Ultraconserved elements (UCEs) are strongly depleted from segmental duplications 
and copy number variations (CNVs) in the human genome, suggesting that deletion 
or duplication of a UCE can be deleterious to the mammalian cell. Here we 
address the process by which CNVs become depleted of UCEs. We begin by showing 
that depletion for UCEs characterizes the most recent large-scale human CNV 
datasets and then find that even newly formed de novo CNVs, which have passed 
through meiosis at most once, are significantly depleted for UCEs. In striking 
contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted 
for UCEs and can even become significantly enriched. This observation raises the 
possibility that CNVs that arise somatically and are relatively newly formed are 
less likely to have established a CNV profile that is depleted for UCEs. 
Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the 
diseased state. In support of this latter explanation, somatic CNVs that are not 
associated with disease are depleted for UCEs. Finally, we show that it is 
possible to observe the CNVs of induced pluripotent stem (iPS) cells become 
depleted of UCEs over time, suggesting that depletion may be established through 
selection against UCE-disrupting CNVs without the requirement for meiotic 
divisions.