Re: IC (Challenge)

Tim Ikeda (
Sun, 21 Mar 1999 01:40:46 -0500

About the in vitro exon rearrangement example...

There's a interesting parallel in polyketide synthesis. As produced by
organisms, polyketides comprise a large and diverse class of molecules,
with diverse uses. One question about these molecules was: How was the
chemical diversity seen in polyketides generated? Complicating the
picture was the observation that even organisms which were fairly
closely related could produce quite different polyketides. Because
polyketides are generated in long and complicated reaction pathways
and because the type of polyketide made in a cell depends on a specific
series of reactions, it was not immediately clear how such variety could
be generated in relatively short periods of evolutionary time. It seemed
as if many parts of a polyketide synthesis pathway would have to be tweaked
to generate a novel structure.

While it may be one thing to see how mutations in a gene map
to the protein encoded by that gene, it was not at all clear how
mutations could map to the generation of different polyketides.

The answer seems to be that polyketide synthesis depends on the order
in which different enzyme domains are arranged in the polyketide
synthase genes. Each domain is responsible for catalyzing a specifc
type of reaction. Each domain also appears to pass its product on to
the next domain. So the type of domain determines what parts of the
polyketide are altered, and the linear order of the domains determine
the order of reactions. This makes polyketide synthesis an assembly
line process. Swapping domains or changing their order can drastically
alter the type of polyketide produced. Thus, a relatively "simple"
process of recombination is harnessed to generate a tremendous amount
of chemical diversity (Immunoglobin diversity is another example).

In addition to being examples of naturally generated IC, these are
also examples of the generation of novel functionality. Perhaps these
examples address part of that question posed earlier by Jason.

Tim Ikeda (despam address before use)