One possible scenario for the evolution of hh and hh-related genes in metazoa. Different phylogenetic branches are outlined, and gene families known at present are shown. Dotted lines indicate uncertain evolutionary connections. Hedgling genes are currently known only from sponges and Cnidaria [8, 10, 19]. The Hh family could have originated in two possible ways. (a) The Hedge domain evolved concomitantly with the Hog domain from a protist Hog protein before the emergence of the Metazoa. A duplication of the Hedge domain and merger with an extracellular protein gave rise to the Hedgling gene. (b) No hh gene existed at the emergence of sponges. The Hedge domain of a Hedgling gene duplicated and merged with a Hog gene to give rise to hh in early Eumetazoa. Cnidaria, Lophotrochozoa and nematodes contain both Hh as well as other Hog family genes. The phylogenetic analysis cannot unequivocally resolve whether these other families originated from a single ancestor in Eumetazoa - as shown here with dotted lines - or whether, at least in some phyla, duplication and divergence from a hh gene gave rise to new families in particular phyla.