Homeotic (Hox) genes are usually clustered and arranged in the same order as 
they are expressed along the anteroposterior body axis of metazoans. The 
mechanistic explanation for this colinearity has been elusive, and it may well 
be that a single and universal cause does not exist. The Hox-gene complex 
(HOM-C) has been rearranged differently in several Drosophila species, producing 
a striking diversity of Hox gene organizations. We investigated the genomic and 
functional consequences of the two HOM-C splits present in Drosophila buzzatii. 
Firstly, we sequenced two regions of the D. buzzatii genome, one containing the 
genes labial and abdominal A, and another one including proboscipedia, and 
compared their organization with that of D. melanogaster and D. pseudoobscura in 
order to map precisely the two splits. Then, a plethora of conserved noncoding 
sequences, which are putative enhancers, were identified around the three Hox 
genes closer to the splits. The position and order of these enhancers are 
conserved, with minor exceptions, between the three Drosophila species. Finally, 
we analyzed the expression patterns of the same three genes in embryos and 
imaginal discs of four Drosophila species with different Hox-gene organizations. 
The results show that their expression patterns are conserved despite the HOM-C 
splits. We conclude that, in Drosophila, Hox-gene clustering is not an absolute 
requirement for proper function. Rather, the organization of Hox genes is 
modular, and their clustering seems the result of phylogenetic inertia more than 
functional necessity.