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| Mike Gene - Error Correction Runs Deep | Pages: 1 - 2 - 3 - 4 - 5 |
| Posted by Mike Gene (Member # 149)
on 25. November 2002, 17:08: 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: And, as a consequence of RNA editing (using C-U transitions), G&B found: quote: 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: 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. Posted
by Jules (Member # 181) on 26. November 2002, 21:54: Posted by Mike Gene (Member # 149) on 27. November 2002, 00:09: Sure. It's the product of cytosine deamination. To connect the dots, you need two dots. Posted by Frances (Member # 169) on 27. November 2002, 00:28: 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] Posted by Mike Gene (Member # 149) on 27. November 2002, 00:59: 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. Posted by Jules (Member # 181) on 29. November 2002, 13:23: Posted by Jules (Member # 181) on 30. November 2002, 11:06: Posted
by Janitor@MIT (Member # 125) on 30. November 2002, 13:51: Posted by rafe gutman (Member # 134) on 01. December 2002, 18:50: quote: 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: Posted by Frances (Member # 169) on 02. December 2002, 01:10: Posted
by Jules (Member # 181) on 02. December 2002, 21:44: Posted
by Mike Gene (Member # 149) on 02. December 2002, 22:27: 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. Posted by Mike Gene (Member # 149) on 02. December 2002, 22:29: 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. Whether this is "the answer" remains to be explored. It does, however, seem to be a plausible "answer" to the question. Posted
by Mike Gene (Member # 149) on 02. December 2002, 22:30: 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. Posted by Mike Gene (Member # 149) on 02. December 2002, 22:37: 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. Posted
by Frances (Member # 169) on 03. December 2002, 02:28: Your use of the term 'designed' seems to lose much of its similarity
as used in the intelligent design movement. Posted by rafe gutman (Member # 134) on 03. December 2002, 04:06: quote: 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: 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: 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: 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: 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. |
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