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

Abstract

The mating-type switching endonuclease HO plays a central role in the natural life cycle of <i>Saccharomyces cerevisiae</i>, but its evolutionary origin is unknown. <i>HO</i> is a recent addition to yeast genomes, present in only a few genera close to <i>Saccharomyces</i>. Here we show that <i>HO</i> is structurally and phylogenetically related to a family of unorthodox homing genetic elements found in <i>Torulaspora</i> and <i>Lachancea</i> yeasts. These <i>WHO</i> elements home into the aldolase gene <i>FBA1</i>, 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 <i>Torulaspora delbrueckii FBA1</i> efficiently and in an allele-specific manner, leading to DNA repair by gene conversion or NHEJ. The DNA rearrangement steps during <i>WHO</i> element homing are very similar to those during mating-type switching, and indicate that <i>HO</i> is a domesticated <i>WHO</i>-like element.