Excessive replacement changes drive evolution of global sheep prion protein (PRNP) sequences

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dc.authoridSezgin, Efe/0000-0002-8000-7485
dc.authorscopusid7003392648
dc.authorscopusid57216545326
dc.authorscopusid24779770200
dc.authorscopusid56201904300
dc.authorwosidSezgin, Efe/B-8418-2012
dc.contributor.authorSezgin, Efe
dc.contributor.authorTeferedegn, Eden Yitna
dc.contributor.authorUn, Cemal
dc.contributor.authorYaman, Yalcin
dc.date.accessioned2023-01-12T19:58:39Z
dc.date.available2023-01-12T19:58:39Z
dc.date.issued2022
dc.departmentN/A/Departmenten_US
dc.description.abstractSheep prion protein (PRNP) is the major host genetic factor responsible for susceptibility to scrapie. We aimed to understand the evolutionary history of sheep PRNP, and primarily focused on breeds from Turkey and Ethiopia, representing genome-wise ancient sheep populations. Population molecular genetic analyses are extended to European, South Asian, and East Asian populations, and for the first time to scrapie associated haplotypes. 1178 PRNP coding region nucleotide sequences were analyzed. High levels of nucleotide diversity driven by extensive low-frequency replacement changes are observed in all populations. Interspecific analyses were conducted using mouflon and domestic goat as outgroup species. Despite an abundance of silent and replacement changes, lack of silent or replacement fixations was observed. All scrapie-associated haplotype analyses from all populations also showed extensive low-frequency replacement changes. Neutrality tests did not indicate positive (directional), balancing or strong negative selection or population contraction for any of the haplotypes in any population. A simple negative selection history driven by prion disease susceptibility is not supported by the population and haplotype based analyses. Molecular function, biological process enrichment, and protein-protein interaction analyses suggested functioning of PRNP protein in multiple pathways, and possible other functional constraint selections. In conclusion, a complex selection history favoring excessive replacement changes together with weak purifying selection possibly driven by frequency-dependent selection is driving PRNP sequence evolution. Our results is not unique only to the Turkish and Ethiopian samples, but can be generalized to global sheep populations.en_US
dc.identifier.doi10.1038/s41437-022-00520-6
dc.identifier.endpage385en_US
dc.identifier.issn0018-067X
dc.identifier.issn1365-2540
dc.identifier.issue5en_US
dc.identifier.pmid35273383en_US
dc.identifier.scopus2-s2.0-85126025437en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage377en_US
dc.identifier.urihttps://doi.org/10.1038/s41437-022-00520-6
dc.identifier.urihttps://hdl.handle.net/11454/76981
dc.identifier.volume128en_US
dc.identifier.wosWOS:000767012500002en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringernatureen_US
dc.relation.ispartofHeredityen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectGene Prnpen_US
dc.subjectHaplotype Reconstructionen_US
dc.subjectStatistical Propertiesen_US
dc.subjectMolecular Evolutionen_US
dc.subjectScrapieen_US
dc.subjectNeutralityen_US
dc.subjectResistanceen_US
dc.subjectBovineen_US
dc.subjectTestsen_US
dc.subjectMiceen_US
dc.titleExcessive replacement changes drive evolution of global sheep prion protein (PRNP) sequencesen_US
dc.typeArticleen_US

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