The Nature of Consciousness

Piero Scaruffi

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These are excerpts and elaborations from my book "The Nature of Consciousness"

Somatic Mosaicism

A dogma of biology is that every cell of a body has the same DNA. In reality, many cells contain variations on that DNA. DNA replication is an imperfect process: mistakes are introduced. Before birth and during the first years of life, our brain's neural stem cells and progenitor cells undergo tens of billions of cell divisions to generate the roughly 80 billion neurons in our adult brain. If DNA replication were 100% perfect, each of these neurons would receive exactly the same DNA, but in reality "somatic mutations" take place during replication: somatic short variants like single-nucleotide variants (SNVs) and insertion/deletion mutations (indels), as well as copy number variations (CNVs) and "mobile element insertions" (MEIs). These are rare but "rare" multiplied by billions of divisions yield a significant number. Richard Redon at the Wellcome Trust Sanger Institute estimated that around 12% of the human genome contains CNVs alone ("Global variation in copy number in the human genome", 2006). A post-zygotic mutation is a change in the DNA of an organism that takes place during its lifespan. This is the case of cancer, but there are also post-zygotic mutations outside of cancer, mutations that don't seem to harm the organism, at least in the short run. In particular, in 1976 Susumu Tonegawa's team discovered that cells of the immune system contain slightly different genomes that produce useful antibody diversity. This proved William Dreyer's theoretical conjecture of a decade earlier, that the DNA doesn't contain enough information to encode the astronomical diversity of antibodies produced by the immune system ("The molecular basis of antibody formation", 1965). Since then, more and more genetic mutations have been discovered in all sorts of cells. De facto, every individual contains a multitude of genomes. Genetic mosaicism is widespread, and our adult life may be determined by the generation of DNA variants and by their interactions. Human neurons are no exception. Dreyer had already speculated that his conjecture applied to the brain as well as to the immune system ("The genetic, molecular and cellular basis of antibody formation", 1967) and, four decades later, Jerold Chun's team provided the empirical evidence that not all neurons are genetically alike: some neurons have genomes that have undergone this kind of mutations, in particular copy-number variations ("Chromosomal variation in neurons of the developing and adult mammalian nervous system", 2001). Then his former student Michael McConnell showed that between 13% and 41% of the frontal cortex neurons have copy-number variations ("Mosaic copy number variation in human neurons", 2013). There might be neurons that have a different genome than any of their neighbors. This mosaicism physically alters neural circuits, with still unknown consequences. This fact may also explain why neurons in the temporal lobe are the first to die in Alzheimer's disease and why dopaminergic neurons are the first to die in Parkinson's disease.

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