Ultraconserved elements in the genome: Are they indi...( BERKELEY CA -- Three years ago ultr...)

BERKELEY, CA -- Three years ago, "ultraconserved elements" were discovered in the genomes of mice, rats, and humans. These are DNA sequences 200 base pairs in length or longer -- some are over 700 base pairs long showing 100-percent identity among the three species. They have been perfectly conserved since the last common ancestor of mice, rats, and humans, which lived some 85 million years ago.

These and other highly conserved sequences are thought to have persisted with little or no change because they are indispensable, performing functions vital for viability or reproduction. Scientists in the Genomics Division of the Department of Energy's Lawrence Berkeley National Laboratory and DOE's Joint Genome Institute set out to test this hypothesis by engineering four different "knockout" mice, each lacking one selected ultraconserved element.

If truly indispensable, mice lacking an ultraconserved element should either die or be unable to produce viable offspring. Remarkably, as the researchers report in the September, 2007 issue of PLoS Biology, the knockout mice in this study showed almost no ill effects at all.

"For us, this was a really surprising result," says Nadav Ahituv of Berkeley Lab's Genomics Division and DOE's JGI, a human geneticist who led the experiment. "We fully expected to demonstrate the vital role these ultraconserved elements play by showing what happens when they are missing. Instead, our knockout mice were not only viable and fertile but showed no critical abnormalities in growth, longevity, pathology, or metabolism."

Edward Rubin, Director of the Joint Genome Institute and Berkeley Lab's Genomics Division, who directed the study, said, "Many scientists had speculated that the reason for absolute identity of sequences over the 80 million years since humans and rodents diverged was that these sequences are crucial for life: if a base changes, the organism would die, so that's why we see absolutely n
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