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Genetic Stowaways May Contribute To Evolutionary Change: Adjacent Sequences Tag Along With Mobile DNA Elements, Study Shows

assistant professor of human genetics and internal medicine at the University of Michigan Medical School. "This mechanism, however, provides a relatively straightforward and powerful means for generating genomic diversity."

Working with a family of retrotransposons called long interspersed nuclear elements, also known as LINE-1s or L1s, the scientists performed two groups of experiments in cultured human cells. Between 30 and 60 active L1s are estimated to exist within the human genome. Other species, such as the mouse, are thought to have as many as 3,000 such elements in their DNA.

The aim of the first experiments was to discover whether L1s retrotranspose efficiently into genes and, if so, how often. To do this, the investigators engineered an L1 to include a marker sequence that would only be activated when the mobile L1 inserted itself into a working gene, a gene subject to transcription. The results showed that a minimum of 6 percent of all retrotransposition events effectively targeted genes. Because the total fraction of the human genome estimated to be functioning genes is only about 15 percent, this finding suggests little or no bias against genes as sites for retrotransposition.

The second set of experiments was designed to ascertain whether L1s are capable of copying and moving DNA sequences adjacent to themselves during retrotransposition. Earlier results had suggested this possibility, beginning with the surprising observation that a flanking sequence had accompanied an instance of retrotransposon insertion into the gene responsible for Duchenne's muscular dystrophy. Additional examples of such stowaway DNA with the L1s were subsequently found.

"Several years ago, we found a retrotransposon insertion into a dystrophin gene that carried about 600 base pairs of flanking sequence," says Kazazian. "When we looked elsewhere in the genome for the precursor of that insertion, we found that same 600 base pairs w
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Contact: Franklin Hoke
hokef@mail.med.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
5-Mar-1999


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