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Author
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Topic: Error Correction Runs Deep
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nobody
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Member # 145
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posted 13. November 2002 03:34
Art says:
quote:
Off the top of my head, I think that the ideas regarding these subjects do not apply to the RNA World. This would seem to me to be a fertile subject for exploration vis-a-vis MDT
What RNA World? I thought that was considered scientifically to be a dead horse. There is no evidence of it, only speculation AFAIK. Mike Gene might be able to help you out.
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Art
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posted 13. November 2002 08:32
Hi nobody,
You said: quote:
What RNA World? I thought that was considered scientifically to be a dead horse. There is no evidence of it, only speculation AFAIK. Mike Gene might be able to help you out.
Far from being a "dead horse", the RNA World is alive and well, in many, many more ways than, say, any manifestation of ID theory.
As for Mike Gene helping me out, it is precisely his logic that allows us, in this thread, to accept the RNA World as a fact, as more certain than the much fuzzier notions of ID that are bandied around on Brainstorms. Recall that Mike's approach is to equate the usefulness of a concept in guiding productive research with evidence for the veracity of the concept. By this standard, the RNA World is light-years ahead of ID - so much so that, if ID is to be taken as a reasonable hypothesis, the RNA World must be fact. ID theory has given us some interesting but entirely unconfirmed speculation, and not much of anything else (at least by way of wet-bench, nitty-gritty scientific understanding). The RNA World idea has given us the catalytic center of peptidyl transferase, a whole slew of different catalytic RNAs, another whole slew of RNA aptamers that are being developed for research and medical uses, the "micro-RNA World", the catalytic center for pre-mRNA splicing, and the life cycle of viroids, just to name a few examples off the top of my head. Any one of these would constitute an advance that is far greater than anything ID theory has given us; the total package (which is not completely listed in this post) absolutely dwarfs ID. There is simply no comparison.
Therefore, if Mike's approach is to be accepted - and, since this is his thread, I would suggest that we not even bother questioning the approach - then we should be willing to follow the application of this logic in other areas to its rightful conclusions, such as this one. IOW, we really should be accepting the RNA World as a pretty solid fact (moreso than origin-of-life researchers, who almost to a person have no problems with the concept, do).
But all of this is but a sidetrack to the theme of the thread, and to Mike's latest remarks. I think I am highly justified to raise the issues I raise, and think that your remarks, nobody, are rather out of place and uncalled for. I'd like to see Mike analyze all of the interactions that are seen in RNAs using the parity code concept, and to speculate on the myriad of base modifications and editing events that contribute to RNA functionality. I think MDT is a much better framework for explaining the contrast between RNA and DNA than SDT, but I'd be willing to read alternative POVs.
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nobody
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posted 13. November 2002 13:08
Art claims:
quote:
Far from being a "dead horse", the RNA World is alive and well,
I see. So how many RNA World forms of life have been analyzed to reach your conclusion? I am not aware of any, but I am willing to be educated if I missed something. I think having a sample of at least one RNA World life would be a minimal requirement to call anything alive and well.
As I said earlier, Mike can help you out on this topic much more than I can. He's spent years on things like this. However, your RNA claims appear to be hijacking the thread away from Mike's original post so we should not continue our discussion here.
You can always choose to begin a thread of your own to explain your current support for the RNA World hypothesis. This thread is about error correction.
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Moderator
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posted 13. November 2002 14:24
Art, nobody,
I see hostility brewing. Try to keep it civil.
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nobody
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posted 13. November 2002 15:14
Sorry. None intended here. Just trying to keep a very interesting thread on track. I'm sure an RNA World thread could be interesting also.
[ 13. November 2002, 15:14: Message edited by: nobody ]
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Mike Gene
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posted 24. November 2002 10:11
I would rather this thread be devoted to any discussion of my two web page articles rather than another discussion about the RNA world. Nevertheless, since the issue was raised, let me address it this one time.
Art writes: Therefore, if Mike's approach is to be accepted - and, since this is his thread, I would suggest that we not even bother questioning the approach - then we should be willing to follow the application of this logic in other areas to its rightful conclusions, such as this one. IOW, we really should be accepting the RNA World as a pretty solid fact (moreso than origin-of-life researchers, who almost to a person have no problems with the concept, do).
