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Well known examples include variant Creutzfeldt-Jakob Disease (vCJD) in humans, BSE in cattle, chronic wasting disease in deer and scrapie in sheep and goats. In humans, sheep and deer, disease susceptibility is determined by host genotype at the prion protein gene (<jats:italic>PRNP<\/jats:italic>). Here I examine the molecular evolution of<jats:italic>PRNP<\/jats:italic>in ruminants and show that variation in sheep appears to have been maintained by balancing selection, a profoundly different process from that seen in other ruminants. Scrapie eradication programs such as those recently implemented in the UK, USA and elsewhere are based on the assumption that<jats:italic>PRNP<\/jats:italic>is under positive selection in response to scrapie. If, as these data suggest, that assumption is wrong, eradication programs will disrupt this balancing selection, and may have a negative impact on the fitness or scrapie resistance of national flocks.<\/jats:p>","DOI":"10.1098\/rspb.2005.3259","type":"journal-article","created":{"date-parts":[[2005,9,26]],"date-time":"2005-09-26T16:15:17Z","timestamp":1127751317000},"page":"2371-2377","source":"Crossref","is-referenced-by-count":22,"title":["Molecular evolution of the sheep prion protein gene"],"prefix":"10.1098","volume":"272","author":[{"given":"Jon","family":"Slate","sequence":"first","affiliation":[{"name":"Department of Animal &amp; Plant Sciences, University of SheffieldSheffield, S10 2TN, 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