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Old 01-06-2002, 08:30 PM   #1
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Post The RNA World

We all know of Michael Behe's conception of irreducible complexity. I wonder if there is any way of defining it that is not excessively ambiguous and subjective.

But one possible example might be the DNA -> RNA -> protein system, at least at first sight. DNA acts as the master copy, RNA as an intermediate copy and a protein-assembly helper (ribosomal and transfer RNA), and proteins as enzymes -- catalysts that make all the necessary chemical reactions happen, such as assembly of all these molecules.

But could there initially have been only one kind of important biomolecule instead of three? If so, then that would produce an enormous simplification of the origin-of-life problem. But it would also require that one kind to be both self-replicating and doing enzyme duty. But which one?

If proteins are first, then there would have to have been some kind of self-replicating protein, and it would have to be a very unusual protein to do that. But self-replication for nucleic acids is a no-brainer; Watson and Crick had quickly recognized a mechanism for that when they worked out DNA's double-helix structure.

That nucleic acids could act as enzymes was discovered by Thomas Cech in 1986, when he discovered self-splicing RNA; since then, various other pure-RNA enzymes ("ribozymes") have been discovered. However, there appear to be few, if any, DNA enzymes. DNA is a close chemical relative of RNA, which makes this discrepancy odd.

Adding to this conundrum is the presence of RNA in contexts that do not suggests its necessity, and also RNA in persistent roles (transfer and ribosomal RNA) like DNA as well as in transient roles (messenger RNA). Here are some examples of stray RNA:

A short strand of RNA is needed as a primer for the enzyme DNA polymerase, which helps assemble DNA molecules (why RNA and not DNA?).

Bits of RNA are present in several cofactors, molecules that work with enzymes, such as NAD, FAD (both handle electrons), CoA (handles acetate), and Vitamin B12 (handles methyl groups).

An RNA nucleotide is present in the energy intermediate ATP (adenosine triphosphate); the energy is in the phosphate-phosphate bonds and the adenosine is presumably a handle.

This abundance of persistent and stray RNA suggests that RNA had been the original nucleic acid -- and also enzyme material -- and that its continued presence in such contexts is a vestigial feature. There are numerous vestigial features known in other contexts, making this a plausible inference.

I note in passing that vestigial does not mean functionless; many vestigial features do have functions -- but functions different from the functions of full-scale versions of those features. Thus, the RNA in those cofactors or ATP is not doing information transmission but is taking part in energy metabolism or molecule assembly and disassembly.

The result of these discoveries and inferences is the "RNA world", in which RNA serves both as information storage and as enzyme material. Our current world would have evolved from it with the help of two steps:

The emergence of DNA as a modification of RNA for master-copy duty -- and nothing else.

The development of multi-amino-acid cofactors for RNA enzymes; these cofactors could have grown in bulk and importance by natural selection until the original RNA becomes a vestigial feature or disappears outright.

The RNA-world hypothesis begs the question of the original RNA; we turn to prebiotic chemistry for answers to that. In experiments with such chemistry, RNA bases can be readily formed, but the other organic part, ribose, requires relatively unusual conditions. Thus, an RNA molecule might seem like an example of irreducible complexity.

For that reasons, there has been work on possible RNA ancestors like pyranosyl RNA (p-RNA) and Peptide Nucleic Acids (PNA). So the first organism could have been a p-RNA or a PNA one or some other such, with RNA resulting from ribose being substituted for something else.

Although the origin of life continues to be an unsolved problem, the "RNA world" hypothesis significantly narrows the gap between known prebiotic chemistry and the first organisms. And it suggests that one will have to be careful before one pronounces some feature "irreducibly complex."
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Old 01-07-2002, 11:48 AM   #2
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Quote:
Originally posted by lpetrich:
<strong>

That nucleic acids could act as enzymes was discovered by Thomas Cech in 1986, when he discovered self-splicing RNA; since then, various other pure-RNA enzymes ("ribozymes") have been discovered. However, there appear to be few, if any, DNA enzymes. DNA is a close chemical relative of RNA, which makes this discrepancy odd.

Adding to this conundrum is the presence of RNA in contexts that do not suggests its necessity, and also RNA in persistent roles (transfer and ribosomal RNA) like DNA as well as in transient roles (messenger RNA). Here are some examples of stray RNA:

A short strand of RNA is needed as a primer for the enzyme DNA polymerase, which helps assemble DNA molecules (why RNA and not DNA?).

Bits of RNA are present in several cofactors, molecules that work with enzymes, such as NAD, FAD (both handle electrons), CoA (handles acetate), and Vitamin B12 (handles methyl groups).

An RNA nucleotide is present in the energy intermediate ATP (adenosine triphosphate); the energy is in the phosphate-phosphate bonds and the adenosine is presumably a handle.

This abundance of persistent and stray RNA suggests that RNA had been the original nucleic acid -- and also enzyme material -- and that its continued presence in such contexts is a vestigial feature. There are numerous vestigial features known in other contexts, making this a plausible inference.

</strong>
In addition, the protein synthesis activity of the ribosome has been demonstrated to reside in the ribosomal RNA. Indeed, one can strip away the proteins from ribosomes by vigorous means (denaturation with detergents and digestion with proteinase K followed by phenol extraction), and protein synthesis activity remains. Also, synthetic RNAs have been made by in vitro selection that can catalyze peptide bond formation.
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Old 01-08-2002, 07:09 AM   #3
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Thanx. I had neglected to mention that about ribosomes' primary component being their RNA.

I recall from somewhere some attempts to construct transfer RNA's with the RNA replaced by DNA; I don't recall how well these transfer DNA's had done.

And in a search for pages on DNA enzymes (deoxyribozymes? d-ribozymes?), I found this one on artificial DNA enzymes:

<a href="http://www.yale.edu/opa/ybc/v25.n20.news.19.html" target="_blank">http://www.yale.edu/opa/ybc/v25.n20.news.19.html</a>

(found with a web search for "ribozymes DNA" (without quotes))

So the lack of DNA enzymes in organisms may be another vestigial feature of the RNA world; alternatively, it could be an adaptation for the protection of DNA as a master-copy molecule by keeping it exclusively confined to that role.

Also, those RNA-containing cofactors suggest that the RNA world had had electron transport and handling of acetyl and methyl groups; the next question is what other sorts of metabolism had existed in the RNA world.
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Old 01-10-2002, 09:22 AM   #4
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One other possible reason for the lack of DNA enzymes: DNA is missing the 2' hydroxyl group which is often used in ribozymes as a nucleophile.
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