Scientists find that neurons in the brain can modify their own genes.
It has been known since the 1970s that some cells in the human body can rearrange and modify their own DNA. For instance, B cells can recombine sections of genes that code for proteins that detect or fight pathogens to create new genes, enabling them to potentially produce as many as one quadrillion different antibodies.
This genetic reshuffling is known as somatic recombination. Some data has suggested that it occurs in the brain, but a recent study is the first to definitely confirm that neurons can undergo somatic recombination.
Genetic recombination in neurons in the brain is important because these neurons already differ from one another, often having different genetic sequences than the neurons around them. Researchers at Sanford Burnham Prebys Medical Discovery Institute in San Diego, California found that the neurons in patients with the noninherited form of Alzheimer’s disease have thousands of variants of the gene for the amyloid precursor protein (APP), which is the source of the plaques in the brains of people with Alzheimer’s disease.
Many different changes were observed, including the switching of single nucleotide bases to the deletions of genetic sequences. In addition, the patients with Alzheimer’s disease had approximately six times as many varieties of the APP gene as healthy people.
The researchers suggest that the ability to make different forms of the APP gene may enhance learning, memory or other brain functions. The downside for some people may be that having so many different APP gene variants is harmful to the brain in some way.
The believe somatic recombination in brain neurons is mediated by the reverse transcriptase enzyme, which makes DNA copies of RNA molecules. Variants could be produced when, during normal cell activity, a neuron produces an RNA copy of the APP gene and then is incorrectly copied to make a DNA duplicate by reverse transcriptase.
Interestingly, drugs have been developed that block reverse transcriptase –– as treatments for HIV infection. It is possible they may be effective against Alzheimer’s disease.
The researchers hope that other groups can replicate their work and confirm their results. If they do, then somatic recombination could be a potential mechanism –– and drug target ––– for not only Alzheimer’s, but also other brain diseases.
