Dataset Information

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.

SUBMITTER: Brunelle BW

PROVIDER: S-EPMC4880211 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Disparate Modes of Evolution Shaped Modern Prion (PRNP) and Prion-Related Doppel (PRND) Variation in Domestic Cattle.

Brunelle Brian W BW O'Grady Allison M AM Nicholson Eric M EM Seabury Christopher M CM

PloS one 20160525 5

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 physio ...[more]

PMID: 27224046

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Project description:We investigated the expression of prion protein gene both on mRNA and protein levels in bovine and ovine female reproductive organs during gestation and various tissues of their fetuses. The fetal tissues of both species included brain, cotyledon, heart, intestine, kidney, liver, lung, and muscle. In cattle, prion protein gene (PRNP) transcripts were detected by semiquantitative RT-PCR in reproductive tissues such as ovary, oviduct, endometrium, myometrium, follicles, and granulosa cells. In various tissues of 2-month-old fetuses, higher expression levels were found in brain and cotyledon compared to the other tissues. To detect the expression of the gene transcript in in vivo preimplantation embryos and 1-month-old fetuses, real-time PCR was performed showing that the level of gene expression in zygote stage was significantly higher (p < or = 0.05) than that of the other stages. Sheep were categorized as resistant (RI) or high susceptible (R5) to scrapie according to their PRNP genotype. In both genotype groups, the PRNP mRNA was detectable in all tissues studied including ovary, oviduct, endometrium, myometrium, and caruncle of ewes and all tissues of 2-month-old fetuses of both groups. Comparison between reproductive organs demonstrates the highest expression level in caruncle tissue of R1 ewes, whereas the level was high in brain and low in liver of both R1 and R5 fetuses. In addition, real-time RT-PCR was performed in immature oocytes, mature oocytes, in vivo embryos at morula stage, and 1-month-old fetuses. The results showed that the relative expression levels of the ovine PRNP mRNA in mature oocytes and morula stage embryos were significantly lower than those in immature oocytes and 1-month-old fetuses (p < or = 0.05). Western blot analyses revealed the immunoreactive bands corresponding to the cellular prion protein (PrPc) in all maternal and fetal tissues examined of both cattle and sheep. Moreover, immunohistochemical staining implicated localization of the PrPc in ovarian cortex and ovarian medulla of both species. However, PrPc was not detected in oocyte, granulosa cells, theca cells, and corpus luteum in this study.

Dataset Information

Disparate Modes of Evolution Shaped Modern Prion (PRNP) and Prion-Related Doppel (PRND) Variation in Domestic Cattle.

Publications

Disparate Modes of Evolution Shaped Modern Prion (PRNP) and Prion-Related Doppel (PRND) Variation in Domestic Cattle.

Similar Datasets

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