If the human brain – with 100 billion neurons forging trillions of connections – were not complicated enough, new research suggests that every neuron may have its very own genome.

A study of the genomes of individual human neurons created from reprogrammed stem cells reveals huge variability between neurons from the same person. Such variation could explain differences in behaviour and susceptibility to mental illness, says Mike McConnell, a stem cell biologist at the Salk Institute in La Jolla California. He presented the work 13 October at the Society for Neuroscience conference in Washington D.C.

“Monozygotic twins can, from time to time, be discordant for things like schizophrenia, for things like autism. They grew up together. They have the same genome, why are they different,” he says.

McConnell has been exploring this phenomenon for more than a decade. In a 2001 paper, he and his colleagues found that individual mouse cells destined to develop into neurons contain substantial chromosomal changes called aneuploidy. A few years later, he showed that neurons with these changes are active in the mouse brain.

Because humans are born with most of the neurons they will use throughout life, genetic variability among them could have a long-lasting effect on how people behave, McConnell says.

To see if human brain cells are genetic mosaics, McConnell turned to induced pluripotent stem (iPS) cells. They are created by treating adult cells with a suite of reprogramming factors that transform the cells into an embryonic-like state in which they can form other tissues.His team transformed iPS cells from two people into neuron cells and then examined the genomes of individual neurons, looking for places where the a huge chunk of the genome is missing or duplicated.

No brain cell’s genome looked the same. They all contained numerous duplications and deletions, but never the same pattern. His team also examined the genomes of the adult cells that were reprogrammed into iPS cells and then neurons, and these cells contained numerous insertions and deletion, but not the same ones as the neurons. McConnell says that this suggests that cells acquire their own genomes as they turn into neurons.

Right now, McConnell can only speculate on whether these changes might influence behaviour. But he is eager to go looking for signs of genetic mosaicism in real human brains, as well as reprogrammed neurons from people with conditions such as schizophrenia.

The sorts of genetic changes he found in the mosaic neurons – deletions and duplications – have been linked, in rare cases, to neuropsychiatric and neurodevelopmental diseases such as schizophrenia, bipolar syndrome and autism. Geneticists discovered these mutations in the germ lines of people with these conditions, i.e. every cell in their body contains the mutations. But McConnell hypothesizes that these mutations could also form in individual neurons in the developing brain.

Add McConnell’s observation to the overwhelming evidence that epigenetic modifications influence traits such as obesity, or the suggestion that the sequences of many genes are subtlty altered after being transcribed, and you get the sense that organism are not content to stick with the genome they were born with.

(via Nature)