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Author
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Topic: Error Correction Runs Deep
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Jules
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Member # 181
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posted 30. November 2002 11:06
OK, thinking it over, maybe I get it, now. A designer who wanted to use evolution to unleash (unlock? activate? download?) front-loaded designs, would want the code for proteins to have a uracil base. That way when cytosine deaminated into uracil, another front-loaded design could emerge. Therefore, it was necessary that RNA have a uracil base to begin with. Do I get it now, Mike?
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Janitor@MIT
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Member # 125
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posted 30. November 2002 13:51
Very interesting essay, Mike Gene! I have a question that goes beyond error-correction to the possibility of error-correction + “orthogenetics.”
I noticed that the occurrence of unmethylated CpG islands (in vertebrates especially) is strongly correlated (“paradoxically”?! Jones, P.A. “The DNA methylation paradox,” Trends Genetic 15 (1): 34-37, Jan. 1999.) with proximal promoters (TATA box and Inr). The question is then about a front-loaded transition bias acting as a stochastic (evolutionary) “switch.” Is this just off-the-wall, or just plain wrong? Or is it worth investigating?
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rafe gutman
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Member # 134
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posted 01. December 2002 18:50
quote:
jules:
Mike has suggested that a designer of evolution would want to use cytosine. What I'm wondering about is the uracil in RNA. Assuming that RNA didn't come first (from some RNA world), then some designer decided to design RNA using uracil as one of the bases. Is there some design advantage to uracil?
jules, this is the best question i've ever heard you ask (if you are also bilbo on ARN). it looks like mike's thesis is that the instability of cytosine could by utilized by a designer for front-loading. i would guess since the deamination of cytosine to uracil is more common than a designer would prefer, the use of thymidine instead of uracil in the genetic code would help to safeguard against overmutation. that being said, it doesn't seem like there is an advantage to having uracil in the RNA code. deamination of mRNA would not be carried to germline, so it wouldn't "unlock" any front-loaded designs. additionally, i don't see why RNA editing requires uracil in the code. RNA editing would probably work just as well if thymidine was in the code.
here's your question again, i'd like to see what mike's answer is:
quote:
My question is why have uracil in RNA to begin with?
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Frances
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Member # 169
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posted 02. December 2002 01:10
These are all excellent questions to deal with. My problem with 'front loading' or 'stacking the deck' is that it proposes a purely naturalistic pathway from an initial state. The only question remaining if the initial state required intelligent design or not. So far I am still trying to understand what front loading would give us that present day science doesn't?
How does front loading fit in with Intelligent Design?
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Jules
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Member # 181
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posted 02. December 2002 21:44
Gosh, Rafe, I've asked a lot of great questions over the last year and a half (and yes, I am Bilbo). Are you sure this is my best?
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Mike Gene
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Member # 149
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posted 02. December 2002 22:27
Janitor: The question is then about a front-loaded transition bias acting as a stochastic (evolutionary) “switch.” Is this just off-the-wall, or just plain wrong? Or is it worth investigating?
That's an interesting thought. Are you suggesting that C-T transitions would be one way to take a position "off-line" such that is escapes the regulatory circuit involving C-methylation (and its associated effects)? As I mentioned before, I have not got around to pondering the genomic opportunities provided by such biased mutations.
One thing that is interesting from the paper you mention is the observation that transcription through CpG islands is associated with increased methylation rates. Transitions involving Me-C result in the production of thymine directly, which allows cells to escape the ung-directed error correction. Couple this to the fact that deamination is associated with transcription also and the opportunity exists for accelerated sequence evolution of expressed genes.
[ 02. December 2002, 22:28: Message edited by: Mike Gene ]
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Mike Gene
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Member # 149
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posted 02. December 2002 22:29
Rafe: jules, this is the best question i've ever heard you ask (if you are also bilbo on ARN). it looks like mike's thesis is that the instability of cytosine could by utilized by a designer for front-loading. i would guess since the deamination of cytosine to uracil is more common than a designer would prefer, the use of thymidine instead of uracil in the genetic code would help to safeguard against overmutation.
