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Phoenix garden

Genes that were once active and produced useful proteins, sometimes become redundant, accumulate mutations and stop producing protein. Can such a gene, after it "died", be resurrected and start functioning again?

A mathematical analysis of the human genome led researchers to the conclusion that what is known as
A mathematical analysis of the human genome led researchers to the conclusion that what is known as

During evolution, animals acquire new traits - and also lose existing traits. In the process, genes that were once active and produced useful proteins, sometimes become redundant, accumulate mutations and stop producing protein, or produce a damaged protein that does not function. Such genes join the "junk-DNA", which constitutes the majority of the DNA in our cells: DNA that does not code for proteins, nor does it have any other known purpose.

But can such a gene, after it "died", be resurrected and start functioning again, millions of years after mutations made it inactive? Seemingly, there is no reason for this not to happen - with one mutation can damage the activity of the gene, another mutation can turn the situation around and return it to activity. The problem is that there are many more ways to damage a gene than to repair it - moreover, from the moment a gene becomes inactive, and assuming that the loss of its activity is not harmful, natural selection no longer affects it, and it accumulates more and more mutations. Therefore, the possibility that a gene will "come back from the dead" seems completely improbable - but this is exactly what a group of researchers from the USA, Spain, Italy and Germany discovered, which traced the evolution of the IRGM Immuno-Related GTPase M- gene.

This garden has a strange history. In most mammals, three genes with a similar structure appear, but in primates - the group that includes monkeys, apes, great apes and man himself - things start to get complicated. When the researchers tested these genes in lemurs, a type of ape, it turned out that in them two of the genes no longer functioned. In monkeys, on the other hand, the third gene also stopped functioning, following the random insertion of a foreign DNA segment into the beginning of the gene. The exact same segment is also found in the Old World monkeys, living in Africa and Asia, and also in the New World monkeys, the Americans. From this, the researchers concluded that the mutation occurred before the two lineages separated from each other - that is, more than 35 million years ago. Since then, the gene has been inactive, and has accumulated additional critical mutations - for example, mutations that caused the creation of a DNA sequence that means "finished making a protein" at a too early stage of the gene, so that the resulting protein will be very short and inactive.

Apparently another dead gene, like countless other genes. But there is various evidence that the IRGM gene is active in humans - it produces a protein, although it is shorter than the protein produced by mice and other mammals, and previous studies have shown that the protein is apparently active, and helps protect against certain strains of bacteria. Another proof that the gene is active in most people comes precisely from those in whom it is defective: a certain mutation in this gene (a new mutation, which exists only in humans), was found to increase the risk of contracting Crohn's disease, a chronic intestinal disease. Man is also, as mentioned, a primate, and we are descendants of the same ancient ape that is the father of the modern apes. If more than 35 million years ago the lineage leading to man lost the IRGM gene, how did it happen that, like the phoenix, he suddenly came back to life?

It turned out that three different mutations were required to restore the gene to activity. One of them was, again, the introduction of a foreign DNA segment. This DNA segment once belonged, in the distant past, to a retrovirus - viruses with a unique method of operation, in which they insert their genetic material into the DNA of the cell they infect. If such a virus infects a gamete, its genetic material is transferred to the embryo and becomes part of its genome, thus passing on to its offspring. Originally, the genetic material introduced into the cell is supposed to produce more and more viruses, but the DNA of viruses also undergoes mutations, and after a while only a meaningless remnant of what was once the genetic material of a virus remains in the cell. During evolution, humans "acquired" DNA from many viruses in this way - some estimate that about 8% of our genome consists of inactive retroviruses. And here, part of such an inactive retrovirus enters, by chance, right before the IRGM gene.

Why is this important? Because this part still retained its original function, from the days when it was part of an active viral DNA - to be a promoter, that is, a DNA sequence that signals the cell's proteins: here is a gene that needs to be copied. For the first time in millions of years, since the first deleterious mutation, the cell treated the IRGM DNA sequence as a real gene. But it was not enough: as mentioned, two more, more conventional mutations were required to restore the gene to activity. One of them created a new DNA sequence that marks the beginning of protein creation, right after the new precursor. The second canceled one of the previous mutations, which created a premature termination sequence.

When did these mutations happen? It turned out that they are not unique to humans, but are also shared by African apes, chimpanzees and gorillas, meaning that the gene came back to life before these three lineages separated from each other. Even more interesting is the situation with the Asian apes, the gibbon and the orangutan: the first two mutations, the introduction of the viral DNA and the creation of the sequence that signals the start of protein production, are also found in them. The third mutation, which eliminated the termination sequence, is also found - but not in all individuals. That is, the new form of the gene has not yet been established in the population, and you can find both forms, the active and the inactive. From this it is possible to learn the relative order in which the mutations occurred, and that they happened more than 18 million years ago - when the lineages of the African and Asian great apes separated.

This is the first time that a gene has been found that has "come back to life" after mutations made it inactive - one of the scientists compared this situation to "lightning striking twice in the same spot". Many questions still remain open: how could the monkeys "give up" the gene, without it harming them (the loss of the corresponding gene in mice leaves them very vulnerable to diseases)? And if the gene was unnecessary, what led to its "return to life" in the apes? It is possible that this study will lead other researchers to look with new interest at the "dead" genes that are still found in our genomes and those of other creatures - and perhaps these studies will direct us to the answers.

