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'Jumping genes' contribute to the uniqueness of individual brains
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.
It has been known for a long time that L1 elements are active in testis and ovaries, which explains how they potentially play
a role in evolution by passing on new insertions to future generations. "But nobody has ever demonstrated mobility
convincingly in cells other than germ line cells," says Gage.
Apart from their activity in testis and ovaries, jumping L1 elements are not only unique to the adult brain but appear to
happen also during early stages of the development of nerve cells. The Salk team found insertions only in neuronal precursor
cells that had already made their initial commitment to becoming a neuron. Other cell types found in the brain, such as
oligodendrocytes and astrocytes, were unaffected.
At least in the germ line, copies of L1s appear to plug themselves more or less randomly into the genome of their host cell.
"But in neuronal progenitor cells, these mobile elements seem to look for genes expressed in neurons. We think that's because
when the cells start to differentiate the cells start to open up genes and expose their DNA to insertions," explains co-
author Alysson R. Muotri. "What we have shown for the first time is that a single insertion can mess up gene expression and
influence the function of individual cells," he adds.
However, it is too early to tell how often endogenous L1 elements move in human neurons and how tightly this process is
regulated or what happens when this process goes awry, cautions Gage. "We only looked at one L1 element with a marker gene
and can only say that motility is likely significantly more for endogenous L1 elements," he adds.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to
fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of
researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the
Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.
Contact: Cathy Yarbrough
yarbrough@salk.edu
858-452-8051
Salk Institute
http://www.salk.edu
"Jumping gene" contribuie la unicitatea individualã creierul - 'Jumping genes' contribute to the uniqueness of individual brains - articole medicale engleza - startsanatate