A fratricidal fungal prion.

Abstract

Once again, 50 years after its discovery, the multifaceted het-s gene of Podospora anserina has surprised us. Long ago, it provided an important early example of heterokaryon incompatibility and cytoplasmic inheritance (1–4). In 1997, the product of allele het-s was shown to form a prion (infectious protein) that leads to cell death in incompatible combinations (5–7). Then, spore-killing meiotic drive factors were discovered in natural populations of Podospora (8). Ability to kill was correlated with heterokaryon incompatibility (9), and some of the killer strains resembled het-s in their effects on ascospore abortion. Now, in this issue of PNAS, Dalstra et al. (10) fit pieces of the jigsaw puzzle together, showing that the het-s prion acts as a spore killer in the sexual phase. It can thus be thought of as a selfish genetic element that promotes its maintenance by actively destroying meiotic products that bear the nonprion allele het-S . Podospora is a filamentous ascomycete related to the orange mold Neurospora crassa . Several characteristics of P. anserina have been important for analysis of the het-s gene. Vegetative growth consists of multinucleate syncytial filaments that may be homokaryotic or heterokaryotic, with nuclei that are haploid. Mating occurs between two physiologically distinct mating types. In the sexual phase, all four products of each meiosis are retained together in an ascus containing large spores that are pigmented when viable but unpigmented when inviable. Detection of spore killing and the implication of prions were aided by the curious and precise programming of ascus development in P. anserina , which produces individual ascospores that are normally heterokaryotic for mating type and for any other genes that are segregated into separate nuclei at the second meiotic division, but homokaryotic for genes segregating at the first division. As in other filamentous ascomycetes, …