I don't think my approach can deliver "facts," let alone "solid facts," whether we're talking about ID, FLE, or the RNA World. It's merely a heuristic approach that delivers research guidance with the potential to render any scenario intellectually plausible. That is, one might have reason to think a particular scenario intersects with the truth (as this would nicely explain the success of an approach), but I don't think this can be established in any factual sense.
Now, yes, I think the RNA World is plausible and is supported by the success of the metaphor and some circumstantial evidence. I don't think it is a "dead horse." But ironically, RNA World proponents are in the same boat as teleologists, in that it's not clear that the success of their metaphor translates as valid historical insight, as there are complicating factors.
The success of the metaphor needs to be balanced with the history of science. Nucleic acids have always been underestimated. Since biochemistry matured by studying proteins and protein enzymes, and biochemists were intrigued by their abilities, it was only natural proteins would be on the pedestal. The first ones to get to the party can often define the mood of the party. Do not forget the biologists originally thought that proteins were the genetic material. They knew the nucleus contained proteins and DNA, but they originally thought the DNA played some type of inert structural role and assigned proteins another "glory role." Yet when it was determined in the 40s and 50s that DNA was indeed the genetic material, this did not lead to a "DNA World," where each advance, to this day, in understanding the importance and activity associated with DNA was seen as reflecting it as the first biological molecule to enter the stage of history.
As for the comparison between the success of ID and the RNA World, there are two more factors to consider. First, I think it more appropriate to compare the RNA World as metaphor with the Design as metaphor. And it sure seems to me that teleological metaphors have delivered just as much, even more, than the RNA metaphor. Secondly, the concept of "ID" comes with immense historical and sociological baggage. While a good idea may be a necessary ingredient for a fruitful research program, it is not sufficient. It has been pointed out by many that science proceeds as a communal activity. And then 9/10 scientists think the concept of ID is inherently religious, one can see a very real sociological obstacle that the RNA World never really had to face. Sociological factors (and other considerations) simply cannot be excluded if such a comparison is to be made. Keep in mind that I have no a priori reason to reject the RNA World, as an RNA World is clearly front-loaded to become like modern organisms.
I'd like to see Mike analyze all of the interactions that are seen in RNAs using the parity code concept, and to speculate on the myriad of base modifications and editing events that contribute to RNA functionality.
I'll put it on my incredibly large "to do" list.
I think MDT is a much better framework for explaining the contrast between RNA and DNA than SDT, but I'd be willing to read alternative POVs.
On the contrary, I think you underscore the inherent handicap of the MDT approach. While it would view the contrasts between DNA and RNA as a launching pad to begin reverse engineering the psychology of the designers, an SDT approach would stay ground in biotic reality and reverse engineer it , looking for the design logic that weaves the contrast into a coherent whole. Science is often about finding patterns and relationships between things that appear unconnected, or even that appear to be in tension with each other. Thus, while an MDT approach would entail an RNA designer and a DNA designer, an SDT approach would allow us to understand the logic of using both RNA and DNA. I would think the SDT framework is much better. Keep in mind that I invited MDT "proponents" to this thread to apply their model to the choice of cytosine as a nitrogenous base. And while I have found the SDT approach to be fruitful (as shown in my latest web page essay), the MDT "proponents" still offer only promissory notes. There is no evidence to think the MDT approach is a better framework.
Keep in mind also that I have no inherent bias against the MDT approach. Instead, I have merely highlighted some of its problems which render it useless for my interests. For example, I am more the willing to entertain the proposition that the designers are some form of ETI, and this speculation is heuristically productive. But when I asked MDT "proponents" about when we use humans as "single-designers" vs. "multiple-designers," they had no answer. If they cannot make this distinction when it comes to well-known designers, it seems the whole approach crumbles if the designers are some form of ETI.
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Art
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posted 24. November 2002 16:05
quote:
Keep in mind that I invited MDT "proponents" to this thread to apply their model to the choice of cytosine as a nitrogenous base.
Since I’ll be out-of-pocket wrt this discussion for awhile, I’ll expand on my introductory remarks and then see if the MD Theorists are of a mind to explore the idea.
Briefly, Mike, my take on your ideas vis-a-vis cytosine is that you rationalize the seemingly untoward “choice” of cytosine in terms of the novel expectations that C->U demethylation events (in DNA) would lead to. Such expectations have no analogies in the RNA World (pre-biotic or extant - remember that the RNA World is very much a part of all living things). It follows that, when it comes to speculation as to the significance of the use of cytosine in living things, we have two basic positions: cytosine was “chosen” for two different reasons, or your ideas about cytosine in DNA are wrong, and there is in fact a single “reason”. Granting the veracity of your ideas, then two functions is the pretty obvious conclusion. I think that MDT proponents can easily make a case, given this multiplicity of proposed functions.
