Fungal prion

[citation needed] A recent study of candidate prion domains in S. cerevisiae found several specific sequence features that were common to proteins showing aggregation and self-templating properties.

This discovery of sequence specificity was a departure from previous work that had suggested that the only determining factor in prionogenesis was the overall distribution of peptides.

In 1965, Brian Cox, a geneticist working with the yeast Saccharomyces cerevisiae, described a genetic trait (termed [PSI+]) with an unusual pattern of inheritance.

In 1994, yeast geneticist Reed Wickner correctly hypothesized that [PSI+] as well as another mysterious heritable trait, [URE3], resulted from prion forms of the normal cellular proteins, Sup35p and Ure2p, respectively.

[7] The names of yeast prions are frequently placed within brackets to indicate that they are non-mendelian in their passage to progeny cells, much like plasmid and mitochondrial DNA.

[10] It is believed that suppression of nonsense mutations in [PSI+] cells is due to a reduced amount of functional Sup35 because much of the protein is in the amyloid state.

When the strain is grown on yeast-extract/dextrose/peptone media (YPD), the blocked pathway results in buildup of a red-colored intermediate compound, which is exported from the cell due to its toxicity.

When exposed to certain adverse conditions, in some genetic backgrounds [PSI+] cells actually fare better than their prion-free siblings;[14] this finding suggests that the ability to adopt a [PSI+] prion form may result from positive evolutionary selection.

[15] It has been speculated that the ability to convert between prion-infected and prion-free forms acts as an evolutionary capacitor to enable yeast to quickly and reversibly adapt in variable environments.

[citation needed] Prions act as an alternative form of non-Mendelian, phenotypic inheritance due to their self-templating ability.

Many proteins containing prion domains play a role in gene expression or RNA binding, which is how an alternative conformation can give rise to phenotypic variation.

When Sup35 undergoes a conformational change to the [PSI+] prion state, it forms amyloid fibrils and is sequestered, leading to more frequent stop codon read-through and the development of novel phenotypes.

With over 20 prion-like domains identified in yeast, this gives rise to the opportunity for a significant amount of variation from a single proteome.