Comprehensive coverage

Surprising variation between the genomes of individual neurons in the same brain

"Contrary to what was once thought, the genomic composition of the neurons in the brain is not the same, but consists of a patchwork of DNA" says Fred Gage, head of the Center for the Study of Neurological Diseases Associated with Aging at the Salk Institute.

genetics. Illustration: shutterstock
Genetics. Illustration: shutterstock

We were sure that every cell in the human body has the same genetic code, DNA, and that the only way the body works to diversify cells is that each cell can read only the code necessary to function and define that cell type.

This is true for most types of cells in the body, but this is an oversimplification. Studies in the genome of the nerves published in the last decade have shown that there are extra or missing chromosomes, or that pieces of DNA have copied and pasted themselves all over the genome.

The only way to know for sure that a neuron from that person contains unique DNA is by reading the genetic sequence from a single cell and not from a large population of cells, which at best will give the average. Now, using single cell sequencing methods, researchers at the Salk Institute and their partners from around the world have been able to show that the genomic structure of the same person's nerves differs from cell to cell to a greater extent than previously thought. The findings were published on November 1 in the journal Science.

"Contrary to what was once thought, the genomic composition of the neurons in the brain is not the same, but consists of a patchwork of DNA" says Fred Gage, one of the partners in the study, and head of the V and John Adler Center for the Study of Neurological Diseases Associated with Aging at the Salk Institute.

In the study, led by Prof. Mike McConnell from the Center for Theoretical and Computational Biology at the Salk Institute, the researchers isolated about 100 neurons from the bodies of three people who underwent post-mortem surgery. The scientists looked at an overall view of the entire genome, looking for large deletions and DNA duplications known as copy number variations (or CNVs) and found that up to 41% of the neurons contained at least one unique CNV that formed spontaneously. This means that the CNV spreads throughout the genome. The very small amount of DNA in a single cell must be chemically amplified several times before it can be sequenced. This process is technically difficult, so the team spent a year eliminating errors that resulted from this process and not from the original structure of the genome. To this end, Gage says, many control experiments have been conducted.

In one of the experiments, the researchers tested nerve cells created from induced stem cells extracted from skin cells of three healthy people. It was clear to the researchers that nerve cells produced from a common source would have the same genome but they were fooled. "There were several unique deletions and duplications in each genome of the neurons produced from one line of those induced stem cells."

Surprisingly, there is variation in the skin cells as well, but not on the same scale as in the nerve cells. It is now estimated that the great variation in the genome of nerve cells results from changes in a late stage of embryonic development and are not hereditary. "The problem with nerve cells is that unlike skin cells, they don't replace each other and they are also in contact with each other," said McConnell, now at the University of Virginia. "The fact that the neurons form a large network where each cell has a CNV that makes it different, could have a big impact on the brain."
Spontaneously occurring CNVs are also associated with brain disorders such as schizophrenia and autism, but in these studies many blood cells are usually used and as a result the effect of the CNV is not detected in them.

The purpose of this variation in the brains of adults is unclear, but researchers have some ideas. It is possible that the adaptation may help people absorb new and surprising experiences in life, or they may help survive a major virus epidemic.

Cells with different genomes may produce unique RNA and therefore also unique proteins, but the sequencing method does not allow us to know this. "If and when we have additional methods for sequencing a genome in a single cell, we will be able to see if these different genomes also have different transpososomes (the collection of all types of RNA in the cell) in predictable ways," says McConnell. "In addition, it will be necessary to sequence many more cells, and in particular more types of nerve cells" says Ira Hall, professor of biochemistry and molecular genetics at the University of Virginia. "There is a lot of work ahead of us until we understand in depth to what extent the diseases are related to the fact that the nerve cells are unique or that it is related to different parameters such as the person's age." saying.

For information on the Salk Institute website

21 תגובות

  1. Nir
    Such a theory existed in the past, and was published by Henri Bergso more than 100 years ago. The big problem with the theory is that it doesn't actually explain anything. Huxley said this is like saying a locomotive has "catalytic power" and therefore can move the train.

    If the theory was correct then there would inevitably have to be something fundamental in living things that we could not explain with the help of the laws of physics and chemistry. That is not the case.

  2. In my opinion, Darwin's evolution is not the only theory that explains life. In my opinion the brain/dna/lives when they are in a certain environment - perceive what features are required by them to demand and obtain food and then they send instructions/"programmed" accordingly. There is an intelligent and rational mechanism in the living body that causes them to be created in a finite way according to the environment in which they are found. (of course without anything to do with Olhaim)

  3. I assume that in the last paragraph the reference is to the transcriptome and not transpososomes. In the name of punctuality…

  4. Mike I don't "insist" on comparing anything, I just think that the analogy here is correct and helps to understand things. I did not try to disprove the matter of the differences between humans that result from genetic variation, I only claimed that the differences are negligible, because despite the genetic difference between us we still all go for 2, look broadly the same and have a similar intellectual ability on average.

