Fig. 5. Transitions in the structural evolution of Hox clusters. From the starting type D cluster (red, as in Fig. 4), transitions to type S and, subsequently, to type A `clusters' (downward) are easy to imagine, and could occur concomitantly with the loss of those constraints that keep genes together. These transitions do not call for any particular mechanism other than the occurrence of chromosomal breakpoints. In some cases, these breaks might be beneficial, along with the evolution of an organism towards a different developmental mode for which clustered Hox genes might be an obstacle rather than a solution (see the text). The arrows towards the top illustrate the mechanism of cluster consolidation, which might occur together with genome duplication. Duplication of the locus allows for more (or for different) global regulations to evolve, which in turn further consolidate the various clusters. In this scheme, a meta-cis structure must exist before genome duplication to provide the basis for further co-options. The color code illustrates the passage from a type D to a type O cluster (see also the `consolidation model' in Fig. 4).