Brave New World of Gene Manipulation in Human Brain
New research suggests we can systematically manipulate brain genes.
Posted Jul 06, 2012
In recent years scientists have discovered mobile pieces of genetic material that move around inside cells. These pieces are called retrotransposons. They can copy themselves and insert near and into DNA and thus induce mutations. Australian research recently reported in the journal Nature reveals that retrotransposons can alter the genome of human brain cells. In fact, retrotransposons more effectively penetrate neuron genes than those in blood cells that were used for comparison. Thousands of retrotransposon mutations were seen in two of the five areas examined from brains of human post-mortem donors.
Though these pieces of DNA are not genes, they interact with genes that hop around to different sites within a chromosome (perhaps you heard about Barbara McClintok’s 1983 Nobel Prize winning discovery of “jumping genes”). All cells have enzymes that cut transposons out of a string of DNA, which then insert back in at other locations in the DNA. Sometimes the cut includes an adjacent gene along with the transposon, and thus when reinsertion occurs the gene hitchhikes along to the new location. The jumping around is not random; it occurs preferentially into active protein-coding regions, even sometimes in a different chromosome. The potential for changing function is enormous, yet we don’t know just what functional consequences occur. We do know that the process is most common in humans and higher primates.
We have known for some time that all cells are influenced by epigenetic effects; that is, events in the environment can alter the genome. The mechanism may well involve retrotransposons. Gene manipulation may be especially robust for altering learning and memory. It may be no accident that retrotransposon mutations were seen in the human hippocampus, the brain region most directly involved in forming memories and the one part of the brain where new cells are continuously born in adults. Memory of learned events results from more or less lasting changes in the junctions (synapses) among cells in the circuits that processed the learning. These lasting changes are enabled by new protein production in those synapses. That protein is under genetic control (thus a memory can be sustained because the genes can replace any protein that degrades over time).
Baillie, J. K., et al. (2011) Somatic retrotransposition alters the genetic landscape of the human brain. Nature. 479: 534-537.
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