As expected for an enzyme-coding gene, orthologs of PTEN are detectable in all branches of the tree of life, including prokaryotes, where they belong to the inclusive orthologous group of the tyrosine phosphatases. With the exception of Danio rerio and Arabidopsis thaliana, whose genomes underwent whole-genome duplications (47,48), orthologs of PTEN maintain a strict 1:1 relationship in all eukaryotic branches (Figure 2B). This suggests an early differentiation of PTEN and the maintenance of a strict singleton status during eukaryote evolution.