• Wettstein, Peter J (PI)

Project: Research project

Project Details


Environmental factors have long been presumed to play a prominent
role in directing the evolution of genes which regulate the
mammalian immune response. Of particular interest in this context
are families of genes which are functional in either antigen-
specific presentation of foreign antigens or actual recognition of
foreign antigens. The overall objective of the proposed research
is to evaluate directly the role of environmental factors on the
evolution of these "immunoregulatory" gene families. Toward this
end, we have developed a new rodent model which utilizes the
tassel-eared squirrel, Sciurus aberti, comprised of four subspecies
restricted to four geographically isolated but identical
environments. Genomic blotting protocols will reveal the number
and polymorphism of sequences, exhibited by samples from each
subspecies, included in (1) the major histocompatibility complex
(TSLA) class I and class II families; (2) immunoglobulin heavy
chain region gene families; (3) T cell receptor alpha and beta
subunit variable and constant region gene families; and (4) a
control group of conserved actin and 7S RNA gene families and
mitochondrial DNA. Estimates of average heterozygosity and genetic
distance in each family will be calculated for pairwise
combinations of subspecies and the relationship between these two
values, as determined by linear regression, compared to that
predicted by the neutral mutation hypothesis. If environment
directs the evolution of a specific gene family, significantly
shorter genetic distance should be observed between two subspecies
than that predicted by this theory. The effects of variable
environmental conditions in delineated habitats on the frequencies
of polymorphic sequences included in TSLA and T cell receptor
variable region gene families in a single S. aberti subspecies will
be investigated by yearly correlations of these sequence
frequencies with estimate of food resource and gene swill be
investigated by immunoprecipitation with specific reagents and two-
dimensional gel electrophoresis to estimate functional polymorphism
for comparison with germline polymorphism. In summary, it is
believed that the proposed, comprehensive analysis constitutes the
first analytical approach to the question of the role of
environmental factors in directing the evolution of
immunoregulatory gene families.
Effective start/end date4/1/883/31/93


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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