Jumpin' Jordan! Athletic Gene Yields Biological Clues

Jordan's legendary leaping ability has inspired two cell biologists at Washington University in St. Louis to name a transposon -- a highly specialized gene -- after the sports and cultural icon. A transposon is a type of gene, common in organisms ranging from algae to humans, that literally jumps from one cell site to another.

While transposons are abundant, controlling them for useful research has been nearly impossible, until David Kirk, Ph.D., professor of biology, and Stephen Miller, Ph.D., research associate in biology in Arts and Sciences, found an environmental control for one kind of transposon. The transposon that Kirk and Miller have discovered in Volvox, a green alga, will jump when it's stressed -- not by a harassing New York Knicks doubleteam but by cold temperatures that the biologists use to grow special Volvox cultures.

When it jumps, Kirk and Miller can recognize where Jordan lands by its characteristic genetic signature, as recognizable to a biologist peering through a microscope as a player's slam dunk is to a fan watching replays. They then use Jordan to isolate genes of interest to understand their form and function. The Jordan jumping gene has helped the developmental biologists discover and analyze two important genes that play key roles in one of life's greatest mysteries: how individual cells reproduce and become specialized.

Kirk and Miller report the sequencing, or genetic analysis, of a key gene necessary for cell division and another "master control" gene that regulates cell type in Volvox in the Feb. 15, 1999, issue of the journal Development. Their research is sponsored by the National Science Foundation and the United States Department of Agriculture.

"Jordan has two special genetic sequences at its ends that permit the gene to cut its way out of a cell at one location and reinsert itself at another," explains Kirk. "That's what's called jumping. We can recognize the Jordan mutation in the gene where it lands, and then extract that gene's pre-existing DNA and study it. Having Jordan in a gene gives us a handle to pull out the DNA of interest. That's how we found these two genes, and their discovery has led to a far deeper understanding of Volvox than we've ever had before."

The finding sheds light on a simple organism that has been studied for 300 years, and has implications for how organisms across species reproduce and develop specialized cells. Also, Kirk and Miller's work advances the understanding of how transposons in general may someday work as vectors, or carriers, of DNA for gene therapy and how transposons may cause cells to become cancerous. It's estimated that 50 percent of all spontaneous mutations are due to transposon insertions into other genes.

The genes Jordan landed in are glsA and regA. Kirk and Miller report that glsA is essential for "asymmetric division" in Volvox, whereby only large cells become germ cells and only small cells become body cells. The glsA gene has a counterpart in humans called MPP11. MPP11 is known to play a role in cell division. And its genetic composition is more than 50 percent identical to that of the glsA gene.

"This was astonishing to us," says Kirk. "The similarity is really close for organisms separated by at least one billion years of evolution." Only five other genes similar to glsA have been found throughout the biosphere, three in mammals and one each in fungi and algae.

RegA, on the other hand, is found to prevent the body cells from becoming germ cells by harnessing the activity of 18 other genes that inhibit the formation of chloroplasts in the body cells. Because Volvox is a green alga, it gets its energy from photosynthesis; without the formation of new chloroplasts, the body cells have just a limited time to carry out their function and then they die. "Volvox interests biologists because it has only two cell types, somatic or body cells that fulfill their functions and die within five days, and germ cells, which reproduce," explains Kirk, whose laboratory is one of only three in the world devoted to Volvox studies. "This is what makes Volvox an important system. We're trying to get a big picture of basic cell development with just two cell types as opposed to trying to understand the basics in mammals where as many as 200 different cell types are developing all at once."

A Cold Jolt

Kirk and his colleagues spent six years developing techniques to find Jordan. Finally in 1994, Miller, then a beginning postdoctoral fellow in Kirk's laboratory, isolated the jumping gene and named it based on its obvious attributes.

So, just how far does Jordan jump? There is no counterpart to a vertical leap in cell biology, but Kirk and Miller found that Jordan jumps half the time to a nearby location and the other half to random locations across the Volvox genome, or collection of genes. There are five families of transposons found in Volvox, but Jordan is the only one that can be made to jump.

Kirk and Miller found that growing Volvox in their laboratory at lower temperatures stresses the organism and forces Jordan to jump.

"We found that simply by growing cultures of Volvox at lower temperatures, we can increase Jordan's jumping 30- to 50-fold," he says. "It's important to have Jordan jumping frequently because for every thousand times it jumps in Volvox, maybe only once will it land in a gene we're interested in."

Meanwhile, Kirk knows when he has a "hot hand." He and Miller plan to use Jordan to help find at least two other genes that they think work with glsA in cell division and to locate other germ cell genes.