'Jumping genes' create diversity in human brain cells

Instead of just fixing in a DNA sequencing way, human brain cells have surprisingly diverse genetic levels. This is the result of a study by scientists from the Salk Biological Research Institute published in Nature on August 5. This result helps explain the development and specific characteristics of the brain in each person, while opening new perspectives on neurological diseases.

Head of the research team is Dr. Fred Gage, a member of the Salk Institute Genome Laboratory and Chair of the Research Institute for Neurological Disorders related to old age. The team found that human brain cells contain a large number of flexible elements - unusual DNA fragments that add the same segments of themselves throughout the genome through repetitive replication.

'This is the potential mechanism for creating neutral diversity that makes each person have a unique brain characteristic,' Gage said. 'The brain has 100 billion neurons with trillions of connections, but flexible DNA fragments can make each neuron slightly different from another neuron.'

In the human body, only the brain cells and immune system cells are able to rearrange their genomes.Antibody genes have the flexibility to create the necessary diversity to help antibodies recognize different antigens.

In a previous work, Gage showed that flexible DNA fragments, such as LINE-1 element (Long interspersed element 1), for example, randomly added clones to the mouse brain's genome. . But the controversial question at the time is whether this process, called 'gene jumping' , happens in nerve cells in the human brain.

'It is well known that these versatile elements are important in some low-level organisms, for example, some plants or yeast, but in mammals, they are often regarded as signs. The remainder is transmitted from our ancestors, ' Gage said.

'But they appear too much. Nearly 50% of the total human genome is made up of the remnants of this flexible element. If these factors are not needed, evolution must have eliminated them long ago. '

'Genetic jump' can help explain the development and specific characteristics of each person's brain. (Photo: © Jamie Simon Salk Biological Research Institute)

Initially, the Salk Institute researchers only tried to determine the phenomenon of 'gene jumping' in human brain cells on a plate as seen in mice. They succeeded, but the Gage and the research team were not satisfied.They want to know if this phenomenon occurs on the human body.

In mice, gene jumping occurs only in brain cells and germ cells because these rapid changes will be harmful to essential organs such as the heart or kidneys. If the LINE-1 elements actually move in the human body, the transcription sequences are more likely to appear in the brain than in the heart or the liver, the parts that the Gage group does not think of jumping the LINE gene- 1 may appear.

When Coufal measured samples (brain tissue and other tissues in the body) from different people, she found that some brain samples had up to 100 copies in each cell . 'This proves that these elements are actually moving in neurons,' Coufal explained. Notably, this means that not all cells are created exactly the same - DNA in brain cells differs from DNA in the remaining cells.

Thus, flexible elements may actually contribute to the evolution process, creating greater diversity than conventional cell division.'This is a new way of looking at diversity,' Gage said. 'The brain lives up to 80 years with unusual changes in the environment, and this is a new element that contributes to human adaptability.'

While trying to explain why only new brain cells contain flexible elements, Coufal examined the LINE-1 activator. This is a substance that can 'turn' on and off the LINE-1 element, and she discovered that in the brain, almost LINE-1 is always on, while in other tissues, it is set to default. in the 'off' state.

Importantly, LINE-1 elements with changes in the brain provide a new perspective on neurological disorders. Coufal explained: 'It is possible that the' wrong gene jump 'could lead to problems in these disorders.' Salk Institute researchers are planning to consider changes in the frequency of 'gene jumping' in the brain of people with Rhett syndrome and many other diseases.

In addition to Dr. Coufal and Gage, other researchers involved in the study include: Gene Yeo, Yangling Mu, and Michael Lovci currently working at the University of California, San Diego; José Garcia-Perez, Maria Morell and K. Sue O'Shea at the University of Michigan Pharmacy School, and John V. Moran, staff of Howard Hughes Medical Research Institute.