A new study has highlighted how a single neuron contains a record of thousands of genetic mutations and these may be individually unique to each neuron. How these mutations occur is currently being investigated with many questions that still need to be answered.
Neurons are unique in the fact that the mature cells oppose division to create new cells after development in the foetus. Neurons are one of the longest living cells because of this and many are still functioning in old age. Neurons are vulnerable to DNA degradation particularly during transcription or the expression of genes (the process by which the genotype synthesises a functional product, either a protein or RNA (an enzyme)). Constant mutations in all cells mean that it is unlikely for a brain cell to be genetically identical and some mutations may naturally result in cancer as a consequence of this process particularly in body cells. An individuals’ DNA is constantly altered by mutagens which are chemical or biological agents within the brain or body and which may elicit mutations. These mutations are somatic mutations (acquired mutations) and have not been inherited and also are averted from being passed onto offspring.
The new study by Lodato and colleagues was published in the journal science. The team focused on somatic single nucleotide variants (SNVs) by analysing 36 neurons of 3 individuals’ post-mortem using single cell sequencing. The team discovered thousands of these genetic variants within the neurons from the cerebral cortex. The team found genes with a high expression may have more SNVs when compared to genes that were shown to have little activity. This supported the idea that neuronal mutations are more likely during expression and are affected by mutagenic factors.
The results of the study show that during its life each neuron may have a profoundly unique genome and that within this genome exists a record of an individual neurons developmental history. This history may be traced from initial cell division during development to the neuron which stays undivided and unreplicable for the life of an individual. Some mutations were identified to have occurred when future brain cells were still dividing prior to birth so a unique genome for particular neurons was already advancing prenatally. The team has suggested that an advantage of having many unique neurons with different developmental paths may protect the brain from developing detrimental mutations. However, when genes undergo many mutations throughout the brain in numerous neurons it may cause conditions of the brain.
The idea of continual genetic mutation may be supported by studies on identical twins which may show that the DNA code is actually un-identical in each twin when analysed after birth or in adulthood. It was suggested previously only the epigenetic expression was different between identical twins.
Overall the study adds further evidence to how our neurons function as they do at a specific point in an individuals’ life and points to continual adaptation in relation to unknown factors. The prospect for the future is the historical record of genes may help to prevent adverse conditions by identifying what these factors are. It also suggests that a significant amount is still to be discovered that illuminates the true role of genetics and any influences upon it. Christopher Walsh a co-author commented, “the genome of a single neuron is like an archaeological record of that cell, we now know that if we examined enough cells in enough brains, we may deconstruct the whole pattern of development of the human brain.”
What productive insights does research in genetics still have to uncover?