Genetic Elements on the Move in More Ways Than One, a Department of Health Researcher Finds

Albany, April 27 – Non–coding DNA sequences that roam genomes, moving from one location and inserting themselves in another, have more options for landing sites than once thought. The mobility of these genetic elements, called introns, can have dire consequences for an organism, such as when one alights in the midst of a critical gene, disrupting its function.

Until now it was thought that introns could only "go home again." Specifically, when genomes are paired, and only one has an intron, the "homing" mechanism was thought to always return the intron to the same place in the other genome. In the April 27 issue of Nature, a Department of Health scientist has demonstrated for the first time what had only been suggested circumstantially: Introns can also move to new sites in the genome, and they accomplish this by transposition, a mechanism distinct from homing. Both of these mechanisms are mediated by RNA. Because introns move using their RNA, they are called retroelements, much like some RNA viruses are called retroviruses.

Marlene Belfort, Ph.D., one of the discoverers of introns in bacteria and a member of the National Academy of Sciences, is the paper's senior author. Her group's findings reinforce the idea that DNA is not cast in immutable form, but evolves. When introns careen around a genome, the organism either adapts to the intrusion and survives, or fails to adapt and becomes ill or dies.

Dr. Belfort and her team investigated group II introns in Lactococcus lactis, a harmless, easy–to–grow bacterium found in milk. "These studies give us a model system for investigating questions of how organisms adapt to unfavorable genetic events. We can identify cells that have adapted, and learn from them," says Dr. Belfort, who is director of the Division of Genetic Disorders at Wadsworth Center, the Department's public health research laboratory. The paper, "Retrotransposition of a bacterial group II intron," is particularly important because group II introns are the likely progenitors of nuclear introns found in higher organisms, including mammals. They and related elements, called L1 retrotransposons, constitute as much as 30 percent of the human genome. Missteps by these retrotransposons are associated with several blood and cardiac disorders, as well as colon cancer and Duchenne muscular dystrophy.

Introns had been dismissed as "junk DNA" because they intervene between the real genetic jewels, protein–coding sequences or exons. In a disappearing act worthy of Houdini, introns turn themselves into loops, or lariats, then cut themselves out of the linear genetic sequence after it has been transcribed into RNA. This allows the exons to splice together and become the template for messenger RNA, the precursor of proteins, the molecular workhorses of life. Group II introns, true survivalists, are further distinguished by their selfish ability to catalyze their own reaction; they literally encode the RNA and proteins needed to splice and move. It now appears as if they are even more selfish than once thought: like self–absorbed conversationalists, they will insert themselves given almost any opening.