Homeobox cluster genes (Hox genes) are highly conserved and can be use
fully employed to study phyletic relationships and the process of evol
ution itself. A phylogenetic survey of Hox genes shows an increase in
gene number in some more recently evolved forms, particularly in verte
brates. The gene increase has occurred through a two-step process invo
lving first, gene expansion to form a cluster, and second, cluster dup
lication to form multiple clusters. We also describe data that suggest
s that non-sox genes may be preferrentially associated with the Hox cl
usters and raise the possibility that this association may have an ada
ptive biological function. Hox gene loss may also play a role in evolu
tion. Hox gene loss is well substantiated in the vertebrates, and we i
dentify additional possible instances of gene loss in the echinoderms
and urochordates based on PCR surveys. We point out the possible adapt
ive role of gene loss in evolution, and urge the extension of gene map
ping studies to relevant species as a means of its substantiation.