One neuron may have over 1,000 mutations

A single neuron in a normal adult brain may carry more than a thousand genetic mutations most of which may be harmless, new research has found.

The majority of these mutations appear to arise while genes are in active use, after brain development is complete, found the study by Maryland-based Howard Hughes Medical Institute (HHMI) scientists. 

"We found that the genes that the brain uses most of all are the genes that are most fragile and most likely to be mutated," said lead research Christopher Walsh, HHMI investigator at Boston Children's Hospital. 

For the study, the scientists isolated and sequenced the genomes of 36 neurons from healthy brains donated by three adults after their deaths. 

For comparison, the scientists also sequenced DNA that they isolated from cells in each individual's heart. 

What they found was that every neuron's genome was unique. 

Each had more than 1,000 point mutations - mutations that alter a single letter of the genetic code.

What is more, the nature of the variation was not quite what the scientists had expected.

"We expected these mutations to look like cancer mutations," Walsh said explaining that cancer mutations tend to arise when DNA is imperfectly copied in preparation for cell division, "but in fact they have a unique signature all their own. The mutations that occur in the brain mostly seem to occur when the cells are expressing their genes".

Although most of the mutations the scientists catalogued were harmless, they did encounter mutations that disrupted genes that, when impaired throughout the brain, can cause disease.

The findings, published in the journal Science, could also lead to new information about how the human brain develops.