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

Abstract

SummaryThe mating-type switching endonuclease HO plays a central role in the natural life cycle ofSaccharomyces cerevisiae, but its evolutionary origin is unknown.HOis a recent addition to yeast genomes, present in only a few genera. It resembles a degenerated intein fused to a zinc finger domain. Here we show thatHOis structurally and phylogenetically related to a family of unorthodox homing genetic elements found inTorulasporaandLachanceayeasts. TheseWHOelements integrate into the aldolase geneFBA1, replacing its 3’ end each time. Their structural organization is different from all known classes of homing elements. We show that a WHO protein cleavesTorulaspora delbrueckii FBA1efficiently and in an allele-specific manner, leading to DNA repair by gene conversion or NHEJ. The DNA rearrangement steps duringWHOelement homing are very similar to those during mating-type switching, and indicate thatHOis a domesticatedWHO-like element.