Model of zic gene evolution. (A) gli and glis genes were probably present at the base of the metazoan tree (A, green circle). A duplication event occurred either at the base of the Metazoa (A, blue circle 1) or in the last common ancestor of placozoans/cnidarians/bilaterians (A, blue circle 2), which gave rise to the zic sub-family. According to this phylogeny placozoans probably lost the gli/glis/nkl-like gene(s) (A, orange hexagon). The nkl family radiated prior to the cnidarian and bilaterian divergence (A, magenta square). (B) The Zic 1-3 odd paired conserved (ZOC) domain was present in the common ancestor of the bilaterians and cnidarians, but may have emerged in the placozoan/cnidarian/bilaterian common ancestor (B, red boxes with question mark). The ZF-NC domain probably arose in, or just prior to, the cnidarian/bilaterian common ancestor (B, green box).