The Questions of Developmental Biology

Changes in Hox gene number
The number of Hox genes may play a role in permitting the evolution of complex
structures. All invertebrates have a single Hox complex per haploid genome. In the most simple
invertebrates such as sponges there appear to be only one or two Hox genes in this complex
(Degnan et al. 1995; Schierwater and Kuhn 1998). In the more complex invertebrates, such as
insects, there are numerous Hox genes in this complex. Comparing the Hox genes of chordates,
arthropods, and molluscs suggests that there was a common set of seven Hox genes in the
Urbilaterian ancestor of the protostomes and deuterostomes. Indeed, in invertebrate
deuterostomes (echinoderms and amphioxus, an invertebrate chordate), there is only one Hox
complex, which looks very much like that of the insects (Figure 22.11; Holland and Garcia-
Fernández 1996). By the time the earliest vertebrates (agnathan fishes) evolved, there were at
least four Hox complexes. The transition from amphioxus to early fish is believed to be one of the
major leaps in complexity during evolution (Amores et al. 1998; Holland 1998). This transition
involved the evolution of the head, the neural crest, new cell types (such as osteoblasts and
odontoblasts), the brain, and the spinal cord. As we saw in Chapter 11, the regionalization of the
brain and spinal cord is dependent upon Hox genes, and the regional specification of the somitic
segments depends upon the paralogous members of the different Hox clusters. For instance,
deletions of Hoxa-3 (from the A cluster) affect the neural crest-derived glands of the neck;
deletions of Hoxd-3 (its paralogue from the D cluster) affect the somite-derived skeleton of the
neck. This distinction may be due to the different levels of expression of these genes within the
same tissues (Greer et al. 2000). Holland (1998) speculates that the generation of these new
structures was allowed by the fourfold duplication of the Hox gene complex.
*The reason for this remarkable conservation of structure in the Hox gene complex is thought to be the
sharing of cis-regulatory regions by neighboring genes. If a Hox gene is moved to a different region within the
complex, its regulation is altered. The critical regulatory regimes might be the binding sites for the Polycomb proteins.
These proteins are also conserved throughout evolution, and they silence the Hox genes at specific times and places.
Here, then, we see a "phyletic constraint" at the molecular level (Chiang et al. 1995; Müller et al. 1995; Kmita et al.
2000).