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Ultraconserved elements in the genome: Are they indispensable?
Date:9/4/2007

Instead of the expected drastic results, however, all four lines produced normal litters of healthy mice. Their weight was normal during 10 weeks of monitoring; the mice were watched for six months (and by now, many have been watched much longer) and not only survived but thrived. They were subjected to numerous clinical assays with no signs of abnormality, and no significant differences compared to the wild-type controls.

If not crucial, why conserved?

"There is plenty of evidence that highly conserved sequences do perform vital functions," says Ahituv. "Indeed, locating noncoding sequences that have been unchanged by evolution is one of the main tools scientists use to find important functional elements in a genome."

While it's conceivable that conserved sequences are somehow immune to mutations for reasons that have nothing to do with evolutionary pressures, the mechanism of such "sequence armoring" is hard to imagine. The 731-base pair sequence, uc467, should normally have accumulated some 334 nucleotide changes in the more than 80 million years that mice, rats, and humans have been evolving along separate paths.

Much more plausible is the assumption that these identical DNA sequences persist because nucleotide substitutions in them would render the organism less fit; thus evolution selects against them. So why don't problems show up immediately in mice that are missing a conserved sequence"

"Evolution and natural selection do not happen overnight," says Len Pennacchio, a Berkeley Lab senior scientist who is one of the primary authors of the study. "The deletion of these elements likely has relatively mild effects on fitness that are gradually selected against over time -- several or more generations from when they arise -- but not on observable time scales. The observation is that ultraconserved elements do not tolerate substitions since their last common ancestor over 80 million years ago -- but this
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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert

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