Molecular Geneticist Wins NSF CAREER Award
R. Keith Slotkin, assistant professor, molecular genetics, just received the National Science Foundation’s highest award for the country’s most promising young scientists, the NSF CAREER Award. These grants are given to researchers who early in their careers have clearly demonstrated their potential for making significant discoveries in their fields. Slotkin studies transposable elements, sometimes called “jumping genes,” that are stretches of DNA that can duplicate or move from one location in the genome to another.
“These are fragments of DNA that reside in the genomes of multicellular organisms,” Slotkin said. “They’re not considered actual genes, but they’re like little genomic parasites. They are out only to duplicate themselves--not to help the organism they reside in.”
Their highly-successful ability to do just that has resulted in transposable elements occupying vast amounts of most plant and animal genomes. “For example, they occupy nearly half of the human genome, and 85% of corn,” Slotkin said.
In Arabidopsis thaliana, the plant that Slotkin and his students work on, transposable elements account for 20% of the genome.
Although often overlooked or dismissed as “junk DNA,” transposable elements have played an important role in the structure and evolution of these genomes.
One of the key questions is why transposable elements have been conserved through time.
“Maybe,” Slotkin said, “they have a key function in the organism. But we don’t yet know whether they are pure parasites or have another function.
“But we do know that when transposable elements are active—that is when they ‘jump,’ they cause damage, which includes chromosome breakage, instability, and disease and can destroy an organism very quickly from inside.”
It is no wonder that an organism puts a lot of its energy into suppressing or silencing transposable elements. To be successful, an organism must be able to determine which stretches of its genome are transposable elements and then shut them down.
This leads to questions of how a cell can tell transposable elements and regular genes apart and how a cell knows when to initiate silencing. The detailed molecular mechanism of how a cell determines which regions of DNA are composed of transposable elements, and how the silencing of transposable elements is initiated, are the key topics being addressed in the new NSF grant.
“Once they are silenced,” Slotkin said, “the organism is very good at keeping them silenced.
“In an animal, that silencing can be maintained only until it reproduces, because animal cells go through a re-setting process in utero.
“But in plants, this silencing can be passed down from mother to child, trans-generationally. This is not a mutation, but is epigenetic, or outside the genome; these are not changes to DNA sequence but are still inherited from cell to cell and in plants from parent-to-offspring.
“Plants offer a unique opportunity to study transposable elements,” Slotkin said. “Unlike animals, plants lack a germline that is set-aside early in embryonic development, meaning that epigenetic changes that occur during plant development are more likely to be transmitted to the next generation.
“Also plants have evolved a particularly diverse suite of mechanisms for encoding and propagating epigenetic modifications, such as forms of DNA methylation that specifically mark sites targeted by small RNA-based silencing.”
Studies into the location and timing of transposable element silencing in eukaryotes led to the identification of germ cells as the key spatial and temporal point of the lifecycle where this regulation and the initiation of transposable element silencing occurs.
Male germ cells (the equivalent of animal sperm cells) in flowering plants are housed in pollen grains. In Arabidopsis, mature pollen is a three-celled structure, containing two sperm cells embedded into a larger vegetative cell.
“Transposable element silencing is lost specifically in the pollen vegetative cell, resulting in the reactivation and mobilization of transposable elements,” Slotkin said.
“My laboratory studies transposable element epigenetic regulation at key developmental points in the plant life cycle, with particular interest in germ cells and pollen.
“We hope to discover how these mutagenic transposable elements are epigenetically repressed from generation to generation, as well as how this system has been adopted over evolutionary time to regulate non-transposable element genes,” Slotkin said.
They are asking several questions--how the cell recognizes which regions of the genome are genes and should be expressed, and which are transposable elements and should be selectively silenced; how epigenetic information targeting transposable elements for silencing is propagated from generation to generation, protecting each generation from new mutations; and how the recruitment of epigenetic control to transposable elements has been co-opted over evolutionary time to produce novel and interesting examples of gene regulation.
We look forward to the answers.