The right move
The discovery of a giant transposable element may lead to breakthroughs in gene therapy
Nematodes, sea urchins and clawed frogs have something in common with the scrumptious Dover sole served up in pricey restaurants, and no sense making you guess. Their genomes are all full of Mavericks, a newly discovered, giant-sized transposable element.
Transposable elements, or transposons, are mobile genetic elements that jump around in genomes. Biology Assistant Professor Ellen Pritham likens a genome to an ecosystem. Each chromosome is a distinct geographic locale teeming with populations of these mobile elements.
In science, the honor of naming goes to the discoverer. Because the bold and distinctive little movers were discovered at UT Arlington, Dr. Pritham and her husband, biology Assistant Professor Cédric Feschotte, named them after UT Arlington’s mascot.
Nearly every organism’s genome has active transposable elements. About half of the human genome is made up of these “jumping genes.” The transposon’s movement may or may not affect genes. If it does, the impact can be positive or it can lead to disease, including cancer.
“Transposable elements are thought to have no function,” Pritham said. “They are just the baggage carried along by the genome.”
She and Dr. Feschotte were working on the genome of a disease-causing organism called Trichomonas vaginalis when they discovered the new group of mobile genetic elements.
“One very distinctive feature is their size,” Pritham said. “You could safely say they are eight to 10 times bigger than any other mobile element ever reported. So big, in fact, that together they comprise one-third of the Trichomonas genome.”
The missing link?
The professors and undergraduate student Tasneem Putliwala published a journal article in the August 2006 issue of GENE that detailed how they used computational tools to pinpoint the presence of Mavericks in the genomes of animals as diverse as worms, beetles and fish and in the human parasite Trichomonas vaginalis, where they amount to more than 1,000 copies.
While Mavericks do not inhabit the human genome, their presence in Trichomonas vaginalis is responsible for one of the most widespread sexually transmitted diseases worldwide, trichomoniasis.
“What we learn about transposable elements in the genome of Trichomonas could help us understand how pathogens can change quickly and how they can become resistant to drugs and chemicals,” Pritham said.
Mavericks appear to be evolutionary and related to adenoviruses, which infect humans and other mammals and have been harnessed as a promising tool for gene therapy. Studying the way Mavericks move within the genome will likely give researchers much more information about adenovirus replication in humans. Pritham and Feschotte further hypothesize that Mavericks represent a missing evolutionary link between seemingly disparate invasive DNA elements such as adenoviruses, plasmids and bacteriophages, the viruses that infect bacteria.
The first transposons were discovered in the 1940s by Barbara McClintock, the third woman elected to the National Academy of Sciences. Dr. McClintock’s work on the structure, formation and function of cells (cytogenetics) of corn led her to theorize that genes can move around, an inference she drew by observing changing patterns of coloration in corn kernels.
Many scientists gave little credence to the theory or thought it had no implications for anything but corn. Eventually, other scientists confirmed McClintock’s breakthrough and expanded her findings to many organisms. She received the Nobel Prize in 1983.
Research takes flight
Feschotte and Pritham, who met at the University of Georgia and married in 2004, may be the only husband and wife team focused on transposon research. The partnership assures that work is not left behind at the end of the day. One evening they were sitting on the couch after dinner perusing a scientific journal when they read an article by a scientist identifying—incorrectly, they believed—a new family of genes.
“We were up all night, identifying elements,” Pritham said. Turns out the researcher was indeed incorrect. The DNA sequences were not new genes, but part of giant and selfish mobile elements.
Lately, the duo’s research has focused on bats. In the Feb. 6 issue of Proceedings of the National Academy of Sciences, they report on their latest discovery: the massive proliferation of rolling-circle transposons, or Helitrons, in a small brown bat, Myotis lucifugus, also called a vesper bat. Helitrons are another newly recognized group of transposable elements that previously had been identified only in the genomes of plants, invertebrates and zebrafish.
“This is the first time that Helitrons were discovered in a mammalian genome,” Feschotte said. “This is exciting because these types of elements are known in plants to cause numerous chromosomal rearrangements and to shuffle genes around as they move within the genome.”
Pritham and Feschotte got to name those elements as well, christening them HeliBats. In their preliminary analysis of the bat genome sequence, they found an amazing quantity of HeliBats—more than 115,000 distinct copies, the largest number of Helitrons ever reported in any species. It was not an overnight invasion. Sequence divergence and cross-species analysis indicate that HeliBats have amplified within the last 30 million-36 million years and are restricted solely to the lineage of vesper bats.
Feschotte said the mammalian transposable element landscape has been finely delineated for the genomes of humans, mice, rats and dogs. With graduate student John Pace, he recently established the first comprehensive catalog of human DNA transposons. The study published in the April issue of Genome Research shows that the human genomic landscape is rich in varied types of DNA transposons, but no Helitrons have been identified.
Furthermore, only retrotransposons are known to be recently active in humans and rodents. There has been no evidence of any primate DNA transposons jumping within the last 50 million years. In contrast, Helitrons and many other DNA transposons have exploded in the vesper bat lineage.
Among mammals, only rodents are more speciose than bats. Among bats, the vesper has the largest number of species as well as the broadest geographic distribution.
“The impact that HeliBats may have played in altering the genome organization and contributing to the extraordinary diversification of bats is a fascinating question that we are now actively pursuing,” Feschotte said.
And one that may impact gene therapy.
— Sue Stevens