[UA] The Unexplained?

[Allen Smith]

On Dec 13, 10:58am, Gregory Paul Stolze wrote:
> -Vampires -- Fabrication, but the stuff about limited lifespan being
> programmed is true, as is the bit about extending lifespan in simple
> organisms by DESTROYING genes.  So it's really pretty plausible, I think.

As a geneticist, I'll pipe in here... the material on Vampires is
overall pretty good, although there are a few things that I'd add
and/or change:

	A. It should probably be a bit clearer regarding "genetic
	   damage" and inbreeding. Inbreeding does not cause
	   mutations. What it does is make a recessive trait (one that 
	   has to be inherited from both parents, essentially) much
	   more likely to emerge. You were thus quite correct in
	   making it a recessive gene... although it's more likely to
	   be a set of recessive genes, held together through various
	   mechanisms (namely inversion - a section of the chromosome
	   got flipped, making it rather hard to "cross over" at that
	   point except with another person with about the same
	   section flipped - combined with probable selection (such as 
	   caloric restriction genes offsetting others contributing to 
	   cancer - see below)).
	B. Most mutations are recessive; quite simply, it's _much_
	   easier to _stop_ a gene from working than to get it to work 
	   more or better, but the corresponding gene (technically,
	   "allele") from the other parent can take over just fine in
	   most cases. Mutations with a negative effect on one's
	   number of surviving offspring are particularly likely to be 
	   recessive, since otherwise they are selected out with each
	   generation, instead of only when they happen to be paired
	   with another mutated allele. (For instance, Huntington's is 
	   one of the few dominant genetic diseases - and it strikes
	   after the reproductive period; see below.) Genes causing
	   things like anemia, etcetera would be in this
	   category... and would be more likely to show their effects
	   in individuals who were inbreeding. (On the other hand, they
	   would also be eliminated from said population much faster,
	   due to more selective pressure against them - more often
	   happening with inbreeding. However, if the population has a 
	   long reproductive lifespan and is thus slow to respond to
	   selective pressures, this state of affairs could be
	   preserved for quite a while. If it's been 1000 years since
	   the Dracul twins discussed in UA, and the overall
	   generational time (normally assumed to be about 25 for
	   humans, although in modern society this is increasing among 
	   some populations, namely middle and above in developed
	   countries) is multipled by 10 by a combination of
	   the longer lifespan with reproductive problems, that means
	   only 4 generations of 250 years each since the event in
	   question - not nearly enough time for significant selection 
	   to take place. Even if one uses a more conservative time of 
	   115 years (15 years average pubescence duration plus 100
	   years thereafter), that's still only ~9 generations - the
	   equivalent of only 225 years of normal human generations.)
	C. Aging appears to be due to a combination of various
	   causes. Some of these are indeed directly genetic (by which 
	   I'm meaning that they're not a matter of genetic
	   susceptibility to something or other things that heavily
	   interact with environment). There is a large amount of
	   debate over _why_ these are present; the argument presented 
	   in UA is a possible one, but is not likely to be the only
	   one. Genetic "defects" of this sort quite often remain
	   around for the simple reason that they don't limit
	   reproduction very much. If you're going to die by accident, 
	   something eating you, etcetera before your reproductive
	   lifespan runs out, there's no selective pressure for
	   keeping that length of reproductive lifespan. In turn,
	   there's no selective pressure for surviving significantly
	   beyond your reproductive lifespan (I say _significantly_
	   because parental care does make a difference in
	   reproductive rate; however, this does not appear to be true 
	   of grandparents in humans). Even after the expected
	   lifespan went up beyond the reproductive lifespan, once
	   multiple genes were giving rise to that limited
	   reproductive lifespan, it was rather unlikely that they
	   would all get changed.
	D. Some genes (and related things, such as the regulatory
	   elements near them) are beneficial early on but not later
	   on, or are beneficial for reproduction but not for
	   long-term survival (e.g., insects that save weight in the
	   adult stage, needed for reproductive flight, by not having
	   digestive tracts...). One less-obvious instance is the
	   shutdown of the telomerase gene after the fetal stages,
	   which probably acts to reduce cancer (cancers have
	   telomerase reactivated). (Telomerase is an enzyme which
	   extends the ends of chromosomes (the "telomeres") which
	   otherwise get shorter with each cell division.) Whether it
	   is the cause of the "Hayflick limit" (a limit on the number 
	   of times cells can divide, not present in cancer and fetal
	   cells (thus one attraction of fetal stem cells...)) is
	   under debate; it probably does at least _contribute_,
	   however... and the other genes inhibiting cell growth would
	   also observe the same balance: cell growth for longer
	   equals longer potential youth but also more likelihood of
	   cancer.
	E. There are also genes that interact with the
	   environment. Some things that give long lifespan under one
	   setting don't do so under others. An eminent example of
	   this is the recently-described "I'm Not Dead Yet!" gene,
	   which restricts energy intake in fruit flys. It increases
	   lifespan through caloric restriction (see below), but would 
	   probably result in a dead fly in the wild due to varying
	   food quality.
	F. Caloric restriction is the technique whereby, by cutting
	   caloric intake to 60% or so of the normal level while
	   keeping up other nutrients, lifespans in almost all animals 
	   studied can be extended greatly (20% to over twice as
	   long). (It is, incidentally, the _only_ such method known
	   that increases _maximum_ lifespan in many animal
	   species. Other techniques that work cross-species have been 
	   found to be causing it indirectly; for instance, feeding
	   heavy doses of antioxidants to animals makes them nauseous
	   and results in them eating less.) The effects of
	   the aforementioned "I'm Not Dead Yet!" gene appear to be
	   due to this, although actually to a lesser degree than can
	   be done through diet. However, the diet in question also
	   limits reproduction (females stop menstruating), so genes
	   causing it would be ruled out by "D" above. It is also
	   associated with a decreased risk of cancer (note the
	   connection to telomerase above) and an improved immune
	   system. See http://www.infinitefaculty.org/sci/cr/cr.htm.
The end point of the above is that, yes, a combination of genetic
changes could well extend lifespan, and one effect of this would be to 
limit reproduction. Another, not noted in the description in UA but
certainly tallying with other descriptions of vampires, is that they'd 
be quite thin. (I'm on caloric restriction (of varying intensity
depending on my state of health) and am 6'1" and 140-145 pounds.)

	-Allen

P.S. I am taking a break from grading lab reports to write
this... some of the above may not be too coherent, given that. Let me
know if you need anything explained further.

-- 
Allen Smith				easmith at beatrice.rutgers.edu
	

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