A large-scale enhancer detection screen was performed in the zebrafish using a 
retroviral vector carrying a basal promoter and a fluorescent protein reporter 
cassette. Analysis of insertional hotspots uncovered areas around developmental 
regulatory genes in which an insertion results in the same global expression 
pattern, irrespective of exact position. These areas coincide with vertebrate 
chromosomal segments containing identical gene order; a phenomenon known as 
conserved synteny and thought to be a vestige of evolution. Genomic comparative 
studies have found large numbers of highly conserved noncoding elements (HCNEs) 
spanning these and other loci. HCNEs are thought to act as transcriptional 
enhancers based on the finding that many of those that have been tested direct 
tissue specific expression in transient or transgenic assays. Although gene 
order in hox and other gene clusters has long been known to be conserved because 
of shared regulatory sequences or overlapping transcriptional units, the 
chromosomal areas found through insertional hotspots contain only one or a few 
developmental regulatory genes as well as phylogenetically unrelated genes. We 
have termed these regions genomic regulatory blocks (GRBs), and show that they 
underlie the phenomenon of conserved synteny through all sequenced vertebrate 
genomes. After teleost whole genome duplication, a subset of GRBs were retained 
in two copies, underwent degenerative changes compared with tetrapod loci that 
exist as single copy, and that therefore can be viewed as representing the 
ancestral form. We discuss these findings in light of evolution of vertebrate 
chromosomal architecture and the identification of human disease mutations.