For an article published in PLoS Genetics

More of the topic in Hayadan:

24 תגובות

  1. Beyond that there are many other genes that are similar in humans and chimpanzees and different in the other monkeys. This is not the author's assumption, but what is accepted among evolution researchers, relying, among other things, on the genomes of the various animals.

  2. Even in humans and apes, the destructive mutation exists, the "constructive" mutations exist in addition to it, so the proposed explanation is the most logical

  3. The author assumed, in my opinion possibly wrongly, that the evolutionary split of the human and ape groups from the ape and ape groups took place after the evolutionary development of the apes and apes.
    Is this assumption certain?
    I think it is possible and she is wrong. It is possible that man and apes split from primitive primates at an earlier evolutionary stage, before the development of monkeys and apes, and therefore, they do not have the same mutation that exists in apes and monkeys, which also constitute an evolutionary development in relation to the primitive primate from which they split.
    It is thus possible that the mutation distinguished in them is late in relation to human development and therefore, there is no certainty that the explanation of constructive mutations on top of destructive mutations is the correct explanation.

  4. Following on from my 7th comment, I just wanted to point out that the discussion on this issue with Adi Marcuse Hess has started Link below:

    So, as mentioned, I have not yet reached the conclusions I presented in response 7

  5. hybrid:
    Logic at its best!
    Since no two people have the same DNA - let's also conclude - according to the best tradition you are trying to instill in us - that there are no two people born to the same father (or mother) or - in other words - that siblings are just science fiction.
    The presentation of reality as science in fiction goes well with the presentation of fictional "science" as reality.

  6. The fact that there is a difference between humans can indicate that we were not all created from the same ancestor,
    The fact that mice can be manipulated can indicate that humans can also be manipulated.
    Yonat's conclusions and the combination of facts may be enough for Yonat to believe herself.
    No one wants to believe that he was just wasting resources.

  7. Yonat... I know it was just a joke.

    Think you didn't have toenails? :O How would you do nail polish?

    It is possible that, like software code, there are unused code parts, but this does not mean that they do not depend on anything, and on the contrary that nothing depends on them.
    So the claim if there is something is simply not yet proven here or there.

    To REVERSE ENGINEER the human DNA... something that will take a good few years.

  8. hybrid:
    But your mission is no longer complete so you can go back

  9. In general - this whole idea of ​​living beings being optimally adapted and the absence of mechanisms that do not confer an advantage is a fundamentally absurd idea and as I have already said once - it is in direct contradiction with evolution and the facts that confirm it.
    After all, evolution is a process in which the most successful variations are selected from among the multitude of existing variations.
    What it means?
    This means that at each stage there are many variations and if the optimal one is chosen then the rest were not optimal.

  10. Gil Dotan -
    The gene of the foot fungus is found in the fungi…

    And seriously:
    Why wouldn't part of the DNA be "just" there?
    Think of it this way: let's say that a segment of DNA that does not code for a gene and has no role in control or any other role (such as a gene that lost its function due to mutations, or a piece of the genome of a virus), is found in the genome of some creature. It is known that such things happened and are happening. Will he disappear? Why? It "picks up" a ride on the inheritance mechanism and is passed on to the next generation, along with all the useful genes. If his presence there is harmful, the individuals in which he is found will produce fewer offspring and he will eventually disappear - this is the natural selection. But if it is not harmful, it will remain there - and after several tens of millions of years quite a few such sequences will accumulate, which are of no use.

    We carry our evolutionary past with us - and it includes residual organs, which have no use today. I won't go into the question of whether the appendix has a role in our body or not (there is a debate about that), but why, for example, do we need toenails? They are there, apparently, because they are not harmful or disturbing, and do not require a particularly large investment of resources - and they used our ancestors as claws. Today they are simply a residual limb. In exactly the same way, a residual garden is also possible - which was once useful, but today is no longer.

    There is much evidence that not all the DNA in cells is essential and important - the fact that there are areas in the human genome where there is great variation from person to person in the DNA sequence, so that it does not seem to code for any important message, and the fact that in mice and other organisms genes can be inserted and thus "disrupt" the sequence in large areas of the genome, without any effect on the development of the organism.
    Again, we may one day discover that all DNA is important and necessary - as far as I know, anyway, there is no particular reason to think so today, other than the belief that "nature is not wasteful" - but evolution does not have an optimization team, and nature can certainly be wasteful in areas certain

  11. In my current experience I am in a human body and therefore I am also part of the general process.

    In the current evolutionary process the development is in the subtle bodies and consciousness
    "illuminous" = refers to the "illuminated" "energetic" body

    A person who believes that monkeys can evolve into thinking people has no difficulty believing that humans can evolve into something new and even more wonderful.

    By the way, I will not return "home" until my mission is completed.

