Insect genomes contain larger blocks of conserved gene order (microsynteny) than 
would be expected under a random breakage model of chromosome evolution. We 
present evidence that microsynteny has been retained to keep large arrays of 
highly conserved noncoding elements (HCNEs) intact. These arrays span key 
developmental regulatory genes, forming genomic regulatory blocks (GRBs). We 
recently described GRBs in vertebrates, where most HCNEs function as enhancers 
and HCNE arrays specify complex expression programs of their target genes. Here 
we present a comparison of five Drosophila genomes showing that HCNE density 
peaks centrally in large synteny blocks containing multiple genes. Besides 
developmental regulators that are likely targets of HCNE enhancers, HCNE arrays 
often span unrelated neighboring genes. We describe differences in core 
promoters between the target genes and the unrelated genes that offer an 
explanation for the differences in their responsiveness to enhancers. We show 
examples of a striking correspondence between boundaries of synteny blocks, HCNE 
arrays, and Polycomb binding regions, confirming that the synteny blocks 
correspond to regulatory domains. Although few noncoding elements are highly 
conserved between Drosophila and the malaria mosquito Anopheles gambiae, we find 
that A. gambiae regions orthologous to Drosophila GRBs contain an equivalent 
distribution of noncoding elements highly conserved in the yellow fever mosquito 
Aëdes aegypti and coincide with regions of ancient microsynteny between 
Drosophila and mosquitoes. The structural and functional equivalence between 
insect and vertebrate GRBs marks them as an ancient feature of metazoan genomes 
and as a key to future studies of development and gene regulation.