The yeast mating-type switching endonuclease HO is a domesticated member of an unorthodox homing genetic element family.

The mating-type switching endonuclease HO plays a central role in the natural life cycle of , but its evolutionary origin is unknown. is a recent addition to yeast genomes, present in only a few genera close to . Here we show that is structurally and phylogenetically related to a family of unorthodox homing genetic elements found in and yeasts. These elements home into the aldolase gene , replacing its 3' end each time they integrate. They resemble inteins but they operate by a different mechanism that does not require protein splicing. We show that a WHO protein cleaves efficiently and in an allele-specific manner, leading to DNA repair by gene conversion or NHEJ. The DNA rearrangement steps during element homing are very similar to those during mating-type switching, and indicate that is a domesticated -like element.