Under certain conditions, such as dark and under water, starved cells of some cellular slime mould make macrocysts instead of forming mounds and slugs. Some of the cells apparently differentiate into gametes, and after sexual fusion, the zygotes (called giant cells) emit chemoattractant to lure the cells around to form cell aggregates, which are often subdivided into a cluster of aggregates (macrocysts at early stage) of a pretty uniform size.

As in plants and animals, usually two sexes, or mating types, are required for sexual reproduction (heterothalic species), but some species, such as D. mucoroides shown here, and some strains of heterothalic species, can go through the process of sexual reproduction with only one mating type (homothalic strain).

Giant cells engulf the cells clustering around it to become bigger. Eventually all the cells in the young macrocyst are eaten up by the giant cell, which takes its time to digest the engulfed cells. In the meanwhile, the nucleus fuses, and meiosis takes place.

It takes several weeks for a macrocyst to become ready to germinate, releasing many uninucleate cells with recombinant chromosomes.

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