That's one possibility. It may have been even more sophisticated than this. Using thymidine in DNA would allow cells to escape Ung surveillance simply by methylating the cytosines. This is because the deamination product of Me-C is thymine, not uracil. Thus, a cell could theoretically regulate ung and cytosine methylase activities, making it possible to target increased hydrophobicity to specific regions of a protein.
that being said, it doesn't seem like there is an advantage to having uracil in the RNA code.
It doesn't seem there is any disadvantage to having uracil in RNA. After all, natural selection did not replace it with thymine, did it?
deamination of mRNA would not be carried to germline, so it wouldn't "unlock" any front-loaded designs.
Reverse transcriptase may have come in handy here.
additionally, i don't see why RNA editing requires uracil in the code. RNA editing would probably work just as well if thymidine was in the code.
I think I finally "get" the question. You're asking why uracil instead of thymidine.
In RNA, uracil, depending on its context, can actually base pair with all other bases, including itself. This feature is thought to be involved in RNA structure formation in rRNA and even mRNA. Put simply, uracil gives RNA an increased structural flexibility. And now that I think about it, this is roughly analogous to the IHE hypothesis I outlined. Cytosine deamination coupled to translation results in proteins tapping into a hydrophobic pool that may be helpful to tweaking protein structure. In RNA, uracil's ability to act as a "universal partner" may also allow deamination events to increase the range of structural experimentation. The extra methyl group found in thymine would seem to restrict this flexibility.
Whether this is "the answer" remains to be explored. It does, however, seem to be a plausible "answer" to the question.
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Mike Gene
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Member # 149
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posted 02. December 2002 22:30
Frances: These are all excellent questions to deal with. My problem with 'front loading' or 'stacking the deck' is that it proposes a purely naturalistic pathway from an initial state.
Like I said, I am not exactly sure what you mean by naturalistic. Are you under the impression that I have a burden to come up with a supernaturalistic explanation?
The only question remaining if the initial state required intelligent design or not.
No, it's not a question of what is required. It's a question of whether or not ID was involved in the origin of the initial states and how this might pan out.
So far I am still trying to understand what front loading would give us that present day science doesn't?
Let's see. "Present day science" gave us the notion that cytosine deamination was something an engineer would have stripped away, thus it is better viewed as a "frozen accident." My FLE thesis, on the other way, provided the matrix and the impetus to look a little deeper and uncover a pattern that "present day science" has not noticed.
How does front loading fit in with Intelligent Design?
It gets us closer and closer to a "mechanism," the thing that is constantly demanded from ID. It won't be long before ID starts putting its own testable "just-so" stories on the table. ![[Wink]](wink.gif)
[ 02. December 2002, 22:31: Message edited by: Mike Gene ]
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Mike Gene
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Member # 149
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posted 02. December 2002 22:37
Jules: OK, thinking it over, maybe I get it, now. A designer who wanted to use evolution to unleash (unlock? activate? download?) front-loaded designs, would want the code for proteins to have a uracil base. That way when cytosine deaminated into uracil, another front-loaded design could emerge. Therefore, it was necessary that RNA have a uracil base to begin with. Do I get it now, Mike?
Yep. But I don't think in terms of necessity. Rafe claims uracil is not "required." Frances wants to know if ID is "required" behind the initial states. My focus is not on reducing ID to necessity (as if it must fill in for the insufficiencies of Nature). My focus is on just how clever evolution is. Alberts notes that the cell is more sophisticated than any biochemist suspected twenty years ago. Well, I'll go on record as saying that evolution is more sophisticated than most neo-Darwinists today appreciate. Life was designed to evolve.
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Frances
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Member # 169
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posted 03. December 2002 02:28
Mike.
Your use of the term 'designed' seems to lose much of its similarity as used in the intelligent design movement.
