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Mobile DNA part of evolution's toolbox

at the University of California, Berkeley, postdoctoral fellow Nadav Ahituv combined the human version of the LF-SINE sequence with a "reporter" gene that would produce an easily recognizable protein if the LF-SINE were serving as its on-off switch. He then injected the resulting DNA into the nuclei of fertilized mouse eggs. Eleven days later, he examined the mouse embryos to see whether and where the reporter gene was switched on. Sure enough, the gene was active in the embryos' developing nervous systems, as would be expected if the LF-SINE copy were regulating the activity of ISL1.

The discoverer of mobile DNA elements, Barbara McClintock, suggested in 1950 that they might play a role in the regulation of genes -- a hypothesis that was more fully developed by Roy Britten and Eric Davidson in about 1970, when it was discovered that more than half of the human genome consists of remnants of mobile elements. But the mechanisms underlying this process remained obscure. Haussler's work provides direct evidence that even when they land at some distance from a gene, mobile elements like SINEs can be adapted to serve as regulatory elements that have powerful effects in their new locations. "When you activate a gene in a new context," Bejerano points out, "you get processes that did not occur before."

Bejerano and Haussler's results support the hypothesis that the movement of retroposons can generate evolutionary experiments by adding new regulatory modules to genes. Most of these experiments will have no effects or will harm an organism. But every once in a while, the movement of a regulatory element will give an organism an evolutionary advantage. "And to the extent that [such changes] improve the fitness of an organism," says Haussler, "they eventually will become fixed in a population."

"This suggests a lot of exciting evolutionary avenues," says Haussler, "but we don't yet know how prevalent this kind of evolution is." Other labs have found
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
2-May-2006


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