Breaking in order to Build: Part 2

Image Courtesy of Michael Schmidt

I recently wrote about how breaks in neural DNA may be part of the process our neurons use to generate new memories. About the same time, I found a new study in Science that addressed the role of the genome in neurons from a different angle. It turns out that Drosophila (fruit flies) have particularly heterogeneous genomes in the neurons associated with learning and memory. Now let me back up and explain exactly what I mean by heterogeneous genomes and how that can affect learning and memory.

In fruit flies, one of the parts of the brain dedicated to learning and memory is called the mushroom body (MB). In this new study, the mushroom body was labeled with green fluorescent protein (GFP) so that when a fruit fly’s brain is broken down into individual cells the green ones can be sorted out. Once the cells are sorted, differences in gene expression between the green MB cells and other brain cells can be compared. It turns out that the cells focused on learning and memory, have a much higher level of expression of many types of transposons. Transposons are little bits of DNA that are able to hop around the genome inserting themselves and then stealing bits of DNA when they hop out again. Most of the time, they disrupt gene expression either by inserting themselves right into a gene or taking pieces of a gene with them when they hop out. This results in heterogeneous genomes in the brain because a subset of cells have a highly variant genome compared to other cells in the same brain.

Why are there preferentially more of these “disruptive” elements in the parts of the brain critical for learning and memory? It turns out that the genes that normally prevent transposons from hopping around are expressed at a much lower level in the MB. Low expression of the genes that repress transposons may be necessary for learning and memory in some way that is totally unrelated to their role in regulating transposon hopping. The transposon hopping may be a tolerable side effect of the process of memory building. Alternatively, transposons hopping in and out of the genome ends up results in a lot of genetic variance, and this high level of genetic variance may be important for the learning and memory activity of these specific cells. The risk associated with  excessive transposon mobility may be inextricably linked to making memories in these cells. Eventually, the high level of sequence exchange will result in cumulative deleterious changes similar to the situation found with double strand breaks in mammalian neural DNA. As of now, it’s not clear exactly how the high genetic variability in only a subset of neurons is really contributing to learning and memory. It is intriguing to compare the fly data with the mouse data. What is the advantage of high genetic variability in these learning and memory centers in the brain?