The Antennapedia-type homeobox genes have evolved from three precursors separated early in metazoan evolution.

The developmental control genes containing an Antennapedia-type homeobox are clustered in insects and vertebrates. The evolution of these genes was studied by the construction of evolutionary trees and by statistical geometry in sequence space. The comparative analysis of the homeobox sequences reveals the subdivision of the Antennapedia-type homeobox genes into three classes early in metazoan evolution. This observation suggests an important function of these genes even in the most primitive metazoans. Subsequent duplication events generated a cluster of at least five homeobox genes in the last common ancestor of insects and vertebrates. These genes later independently gave rise to the 13 groups of paralogous genes in vertebrates and to the 11 Antennapedia-type genes in the Drosophila complexes.