Gene defects that lead to Rett syndrome, a severe form of autism that predominantly strikes girls, also get jumping genes hopping in neurons, a study in the November 18 Nature shows. If the jumping genes land in parts of the genetic blueprint that are important for brain development or function, they could contribute to the variability of symptoms seen in the disorder.
Rett syndrome is caused by mutations in a gene called MeCP2. Like an orchestra conductor, the protein made by MeCP2 tells genes when to stay silent and when to pipe up. But instead of wielding a baton, MeCP2 does its conducting via a chemical modification to DNA known as DNA methylation. Mutations in the MeCP2 gene lead to the molecular equivalent of a cacophony, with genes making noise when they should be silent. So much molecular noise in the brain leads to speech and movement disorders, repetitive hand-wringing, and other problems associated with Rett syndrome.
Now, researchers show that MeCP2 defects also cause jumping genes to play musical chairs in some brain cells. In brains of people with Rett syndrome a type of jumping gene known as an L1 retrotransposon was more active than in brains of healthy people, says Alysson Muotri, a neuroscientist and molecular biologist at the University of California, San Diego. Retrotransposons are genetic elements that make RNA copies of themselves and then convert to DNA and insert into the genome.
The retrotransposons jumped more only in the brain, Muotri and his colleagues found; hearts taken from people with Rett syndrome showed no more jumping gene activity than those from normal people. That could mean that defects in MeCP2 take the brakes off jumping genes, but an additional factor found only in the brain gets the retrotransposons in gear, Muotri says.
He speculates that some amount of gene jumping is good for the brain, increasing genetic diversity in neurons and possibly making the neurons function better. But too much jumping gene activity increases the likelihood that important genes could get damaged, disabling some brain functions and leading to some of the symptoms of Rett syndrome.
Other scientists aren’t convinced that jumping genes really have a functional consequence. It’s a problem of timing, says Lorenz Studer, a stem cell biologist at the Sloan-Kettering Institute in New York City. Girls with Rett syndrome typically develop normally for the first few years of life and then start to have problems. But jumping genes hop only in dividing cells, such as those in the developing brain. Once neurons reach a mature state they no longer divide, so jumping genes have to make their move long before symptoms of Rett syndrome appear.
Researchers will need to learn to control jumping gene activity so they can do further experiments to show whether hopping contributes to the disease, Studer says. “It might have some important biological function, but until we can switch it on and off we really won’t know.”