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Mike Gene
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posted 24. November 2002 23:27
Art Briefly, Mike, my take on your ideas vis-a-vis cytosine is that you rationalize the seemingly untoward “choice” of cytosine in terms of the novel expectations that C->U demethylation events (in DNA) would lead to. Such expectations have no analogies in the RNA World (pre-biotic or extant - remember that the RNA World is very much a part of all living things).
My hypothesis deals with deamination, not demethylation events. And in this case, there is something better than an analogy in the "RNA World," namely, an example.
In mammals, apolipoprotein B (apoB) is involved in transporting lipids in the aqueous plasma. Given its relationship to atherosclerosis, it has received immense attention from the research community. It has been determined that apoB exists in two forms - a full length apoB100 form, which synthesized in the liver and used in the plasma, and a truncated apoB48 version, which is synthesized in the small intestines and used to form chylomicrons (structures that transport dietary lipids). The two forms exist because of RNA editing , where small intestinal cells express an editosome, including a cytidine deaminase (apobec-1) that modifies the RNA, where a specific CAA codon is converted into a premature UAA stop codon. This may only be the tip of the iceberg. A related deaminase, apobec-2, was recently found to be expressed only in cardiac and skeletal muscle. I have a couple of other interesting examples I'll try to discuss tomorrow.
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Art
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posted 25. November 2002 00:05
quote:
My hypothesis deals with deamination, not demethylation events.
Oops - my bad. Thinking deamination, typing demethylation. Oh well.
quote:
And in this case, there is something better than an analogy in the "RNA World," namely, an example.
In mammals, apolipoprotein B (apoB) is involved in transporting lipids in the aqueous plasma. Given its relationship to atherosclerosis, it has received immense attention from the research community. It has been determined that apoB exists in two forms - a full length apoB100 form, which synthesized in the liver and used in the plasma, and a truncated apoB48 version, which is synthesized in the small intestines and used to form chylomicrons (structures that transport dietary lipids). The two forms exist because of RNA editing , where small intestinal cells express an editosome, including a cytidine deaminase (apobec-1) that modifies the RNA, where a specific CAA codon is converted into a premature UAA stop codon. This may only be the tip of the iceberg. A related deaminase, apobec-2, was recently found to be expressed only in cardiac and skeletal muscle. I have a couple of other interesting examples I'll try to discuss tomorrow.
First and foremost, this example (and others like it) are not really pertinent to the RNA World. What I am speaking about is the applicability of the idea that cytosine is special to RNA functionality. For your proposal to have such an analogy, Mike, you would have to be shown that spontaneous cytosine deamination (got it right this time ![[Smile]](smile.gif) ) has an evolutionary "effect" on RNA structure and function analogous to the one you propose for cytosine deamination in DNA. I am very skeptical of this, because the same "rules" that apply to the matter in DNA simply have no analogy in RNA.
Second, the specific case you mention, Mike, does not seem to be relevant to error correction, or to the proposal you make on your web page.
Third, off the top of my head, I think that RNA editing kind of eliminates the "need" for cytosine in a design sense. This is because C->U editing is not the only sort of editing that occurs, and any of the alternatives that are known could do the same job as C->U editing in terms of mRNA coding. Which makes the special property of cytosine - a propensity to deamination - irrelevant, and reduces cytosine to a "position" no more favored than any other base. IOW, more of a "frozen accident" than a conscious choice. (Or, maybe, a rather nondescript product of the work of an RNA designer that was modified for a more clever purpose by a DNA designer .)
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Mike Gene
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posted 25. November 2002 17:08
Art: the specific case you mention, Mike, does not seem to be relevant to error correction, or to the proposal you make on your web page.
