We have been thought that all human body cells have the same DNA, but that is not true for the brain cells. In fact great portion of the brain cells undergo DNA changes that makes every neuron in the brain a little different form each other.
Some Salk Institute scientists and collaborating researchers have shown that long interspersed nuclear elements or L1s in the DNA is one source of brain cell genome diversity, due to its ability to alter the DNA. L1s or long interspersed nuclear elements can delete and can also insert DNA in healthy neurons of the brain cells. L1s are previously known to be small bits that make up the DNA, about 44 to 63 percent of DNA healthy neurons. L1s are also called “jumping genes” it replicates itself all over the genome by a kind of copy and paste actions in the genome. Research has shown that L1s activities or actions can cause genes deletions that result to variations which have influence on the brain cells development and genes expressions.
The journal of Nature Neuroscience publication of September 12, 2016, contains research reports that support the genomic diversity and uniqueness of brain cells and reasons why identical twins behaves in a differently manner. It was reported there that jumping genes can get abnormally twisted and result to disease or disorder.
In 2005, Rusty Gage’s research team revealed that L1s is an instrument behind genome diversity inside the brain cells. However, it was when the entire genome sequencing of a single cell became possible that scientists were able to describe and quantify brain cell variation and behaviors.
Gage's group used single-cell sequencing in a 2013 Science paper, and detailed result showed that large amounts of DNA were deleted -- or -- inserted into the genomes of the cells.
Although the same study, the mechanisms accountable for causing deletions and insertions were not actually clear, making it hard to tell whether certain regions of the genome are altered more or less.The research result could not show for sure that jumping genes influenced the deletions.
In 2013, Rusty Gage a Salk institute scientist at Salk’s laboratory of genetics and a “holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases” led the study that discovered transposable elements of the DNA, that, diverse neurons inside the same brain have several complements of DNA.“Suggesting that the various DNA complements of the brain cells function slightly differently from each other even within the same person”. The study revealed a novel and astonishing form of distinction that will help us understand the role of L1s in healthy brains and in the brain of patients with schizophrenia and autism.
In the recent study that Rusty Gage co-first authors Jennifer Erwin and Apuã Paquola, with other collaborators; they established a method to enhance the capture of L1-associated variants within healthy neurons for sequencing. Computational algorithm was created to differentiate the variations with better accuracy.
They used stem cells that are coaxed(specific marker) to separate the neurons in a petri dish; the team established that L1s are susceptible to DNA breaks, due to particular enzyme that eats through L1 spots in the genome. Such enzyme is principally active during DNA separation. The research group found that as children inherit some L1s from their parents, the enzyme seems to cut off (part deletions) close to these spots.
Erwin, a staff scientist in Gage's research group said "The surprising part was that we thought all L1s could do was insert into new places. But the fact that they're causing deletions means that they're affecting the genome in a more significant way.”
Gage is certain that genomic diversity can be beneficial for the brain -- after all, roughly half of the human brain cells exist with large portions of inserted or missing DNA caused by L1s alone, however, too much of deletions and insertions can cause disorders and diseases.
Current evidence has revealed that neurons obtained from the brain cells of individuals with schizophrenia or rare cases of autism-associated disorder Rett syndrome, contains more amounts of L1 variations than normal in their genomes.
Gage’s research team recently carried out a study on the examination of schizophrenia-associated gene called DLG2. They established that L1 variations bring about change in genes expression and neurons maturation activities. The next research interest of the group is to investigate the effects of L1 variations on brain activity and disease.