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!
8 Responses to Genes != Proteins
Sweetwind
September 21st, 2004 at 1:45 pm
…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! :-)
apsmith
September 21st, 2004 at 2:00 pm
It came last Saturday – sorry :-)
Anonymous
September 22nd, 2004 at 7:47 am
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
Sweetwind
September 23rd, 2004 at 8:29 am
as of Wednesday’s mail. Maybe you live closer to the distributor.
On second thought, this happened before, right about the time this site was founded (so it might have been the October 2002 issue). Every other subscriber I knew had gotten their issues three weeks before, so I called the SciAm customer center and they extended my subscription by an issue to make up for it. But before I bought a replacement copy, the subscription copy finally showed up. It was all wrapped in plastic and contained a promotional CD-ROM for genetic therapies or something, so I figured my P. O. didn’t like the packaging…
Out of pique, today’s quote is from the September issue :-)
Sweetwind
September 24th, 2004 at 7:39 am
Happy happy, joy joy!
But still not online.
Sweetwind
September 28th, 2004 at 9:07 am
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.
Sweetwind
September 28th, 2004 at 9:17 am
The Hidden Genetic Program of Complex Organisms
apsmith
September 28th, 2004 at 8:47 pm
Yes, I think it’s the link between those two things (prokaryote/eukaryote differences in cell structure and in DNA structure) that made me sit up and pay attention. But maybe this is something geneticists have been aware of for years, and is only now reaching a more general public? Any biologists out there to enlighten us?