that needs to be reached.
Oh yes, in kind variation can be explained by mutations that do not affect the shape of the protein, and also by different combinations of genes, recombination, epigenetics, gene duplications, and probably other factors.
THE BARBARIAN
It appears that Plaisted has rediscovered Hoyle's Folly.
Perhaps he'd be interested in thinking about the number of genes in humans, and then the genomes of his great-great grandparents.
Using his "proof", we can show that Plaisted is so unlikely that he is statistically impossible.
So now that he has proven that he and evolution are impossible, how are we to explain those speciations, fossils, biochemical and genetic results, and one slightly off-center web site?
DAVID PLAISTED
I see your point, but to me this does not appear to be related to my article. Maybe if you could explain it more clearly? The possible protein folds appear to be determined by the laws of physics and the question is how they could be generated by evolution. Another thing people may not realize is that all the cytochrome C etc in different organisms has the same shape. What my article is concerned with is not the detailed amino acid sequences, which have an element of randomness, apparently, and to which your argument might apply, but their shape.
THE BARBARIAN
Suppose a series of new enzymes evolves to catalyze a potential food substrate in a species of bacteria. The new enzymes obey the laws of physics in their folding. Why would we expect it to be any different?
Another thing people may not realize is that all the cytochrome C etc in different organisms has the same shape. What my article is concerned with is not the detailed amino acid sequences, which have an element of randomness, apparently, and to which your argument might apply, but their shape.
David, cytochrome c has the same shape in all organisms, because it has the same activity in all organisms. It is essential in glycolosis. The shape of the molecule is dictated by its activity. While some minor folding can be different, cytochrome c would lose its effectiveness if the active sites were different.
DAVID PLAISTED
David, cytochrome c has the same shape in all organisms, because it has the same activity in all organisms….
The problem is that the protein folds are separated by many mutations, to our best knowledge. In between is a wasteland of reduced fitness. Evolution always climbs the fitness landscape, or at least does not descend it. Therefore it cannot cross from one peak to another. The mechanism proposed to get around this has to do with "useless genes" and this is the subject of my paper. Typical beneficial mutations (if there are such) just change an amino acid and this requires only one mutation, so it does not require evolution to cross a fitness valley.
Harmful mutations tend to be eliminated from the population and beneficial ones tend to be retained, as well as some of the neutral ones. It is possible that harmful mutations could accumulate and render a population or individual less fit temporarily. However this will eventually result in a higher death rate for the population. Anyway, this has all been treated in population genetics studies and formal models have been developed to describe what happens. What we have to deal with is the probability of evolution behaving in a certain way and the probability of crossing a wide fitness valley is very low.
THE BARBARIAN
The problem is that the protein folds are separated by many mutations, to our best knowledge.
But where in the biochemical phylogeny of cytochrome c, are there many mutations? How many mutations do you think there can be in a molecule that size? Why do you suppose that there are some constant regions that rarely or never are changed?
In between is a wasteland of reduced fitness.
Show me. Between which two forms is there this "wasteland", and how do you know that?
Evolution always climbs the fitness landscape, or at least does not descend it. Therefore it cannot cross from one peak to another.
First, since all cytochrome c seems to have about the same ability to catalyze reactions, there seems to be no "fitness peak" with regard to the existing variations. Second, you are very wrong in thinking that a population cannot descend from a fitness peak. Indeed, you seem to be assuming that "fitness peaks" are a constant, and do not move about themselves. This they also do. A nice description of the process could be found in most introductory texts on evolution.
Changes in cytochrome c happen to be "just one amino acid". And there is no evidence whatever that such change involves a trek across a fitness valley, even if such "valleys" were a constant.
DAVID PLAISTED
There's a miscommunication here. Differences between cytochrome C in different organisms do not involve a change of shape. Thus there is no fitness valley to cross. The problem is how evolution could generate proteins having new shapes. This would involve many mutations to change from one shape to another and in between the protein would be useless. You should read the paper for details.
THE BARBARIAN
Dave, would you be interested in some research that shows proteins being changed to entirely new functions?
One way that the "fitness valley" can be avoided, is by duplicate genes. One of several to many copies can be modified, while the rest serve their original function. In this way, there is no "fitness valley".
But we know for a fact that useful new proteins can evolve, because we have seen it happen. So, we end up wondering whether we should go with the "new proteins are impossible" theory or the reality that they do evolve.
RUFUS ATTICUS
Evolution always climbs the fitness landscape, or at least does not descend it. Therefore it cannot cross from one peak to another.
You are 100% wrong. You seem to be using Wright's work without reading the entire volume. Populations can and do shift between "adaptive peaks" by genetic drift. Evolution is not all about positive selection. Selection does not always climb the hill either. I have personal experience with a frequency-dependent selection model in which the fitness of a population can decrease from natural selection alone. I hope you will fix your argument to take this into account.
