homologous recombination differences

stockemg at ucbeh.san.uc.edu stockemg at ucbeh.san.uc.edu
Fri Dec 17 19:46:16 EST 1993


     I have a little idea that I want to try out on an
informed audience.  This goes back to when I finished my
coursework and started on my thesis project.  I was doing
gene targeting in ES cells and was frustrated to learn that
although homologous recombination is easy in such
unicellular organisms as E. coli and yeast, it's very
difficult in the cells of higher eukaryotes,  as in cell
culture.
     I wondered why this was, and the most interesting idea
I had was that there is selection for the integration of any
homolgous DNA that comes along in unicellular oganisms, and
if anything selection against such behavior in individual
cells of a multicellular organism.

     For microorganisms, I think there would be little risk
in an individual bug taking up stray DNA and replacing its
own version of a gene with some newly encountered one.  The
cell most likely is one of thousands/millions of identical
cells.  If it is killed by the new gene or the loss of the
old, the natural selection impact of this event is almost
nothing.  If the new version is beneficial, the cell gains
an advantage over the rest of the colony, and becomes a new
emergent subclone.  On the other hand, though, a phage 
exploiting this sort of behavior would wreak havoc.

     For multicellular organisms, however, this sort of
improvisational behavior on the part of its constituent
cells can only lead to trouble for the organism as a whole. 
There's almost no way a genetic change in a single cell can
benefit the whole organism; for examples, a
better-functioning enzyme in a single cell would be
meaningless, and a growth advantage to a single cell would
be one step toward malignant transformation of that cell.

     I know that this model is awfully -ahem- teleological,
and probably untestable (although the homologous
recombination policies of such loosely multicellular 
organisms as sponges and volvox might be interesting),  but
it was fun to think of anyway.  I'd like to hear what people
think about this.  Thanks!

Michael Stockelman          stockemg at ucbeh.san.uc.edu
U. Cincinnati
Cin, OH     45267-0521



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