Alternative models for evolution of the Pax classes. (A) This model is based on our previous scheme (18) but accommodates the data reported in this study. Herein, we view Pax-Aam and Pax-Cam as representing the before and after states of a fusion event between a Pax-A/Pox-n-like gene and a paired-like homeobox gene. (B) An alternative model, in which Pax-B/sPax-2/5/8 (rather than Pax-Cam) is seen as reflecting the ancestor of most of the metazoan Pax genes. The models also differ in interpreting the Pax-A/Pox-n class as ancestral (A) or derived (B). In both schemes, Pax-Cam corresponds to the ancestor of the Pax-6 class, and Pax-Dam the precursor of the Pax-3/7 class; the Pax-1/9 class is related to the Pax-3/7 class via loss of the homeobox. Common ancestry of Pax genes is implied by the fact that all of the cnidarian Pax HDs are intermediate between those of the Pax-6 and Pax-3/7 classes (although that in Pax-Dam is very close to the latter class) and share splice sites. Pax-Aam, Pax-Bam, and Pax-Dam have an intron at positions corresponding to the first codon of the PD that is also present in a number of other Pax genes, and each of the Acropora Pax homeoboxes contains an intron at a position corresponding to amino acids 46/47 of the HD (these are indicated by inverted triangles in the scheme). Green box, PD; red box, HD; blue circle, octapeptide.