Sequence conservation

In evolutionary biology, conserved sequences are similar or identical sequences in nucleic acids (DNA and RNA), proteins, or polysaccharides across species (orthologous sequences) or within different molecules produced by the same organism (paralogous sequences). Conservation across species indicates that a sequence has been maintained by evolution despite speciation. A highly conserved sequence is one that has remained unchanged far back up the phylogenetic tree, and hence far back in geological time. For example, the homeobox sequences have been conserved across different phyla including the arthropods (such as fruit flies) and vertebrates (such as mice and humans), so these sequences have remained little changed since the Cambrian explosion of animal body plans some 500 million years ago. Parts of the 16S and 23S ribosomal RNA genes have been identified as the most conserved DNA sequences across the domains of life. Highly conserved regions typically indicates that natural selection has continually eliminated forms with mutations in that sequence.

Highly conserved DNA sequences are thought to have functional value. The role for many of these highly conserved non-coding DNA sequences is not understood. Ultra-conserved elements or sequences (UCEs or UCRs, ultra-conserved regions) that share 100% identity among human, mouse and rat were first described by Bejerano and colleagues in 2004. One recent study that eliminated four highly conserved non-coding DNA sequences in mice yielded viable mice with no significant phenotypic differences; the authors described their findings as "unexpected". Many regions of the DNA, including highly conserved DNA sequences, consist of repeated sequence elements. One possible explanation of the null hypothesis above is that removal of only one or a subset of a repeated sequence could theoretically preserve phenotypic functioning on the assumption that one such sequence is sufficient and the repetitions are superfluous to essential life processes; it was not specified in the paper whether the eliminated sequences were repeated sequences. Although most of the conserved sequences' biological function is still unknown, few conserved sequences derived transcripts showed that their expression is deregulated in human cancer tissues.

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