True, as I did get ahead of myself (on ARN, I noted that I was already working on extensions of the evolution-through-deamination hypothesis). So let me offer a brief preview. Each of the three stop codons (UAG, UGA, and UAA) can be reached by a single cytosine deamination event. If we consider both strands, the CG:UA transitions can reach 7/9 positions. In contrast, the stop codons themselves are not nearly as prone to mutation through deamination (none contain cytosine). This asymmetry suggests that base substitutions are more likely to generate nonsense mutations than chain elongation mutations (not to mention that the codon pool to reach nonsense mutations is larger than the codon pool to reach chain elongation mutations). This makes sense from a front-loading perspective, as premature termination might unleash a subset of domains roughly analogous to Force's DDC hypothesis. This could then set up selective pressure for recombination of domains. Chain-elongators, on the other hand, simply end up translating noise, which is probably less useful from an evolutionary perspective. This thus intersects with error correction and my thesis, where apoB is a good proof-of-concept example. Anyway, I'll expand on this in a latter essay.
this example (and others like it) are not really pertinent to the RNA World. What I am speaking about is the applicability of the idea that cytosine is special to RNA functionality. For your proposal to have such an analogy, Mike, you would have to be shown that spontaneous cytosine deamination (got it right this time ) has an evolutionary "effect" on RNA structure and function analogous to the one you propose for cytosine deamination in DNA. I am very skeptical of this, because the same "rules" that apply to the matter in DNA simply have no analogy in RNA.
I'm afraid I don't take the RNA World this literally. That is, I see RNA functionality as being tied up in the overall biochemistry of the entire cell. A designer only need make use of RNA such that it serves a larger function. And if cytosine deamination can be exploited by such processes as RNA editing, it doesn't matter if cytosine didn't play a "serve RNA only" role. Cytosine would be incorporated into RNA to further extend the useful aspects of deamination.
I just ran across a recent paper that illustrates this: Philippe Giegé and Axel Brennicke. 1999. RNA editing in Arabidopsis mitochondria effects 441 C to U changes in ORFs. PNAS Vol. 96, Issue 26, 15324-15329.
Giege and Brennicke (G&B) surveyed the effects of 441 C-U transitions among mitochondrial genes caused by RNA editing. They found exactly what my web page article predicts. Unaware of the G&B paper at the time, I wrote:
quote:
Since hydrophobic interactions play a large role in protein folding and structure, the effects illustrated in figure 3 suggest C-T transitions may play a significant role in protein evolution. What's more, figures 5 and 6 suggest C-T transitions may also result in both alpha helix and beta sheet elongation/formation. This raises the intriguing possibility that the genetic code was not only designed to minimize deleterious mutations, but that this design objective was balanced against a seemingly contrary objective to evolve new proteins through what I will call the Increasing Hydrophobicity Effect (IHE).
And, as a consequence of RNA editing (using C-U transitions), G&B found:
quote:
RNA Editing Increases the Overall Hydrophobicity of Mitochondrial Proteins. One of the potential consequences of RNA editing in mRNAs and the corresponding change of the specified amino acid could be a modification of the overall biochemical nature of the affected mitochondrial proteins. The general tendency of the effect of RNA editing in Arabidopsis mitochondria is to increase the proportion of hydrophobic amino acid codons. As an example, the three most frequent amino acid transitions (93 S to L, 80 P to L, and 47 S to F) all result in codons for hydrophobic amino acids. In the overall analysis of RNA editing in Arabidopsis mitochondria, 35% of the modifications are hydrophilic to hydrophobic, and 35% are hydrophobic to hydrophobic codon alterations. Only the 27 P to S codon transitions reverse the tendency by creating codons for hydrophilic amino acids from those for hydrophobic ones. In the 425 modified codons detected, 41.5% specify hydrophobic amino acids before editing and 84.9%, after editing (Fig. 1). Thus RNA editing increases the hydrophobicity of mitochondrial proteins.
Thus, RNA's use of cytosine is involved in the very same role I originally envisioned for the DNA/protein worlds.
However, for the RNA world purists, there is suggestive evidence of the analogy you seek. From the same article:
quote:
The Arabidopsis mitochondrial intron population is exclusively composed of organellar group II introns with a well-conserved secondary structure, which has been shown to be important for splicing. Some of the editing sites affecting group II intron sequences are predicted to improve the quality of the intron folding and thus very likely to improve functional splicing.
Nevertheless, I just don't see the problem of RNA-only functionality. In addition to things I mention above, there is also the possibility that the RNA World was front-loaded by a bacteria-like state. After all, many aspects of the RNA World may very well be recently derived and not reflective of some primordial state. RNA editing itself may be only of the processes front-loaded, partially by including cytosine in the RNA.
off the top of my head, I think that RNA editing kind of eliminates the "need" for cytosine in a design sense. This is because C->U editing is not the only sort of editing that occurs, and any of the alternatives that are known could do the same job as C->U editing in terms of mRNA coding. Which makes the special property of cytosine - a propensity to deamination - irrelevant, and reduces cytosine to a "position" no more favored than any other base. IOW, more of a "frozen accident" than a conscious choice. (Or, maybe, a rather nondescript product of the work of an RNA designer that was modified for a more clever purpose by a DNA designer .)
