brain plasticity: loaded with new mutations (Introduction)

by David Turell , Monday, October 05, 2015, 14:37 (3338 days ago) @ David Turell

More on the subject:-http://www.sciencedaily.com/releases/2015/10/151001153931.htm-"A single neuron in a normal adult brain likely has more than a thousand genetic mutations that are not present in the cells that surround it, according to new research from Howard Hughes Medical Institute (HHMI) scientists. The majority of these mutations appear to arise while genes are in active use, after brain development is complete.-"'We found that the genes that the brain uses most of all are the genes that are most fragile and most likely to be mutated," says Christopher Walsh, an HHMI investigator at Boston Children's Hospital who led the research. Walsh, Peter Park, a computational biologist at Harvard Medical School, and their colleagues reported their findings in the October 2, 2015, issue of the journal Science.-"It's not yet clear how these naturally occurring mutations impact the function of a normal brain, or to what extent they contribute to disease. But by tracing the distribution of mutations among cells, Walsh and his colleagues are already learning new information about how the human brain develops. "The genome of a single neuron is like an archeological record of that cell," Walsh says. "We can read its lineage in the pattern of shared mutations. We now know that if we examined enough cells in enough brains, we could deconstruct the whole pattern of development of the human brain."-***
"What they found was that every neuron's genome was unique. Each had more than 1,000 point mutations (mutations that alter a single letter of the genetic code), and only a few mutations appeared in more than one cell. What's more, the nature of the variation was not quite what the scientists had expected.-"'We expected these mutations to look like cancer mutations," Walsh says, explaining that cancer mutations tend to arise when DNA is imperfectly copied in preparation for cell division, "but in fact they have a unique signature all their own. The mutations that occur in the brain mostly seem to occur when the cells are expressing their genes."-"Neurons don't divide, and most of the time their DNA is tightly bundled and protected from damage. When a cell needs to turn on a gene, it opens up the DNA, exposing the gene so that it can be copied into RNA, the first step in protein production. Based on the types and locations of the mutations they found in the neurons, the scientists concluded that most DNA damage had occurred during this unwinding and copying process.-"While most of the mutations in the neurons were unique, a small percentage did turn up in more than one cell. That signaled that those mutations had originated when future brain cells were still dividing, a process that is complete before birth. Those early mutations were passed on as cells divided and migrated, and the scientists were able to use them to reconstruct a partial history of the brain's development.-"'We knew that cells that shared a certain mutation were related, so we could look at how different cells in the adult were related to each other during development," explains Mollie Woodworth, a postdoctoral researcher in Walsh's lab. Their mapping revealed that closely relatedly cells could wind up quite distant from one another in the adult brain. A single patch of brain tissue might contain cells from five different lineages that diverged before the developing brain had even separated from other tissues in the fetus. "We could identify mutations that happened really early, before the brain existed, and we found that cells that had those mutations were nestled next to cells that had totally different mutations," Woodworth says. In fact, the scientists found, a particular neuron might be more closely related to a cell in the heart than to a neighboring neuron."-Comment: my conclusion is different than the researchers' confusion. Newborn brain is a clean slate, and the mutations are part of the plasticity and cooperation between the developing human person and his/her brain.