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vertebrate gene numbers and immune evolution

Marc Buhler marcb at westgate.wh.usyd.edu.au
Wed Aug 22 00:33:47 EST 2001

Not realizing that there was a "trap" which I fell into, I submitted
the abstract below to the GeneMapper's workshop held in Cairns,
Australia recently. The trap was that (despite the phrases saying
"submitted abstracts will NOT be required to be presented as
posters" but would be included in the workshop booklet and that only
a few might be given talks) all submitted abstracts were given talks!

So having raised the question at my talk in this workshop, I'm
now looking for further comment on this question.  Any thoughts?

[ The one question directed at me after the talk was to do with the
transgenic TCR mouse models and such related to "plasticity" of
the immune response.... I fumbled some reply as it was a question
from another speaker on the same part of the program to whom I
had briefly outlined my talk just before the session started, and who
had felt at the onset that he didn't agree with me. The chairman was
John Blangero and he was quick to move us on to other talks. While
the question was a good one, I later realized that it was focussed on
higher-order (mammalian) vertebrates while my abstract is directed
at the entire path of vertebrate and immune evolution.]

(signed) marc buhler

Could Immune Evolution Put A Cap On Vertebrate Gene Numbers?

Recent analysis of the human genome caused surprise with the number of
genes put at one third of the number expected with some comparison made
against some invertebrate genomes, with the yeast genome or with plant
genomes in the lay press. While the total numbers of genes in many
species will still be some years in resolving it is likely that the gene
number in various vertebrate species will show an upper limit determined
by the need to optimize the constraints on immune repertoire
construction. The greater the number of "self" epitopes expressed in the
thymic education of T-cells, the greater the number of holes created in
the repertoire. Levels of non-self recognition in individuals must be
optimal while populations need extensive polymorphism for MHC class I
and II yet the limit on MHC loci is such that only a dozen of the
hundreds of available MHC alleles are expressed in any individual (two
alleles each of six class I and II genes). MHC alleles and TcR
haplotypes act with the limited polymorphism in other self antigens to
define individual immune repertoires. Besides a cap on overall gene
numbers, immune evolution similarly may limit the extent of polymorphism
in general and acts in the shaping of localized regions of linkage
disequilibrium (LD). This is clearly seen across the MHC region with
extensive LD and in the several antigen-recognition genes (TcR and Ig
molecules) where recombination hotspots act to reduce LD and ensure
haplotype variation in populations. Regions surrounding many other
immune response genes are also likely to show local LD effects in
populations where pathogens have had selective effects. For example, the
delta-32 allele of the chemokine receptor CCR5 occurs at a 10% frequency
in most Caucasian populations but has an origin within the last 2000
years and microsatellite association is detectable over several cM.

[ note:  this example involving CCR5 leads into another abstract which I
presented after the genemappers workshop, as a talk at the HGSA meeting,
on the Ashkenazi Jewish origin of the delta-32 CCR5 allele.]



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