Molecular Genetics

Not all hereditary information is carried by DNA or RNA.

Facts

• Several slow neurological diseases (scrapie, bovine spongiform encephalopathy, Creutzfeld-Jakob disease) are related infectious diseases.
• An infectious agent can be isolated from brains of scrapie- infected animals (sheep, hamsters, mice).
• The infectious agent, called a prion, of scrapie consists principally of a single protein, Pr SC, of 26K mol. wt. and does not contain detectable nucleic acid.
• Pr SC is identical in amino acid sequence to a normal brain protein, Pr P.
• Injection of Pr SC, but not of Pr P, in normal mice causes disease.
• Injection of Pr SC into mice incapable of making PrP does not lead to disease.

Interpretations

• The "genetic" information for the causation of scrapie is carried by a protein, Pr SC.
• Pr SC must transfer its information to PrP creating more PrSC.
• One plausible hypothesis is that Pr SC and Pr P are two conformations of the same polypeptide. The Pr SC conformation is a catalyst that converts the PrP conformer to Pr SC.
• Not all heritable information is stored in DNA or RNA.

Further information

• Our understanding of proteinaceous infectious agents, prions, advanced by the work of Stanley Prusiner and others, reveals that some inheritance may be through proteins.
• Strains of prion disease agents that differ in their propagation properties have been identified. The existence of these strains and the heritability of their strain-specific properties are difficult to explain with a protein-only model of prion diseases. Thus, the interpretation that PrSC is the only component of the causative agent of scrapie and related diseases is not universally accepted (ref).
• Two yeast genetic determinants have properties analogous to those of mammalian prions (ref).
• There are other examples of inheritance not mediated by nucleic acids. The abnormal hyperacetylated state of histones in centromeric nucleosomes is heritable.
• PrSC binds G-quartet RNA structures (Ref). The significance of this observation is unclear.