Brave New World of Gene Manipulation in Human Brain

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 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. In fact, retrotransposon activity may explain the very recent discovery that every brain cell seems to have a unique genome. I explained this finding in an earlier post.

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. And these are not "random" mutations.

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 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). 

The implications of this discovery for learning and memory―and brain function in general―are inestimable. More importantly, and here is where the “Brave New World” comes in, there should be the potential for manipulating gene functions in predictable and lasting ways by using synthetic transposons (which should be easy to manufacture).  Transport of synthetic retrotransposons into neurons might be accomplished by packaging them with a harmless virus; the basics of “transfection” technology are already well established. The hard part will be in discovering what transposons produce desired changes in brain function. But it seems reasonable to test various retrotransposons in the hope that some can be found that will help to cement or magnify memories and perhaps others that erase unwanted memories, as occur in post-traumatic stress syndrome. There is a potential down-side, however. Some retrotransposons may be a cause of cancer.

Source:

Baillie, J. K., et al. (2011) Somatic retrotransposition alters the genetic  landscape of the human brain. Nature. 479: 534-537.