title: Disparate Modes of Evolution Shaped Modern Prion (PRNP) and Prion-Related Doppel (PRND) Variation in Domestic Cattle.
abstract: Previous investigations aimed at determining whether the mammalian prion protein actually facilitates tangible molecular aspects of either a discrete or pleiotropic functional niche have been debated, especially given the apparent absence of overt behavioral or physiological phenotypes associated with several mammalian prion gene (PRNP) knockout experiments. Moreover, a previous evaluation of PRNP knockout cattle concluded that they were normal, suggesting that the bovine prion protein is physiologically dispensable. Herein, we examined the frequency and distribution of nucleotide sequence variation within the coding regions of bovine PRNP and the adjacent Doppel (PRND) gene, a proximal paralogue to PRNP on BTA13. Evaluation of PRND variation demonstrated that the gene does not depart from a strictly neutral model of molecular evolution, and would therefore not be expected to influence tests of selection within PRNP. Collectively, our analyses confirm that intense purifying selection is indeed occurring directly on bovine PRNP, which is indicative of a protein with an important role. These results suggest that the lack of observed fitness effects may not manifest in the controlled environmental conditions used to care for and raise PRNP knockout animals.
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa 50010, United States of America.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Brunelle
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa 50010, United States of America.
authors.forename: Allison M
authors.initials: AM
authors.lastname: O'Grady
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa 50010, United States of America.
authors.forename: Eric M
authors.identifier: 0000-0002-2217-0161
authors.initials: EM
authors.lastname: Nicholson
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4467, United States of America.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Seabury
mesh_terms: D000818:Animals; D002417:Cattle; D019143:Evolution, Molecular; D000072002:Prion Proteins / Q000235:genetics*
chemical_list: D000072002:Prion Proteins