Being Consistent with Selection
Ok... You heard it here first. I suspect.
Update: April 22, 2004
UCI (University of California, Irvine) had a Dr. Thompson this Tuesday speaking on her specialty, Huntington's Disease, and the genomics thereof. If you ever get a chance to hear this lady, do it. She is not only very smart and very good at communicating, but she is also a FOX! Definitely some genes worth preserving there, which is my only motivation, of course....
Anyway, turns out that there are about 10% of the Huntingtons victims who do not have an apparent genetic background. The disease is basically related to a genetic sequence that gets repeated too many times and makes too much of a protein, leading to all kinds of terrible results, including psychiatric/behavioral symptoms such as paranoia, depression, and others, and a general physical deterioration, involving loss of weight and a dance-like trembling. The damage to the brain and CNS is dramatic and progressive.
Fortunately, Dr. Thompson has made real progress in identifying the pathways of the actual damage and is at least partially responsible herself for a number of successful drug interventions in transgenetic mice with Huntingtons, as well as fruit flies. These drugs are now going into clinical trials for safety with humans, and there is every indication that the disease will be successfully treated in the near future.
So, meanwhile, related to the more general subject of this blog article, I asked her after the talk if she had considered the idea that the 10% might be a result of Darwinian selection within the cytoplasm of a germ cell. I could tell that this was a new idea for her, as she kind of jumped back a few inches, her great big eyes that a man could just drown it widened even more, and suddenly you could see the wheels turning. Not that I had much more to say on the subject, especially as my focus was drifting, but I at least wanted to see her reaction, and possibly plant the suggestion, in the hopes that it might pay off. (My phone number is available by special request, Dr. Thompson....)
The reason that I suspect that the Darwinian hypothesis I'm advancing might apply is that the protein encoding sequence itself varies typically in length from generation to generation, which itself ought to make one wonder... I mean, IF it varies, and it does, dramatically, then how come we don't see a whole LOT MORE Huntington's???? DUH... OK, it is pretty stable for most of the population, but for the people who carry the disease genetically, the length varies between generations. So, there has to be a mechanism that controls the number of repeats of the gene, right? And it looks like it's that mechanism that is failing.
So, is this a special case, or is there a more general Darwinian contest going on within the cell over which gene sequences get expanded, reverse transcribed, etc.? And, BTW, do Huntington's patients also show variations in the number of repeats of other genes? Shades of Lamark. Anyway, that's as far as my analysis goes for the moment. I wonder what kind of odds and pre-pay-off sale of rights I could negotiate on my share of the Nobel at this point? End of update. We now return you to the past....
We know that whenever a species acquires an ecological niche, it then focuses most selection energy on intraspecies competition. Giant male elk battle each other a lot more than wolves. Internal competition is necessary to keep species that already have a huge acquired advantage in their niche from degenerating and becoming vulnerable to a takeover by some competiing speciesr or overpopulatiing. In Vanuatu, ritual canibalism kept human populations stable, for example, over many centuries, in spite of ample resources of food.
So, what about cells, internally? Recent information - the subject of major articles in "Scientific American" - tells us that all that "junk DNA" that makes up over 90% of our genetic material may not be junk after all, (a position I argued in support of for the past three decades). In fact, the junk is coding for small fragments of RNA, among other things. Considering all the things that these fragments are good for, some of which have been identified - but millions probably remain, it suddenly occurred to me to use standard selection analysis on the inside of the cell.
Suppose that what goes on inside the cell is again a competition for resources - material and energy - by various cellular components? The various potential cellular configurations and structures battle over strategies, attempting to shut off DNA sections that work against them and turn on those that support them. This is a complication to the whole picture of cellular machinery that will not please many of the more deterministic researchers, if true. But how could it NOT be true?
You heard it here, first.