Perhaps life was 'designed to evolve' since the natural laws made evolution an almost inevitable fact. But how this relates to intelligent design is beyond me.
If I understand your usage of the term design, it merely points to certain initial conditions but so far all the steps seem to be purely naturalistic. Evolution indeed may be 'clever', far more clever than any intelligent designer could be.
So why the need for the term intelligent designer if we cannot distinguish between ID and natural processes?
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rafe gutman
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Member # 134
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posted 03. December 2002 04:06
quote:
mike: Using thymidine in DNA would allow cells to escape Ung surveillance simply by methylating the cytosines. This is because the deamination product of Me-C is thymine, not uracil.
i could be wrong on this, but isn't the rate of deamination of methylated cytosine vastly lower than unmethylated? i thought that was the driving force behind methylation (at least according to the evolutionary model). if so, mutation of methylated cytosine to thymine wouldn't really be a factor.
quote:
rafe: that being said, it doesn't seem like there is an advantage to having uracil in the RNA code.
mike: It doesn't seem there is any disadvantage to having uracil in RNA. After all, natural selection did not replace it with thymine, did it?
i don't think evolutionary theory makes a prediction one way or the other on whether uracil is better than thymidine in RNA. if it would take a large number of unselectable mutations to switch RNA from uracil to thymidine, it might have been too difficult. i do think that ID would predict a benefit of uracil here, but that's just my opinion.
quote:
rafe:deamination of mRNA would not be carried to germline, so it wouldn't "unlock" any front-loaded designs.
mike: Reverse transcriptase may have come in handy here.
why deaminate the mRNA when you can just deaminate the DNA directly? this seems to be a more direct route to "unlocking" designs than RNA editing. i'm not saying your theory is wrong, i just don't think RNA editing would have anything to do with it.
quote:
mike: You're asking why uracil instead of thymidine.
In RNA, uracil, depending on its context, can actually base pair with all other bases, including itself. This feature is thought to be involved in RNA structure formation in rRNA and even mRNA. Put simply, uracil gives RNA an increased structural flexibility. And now that I think about it, this is roughly analogous to the IHE hypothesis I outlined. Cytosine deamination coupled to translation results in proteins tapping into a hydrophobic pool that may be helpful to tweaking protein structure. In RNA, uracil's ability to act as a "universal partner" may also allow deamination events to increase the range of structural experimentation. The extra methyl group found in thymine would seem to restrict this flexibility.
Whether this is "the answer" remains to be explored. It does, however, seem to be a plausible "answer" to the question.
i don't know a whole lot about this, but you seem to be suggesting that uracil is important for generating certain secondary structures in RNA that are required for function. that may very well be true, but aside from mRNA and the anti-codon on tRNA, i don't see a reason why these secondary structures would even be required (from an ID perspective). i think that most RNAs could be replaced by proteins, except for the two molecules i mentioned above. i'm not trying to say that that's a major problem for ID, but it makes perfect sense from an evolutionary perspective. i agree that your answer is plausible.
quote:
(in a later post) mike: Rafe claims uracil is not "required."
hold on now, i never said that. all i said was that "it doesn't seem like there is an advantage to having uracil in the RNA code." i just wanted to make this clear, because this could lead to a misunderstanding later on.
[ 03. December 2002, 04:11: Message edited by: rafe gutman ]
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Mike Gene
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Member # 149
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posted 03. December 2002 08:58
Rafe: i could be wrong on this, but isn't the rate of deamination of methylated cytosine vastly lower than unmethylated? i thought that was the driving force behind methylation (at least according to the evolutionary model). if so, mutation of methylated cytosine to thymine wouldn't really be a factor.
Actually, the rate of 5-meC deamination is 2-4 times higher than the deamination rate of unmethylated C.
I'll try to address the other questions tonight.
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Mike Gene
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Member # 149
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posted 04. December 2002 01:20
Frances: If I understand your usage of the term design, it merely points to certain initial conditions but so far all the steps seem to be purely naturalistic.
