A heterokaryon is a multinucleate cell that contains genetically different nuclei. Heterokaryotic and heterokaryosis are derived terms. This is a special type of syncytium. This can occur naturally, such as in the mycelium of fungi during sexual reproduction, or artificially as formed by the experimental fusion of two genetically different cells, as e.g., in hybridoma technology. Heterokaryon is from neo-classic Greek hetero, meaning different, and karyon, meaning kernel or in this case nucleus. The term was coined in 1965, independently by B. Ephrussi and M. Weiss, by H. Harris and J. F. Watkins, and by Y. Okada and F. Murayama. Heterokaryons are found in the life cycle of yeasts, for example Saccharomyces cerevisiae, a genetic model organism. The heterokaryon stage is produced from the fusion of two haploid cells. This transient heterokaryon can produce further haploid buds, or cell nuclei can fuse and produce a diploid cell, which can then undergo mitosis. The term was first used for ciliate protozoans such as Tetrahymena. This has two types of cell nuclei, a large, somatic macronucleus and a small, germline micronucleus. Both exist in a single cell at the same time and carry out different functions with distinct cytological and biochemical properties. Many fungi (notably the arbuscular mycorrhizal fungi) exhibit heterokaryosis. The haploid nuclei within a mycelium may differ from one another not merely by accumulating mutations, but by the non-sexual fusion of genetically distinct fungal hyphae, although a self / non-self recognition system exists in Fungi and usually prevents fusions with non-self. Heterokaryosis is also common upon mating, as in Dikarya (Ascomycota and Basidiomycota). Mating requires the encounter of two haploid nuclei of compatible mating types. These nuclei do not immediately fuse, and remain haploid in a n+n state until the very onset of meiosis: this phenomenon is called delayed karyogamy.

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