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\title{Science AMA Series: We are Mollie Woodworth and Michael Lodato
(Harvard). We sequenced single neurons from normal human brain and found
\textasciitilde{}1700 mutations per neuron. We're here to talk about
these ``somat}



\author[1]{somatic_mutations }%
\author[1]{r/Science AMAs}%
\affil[1]{Affiliation not available}%


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  \date{April 23, 2026}


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\begin{abstract}
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.%
\end{abstract}%



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