Phylogenetic tree and domain characteristics of SET domain proteins from P. falciparum.SET proteins were retrieved through reciprocal blastp searches and analyzed using maximum-likelihood and Bayesian inference. The upper, dark gray box indicates the strong grouping of P. falciparum ‘Set2’ with Ashr3 sequences from green plants. The larger, lighter gray box below defines canonical Set2 sequences defined in model organisms. Although both are included in a larger clade of putative H3K36 modifying proteins, apicomplexan ‘Set2’ homologs do not group with their ostensible alveolate sister group, the ciliates (represented by Tetrahymena and Paramecium). The strong phylogenetic association with plant Ashr3 proteins is further supported by overall domain architecture, including (and unlike canonical Set2 and ciliate homologs) the shared C-terminal location of the SET domain, as well as a highly conserved PHD region that is proximal to the SET domain in both. In the alignment of this region included, residues that are invariable among plant and apicomplexan sequences are shaded green, those with conservative substitutions are in yellow. The only SET-containing sequence from Perkinsus marinus with significant similarity to Set2, is strongly supported as a member of the Set1 subfamily, and (as expected) as sister to the P. falciparum Set1 paralog.