Figure 4. Proposed mechanism of WHO element homing.

(A) Similarity of mechanisms of action of WHO, VDE and HO. The mechanism we propose for WHO elements integrating at FBA1 is compared to the known mechanisms for VDE integrating into VMA1 and for HO-mediated switching of the MAT locus (Gimble and Thorner, 1992; Lee and Haber, 2015). WHO and VDE homing occur between allelic chromosomes in a diploid cell, whereas mating-type switching occurs between MAT and HML/HMR loci in a haploid cell. Gray rectangles indicate regions of sequence identity. The column on the right shows mating-type switching from MATα to MATa in S. cerevisiae. Switching from MATa to MATα occurs by an identical mechanism; the core of the HO recognition site (CGCAACA) is the first 7 nucleotides of the Z region, which is present in both of the MAT alleles even though it is part of the MATα1 gene sequence. The HO gene is on a different chromosome than MAT-HML-HMR. (B) Model for WHO cluster formation by successive integration of WHO elements. Every time a WHO element integrates into the locus, the 3’ end of the full-length FBA1 gene is replaced. The previous 3’ end is pushed rightwards, together with any older WHO genes, after which they can decay into pseudogenes. The complete WHO mobile element unit consists of a WHO gene and the upstream 3’ end of FBA1, which confers resistance to it.