MR BEN
This is where you make your fundamental mistake in your reasoning: The probability of evolution producing a particular pattern is not simply the naive number of permutations of that pattern, it is the cumulative probability of a mutation at each stage producing a better protein.
By your reverse probability reconing, I should not exist, as the probability of my parent meeting each other, falling in love, conceiving me, not to mention the specific random genes that I am made of, are astronomically huge.
But probability can only be worked in the forward direction. How probable is it that somebody 'like' myself would be born. Quite probable actually.
By the same token, applying probability forward on your 34 genes.. we can se that at any given stage (from 1 to 34), the probability that the odd beneficial mutation would come along to advance the utility of the sequence and eventually produce something 'like' the final result is quite high. That doesn't mean that if we did it again, we'd get the same 34 pairs. That would be very very unlikely (just like the chances of a genetic twin brother of myself being conceived by my parents), but we easily get another protein 20-40 that would do more or less the same thing.
So, you must ask yourself.. what are the chances that any mutation on a given genome in any protein will produce a better adapted individual. The answer is small, but large enough to happen all the time by chance.
DAVID PLAISTED
To Barbarian: Yes, I believe proteins can assume new functions by mutations. But this does not create proteins of new shapes.
But I would be interested in your examples anyway.
You say that the fitness valley problem can be avoided by duplicate genes. Yes, this is a very good observation and it is exactly this possibility that my article discusses in detail.
To RufusAtticus: All my argument assumes is that mutations that are harmful are eliminated from a population. It could happen that genetic drift would even make a whole population decrease in fitness since harmful mutations might spread to the whole population before they were eliminated. But this would require a small population and a very high probability of harmful mutation, it seems to me. Actually one can even have error catastrophe if the mutation rate is too high and the whole population could die out. In that case of course one would not have proteins of new shapes evolving either so it would not affect my argument. The question is how proteins of new shapes could evolve. But your frequency-dependent selection model sounds interesting -- is it in the literature anywhere or is there some way I can learn more about it?
To Mr. Ben: I believe I answered your objection in an earlier reply.
THE BARBARIAN
Yes, I believe proteins can assume new functions by mutations. But this does not create proteins of new shapes.
That would have to happen, if it had a new function. Maybe not a large change, but a change. What keeps that from accumulating small changes? We also know that happens.
But I would be interested in your examples anyway.
"Evolution on a Petri Dish : The evolved B-galactosidase system as a model for studying acquisitive evolution in the lab", Barry G Hall, Evolutionary Biology (1982) #15, pg 85-150.
RUFUSATTICUS
Rich Meagher has done some work on the evolution of the actin gene complex in plants. The genetic phylogenies indicate multiple gene duplication events with sequental diversifications. All gene families are basically formed the same way.
Molecular evidence from comparing the "same" gene from multiple species indicates that not every residue evolves at the same rate. Concerved regions, like active sites, don't evolve much. Initial evolution of the protein has basically optimized it. Protein evolution can also occur because of evironmental shifts. The old protein no longer functions "optimally" (but still functions), so some mutants can arise that are more fit than the old one.
You also need to remember that "less fit" is not equivilent with harmful.
But your frequency-dependent selection model sounds interesting -- is it in the literature anywhere or is there some way I can learn more about it?
The work that I am directly a part of is in preperation. (My advisor is in NZ now writing it up.) It is based on some earlier work by her. I can't recall off hand if she fleshed out the possible trajectories in that paper but here is the PubMed reference. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2341034&dopt=Abstract
I honestly don't know of any additional FDS models that show the same effect, but I suspect they exist. You might want to try a literature search.
DAVID PLAISTED
Can a different selection model help protein evolution? I can't see how it could. Someone referred to "frequency based selection" and it took a while for that to sink in. The idea is that some mutations may be preferred based on their frequency, if for example individuals preferred mates that were unusual in some way. But I've thought about this and can't think of any reasonable selection model that would materially help the evolution of new protein shapes.
I think the largest misunderstanding has to do with protein folding. People really need to understand more about protein structure. I'll try to give some basics here. Proteins are composed of sequences of amino acids (the primary structure). Some parts of this sequence fold into regular structures called alpha helices and beta sheet (secondary structure), typically about half of a protein. Alpha helices are spirals and beta sheets are parallel or antiparallel and more or less straight. The rest of the protein is irregular. Then these structures fold together into some geometrical configuration called the tertiary structure, which is what I am concerned about. This has to do with how two alpha helices may rest against each other and so on. This tertiary structure can be called a "fold," though I'm not sure that is the exact use of this term. Now, the question is how new folds can arise. Less than a thousand folds are known and it is suspected that not many more can exist. (Another way of counting says about 10,000 but I think it means something else -- anyway the number is small). Each fold has restrictions on what kind of amino acid can appear at what position -- not just for the protein to be beneficial but simply for the fold to form. For example hydrophobic residues (amino acids) typically appear on the inside of a protein and other amino acids typically appear on the outside, but at least one amino acid can appear either place. Each fold has tight restrictions of this nature. If one replaces an amino acid by a similar one, the fold will probably not change, and this is the kind of changes in the different versions of cytochrome c. However, a random sequence of amino acids is highly unlikely to have the right kind of amino acids for _any_ fold and will become a useless glob that will probably react in harmful ways.
