Evolutionary biology and the risk of scrapie disease in sheep

Scrapie in sheep occurs in two forms. Classical scrapie, along with chronic wasting disease in deer, differs from all other prion diseases in being contagious and occurring as propagating epidemics. By contrast, atypical scrapie occurs sporadically and like most other prion diseases, such as Creutzfeldt-Jakob disease in humans, is regarded as non-contagious under natural conditions. This difference motivates the present study, which uses the perspective of evolutionary biology to explore whether atypical or non-contagious scrapie can transform to classical or contagious scrapie when appropriate evolutionary forces are in play. The study begins with an explanation of relevant evolutionary concepts such as evolvability and object of selection and proposes some explicit definitions of key terms such as variation, replication, heritability and strain. Observations of the behaviour of scrapie strains during serial passage in sheep, goats and mice assign the functions of variation, replication and heritability to the scrapie agent and establish it as an object of selection with a capacity for evolvability. Similar observations of strain behaviour in other prion diseases establish prions in general as objects of selection that are able to evolve. Accordingly, it is tenable that non-contagious atypical scrapie can provide progenitors for the prions causing contagious classical scrapie and can be a latent epidemiological threat. A comparison of atypical and classical scrapie identifies an affinity of the scrapie agent for lymphoreticular tissue and predilections for portals of exit and entry as key gain-of-function mutations that endow prion populations in atypical scrapie with the function of communicability or contagiousness. The present study can be seen as the hazard identification step within a process of risk analysis that systematises knowledge in aid of animal health and welfare and biosecurity. It justifies completion of the remaining steps in risk assessment. This task can be assisted by further comparisons of atypical and classical scrapie enlightened by historical records of scrapie disease, the epidemiology of atypical scrapie, the general behaviour of prions and evolutionary biology.