PMID:
     15477588
Authors:
     Seabury CM, Honeycutt RL, Rooney AP, Halbert ND, Derr JN.
Title:
     Prion protein gene (PRNP) variants and evidence for strong purifying selection in
     functionally important regions of bovine exon 3.
Journal:
     Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15142-7. Epub 2004 Oct 11.
Abstract:
     Amino acid replacements encoded by the prion protein gene (PRNP) have been
     associated with transmissible and hereditary spongiform encephalopathies in
     mammalian species. However, an association between bovine spongiform
     encephalopathy (BSE) and bovine PRNP exon 3 has not been detected. Moreover,
     little is currently known regarding the mechanisms of evolution influencing the
     bovine PRNP gene. Therefore, in this study we evaluated the patterns of
     nucleotide variation associated with PRNP exon 3 for 36 breeds of domestic cattle
     and representative samples for 10 additional species of Bovinae. The results of
     our study indicate that strong purifying selection has intensely constrained PRNP
     over the long-term evolutionary history of the subfamily Bovinae, especially in
     regions considered to be of functional, structural, and pathogenic importance in 
     humans as well as other mammals. The driving force behind this intense level of
     purifying selection remains to be explained.

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