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Orthologs of Human Prion Protein

Prion diseases are not common, the major affected animals are limited to humans, sheep, and cattle, so it is not surprising that few animals have orthologs to the human prion protein.

Figure 1.  Amino acid sequence alignment of human prion protein and six orthologs. From HomoloGene.
HumanNP 898902.1
ChimpanzeeNP 001009093.1
DogXP 542906.2
CattleNP 851358.1
House MouseNP 035200.1
Norway RatNP 036763.1
ChickenNP 990796.1

Figure 2.  A cladogram proposing a phylogenetic tree for the evolution of the prion-encoding gene. From ClustalW.

The sequence alignment shows that there is high level of conservation between the prion proteins of the various species.  These six are a limited selection of the orthologs found, but representative as all were vertebrates, mostly mammals with the occasional bird and amphibian.  Orthologs were looked for in Arabidopsis, yeast, C. elegans, E. coli, and Drosophila, but none were found.

The Centers for Disease Control and Prevention argues that there is evidence that many of the human and non-human prion diseases are descended from each other.  On their website the CDC writes that bovine spongiform encephalopathy (BSE or mad cow) could have resulted from feeding cattle scrapie-infected, a sheep prion disease, sheep products.  There is also evidence that the human prion disease variant Creutzfeldt-Jakob disease (vCJD) resulted from exposure to BSE-contaminated food.  The fact that one species's prions can also cause disease in another species speaks to the high conservation.

Works Cited
ClustalW2.  EMBL-EBI.  http://www.ebi.ac.uk/Tools/es/cgi-bin/clustalw2/result.cgi?tool=clustalw2&jobid=clustalw2-20100310-0348149342&treendisp=hide&treetype=new&sortby=seqno&color=no. 2010 March 7.

HomoloGene:7904.  NCBI. http://www.ncbi.nlm.nih.gov/sites/homologene/7904.  2010 March 7.

Prion Diseases.  Centers for Disease Control and Prevention.  http://www.cdc.gov/ncidod/dvrd/prions/. 2010 March 7.
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Please direct questions and comments to mamiller@davison.edu