Getting the proto-Pax by the tail.

Pax genes encode transcription factors governing the determination of different cell types and even organs in the development of multicellular animals. Pax proteins are characterized by the presence of three evolutionarily conserved elements: two DNA-binding domains, the paired domain (PD) and paired-type homeodomain (PtHD), and the short octopeptide sequence (OP) located between PD and PtHD. PD is the defining feature of this class of genes, while OP and/or PtHD may be divergent or absent in some members of the family. Phylogenetic analyses of the PD and PtHD sequences do not distinguish which particular type of the extant Pax genes more resembles the ancestral type. Here we present evidence for the existence of a fourth evolutionarily conserved domain in the Pax proteins, the paired-type homeodomain tail (PHT). Our data also imply that the hypothetical proto-Pax protein most probably exhibited a complex structure, PD-OP-PtHD-PHT, which has been retained in the extant proteins Pax3/7 of the ascidia and lancelet, and Pax7 of the vertebrates. Finally, based on structural considerations, a scenario for the evolutionary emergence of the proto-Pax gene is proposed.