THE MOSAIC BRAIN During development neural stem cells generate committed precursor cells that differentiate into the many specialized neural populations that comprise the adult brain. Mutations can arise at any step in the series of >100 billion cell divisions required to generate the number of neurons found in the fully developed brain, resulting in variably sized populations of neurons that share a unique somatogenetic inheritance. Chances are high that an individual who inherits a recessive mutation in a critical gene will have some subset of neurons in which the same gene is also mutated. This may represent an entire brain structure (e.g., cerebellum), smaller regional structures, or even scattered populations of neurons that migrate throughout the brain after neurogenesis. LUCY READING - IKKANDA
Cell division is a risky business. DNA damage unavoidably accompanies the enormous number of cell divisions required to generate the human body from a single fertilized egg. In most tissues, cell turnover and regeneration ameliorate the deleterious effects of somatic mutation. The nervous system, however, has a unique vulnerability—neurons generally don’t turn over. As a result, we are all cursed to live our entire lives with somatic mutations acquired during the embryonic development and differentiation of neural progenitor cells.
A conservative mutation rate of 5 x 10-7 mutations/cell/generation would mean that every adult human brain harbors around 5 x 104 somatic mutations in its neurons. Of course, the number of cells carrying each of these mutations depends on when the mutations arise during development, with ...
