Brains are marvels of diversity: no two look the same -- not even those of otherwise identical twins. Scientists at the Salk Institute for Biological Studies may have found one explanation for the puzzling variety in brain organization and function: mobile elements, pieces of DNA that can jump from one place in the genome to another, randomly changing the genetic information in single brain cells. If enough of these jumps occur, they could allow individual brains to develop in distinctly different ways.
"This mobility adds an element of variety and flexibility to neurons in a real Darwinian sense of randomness and selection," says Fred H. Gage, Professor and co-head of the Laboratory of Genetics at the Salk Institute and the lead author of the study published in this week's Nature. This process of creating diversity with the help of mobile elements and then selecting for the fittest is restricted to the brain and leaves other organs unaffected. "You wouldn't want that added element of individuality in your heart," he adds.
Precursor cells in the embryonic brain, which mature into neurons, look and act more or less the same. Yet, these precursors ultimately give rise to a panoply of nerve cells that are enormously diverse in form and function and together form the brain. Identifying the mechanisms that lead to this diversification has been a longstanding challenge. "People have speculated that there might be a mechanism to create diversity in brain like there is in the immune system, and the immune system's diversity is perhaps the closest analogy we have," says Gage.
In the immune system, the genes coding for antibodies are shuffled to create a wide variety of antibodies capable of recognizing an infinite number of distinct antigens.
In their study, the researchers closely tracked a single human mobile genetic element, a so-called LINE-1 or L1 element in cultured neuronal precursor cells from rats. Then they introduced it into mice. Every time the engineered L1 element jumped, the affected cell started glowing green [WHY?]. "We were very excited when we saw green cells all over the brain in our mice," says research fellow and co-author M. Carolina N. Marchetto, "because then we knew it happened in vivo and couldn't be dismissed as a tissue culture artifact."
Transposable L1 elements, or "jumping genes" as they are often called, make up 17 percent of our genomic DNA but very little is known about them. Almost all of them are marooned at a permanent spot by mutations rendering them dysfunctional, but in humans a hundred or so are free to move via a "copy and paste" mechanism. Long dismissed as useless gibberish or "junk" DNA, the transposable L1 elements were thought to be intracellular parasites or leftovers from our distant evolutionary past.