brain plasticity: gene content of each neuron can vary (Introduction)

by David Turell @, Tuesday, September 20, 2016, 15:12 (2777 days ago) @ David Turell

Another article on this topic discussing transposons and their role: - http://www.the-scientist.com/?articles.view/articleNo/47069/title/Sequencing-Reveals-Ge... - "Somatic mosaicism—the variation of the genome between individual cells—is particularly consequential in the brain. Neuroscientists have found that small changes to the genome of even a few neurons can have neurological consequences. In a study published in Nature Neuroscience this week (September 12), scientists set their sights on one source of this variation. Using single-cell sequencing and machine learning algorithms, they have examined the extent of long interspersed element-1 (LINE-1, or L1) retrotransposition in the healthy human brain. - "In the 1940s, Barbara McClintock and colleagues discovered transposons, or “jumping genes,” scraps of DNA able to move from one position in the genome to another. By 2005, Fred “Rusty” Gage of the Salk Institute for Biological Studies and colleagues identified L1 transposons as a source of genomic mosaicism in human neurons. Now, Gage and his colleagues have shown that L1s don't just jump around: these mobile elements can also spontaneously trigger the deletion of certain genes.
“The main aspect that's new in this paper is that there seems to be increased changes in these LINE elements that may not be due to insertional changes. . . . They may be something that serve as a potential target for somatic changes,” said Jerold Chun of the Scripps Research Institute in La Jolla, California, who was not involved in the present study. “That's an interesting concept, and I think it will be interesting to see what that entails.” - *** - "L1 transposons create unique alterations to neuronal genomes, on the order of 0.5 to one alteration per cell, and L1-associated changes can be found in 44 percent to 63 percent of cells in the healthy brain, the researchers found. But when the researchers sought to confirm these L1 insertions using direct molecular methods, they could not find around half of the supposed changes. Upon closer inspection of the stretches of DNA around where the algorithm had flagged a unique change to the genomes, the researchers instead found evidence of large genetic deletions.
L1 elements contain genes for endonucleases, proteins that cleave DNA, which are part of the toolkit they use to splice into new locations. The thought, explained Gage, is that these endonucleases sometimes continue cutting after an insertion, lopping off segments of DNA. If confirmed, this would be a previously unrecognized source of genomic mosaicism in the brain caused by L1 elements.  - *** - "The precise roles of L1 transposons in somatic mosaicism of the human brain remain unclear. Neurons are unique among the body's cells because they do not regularly turn over, but instead can stay with a person for his or her entire life. Genetic changes that occur when a neuron is formed can therefore have permanent effects." (my bold) - Comment: This is a major way brain plasticity occurs. Note these changes last a lifetime as each of us makes use of our brain to form it to our needs. There is an evolutionary aspect to this. Our DNA is 98% similar in overall appearance when total bases are counted compared to chimps, but our brains are vastly different. I think we are looking one of the reasons. Chimp brain genetic mosaic changes will be found to not be equal to this finding.


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