Fungal prions

Fungal prions have been investigated, leading to a deeper understanding of disease-forming mammalian prions.

Prion-like proteins are found naturally in some plants and non-mammalian animals. Some of these are not associated with any disease state and may possibly even have a useful role. Because of this, scientists reasoned that such proteins could give some sort of evolutionary advantage to their host. This was suggested to be the case in a species of fungus, Podospora anserina. Genetically compatible colonies of this fungus can merge together and share cellular contents such as nutrients and cytoplasm. A natural system of protective "incompatibility" proteins exists to prevent promiscuous sharing between unrelated colonies. One such protein, called HET-S, adopts a prion-like form in order to function properly. The prion form of HET-S spreads rapidly throughout the cellular network of a colony and can convert the non-prion form of the protein to a prion state after compatible colonies have merged. However, when an incompatible colony tries to merge with a prion-containing colony, the prion causes the "invader" cells to die, ensuring that only related colonies obtain the benefit of sharing resources.

Sup35p & Ure2p
In 1965, Brian Cox, a geneticist working with the yeast Saccharomyces cerevisiae, described a genetic trait (termed PSI+) with an unusual pattern of inheritance. Despite many years of effort, Cox could not identify a conventional mutation that was responsible for the PSI+ trait. In 1994, yeast geneticist Reed Wickner correctly hypothesized that PSI+ as well as another mysterious heritable trait, URE3, resulted from prion forms of certain normal cellular proteins. It was soon noticed that heat shock proteins (which help other proteins fold properly) were intimately tied to the inheritance and transmission of PSI+ and many other yeast prions. Since then, researchers have unravelled how the proteins that code for PSI+ and URE3 can convert between prion and non-prion forms, as well as the consequences of having intracellular prions. When exposed to certain adverse conditions, PSI+ cells actually fare better than their prion-free siblings ; this finding suggests that, in some proteins, the ability to adopt a prion form may result from positive evolutionary selection. It has been speculated that the ability to convert between prion infected and prion-free forms enables yeast to quickly and reversibly adapt in variable environments. Nevertheless, Wickner maintains that URE3 and PSI+ are diseases.

Classification
As of 2003, the following proteins in Saccharomyces cerevisiae had been identified or postulated as prions:
 * Sup35p, forming the [PSI+] element;
 * Ure2p, forming the [URE3] element;
 * Rnq1p, forming the [RNQ+] element (also known as [PIN+])
 * A fifth prion protein, forming the [ISP+] element remains to be identified.