Active Jumping Genes Found In A Mammal For The First Time
April Flowers for redOrbit.com – Your Universe Online
Jumping genes, or transposable elements, are strange rogue sequences from which most of our DNA can be traced, but are largely idle in mammals. Johns Hopkins researchers report, however, that they have identified a new DNA sequence moving around in bats. This is the first member of the transposable elements class found to be active in mammals.
The findings of this study, published online at the Proceedings of the National Academy of Sciences website, offer a new means of studying evolution, and may help in developing tools for gene therapy.
“Transposable elements are virtually everywhere in nature, from bacteria to humans,” says Nancy Craig, Ph.D., a Howard Hughes investigator and professor in the Johns Hopkins University School of Medicine’s Department of Molecular Biology and Genetics. “They’re often seen as parasites, replicating themselves and passing from generation to generation without doing anything for their hosts. But in fact they play an important role in fueling adaptation and evolution by adding variability to the genome.”
Jumping genes, as the name suggests, can move from place to place in the genome, sometimes inserting themselves into the middle of another gene. Some jumping genes work by replicating themselves and inserting the copies into new places in the genome. Retroviruses such as HIV are made up of this type of jumping gene, which enables the host cell to be hijacked to make more virus particles. A third class of jumping gene, known as “DNA cut-and-paste,” doesn’t create copies of itself, rather it cuts itself out of one site in the genome before jumping into another. In mammal genomes, most jumping genes are of the copy and paste variety, according to Craig, and most of these are fossils that are mutated to the point they can no longer move around. Until now, even though some remnants of cut-and-paste jumping genes have been unearthed in mammals, they have all been inactive.
The Hopkins research team was studying piggyBac, an active cut-and-paste jumping gene in insects when they made the discovery. PiggyBac hitches a ride from one host to another on a virus, which is how it got its name. The research team used computational methods to search for piggyBac-like DNA sequences in the genome of some species – such as the little brown bat – while studying how the jumping gene works. They found a sequence similar to piggyBac without any of the mutations that would render it inactive. Near identical copies were sprinkled throughout the genome, indicating a relatively recent jump for the sequence. Craig named the new sequence piggyBat, which has been found to be able to move within bat cells, other mammalian cells and yeast. This reveals that it is a still-active DNA element.
Craig explains that many species have developed systems to decrease the frequency of movement for jumping genes. Some of these systems are a component of immunity, protecting mammals from retroviruses, as well as from the risk that jumping genes will wreak havoc by interrupting an important gene.
Most mammalian jumping genes have been rendered inactive by these systems. Finding that a bat species is host to an active jumping gene, combined with the fact that bats are very susceptible to viruses, indicates that the systems to protect us from dangerous genetic material are not as well developed as in bats, according to Craig. The discovery of piggyBat “opens up a window for studying jumping gene regulation in a mammal where the element is still active,” she says.
Future research will focus on the workings of jumping genes themselves, as well as the protective systems that keep them in check. Her group hopes to ultimately custom-design jumping genes that can be used for targeted, safe and effective gene therapy.