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Updated: Sep 30, 2025
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Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay
Published on: March 10, 2015
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Excessive replacement changes drive evolution of global sheep prion protein (PRNP) sequences
Efe Sezgin1, Eden Yitna Teferedegn2,3, Cemal Ün2
1Department of Food Engineering, Izmir Institute of Technology, Urla, Izmir, Turkey. efesezgin@iyte.edu.tr.
Heredity
|March 11, 2022
Summary
Sheep prion protein (PRNP) evolution is complex, driven by frequent genetic changes and weak purifying selection. This pattern, observed globally, suggests frequency-dependent selection influences scrapie susceptibility in sheep.
Area of Science:
- Genetics
- Evolutionary Biology
- Molecular Biology
Background:
- Sheep prion protein (PRNP) is a key genetic factor influencing scrapie susceptibility.
- Understanding PRNP's evolutionary history is crucial for managing prion diseases in sheep.
Purpose of the Study:
- To investigate the evolutionary history of sheep PRNP, focusing on ancient populations from Turkey and Ethiopia.
- To analyze PRNP sequence diversity and selection pressures across global sheep populations and scrapie-associated haplotypes.
Main Methods:
- Analysis of 1178 PRNP coding region nucleotide sequences from diverse sheep populations.
- Interspecific comparisons using mouflon and domestic goat as outgroups.
- Neutrality tests and functional enrichment analyses (molecular function, biological process, protein-protein interaction).
Main Results:
- High nucleotide diversity in sheep PRNP, characterized by abundant low-frequency replacement changes.
- Absence of fixation for silent or replacement changes, and extensive low-frequency replacement changes in scrapie-associated haplotypes.
- Neutrality tests did not support simple selection models (directional, balancing, strong negative selection) or population contraction.
Conclusions:
- Sheep PRNP evolution is shaped by a complex selection history favoring excessive replacement changes.
- Weak purifying selection, potentially influenced by frequency-dependent selection, plays a role in PRNP sequence evolution.
- Findings are generalizable across global sheep populations, not limited to the studied ancient breeds.
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