    Regarding the forest, I was talking about forest plots (with trees) and not forest clearings, as far as the animals that live there (birds, rodents...) are concerned, there is almost no difference between a certain forest plot and the one that is 100 meters away, and although there is variation between the trees there, there is not a single tree Which is the same as the tree in the second plot, in terms of functioning as a living environment - one plot is very similar to the one next to it.

    In the same way, I think that the genetic variation between the neurons does not have such a dramatic effect on the functioning of the overall network, the proof of this is that despite the genetic variation between the neurons, most humans still have a similar mental ability (compared to chimpanzees for example who cannot write poetry, theater or books).

  5. Why do you insist on comparing forest clearings and DNA? or between neural networks, to D.N.A. Analogies are made between the most similar and not between the different. And this is even when there is no need for an analogy because it is already factually known that every tiny change in DNA causes any difference between person to person. So you're trying to disprove a fact based on a comparison?
    Apart from that, to say that there is no difference between one forest clearing and another or between one brain and another in terms of their consequences is a statement completely detached from reality.

  6. Meir can be tested in a fairly simple way, testing the brains of mammals that do not use cell phones (laboratory mice for example).

  7. And maybe it's because of the radiation of the cellular devices, DNA that is knocked out only that the cells don't replicate like in cancer.

  8. I think the proof is quite simple, even though there is great variation in the minds of different people, we still all function in a similar way and our average intellectual ability is quite similar.

  9. Uri, the genetic difference between a human and a chimpanzee is only 1.5%. So every small change has meaning. Beyond that, negation of causality requires proof like any other argument.

  10. Perhaps a better example is trees in the forest, although there is great variation between the trees and no tree is the same as the tree next to it yet in all practical respects there is no difference between a particular piece of forest and the one next to it.

    That is, it could be that even if every neuron was exactly the same as every other neuron created according to the same piece of DNA, the neural network would still continue to function in the same way in all practical respects.

  11. Following on from the analogy I brought before (if it is true) this is similar to a car that comes off the production line when it is almost exactly the same as other cars in the line, but over time it gets hit here, bent there, scratches, scuffs and the like.

    Still it is almost no different in its performance from other cars that came off the line. In the same way, it may be that the difference between the neurons is quite negligible in terms of its effect on the function of the neuron as part of the neural network.

  12. You are not paying attention to the more fascinating point. I quote: "It is now estimated that the great variation in the genome of nerve cells results from changes at a late stage of fetal development and are not hereditary."
    That is, not only variation, but also plasticity.

  13. Maybe there is simply no meaning to this difference? That is, it may simply be negligible, just as there is always some variation between engines of the same manufacturer in a certain model of car (piston diameter, level of sealing, etc.) but still the car drives and there is almost no perceptible difference in performance between cars from the same production line.

  14. Fascinating, thanks Mike

    Anonymous user, according to my understanding the genetic variation in the cells of the immune system is very limited. This is not the case with neurons.

  15. The entire system of immune memory is based on genetic variation between the cells of the immune system

  16. יוני
    In the case of a nerve injury, the information in the DNA allows for the reconstruction of the synapse pathways. So that the continuous updating of the DNA following the change of the cell structure, in the event of an injury, enables the restoration of the memory through the rebuilding of the synapses.

    It is also possible that the change in the DNA was done even before the change in the cell structure, which helps the synapse easily find its way in the brain. This is one of the open questions in neuroscience, how the synapse calculates its route.

  17. Interesting response Mike.
    "It is very likely that the DNA that stores the information about the neuron will also change..."
    Why is this assumption reasonable? Where do you think the change comes from? Mutation?
    Why would the DNA in a neuron cell have a higher mutation rate than the rest of the DNA in the body?

  18. I thought so and I'm glad to see I was right. If we take into account that neurons, unlike other cells, are plastic and change all the time, and no two are alike in terms of the number of synapses, and their weight, what's more, in the case of neurons, the location and specific connections of each neuron are also important. It is also very likely that the DNA that stores the information about the neuron will constantly change in certain parts.
    In the future we may be able to collect the DNA of all the neurons from a dead person, and with their help revive the brain.

Leave a Reply

Email will not be published. Required fields are marked *

This site uses Akismat to prevent spam messages. Click here to learn how your response data is processed.