One of the main limits on the pace of discovery of human enhancers has been the difficulty of identifying where they reside in the human genome’s vast noncoding regions. Biologists are now using the preservative power of natural selection to sniff out stretches of noncoding DNA that have been unusually well conserved over long stretches of evolutionary time in the hope of detecting enhancers.
In this article we have been emphasizing changes in enhancers that account for differences among organisms. But it should be easy to appreciate that some enhancers carry out functions that have not changed. While the steady pace of mutation erodes the overall similarity of DNA sequences among species as they diverge, natural selection will maintain the sequences of enhancers that maintain their function, sometimes to an extraordinary degree.
It is common knowledge that lawyers and sharks have a lot of similarities. But who would have guessed that extends to the level of DNA? Yet that is essentially what researchers at the Institute of Molecular and Cell Biology in Singapore and the J. Craig Venter Institute in Rockville, Md., have demonstrated. The team found that despite more than 500 million years of evolution separating sharks and people, we share nearly 5,000 elements in noncoding regions near genes that appear to be enhancers. Remarkably, most of these highly preserved elements are located in the vicinity of body-building genes, reflecting the shared overall body architecture of vertebrates.
Every vertebrate has anatomical features—organs, tissues, cell types, and so forth—that have been preserved throughout their diversification. Over shorter evolutionary distances, the number of shared elements and degree of similarity increases.
The genome-comparison approach is thus rapidly expanding the catalogue of known human, mammalian and vertebrate enhancers and could lead to the identification of sequences involved in the divergence of body forms.
—S.B.C., B.P. and N.G.