Figure 1. The missing link in the evolution of HO.

(A) The HO gene is structurally similar to two other mobile DNA elements, VDE and WHO. All three genes have an intein-like domain (blue rectangle) that includes an endonuclease domain: in HO this domain cuts DNA at the MAT locus. The WHO and HO genes also have a zinc finger domain (green). The WHO gene is also located next to its target, the FBA1 gene. (B) Coughlan et al. propose that the WHO gene homes into the FBA1 gene as follows. First, the enzyme encoded by the WHO gene (blue and green ovals) cuts a target gene, represented as FBA1’ (dark gray box), which is not flanked by WHO. Next, the break is repaired using a template of the FBA1 gene (medium gray) which is adjacent to the WHO gene and a fragment of FBA1 (A1, light gray). The template sequence (including the WHO gene) is copied and inserted into the cleaved site of the target gene. Recombination between the target FBA1’ gene and the template FBA1 gene creates a new FBA1 gene (dark and medium gray) and FBA1 fragment (light gray and dark gray), which sit on either side of the WHO gene. The newly recombined FBA1 gene is no longer susceptible to cleavage by the enzyme encoded by WHO (represented by the T symbol).