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Analysis uncovers critical stretches of human genome

Hundreds of stretches of DNA may be so critical to life's machinery that they have been "ultra-conserved" throughout hundreds of millions of years of evolution. Researchers have found precisely the same sequences in the genomes of humans, rats, and mice; sequences that are 95 to 99 percent identical to these can be found in the chicken and dog genomes, as well.

Most of these ultra-conserved regions do not appear to code for proteins, but may instead play a regulatory role. Evolutionary theory suggests these sequences may be so central to mammalian biology that even small changes in them would compromise an animal's fitness.

Led by Howard Hughes Medical Institute investigator David Haussler, at the University of California at Santa Cruz, the researchers published their findings online May 6, 2004, in Science Express, the Web counterpart of the journal Science. The lead author on the paper was Gill Bejerano in Haussler's laboratory. Also co-authoring the paper were John Mattick and his colleagues from the University of Queensland in Australia.

"It's extraordinarily exciting to think that there are these ultra-conserved elements, so many of which are near well-studied genes, that weren't noticed by the scientific community before because we didn't have the comparative data that highlighted these regions," said Haussler. "The real credit goes to the prodigious efforts in sequencing these multiple genomes, which have given us this tremendous opportunity, opening our eyes to these very unusual genomic elements," he said.

According to Haussler, the researchers were launched on their analysis when initial studies hinted at major regions of conserved DNA sequences. "When we had compared the human and mouse genomes, we found that about five percent of each of these showed some kind of evolutionary selection that partially preserved the sequence," he said. "We got excited about this because only about 1.5 percent of the human genome codes for
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
6-May-2004


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