Sure, a lot of editing includes A-to-I substitutions, some being very important when it comes to human brain function (for example). However, the adenosine deaminases may have evolved from the cytidine deaminases, raising the possibility that such editing events (which are mostly dependent on the existence of intron sequence) may have likewise been front-loaded. However, the utility of C-to-U substitutions is that they can tap into the features of the genetic code that I have explained. If you replace C->U with an alternative, you'd likely have to redesign the entire code to extract the same principle.
Often times, design boils down to a cost/benefit analysis. The benefits of using C in RNA are many - essentially reuse the same bases of DNA, allowing the parity code to participate in transcription, metabolic efficiency (no need to encode a series of different enzymes to synthesize four different RNA nitrogenous bases), and the ability to use RNA editing to tap into the Increasing Hydrophobicity Effect and the unleashing of domains. I'm not sure the cost of deamination in RNA is serious enough to demand an complete overall of the system.
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Jules
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posted 26. November 2002 21:54
No wait. I think I've got this right. Poole et al complain about cytosine. 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?
[ 26. November 2002, 21:54: Message edited by: Jules ]
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Mike Gene
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posted 27. November 2002 00:09
Is there some design advantage to uracil?
Sure. It's the product of cytosine deamination. To connect the dots, you need two dots.
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Frances
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posted 27. November 2002 00:28
Jules raised an interesting issue, what is the design advantage of using uracil for RNA? Mike suggests that it is the product of cytosine deamination but is that the design advantage? What would be the design advantage?
But I would also like for Mike to explain what front loading is going to get us? Front loading seems to be not much different from a naturalistic explanation with the 'intelligent designer' hiding somewhere out there? So far the most likely location would be the big bang. But I would be interested in finding out from Mike how such a front loading scenario differs from a naturalistic pathway?
A paper in particular has caught my eye NATURAL PROVIDENCE (OR DESIGN TROUBLE) by Michael J. Murray
Murray argues that "... that the explanatory filter is fatally flawed, and that detection of detection of design would not undercut methodological naturalism in any case. Friends of IDT fail to see this because they adopt a Newtonian conception of natural providence, while failing even to consider a preferable Leibnizian conception.[/url]
[ 27. November 2002, 00:33: Message edited by: Frances ]
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Mike Gene
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posted 27. November 2002 00:59
Frances: Mike suggests that it is the product of cytosine deamination but is that the design advantage?
Like I said, to connect the dots, you need two dots.
What would be the design advantage?
It's explained in TeleoLogic BRNo.18. The phenomenon of RNA editing can actually work to exploit this principle at an accelerated rate. I'll eventually upload more essays to flesh this out.
But I would also like for Mike to explain what front loading is going to get us?
At the very least, another vantage to approach these questions. Better yet, an approximation of what happened.
Front loading seems to be not much different from a naturalistic explanation with the 'intelligent designer' hiding somewhere out there? So far the most likely location would be the big bang. But I would be interested in finding out from Mike how such a front loading scenario differs from a naturalistic pathway?
I'm not sure exactly what you mean by "naturalistic." Are you talking about the traditional Darwinian view? Or simply processes that do not involve supernatural intervention? Perhaps you can clarify. However, I'll offer only one follow-up, as I really don't want to turn this thread into a generic discussion of front-loading. I dicussed that here.
[ 27. November 2002, 01:01: Message edited by: Mike Gene ]
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Jules
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posted 29. November 2002 13:23
Mike,
No doubt I'm asking a question for which you already provided an answer, but I'm not understanding it. It sounded like you were saying the point of keeping cytosine ( contra Poole) in DNA (and in RNA) was for the purposes of cytosine deamination into uracil unleashing front-loaded designs. My question is why have uracil in RNA to begin with? Unless uracil further deaminates into something else, it's not there to unleash more front-loaded design. Are you saying that the designer may have begun with DNA, counting on cytosine to deaminate into uracil, forming RNA? Or am I just asking questions that need more understanding of biochemistry to understand?
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