Fungal prion
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. The initial discovery of PSI+ was made in a strain auxotrophic for adenine due to a nonsense mutation  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 .
Further investigation found that PSI+ is the misfolded form of Sup35, which is an important factor for translation termination during protein synthesis . It is believed that  causes suppression of nonsense mutations by sequestering functional Sup35 in non-functional aggregates, thereby allowing stop codon readthrough. , in turn, is the misfolded form of the protein Rnq1. However, the normal function of this protein is unknown to date. It is of note that for the induction of most variants of , the presence of  is required. Though reasons for this are poorly understood, it is suggested that  aggregates may act as seeds for the polymerization of  .
Two modified versions of Sup35 have been created that can induce PSI+ in the absence of  when overexpressed. One version was created by digestion of the gene with BalI, which results in a protein consisting of only the M and N portions of Sup35 . The other is a fusion of Sup35NM with HPR, a human membrane receptor protein.
Laboratories commonly identify  by growth of a strain auxotrophic for adenine on media lacking adenine, similar to that used by Cox et al. These strains cannot synthesize adenine due to a nonsense mutation in one of the enzymes involved in biosynthetic pathway. 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. Hence, color is an alternative method of identifying  --  strains are white or pinkish in color, and  strains are red. A third method of identifying  is by the presence of Sup35 in the pelleted fraction of cellular lysate.

# Classification
As of 2003, the following proteins in Saccharomyces cerevisiae had been identified or postulated as prions:
- Sup35p, forming the  element;
- Ure2p, forming the  element;
- Rnq1p, forming the  element (also known as )
- A fifth prion protein, forming the  element remains to be identified.