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Science AMA Series: We are Mollie Woodworth and Michael Lodato (Harvard). We sequenced single neurons from normal human brain and found ~1700 mutations per neuron. We’re here to talk about these “somat
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Ongoing, random mutation to DNA ensures that no two cells in an individual are genetically identical. Since mature neurons can survive for the lifetime of an individual, their DNA is exposed to mutagens (oxygen free radicals, electromagnetic radiation, endogenous transposable elements, etc.) on an ongoing basis. These forces have the potential to induce somatic mutations, and potentially contribute to normal aging and neurodegenerative disease. We sequenced single neurons from normal postmortem human brains to identify rates and patterns of somatic mutations published in the October 2nd issue of Science, layman’s summary at The Atlantic Most of the mutations we identified are unique to a single neuron, and we can use them to say something about the kinds of mutational processes that impact a neuron’s genome. Many of the mutations appear to have happened during the process of gene transcription, which is unfortunate, because it means that the genes a neuron needs most and uses most often are those that are most likely to be mutated. A small fraction of the mutations are shared among multiple neurons. Since neurons don’t divide in the brain after about week 20 of fetal development, we know that those shared mutations happened during embryonic and fetal development in progenitor cells, and then were passed on to their progeny. We can use those shared mutations as tags to mark particular lineages of cells in brain development, much in the same way that we can use viruses or other markers as tags to mark lineages in experimental organisms. Because somatic mutations in the brain represent a durable and ongoing record of neuronal life history, from development through post-mitotic function, our work enables us to make a lineage map to identify family relationships between cells in the brain. tl;dr Mutations are happening in your neurons every day! We looked at individual neurons to find out how many. EDIT: Thanks so much for all your thoughtful questions, and for the great discussion! We had so much fun doing this today.