Fish-mammal genomic comparisons have proved powerful in identifying conserved 
noncoding elements likely to be cis-regulatory in nature, and the majority of 
those tested in vivo have been shown to act as tissue-specific enhancers 
associated with genes involved in transcriptional regulation of development. 
Although most of these elements share little sequence identity to each other, a 
small number are remarkably similar and appear to be the product of duplication 
events. Here, we searched for duplicated conserved noncoding elements in the 
human genome, using comparisons with Fugu to select putative cis-regulatory 
sequences. We identified 124 families of duplicated elements, each containing 
between two and five members, that are highly conserved within and between 
vertebrate genomes. In 74% of cases, we were able to assign a specific set of 
paralogous genes with annotation relating to transcriptional regulation and/or 
development to each family, thus removing much of the ambiguity in identifying 
associated genes. We find that duplicate elements have the potential to 
up-regulate reporter gene expression in a tissue-specific manner and that 
expression domains often overlap, but are not necessarily identical, between 
family members. Over two thirds of the families are conserved in duplicate in 
fish and appear to predate the large-scale duplication events thought to have 
occurred at the origin of vertebrates. We propose a model whereby gene 
duplication and the evolution of cis-regulatory elements can be considered in 
the context of increased morphological diversity and the emergence of the modern 
vertebrate body plan.