Heliyon (Apr 2021)
Considering the use of the terms strain and adaptation in prion research
Abstract
Evolutionary biologists and disease biologists use the terms strain and adaptation in Chronic Wasting Disease (CWD) research in different ways. In evolutionary biology, a strain is a nascent genetic lineage that can be described by a genealogy, and a phylogenetic nomenclature constructed to reflect that genealogy. Prion strains are described as showing distinct host range, clinical presentation, disease progression, and neuropathological and PrP biochemical profiles, and lack information that would permit phylogenetic reconstruction of their history. Prion strains are alternative protein conformations, sometimes derived from the same genotype. I suggest referring to prion strains as ecotypes, because the variant phenotypic conformations (“strains”) are a function of the interaction between PRNP amino acid genotype and the host environment. In the case of CWD, a prion ecotype in white-tailed deer would be described by its genotype and the host in which it occurs, such as the H95 + ecotype. However, an evolutionary nomenclature is difficult because not all individuals with the same PRNP genotype show signs of CWD, therefore creating a nomenclature reflecting and one-to-one relationship between PRNP genealogy and CWD presence is difficult. Furthermore, very little information exists on the phylogenetic distribution of CWD ecotypes in wild deer populations. Adaptation has a clear meaning in evolutionary biology, the differential survival and reproduction of individual genotypes. If a new prion ecotype arises in a particular host and kills more hosts or kills at an earlier age, it is the antithesis of the evolutionary definition of adaptation. However, prion strains might be transmitted across generations epigenetically, but whether this represents adaptation depends on the fitness consequences of the strain. Protein phenotypes of PRNP that cause transmissible spongiform encephalopathies (TSEs), and CWD, are maladaptive and would not be propagated genetically or epigenetically via a process consistent with an evolutionary view of adaptation. I suggest terming the process of prion strain origination “phenotypic transformation”, and only adaptation if evidence shows they are not maladaptive and persist over evolutionary time periods (e.g., thousands of generations) and across distinct species boundaries (via inheritance). Thus, prion biologists use strain and adaptation, historically evolutionary terms, in quite different ways.
