Family tree of neurons in the brain

Darwin built the tree of evolution, where we learn our position in the history of life on Earth. You can build your family tree with your clan pedigree books. A recent paper in Science reports building a linage tree for neurons.

Archeologists use radioactive isotopes to estimate the age of a rock or bone; biologists use DNA labels to trace cell division;  with genome sequencing, geneticists can use gene mutations to trace our ancestors to African apes. In the Science paper, Lodato et al. used whole genome sequencing of single neurons to detect the mutations with which they built a linage tree of neurons for a single person.

We know during early development, all cells divide and the mutations at that stage will be carried to the descending cells; and after the body mature, most cells stop dividing and keep the mutations from their ancestors. But new mutations will continue to appear in the after dividing cells, which could be the cause of diseases. Every neuron in the brain is different, single mutation in one neuron may becomes the seed for Alzheimer disease,  Parkinson disease, Huntington disease, and CJD......For this reason, Lodato et al. wanted to investigate the mutation pattern in single somatic neurons.

They did whole genome sequencing of 36 neurons from 3 normal adult brains, and analyzed the data on single nucleotide variants. By comparing with reference data, they found ~1500 mutations for each neuron, which are more associated with transcription regulating neuronal functions than DNA replication in cell division as in cancer cells. By comparing the mutations in each neuron, they found the neurons could be arranged into four clades clusters, each originating from the same ancestors during fetal development. The result is a beautiful tree of neurons, though the neurons are taken from a brain tissue within millimeters.

This study makes use of the new techniques to prove a concept that somatic mutations can be used to construct the linage tree of neurons, which is important to understand neurodevelopment. It also indicates somatic mutations may have more weight than germ line mutations for the neurological disorders. This method could be extended to patients' brain to search for the most possible culprit of neurological diseases. However, non-localized somatic mutation, like cancer mutation, is hard to be targeted by gene therapy.