  12. hybrid:
    of course!
    And Homo Illuminos will be used for lighting.
    He will be some kind of humanoid firefly that will be attached to your spaceships so that you will be even more careful.
    By the way - why do you say "in front of us"? After all, you've already been down this road a long time ago, haven't you?
    And one more thing - we haven't heard from you in a while. I already thought you went home to the Pleiades.

  13. The evolution of the "homo sapiens" is coded from the beginning of life on the way to the next stage:
    "Homo Illuminos".
    All the genes, even the unknown ones are used to say something.

    There is still a road ahead of us and many discoveries...

  14. Sorry to interrupt, but what are you talking about?
    Maybe you can explain the topic to us in a popular way!

  15. Surely the garden of the fungi in the feet is there somewhere... Because it is quite difficult to resign from it 😀

    It will take a few more good years until we know why there is the rest of the DNA.

    He's just not there...

  16. I saw Hanan Sabat's response and planned to respond something similar to Yonat Ashchar's response, but then I saw her response and it turned out to me that I was late.
    I would add two things to the comment, however.
    One is just part of local culture - I would refer Hanan to the discussion that developed here around the question "how do we know that we know" for further clarification of the term "a garden with a known purpose".
    The second is an emphasis on the fact that retroviruses do tend to integrate into the cell's genome more than normal viruses.
    I remember that I have already come across statements in the past that attributed the combination of DNA to retroviruses and on one occasion I posted on this site a question similar to the one posted by Hanan.
    Adi Marcusa Hess who responded to my response really said that there was no particular reason why she said retro virus and not a virus but after reading some more material and thinking a little more about the subject it seems to me that there must be a reason for the fact that everyone attributes the integration into DNA to a retro virus and not to a virus and such a reason must exist even if Not everyone who expresses himself like that knows what it is.
    My analysis - correct to this point - and I would be happy if someone who really studied the subject and did not guess it like me from information crises - would confirm or refute the things - is as follows:
    A normal virus inserts its DNA into a cell and uses the cell's replication mechanisms to replicate itself.
    However - usually *no* such a virus integrates into the chromosomes themselves.
    Why doesn't he do this?
    Because if it was integrated into the chromosomes themselves, it would become part of the cell and would not reproduce except when the cell itself replicates!
    The DNA of such a virus integrates into the cell separately from the chromosomes "so that" it can replicate at a much higher rate than them!
    What's up with retro virus?
    For him there is no such problem.
    He causes his DNA image to be integrated into the chromosomes using reverse transcriptase followed by integrase and then, for replication, he puts on the mechanism that produces RNA from the DNA.
    This mechanism is activated in the cell non-stop (for example for the production of proteins) and therefore it will produce many copies of the virus without the need for the cell to replicate.
    I would like to add and say that I am really proud of the aforementioned analysis because I could not find it anywhere even though I also asked professional geneticists, but of course if someone who is well versed in the subject gives a better explanation I would be happy to adopt it.

  17. Hello Hanan
    Thanks for the comment…
    Regarding the junk DNA - you are right, there are new studies that show that the part of the DNA that does not code for proteins has important roles, especially in regards to control. Some of them are even copied and create RNA that has a role in the cell, even if it does not turn into a protein. We still don't know everything about this DNA, that's why I wrote "without a *known* purpose", and not "purposeless". However, I do not accept the claim that "nature leaves nothing superfluous". Nature has no plan of action, and there are probably things that are in our genome simply because they were there before - maybe they once had a role, maybe they entered as viruses, etc. - and they are not enough of a nuisance for natural selection to remove them from there. The current theory is that still a large part of the DNA in our body is not used for any purpose. But it is possible, of course, that this is a mistake.

    Regarding retroviruses - not accurate. There are many RNA viruses that do not insert their genetic material into the cell's DNA (like influenza viruses, for example), but only copy it in the cytoplasm. DNA viruses do insert their genetic material into the host's DNA, and retroviruses, as you mentioned, are RNA viruses, which create DNA in the cell according to the template of their RNA, and then insert it into the cell's genome. I didn't want to go into all this virology in the article itself, but anyway - thanks for the clarification.

  18. In recent years, more and more information about what is known as "JUNK DNA" has been accumulating.

    In my opinion, to claim that he has no known purpose is inaccurate.

    These studies raise the possibility that not only are there "dormant" genes (and not necessarily genes that once functioned and accumulated mutations, but genes whose function is not known at all, nor is their origin, since some of them are found only in humans and not in other animals). In addition, it is now thought that part of that DNA is responsible for controlling other processes in the cells, and there are even more far-reaching studies that raise questions about the origin of segments that appear to be coded, but have no equivalent except in humans (and their products are unknown).

    In general, we can say - nature does not leave anything "unnecessary". Not organs, not creatures and probably not genes either.

    In addition, a note - why define a retrovirus as "viruses with a unique mode of action, in which they insert their genetic material into the DNA of the cell they infect"? Every virus works by this mechanism. Retroviruses are unique in that their inheritance molecules are based on RNA and not DNA.

    Hanan Sabat
    http://WWW.EURA.ORG.IL

  19. Quite amazing, on the site where I read about the garden's paralysis and revival, they called it "Jesus' Garden".

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