An effort to extend the time between the recently learned and soon forgotten
Christopher Walsh, a scientist with an appointment at the Broad Institute, has recently published a remarkable article. Walsh's lab took individual neurons from the human brain and demonstrated that the cell's DNA sequences were distinct from one another. Each neuron they sampled had an average of 1500 mutations, meaning that individual neurons are not merely connected differently, but they each contained different genetic material. This is quite contrary to the to the doctrine I was taught in biology class, which claimed instead that every nucleated cell in the body contained an exact copy of the same DNA strands.
Walsh conducted his study by obtaining postmortem brain tissue from three healthy victims of accidents, aged 15, 17, and 42. He then extracted 36 individual neurons from each of these brains, and then extracted the DNA from each neuron and sequenced it. He also took bulk tissue and applied typical genome sequencing techniques to compile an average whole genome sequence for each individual. By comparing the sequence of the DNA in each of the individual neurons to the average sequence he was able to identify specific mutations in each neuron.
While DNA duplication is known to be a source of mutation, that was not the primary mechanism Walsh postulated for explaining the differences between the individual neurons. He noted that transcriptionally active genes were much more likely to be mutated, while genes that were transcribed less frequently were depleted in their mutation counts. He suggests that these mutations arise as an aspect of the transcriptional process, but also points out that these cells, whatever their mutations, live long and apparently healthy lives.
Interestingly, Walsh observes that the mutations were observed more commonly in exons ( which provide the mRNA for proteins) than in introns ( which are not ultimately translated into protein). If exons and introns are transcribed equally, then it seems curious that the exons, which are evolutionarily more conserved than introns, would be the portions of the genes to harbor the most mutations. Could it be that this mutational process is not strictly and aberrant process of destruction, but a purposeful mechanism that provides utility? Perhaps the heterogeneity of neurons is part of what makes brains unique, and allows different people to think so differently from one another? ( Note: this last conjecture was not addressed in Walsh's article, and therefore he can take no blame for this speculation).
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