One of the main dogmas of modern biology is that all somatic (asexual) cells of the body have exactly the same gene. In different cells, it only manifests itself in different way to provide their individuality and functionality. But it turns out that it is not exactly so.
Recent in-depth studies of genomes of nerve cells have shown that they can be both larger and smaller than the standard human chromosome set. New research by American neuroscientists led by Mike McConnell, Ira Hall and Fred Gage expanded the boundaries of the concept “genetic individuality” of neurons even more. “Contrary to the previously held point of view, the genotypes of neurons in the brain are not strictly equal”, sums up Fred Gage.
Authors isolated about hundred neurons of the human brain using postmortem samples and then “scanned” their genomes in search of large deleted or duplicated fragments which lead to variations in the number of gene copies (Copy Number Variation, CNV). In fact, as much as 41% of the neurons were found to have at least one major CNV, unique in each case. It turns out that these variations are not transmitted from parents and must have come as a result of chromosomal rearrangements in the organism.
Sequencing the genome of a single cell is technically quite complex and precise procedure, so before announcing an unexpected result of the work, the authors examined the whole process for about a year to exclude all the possible sources of error.
In addition, the scientists created “artificial” neurons grown from a single skin cell. This method is widely used: the cell is transformed into a pluripotent stem cell, and then propagated to the desired amount and adult nerve cells are grown from it. The surprise was that these neurons also showed a large number of unique genetic variations, even though they were derived from a single cell and were expected to carry quite identical genomes!
This experiment has shown once again that there are genetic variations in the individual development of neurons which are not transmitted from parents to offspring. Within the broad neural networks, which make our brains function, such differences can have very big impact. They may be associated with the risk of a number of neurological disorders and diseases. However, the mission of CNV’s in the healthy brain still remains unclear.
Perhaps they increase the plasticity of the brain, allowing us to more quickly and better adapt to the changing conditions of the environment we face throughout life. Maybe they prevent the invasion of the viral genes and reduce the risk of mass destruction of nerve cells. To test these hypotheses, scientists are experimenting with neurons derived from stem cells.
It would be reasonable to suggest that the differences in the DNA lead to the fact that different neurons produce the unique structure of RNA and proteins. Unfortunately, the study of these processes at the level of individual cells is not yet possible. “Only when the new methods will be applicable to individual cells, we will have the opportunity to find out whether these different genomes create different transcriptomes – sets of RNA molecules derived from DNA,” says McConnell.