As explained many times before, the hypothesis is that the earth was seeded with cells that were the products of bioengineering at the hands of some form of advanced human-like intelligence. The "initial conditions" were the originally designed state of these stem cells.
Evolution indeed may be 'clever', far more clever than any intelligent designer could be.
What I meant by evolution being clever was that the mechanisms of evolution are far more clever than most appreciate. The mechanisms were designed to extract the potential of the originally designed state. And even when it comes to RM & NS, life was designed to make smart use of these phenomena.
So why the need for the term intelligent designer if we cannot distinguish between ID and natural processes?
Perhaps you cannot make the distinction, but that is not important. I make it all the time, which explains why I am able to successfully infer things about the biotic world using ID. I understand "natural processes" sufficiently, such that I am able to draw from both perspectives. If ID offered nothing, I'd abandon it. I only take it seriously because I'm increasingly finding it to be useful - witness my latest web page article.
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Mike Gene
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posted 08. December 2002 00:17
Rafe: i don't think evolutionary theory makes a prediction one way or the other on whether uracil is better than thymidine in RNA.
Agreed. Perhaps this undercuts Frances' claim that the teleological and non-teleological views of biotic history are indistinguishable.
if it would take a large number of unselectable mutations to switch RNA from uracil to thymidine, it might have been too difficult. i do think that ID would predict a benefit of uracil here, but that's just my opinion.
I did. And there is another possibility I hope to raise later.
why deaminate the mRNA when you can just deaminate the DNA directly? this seems to be a more direct route to "unlocking" designs than RNA editing. i'm not saying your theory is wrong, i just don't think RNA editing would have anything to do with it.
I disagree. RNA editing is a smart, active way to make use of mutation and selection. I'll explain this later too.
i don't know a whole lot about this, but you seem to be suggesting that uracil is important for generating certain secondary structures in RNA that are required for function. that may very well be true, but aside from mRNA and the anti-codon on tRNA, i don't see a reason why these secondary structures would even be required (from an ID perspective). i think that most RNAs could be replaced by proteins, except for the two molecules i mentioned above. i'm not trying to say that that's a major problem for ID, but it makes perfect sense from an evolutionary perspective. i agree that your answer is plausible.
Now we're moving to the notion that a designer wouldn't have used RNA to do anything other than it's traditionally recognized roles. I don't buy that for several reasons, including the growing evidence that RNA has probably replaced proteins for some functions. But again, I'll have to eventually address this in more detail.
hold on now, i never said that. all i said was that "it doesn't seem like there is an advantage to having uracil in the RNA code." i just wanted to make this clear, because this could lead to a misunderstanding later on.
I was thinking of this claim: " I don't see why RNA editing requires uracil in the code." And above, you draw again from the same line of thought: "i don't see a reason why these secondary structures would even be required." You seem to be flirting with notions of ID as something to be invoked only when it is "required."
[ 08. December 2002, 01:35: Message edited by: Mike Gene ]
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Mike Gene
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posted 08. December 2002 00:31
Okay, I have fielded several questions concerning my hypotheses. And I'm running up against my self-imposed 50 post/thread limit. So perhaps it is my turn to ask a couple of questions.
1. According to Robert Shapiro, cytosine has not been reported in analyses of meteorites nor is it among the products of electric spark discharge experiments. And because of its predisposition to deaminate, under mild conditions, it was a half life of only about 340 years. Put simply, there is not a convincing case that cytosine would have been among the major players of the prebiotic soup. Furthermore, cytidine is not needed for ribozyme function. Recently, Joyce was able to synthesize a functional ribozyme containing only A,G, and U.
So here's the question for the non-teleologists - why does RNA have cytosine?
2. How does the non-teleologist explain the relationship I discovered between the most common form of DNA mutation and its functional consequence as mediated by the genetic code? Is this yet another example of something that "just happened?"
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