The question is where the folds came from since there are too many for all of them to have been present in the first reproducing system (it would be far too complex). Different folds are separated by many mutations -- to our knowledge, at least 70 percent of the amino acids have to change to change to another fold. As one travels an optimal sequence of mutations between folds, here is what happens: First the original fold becomes more and more unstable. Then the protein will not fold at all and will be a useless glob. Then the new fold will begin to form but will be highly unstable. Eventually the new fold will form and be stable. But even then there is no guarantee that it will benefit the organism. All the proteins on this path will be less useful than the original one, but the new fold may be just as useful. So how could evolution create a new fold? The duplicate gene idea is OK except the problem is that in the process of crossing from one fold to another, many other mutations will also occur that will randomize the rest of the protein and so at the end with very high probability one will have basically a random protein that will not form the desired fold anyway. And it will probably have many harmful added reactions. The details are in the paper and as far as I can see it is completely rigorous and refutes the theory of evolution. But if there is a mistake somewhere, no one in this discussion has pointed it out yet.
Thanks for your input, anyway. It has helped me to see where the argument can be misunderstood.
RUFUSATTICUS
If you really want to work the bugs out of your idea, why are you not consulting experts in protein folding and evolutionary biology?
MESK
I think the largest misunderstanding has to do with protein folding. People really need to understand more about protein structure. I'll try to give some basics here.
<snip explanation of protein folding>
This tertiary structure can be called a "fold," though I'm not sure that is the exact use of this term.
The two terms mean similar things, but are not precisely equivalent. The term "fold" has a broader meaning than "tertiary structure". Two proteins can have the same basic fold, but differ in the precise spatial arrangement of their structural elements (that is, their tertiary structure).
Now, the question is how new folds can arise. Less than a thousand folds are known and it is suspected that not many more can exist. (Another way of counting says about 10,000 but I think it means something else -- anyway the number is small).
The total number depends on how rigorously you define the term "fold", and the precise methods used to evaluate the data. Some estimates are based on the protein structures currently available from online databases, while others used theoretical calculations.
I did a quick Google search on the subject and found this site, which you might find useful:
Protein Origami: Exploring the world of protein folds http://www.cbs.umn.edu/class/fall2000/mimp/8006/review00/FOLDS.HTML
Each fold has restrictions on what kind of amino acid can appear at what position -- not just for the protein to be beneficial but simply for the fold to form. For example hydrophobic residues (amino acids) typically appear on the inside of a protein and other amino acids typically appear on the outside, but at least one amino acid can appear either place. Each fold has tight restrictions of this nature. If one replaces an amino acid by a similar one, the fold will probably not change, and this is the kind of changes in the different versions of cytochrome c.
That's true. Many amino acid differences between cytochrome c proteins are conservative (that is, the two amino acids are chemically similar), and these differences generally don't change the overall fold of the protein. For instance, the cytochrome c of humans and that of the protozoon Tetrahymena have the same basic fold, despite possessing less than 50% amino acid identity.
But don't be fooled into thinking that this means that the structure is somehow "protected" from amino acid changes. Many proteins possess certain residues which are absolutely crucial for correct folding, so that even a conservative change at these sites can change the overall fold of the protein. A similar effect can be achieved by multiple mutations at several different sites.
However, a random sequence of amino acids is highly unlikely to have the right kind of amino acids for _any_ fold and will become a useless glob that will probably react in harmful ways.
Sure, but evolution does not produce "random" proteins. It builds on pre-existing proteins that already possess defined tertiary structures. Changes in these proteins do not generally produce "useless globs", but can simply rearrange the preformed structural elements to generate different folds.
The question is where the folds came from since there are too many for all of them to have been present in the first reproducing system (it would be far too complex). Different folds are separated by many mutations -- to our knowledge, at least 70 percent of the amino acids have to change to change to another fold.
Well, not always. In general, proteins with greater than 30% sequence identity are likely to have the same basic fold. However, it is often possible to change a protein from one fold into another by altering only a few important residues.
As our understanding of the forces governing protein structure grows, researchers in the field of "protein engineering" are discovering precisely which amino acids need to be changed to produce specific changes in protein structure. This can include changes from one protein fold to an entirely different one.
[ January 10, 2002: Message edited by: Administrator ]