Traveling Genes

Mobile DNA Elements Can Disrupt Gene Expression

David SymerThe many short pieces of mobile DNA that exist in the genome can contribute to significant biological differences between lineages of mice, a study at the OSUCCC – James has shown.

These movable pieces are called transposons or “jumping genes” because they can migrate from one chromosomal location to another. Unlike viruses, they are not infectious and do not move from cell to cell. They have accumulated over time in the genomes of mice and humans and now constitute about half of genomic DNA in both.

For this study, researchers mapped the genomic locations of transposons called endogenous retroviruses (ERVs) in diverse mouse strains and compared thosetrains to learn how ERVs might influence gene expression. They found that ERVs can significantly disrupt expression by prematurely halting gene transcription, even when the ERV is more than 12,000 base pairs away in the same chromosome. They also found that the disruptive influence is affected by the gender of the parent who supplied the ERV.

“These findings add an interesting new angle to our understanding of fundamental mechanisms of natural variation and human biology, and possibly cancer and other diseases,” says principal investigator David Symer, MD, PhD, a member of the Viral Oncology Program at the OSUCCC – James.

A mouse gene containing an ERV inherited from the father often produced only an incomplete, truncated form of messenger RNA (mRNA); if the ERV came from the mother, not only the truncated transcript but also nearly normal levels of the full-length mRNA were produced from the gene.

“We believe this is an unusual, interesting example of a well-known phenomenon called DNA imprinting,” Symer says. “We are now conducting experiments to understand how premature termination of gene expression can be triggered by the transposons, and also how the parent-of-origin effect occurs.”

Published in the journal Genome Research.

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