Ultraconserved element

Researchers originally assumed that perfect conservation of these long stretches of DNA implied evolutionary importance, as these regions appear to have experienced strong negative (purifying) selection for 300-400 million years. More recently, this assumption has been replaced by two main hypotheses: that UCEs are created through a reduced negative selection rate, or through reduced mutation rates, also known as a "cold spot" of evolution. However, affected phenotypes were only caused by 112 of these polymorphisms, most of which were located in coding regions of the UCEs. Affected mice were fertile and targeted screens of the nearby coding genes showed no altered phenotype. Computational analysis of human ultraconserved noncoding elements (UCNEs) found that the regions are enriched for A-T sequences and are generally GC poor. However, the UNCEs were found to be enriched for CpG, or highly methylated. This may indicate that there is some change to DNA structure in these regions favoring their precise retention, but this possibility has not been validated through testing. == Function ==

Often, ultraconserved elements are located near transcriptional regulators or developmental genes performing functions such as gene enhancing and splicing regulation. A study comparing ultraconserved elements between humans and the Japanese puffer fish Takifugu rubripes proposed an importance in vertebrate development. Some UCEs are not transcribed, and are referred to as ultraconserved noncoding elements. Indeed, UCEs are often affected by copy number variation in cancer cells much more than in healthy contexts, suggesting that altering the copy number of T-UCEs may be deleterious. == Role in human disease ==

Research has demonstrated that T-UCRs have a tissue-specific expression, and a differential expression profile between tumors and other diseases. The tables below highlight transcripts and polymorphisms within UCRs that have been shown to contribute to human diseases. Regulation mechanisms of disease related ultraconserved element transcripts Phenotype-associated polymorphisms within ultraconserved elements == See also ==