Genomic mosaicism, or why our neurons are like snowflakes

Happy New Year! I realized that I haven’t been posting many updates here because I’ve moved more toward using Instagram for that (@oreillyscienceart). This year I resolve to restore some loyalty to my website, starting with these two images that I made to highlight a recent Nature paper from the Chun lab at the Sanford-Burnham Prebys Medical Discovery Institute. Genomic Mosaicism is a phrase used to describe the fact that neurons from the same brain don’t necessarily share the same DNA sequence. (I was delighted to use this as an excuse to create a mosaic image.) The authors of this paper reveal that a major contributor to this mosaicism is scrambling of DNA sequences through homologous recombination. They envisioned it as a gene bursting out to produce thousands of different variants of a single gene, resulting in an explosion of genetic diversity. By studying this phenomenon in the context of APP, a protein involved in Alzheimer’s, they find a correlation between the extent of scrambling and the onset of Alzheimer’s disease. They also make the enticing discovery that reverse transcriptase is responsible for the scrambling events. That’s right, the same reverse transcriptase that we already have approved drugs for. Another intriguing anecdote is that it is very rare for people being treated for HIV with reverse transcriptase inhibitors to get Alzheimer’s disease. Hopefully testing of these drugs in the context of Alzheimer’s disease will begin soon.

Somatic APP gene recombination in Alzheimer's disease and normal neurons.

Lee MH, Siddoway B, Kaeser GE, Segota I, Rivera R, Romanow WJ, Liu CS, Park C, Kennedy G, Long T, Chun J.

Nature. 2018 Nov;563(7733):639-645. doi: 10.1038/s41586-018-0718-6. Epub 2018 Nov 21.