Human brain harbors single nucleotide somatic variations in functionally relevant genes possibly mediated by oxidative stress

Somatic variationin DNA can cause cells to deviate from the preordained genomic path in both disease and healthy conditions. Here, using exome sequencingof paired tissue samples, we show that the normal human brainharbors somaticsingle base variationsmeasuring up to 0.48% of the total variations. Interestingly, about 64% of these somatic variationsin the brain are expected to lead to non-synonymous changes, and as much as 87% of these represent G:C>T:A transversion events. Further, the transversion events in the brain were mostly found in the frontal cortex, whereas the corpus callosumfrom the same individuals harbors the reference genotype. We found a significantly higher amount of 8-OHdG (oxidative stress marker) in the frontal cortex compared to the corpus callosumof the same subjects (p T:A transversions in the cortex. We found significant enrichment for axon guidanceand related pathways for genes harbouring somatic variations. This could represent either a directed selectionof genetic variationsin these pathways or increased susceptibility of some loci towards oxidative stress. This study highlights that oxidative stress possibly influence single nucleotide somatic variationsin normal human brain.