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Genes != Proteins
By apsmith, Section Commentary
Posted on Tue Sep 21, 2004 at 05:53:14 AM PST

Biology Returning yet again to the subject of junk DNA, a fascinating Scientific American article from the October issue (not yet online) is titled "The Hidden Genetic Program of Complex Organisms," by geneticist John Mattick. The essence of the new view seems to be that proteins are merely the mechanical components of the machinery of life, while the remainder of the genome encodes information that governs what the proteins do, via transcription into "micro-RNA's" and related regulatory signals.

The completion of the Human Genome Project a few years back left us with a rather disappointing count of just 25,000 or so protein-coding genes - hardly more than the number of proteins used by a simple roundworm. Mattick's article points out, however, that more complex organisms, while having almost the same number of protein-coding genes, tend to have larger and larger fractions of their DNA devoted to non-coding "introns," or what was once called "junk." For humans, only about 1.5% of DNA encodes proteins. For bacteria (prokaryotes) essentially ALL the DNA is transcribed to proteins, and there are no 'introns' - in part because bacteria lack a cell nucleus to separate transcription (from DNA to RNA) from translation (to proteins).

Which suggests a question: is all that non-coding DNA actually responsible for the complex structure that distinguishes multi-celled life (eukaryotes) from bacteria? And how does it do that?

One of the keys to organism complexity is differentiation - the process whereby cells in different regions of the organism express different genes and become physically different in character. For humans, 100 trillion cells are placed and differentiated into a large number of organs and regions with specific positions and functions. For each of these cells, what genes exactly it expresses or does not express is determined by the detailed structure of the chromosomes, the way the DNA material has been combined with proteins to open up some regions, and shut off others. Some experiments, according to Mattick, imply that these micro-RNA's are controlling this detailed structure directly.

The previously prevailing view, that proteins are in control, succumbs to a problem of "combinatorial complexity" - the more proteins involved, the proportion of the system devoted to regulation increases, and there's an intrinsic "complexity limit." The rise of multicellular organisms evidenced in the "Cambrian explosion" suggests a transition to a new control structure that could transcend previous limits - and this direct role for regulatory RNA could be the explanation.

Quoting Mattick:

The implications of this [...] are staggering. We may have totally misunderstood the nature of the genomic programming and the basis of variations in traits among individuals and species.

Biologists still have a lot of work to do to understand how life works!

Genes != Proteins | 8 comments (8 topical, 0 hidden)

more toggles and switches (4.00 / 1) (#3)
by Anonymous on Wed Sep 22, 2004 at 03:47:57 AM PST
I mentioned in a commentary on the Sweet Fat story that over evolutionary time biomacromolecules have developed more and more toggles and switches for regulatory integration. This is readily seen in the proteins- forms not only get bigger with time and end up with all sorts of bits and pieces that stick out waiting for interaction, but through RNA editing one can have many variant final protein products from the same underlying DNA. And of course genes duplicate and then diversify their products at the DNA level as well.

t-RNA's have diverse covalently modified forms as well, which may allow tweaking of their activity in different environmental and physiological conditions.

"Junk DNA" regulation just seems to be the natural extension of these regulatory adaptations to the genetic storage forms, just as extra loop material on RNA is.

We're already well aware of the base encoding which allows conversion of nucleic acid sequences to protein, and I mentioned in the Sweet Fat comment the possibility of a state-space sugar code. Why could there not also be an internal nontranscriptional/translational code in the DNA sequencing itself? Partially based on relative position in the strand, partially on tension, shape, and solubility effects at the local level, and of course partially dependent on actual transcript coding sequences as well as the introns.

By the way- the lipid membranes themselves, an assemblage of polymers though not a classical polymer itself, might also exhibit some sort of shape-charge-solubility code at some level. We already know that varying the membrane content of lipids (which tend to zip around rather rapidly) changes the properties of the membrane (melting temperature/glass transition analog, etc.).

Biopolymers have two foci when it comes to purely physical interactions- those they have with themselves (Double helices in nucleic acids- either straight or loopy, secondary and tertiary structure in protein, and so on), and those they have with others of the same or different type.

It all may seem like a mess as new data comes in, but I'm betting not only is the evolved systematicity of the inner workings of living cells NOT a kluge, but should be in many ways iconically based, and any arbitrary symbolicity should be traceable back to original iconicity.

Codemaniac



October SciAm isn't online yet... (none / 0) (#1)
by Sweetwind on Tue Sep 21, 2004 at 09:45:35 AM PST
...and it isn't in my mailbox yet, either! So, apsmith, did you buy it off the newstand (where it usually appears first)? Cuz if you got your subscription copy in the mail AND you've already had time to read an article from it, I'm jealous! :-)



OK, finally read the article! (none / 0) (#6)
by Sweetwind on Tue Sep 28, 2004 at 05:07:26 AM PST
One thing that struck me in Mattick's thesis was the wide gap between the prokaryotes and the eukaryotes. We learn in secondary school that eukaryotes have a cell nucleus that keeps all the DNA inside, and prokaryotes don't, and there never seemed to be an articulated reason WHY. Mattick's article explains exactly WHY -- prokaryotes do everything directly with proteins, so transcription can occur very simply. Eukaryotes need to perform the DNA transcription inside a nucleus so that the second-level information (in the "junk" DNA) can work in privacy to direct HOW the RNA will be transcribed to proteins once it gets outside the nucleus.



  • Yup by apsmith, 09/28/2004 04:47:18 PM PST (none / 0)
SciAm Article Teaser Link (none / 0) (#7)
by Sweetwind on Tue Sep 28, 2004 at 05:17:20 AM PST
The Hidden Genetic Program of Complex Organisms



Genes != Proteins | 8 comments (8 topical, 0 hidden)

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Related Science Links
· junk DNA
· Scientific American
· John Mattick
· rather disappointing count
· prokaryote s
· eukaryotes
· "Cambrian explosion"
· More on Biology
· Also by apsmith

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