Ultraconserved elements (UCEs) are sequences that are identical between 
reference genomes of distantly related species. As they are under negative 
selection and enriched near or in specific classes of genes, one explanation for 
their ultraconservation may be their involvement in important functions. Indeed, 
many UCEs can drive tissue-specific gene expression. We have demonstrated that 
nonexonic UCEs are depleted among segmental duplications (SDs) and copy number 
variants (CNVs) and proposed that their ultraconservation may reflect a 
mechanism of copy counting via comparison. Here, we report that nonexonic UCEs 
are also depleted among 10 of 11 recent genomewide data sets of human CNVs, 
including 3 obtained with strategies permitting greater precision in determining 
the extents of CNVs. We further present observations suggesting that nonexonic 
UCEs per se may contribute to this depletion and that their apparent dosage 
sensitivity was in effect when they became fixed in the last common ancestor of 
mammals, birds, and reptiles, consistent with dosage sensitivity contributing to 
ultraconservation. Finally, in searching for the mechanism(s) underlying the 
function of nonexonic UCEs, we have found that they are enriched in TAATTA, 
which is also the recognition sequence for the homeodomain DNA-binding module, 
and bounded by a change in A + T frequency.