Prion Evolution

Click images to view larger (~50kb) or (~78kb) versions of this figure

Several important issues can be addressed by looking at the figure above:

the bovine (cow) protein (as would be expected) is less similar to the human protein (red pathway in figure) than it is to other farm animals such as sheep (blue pathway in figure), goats and pigs
- the evolutionary branch separating humans from bovines occurred ~70 million years ago
- the evolutionary branch separating bovines from ovines (sheep) occurred only ~20 million years ago
- although the pig is a member of the same phylogenetic 'Order' as cattle and speep, its prion protein is dissimilar being a member of a different family ('family' classification not illustrated in figure but shown in the figure below)
  - whether this separation protects pigs from BSE or Scrapie via consumption of comtaminated feed has not been determined
  - there are no reports of farmed pigs having contracted either BSE or Scrapie or having their own strain of TSE
  - however, as would be expected, BSE can be transmitted to pigs experimentally
- similar to the pigs, there are no reports of chickens having contracted either BSE or Scrapie or having their own TSE
  - the chicken life span may be too short for the expression of non-experimental (endogenous or transmitted) TSE symptoms
since protein sequence conservation has a large role in controlling the species barrier it would seem likely that other domestic animals that have prion sequences similar to that of the cow may be more susceptible to BSE than are humans
- this possibility is the basis for the concern with sheep getting BSE (or sheep as the origin of BSE)
- humans have not contracted Scrapie but have contracted BSE, indicating that other factors beside prion sequence conservation control transmission

The phylogenic tree will vary in shape somewhat dependent on the parameters used for its generation, including whether protein sequence or DNA sequence is used to generate relationships. The phylogenic tree above was generated by Krakauer et. al. using amino acid sequence of the proteins (they also generated trees using DNA sequences). Only the protein tree is presented above. Although the gene (codon) tree has many advantages over the protein tree for visualizing evolutionary changes, the protein tree is the most useful in determining possible connections with the prion diseases as:

the protein sequence determines protein structure and possible interactivity between proteins of different species
- in many cases DNA sequence differences may not result in protein sequence changes
prion disease transmission occurs via protein transfer not genetic material infection

In the figure above, all species are members of the Kingdom:Animalia and Phylum:Chordata, but the chicken is a member of the Class:Aves whereas all other species are members of the Class:Mammalia (for reference a detailed description of some of the domestic animal species is shown in the figure below)

Phylogeny classification

Kingdom

Phylum (Subphylum)

Class (Subclass, Infraclass)

Order

Family (Subfamily)

Genus

species (subspecies)