Posted by Mike Gene (Member # 149) on 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.

Posted by Mike Gene (Member # 149) on 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.

Posted by Mike Gene (Member # 149) on 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."

Posted by Mike Gene (Member # 149) on 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?"

Posted by Janitor@MIT (Member # 125) on 13. December 2002, 11:06:

Now, I may be wrong, and I think there is room for accommodating a more traditional evolutionary perspective wrt uracil, but it was Darwin who insisted that such variations must be demonstrably beneficial, must somehow be “improvements.” Usually we have measured “benefit” in terms of a relative growth rate, and although this makes sense and seems to be a necessary corollary of Darwin’s idea, Gould (Wlliams and independently Pittendrigh also) has argued that Darwin, ironically enough, was really invoking a naïve design criteria of “benefit” or “improvement.” (And has pointed out some problems with the “growth rate” measure of evolution.) Uracil should therefore represent a “better design” over whatever it is that it replaces.

Improvements are no doubt important from a design perspective, but there is also a general and purely heuristic principle of design sufficiency or realizability and verifiability that introduces some level of arbitrariness into the selection of materials, etc. Any changes that are made to the design are hopefully not detrimental, but also don’t have to be improvements. (Also the concept of abstraction or seperability comes into play here.)

Engineers (and biologists) recognize that atoms and molecules are the ultimate “smart materials,” but we still design and build with comparatively simple bulk materials. This is because atoms and molecules are smart indeed, smarter than we are—we simply don’t know enough about their properties, especially in combination, to make effective use of them in design. (There are also technical limits to what we can do, unrelated directly to what we know about the materials themselves.)

Accordingly, we do something very interesting in designing a protein to hit a target, a drug, e.g. We employ evolutionary techniques to test many possible combinations/configurations, filtering out those combinations that are comparatively less effective for whatever object we have in mind. Obviously, atoms and molecules are ideal for such an approach. But notice that in doing this, improving an existing drug (or function) may be our object, but in inventing it is not. All that is required ab initio is that whatever we design-evolve is sufficient for our purposes, not that it be the “best.” (Over-designing and over-provisioning, etc. are natural tendencies to be avoided, and it often takes designers some time to learn this.) Later, if there is any impetus for improvement, or increased benefit, we find that the same evolutionary techniques are effective as well, but with refinements on the very process.

(You may have noticed that I’ve made this “refining” an important point: If evolution is conceived as an optimization process then there is reason to believe that there is every “natural impetus” for improving and refining the process of optimization itself. That is to say, the evolutionary process will evolve to “progressively” eliminate its less than optimal aspects. E.g., as in error-correction, it will in some sense systematically reduce the “randomness,” to tolerable (Manageable? Optimal?) levels, which is, of course, exactly what we do, quite intelligently I might add, when we “evolve” something. Which is just to make substantive and predictive what is usually offered as apologetic only: Evolution evolves. Ironic, isn’t it? Purely on a priori design principles I’ve predicted what evolution should look like. I keep forgetting that design has nothing, no insights, theories, predictions, or tests to offer.)

This is not to say that there is not some intrinsically “optimal” functional reason or logic for the selection of uracil. The fact that its usage is universal in this context is telling even from a “non-teleological” perspective.

However, that something “just happened” or is a “frozen accident” is the opposite of a scientific explanation in this context and is to be rejected on principle. These "accidentalist theories” are our last resort, when we’ve exhausted all other possibilities that we can imagine to test. They are not the first theory that we propose, but the last. How can you even test such ideas! Its absurd—anything can be “explained” this way!

Mike Gene’s teleological program is very interesting and recognizes a simple principle of design that is recognized implicitly by biologists: By the “proper” selection and combination of basic materials we can imbue designs with some amazing properties, as I’ve suggested, we can introduce a significant bias into a search or exploratory program, such as DNA. Hey, I can BS, uh, I mean, “brainstorm”…

Posted by Mike Gene (Member # 149) on 14. December 2002, 12:11:

Improvements are no doubt important from a design perspective, but there is also a general and purely heuristic principle of design sufficiency or realizability and verifiability that introduces some level of arbitrariness into the selection of materials, etc. Any changes that are made to the design are hopefully not detrimental, but also don’t have to be improvements. (Also the concept of abstraction or seperability comes into play here.)

I think that's an important point to keep in mind. The original question, "Why C?" was a more serious challenge to my ID hypothesis, as the high rates of deamination appear to contradict the error correction schemes that suggest some form of teleological explanation. The question, "Why U?" is not really a challenge, but an expression of curiosity. In other words, there was a problem with C, but no real problem with U.

Nevertheless, there do seem to be some potentially good "design reasons" for choosing U (as explained above). I found a link that better explains what I was discussing above:
Researchers unlock secret of RNA's versatility

It is thus interesting to note that hydrophobic amino acids and uracil both play "special" roles in structure formation and cytosine deamination can thus access both.

Posted by Mike Gene (Member # 149) on 17. December 2002, 13:29:

I think I'll close this thread out simply be restating what I stated near the beginning:

Rarely do I get the chance to post a new essay that addresses so many issues simultaneously:

1. Would an engineer really preclude cytosine as Nic's citation asserts?
2. What might be a "gas pedal" behind evolution, as implied by Warren?
3. How about a few baby steps toward the "code" Janitor speaks of?
4. Another example where ID can guide research.
5. "Proponents" of MDT have been reluctant to apply their notions to the biological problem posed by cytosine. Features that might appear to indicate multiple designers at first glance make more sense when seen in the larger context of SDT.

http://idthink.net/biot/deam/index.html

More good stuff to come....