RE: Opposite of antagonistic pleiotropy

From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Wed Apr 02 2003 - 21:43:32 MST

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    Oh goody an interesting discussion for a change...
    (paint me tainted...)

    > From: Anders Sandberg [mailto:asa@nada.kth.se]
    (is this not from Anders but a quote from someone else??)

    At any rate:

    > > But what do you call a gene that does the same thing all
    > > the time, but this function is good in youth and bad in old
    > > age? Is it also called AP?

    I'll go you one better (I believe in poker this is called
    raising the stakes) and cite a concrete example -- the regulation
    of iron storage in the human body. Iron is essential -- you
    have to have it to transport oxygen. Men do not lose iron
    every month, women do -- so there are sex specific regulatory
    issues (that do not currently, at least to my knowledge, seem
    to be incorporated into the genome). Reserves of iron are
    essential -- to recover from accidental losses. But iron
    is an essential nutrient for bacteria -- one doesn't want it
    floating around where they can get their hands on it.

    So one has a whole set of genes to absorb iron from the
    environment (transport it under controlled circumstances --
    the transferrin molecule), store it in a protected environment
    (the ferritin molecules) and then probably a collection of
    molecules to store/unstore it in a controlled fashion.

    *But* iron is a pro-oxidant -- the more of it you have
    "available" the more likely it is to produce free radical
    damage that damages your DNA and corrupts your genetic program.

    So you have to *hope* that the genetic program that evolved
    to manage iron transport and storage is doing its job effectively.

    AP? You *need* the iron. You cannot live without it.
    But if the bacteria get their hands on it you are lunch
    for them. If it just gradually accumulates and isn't managed
    *very* well it slowly destroys the genetic program you
    require to survive. Isn't this a Catch-22 situation?

    > > It is the pleiotropy part that I
    > > am worried about, since the gene does not change behavior
    > > in any way.
    >
    On Wed, 2 Apr 2003, Ramez Naam wrote:
    > I'd still call this antagonistic pleiotropy. The gene's 1st order
    > behavior may not be changing, but its overall impact on the organism
    > is.

    This would be true for the entire iron collection and regulatory
    system in the human body. I.e. it is always doing what it does
    because that is necessary for short-term survival. It (probably)
    does not change its "behavior" over the lifetime of the organism.
    The net result -- it may help the organism survive and reproduce
    (the selfish gene concept) but may be ultimately detrimental.

    It isn't that the "impact" on the organism is changing. The
    "impact" may be continual over time -- and it may cause
    detrimental effects due to the accumulation of very small
    side effects over a very long period of time.

    The typical concept of "antagonistic plieotropy" is that something
    is designed to help out early on but ultimately ends up being harmful.

    One needs to take a step back to see that the system is misdesigned
    from the get-go. Either we should not be using iron as an oxygen
    transporter (eliminating the free radical damage it might produce
    if improperly managed) or we should not have a genetic information
    carrier (such as DNA) that can be damaged by free radicals. (Now of course
    if one eliminated the mutation of the genetic information carrier
    one probably puts a significant handicap on evolution so we might not
    even be here to discuss this but these are mere details.)

    Robert



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