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Mitochondrial genomes are very stable

  1. Jan 5, 2004 #1

    Monique

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    I was always thinking that the mitochondrial genomes are very stable, but now I am reading that they have an unusually high rate of mutation, which may contribute to many of the medical problems of old age.

    So which is true maybe it's that mitochondria are passed down from mother to child, and that female germline cells go through a minimum of divisions and are metabolically inert, thus the mitochondria that are passed down the generation ARE stable? And they thus CAN have a high mutation rate..
     
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  3. Jan 5, 2004 #2

    Monique

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    For those who don't know, about one billion year a bacterium invaded a eukaryotic cell (animal) and formed a symbiotic relationship with it. That bacterium evolved into our energy producing machinery, the mitochondrion.

    Evidence for that invasion are the double membrane of the organelle and the genetic code, which is similar to prokaryotes (bacteria) and not to eukaryotes (animals).

    The chloroplast in plants has the same type of origin, only appeared later and thus shows more resemblence to the the original bacterium.
     
  4. Jan 5, 2004 #3
    Had a biochem. prof tell me that most proteins in a mitochondria are actually encoded in nuclear DNA. The mitochondrial DNA only encodes something like 16 proteins, not nearly enough. So I'd guess mitochondria are subject to just as much mutation as we are.
     
  5. Jan 5, 2004 #4

    Monique

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    Well, the genes in the nuclear DNA that code for mitochondrial proteins actually are of prokaryotic origin, but that on the side.

    Directly from my text book:
    "Comparisons of DNA sequences in differtn organisms reveal that the rate of nucleotide substitutions during evolution has been 10 times greater in mitochondrial genomes than in nuclear genomes, which presumably is due to a reduced fidelity of mDNA replication, inefficient DNA repari, or both."

    "Because only about 16500 DNA nucleotides need to be replicated and expressed as RNAs and proteins in animal cell mitochondria, the error rate per nucleotide copied by DNA replication, maintained by DNA repair, transcribed by RNA polymerases, or translated into protein by mitochondrial ribosomes can be relatively high without damaging one of the relatively few gene products."

    "The relatively high rate of evolution of mitochondrial genes makes a comparison of mDNA sequences especially usefull for estimating the dates of relatively evolutionary events, such as the steps in primate evolution."

    So what had been in MY mind the past years is that we were able to trace back our own ancestry to 7 or so Eves, due to the fact that mDNA is well conserved. Apparently the mutation rate is still comparitively high to nuclear DNA..
     
  6. Jan 5, 2004 #5

    Monique

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    The human mitochondrial genome encodes 13 proteins, the largest is 97 genes in Reclinomonas americana.
     
  7. Jan 5, 2004 #6
    why are mitochondria only passed on through the mother? i once heard an explanation for this that mitochondria are coded for on the X chromosome, which comes from the mother. this is a good explanation for men, who have an X chromosome from the mother and a Y chromosome from the father, but a woman, who has two X chromosomes from each parent, why cant she inherit the mitochondria from the X chromosome of the father?
     
  8. Jan 5, 2004 #7

    Monique

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    Hi Mark1, you are confusing the X chromosome story with diseases that are linked to genes on that chromosome. Males ALWAYS inherit the X-chromosome from their mother and an Y chromosome from their father (the father doesn't pass on an X-chrom to his son).

    In this case the mitochondria all come from the mother, because they are organelles that float in the cytoplasm. An egg cell is large and contains about 2000 mitochondria. A sperm is really very small compaired to that, and the mitochondria are all located in its tale. When the sperm fertilizes the egg, the head fuses with the membrane, but leaves the tail behind. So that is why the sperm in doesn't contribute any mitochondria (although I have heard of some data, where a VERY small amount of DNA WAS found back from the father..).
     
  9. Jan 6, 2004 #8
    It seems to me that you are confusing mutation rate with stability. Once a person has died, the mitochondrial DNA can be used for identification purposes, long after death, due to the high stability of the mitochondrial DNA. This has nothing to do with mutation rate, b/c mutations only occur in replication.

    Nautica
     
  10. Jan 6, 2004 #9

    Monique

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    But mitochondrial DNA is used to trace ancestries, it has been used to trace the geographic location from which humans originated, we are supposed to have decended from 7 different mothers, Eve's.

    Mitochondrial DNA is not used for identification purposes, you have the same mDNA as all your siblings and your mother and your grantmother.
     
  11. Jan 6, 2004 #10
    Mitochondrial DNA is used all the time in forensics. Obviously it can not set you apart from siblings, but it can tie it down pretty close.

    Nautica
     
  12. Jan 6, 2004 #11

    Monique

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    I really don't think so, the chromosome is only very small, what is the likelyhood going to be that it is the same to others? And since it is only passed down through mothers, and you would follow the passage of the chromosome from a grantgrantgrantmother through all the daughters, the familyweb that carry the same chromosome would be quite large..

    You have any evidence to support your claim? As far as I know a collection of SNPs is used to identify people.

    Why is mitochondrial DNA more stabile than genomic DNA?
     
  13. Jan 6, 2004 #12
  14. Feb 5, 2004 #13
    Swim Lessons?

    A question form a novice:

    Since the off-spring carries NO mDNA from the father, where is the evolutionary feedback/pressure which rewards the successful reproductive efforts of the organelles in the father's sperm?

    In other words; "survival of the fittest" relies upon the passing on of successful mutations when they occur and yet such performance enhancing mutations as may have occured in a SPERM's organelles which allowed it to sucessfully join with an egg, are lost to subsequent generations.

    Note: the organelles in a sperm are the principal source of energy which the sperm uses to swim... swimming is something unique to sperm among all (higher life-form) eukaryotic cells... How did the sperm learn to swim?

    Any theories?
     
  15. Feb 5, 2004 #14

    Monique

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    Re: Swim Lessons?

    VERY interesting question.. need to think about that one for a while :)

    I don't know why you say the following though:
    Since only sperm which swim the fastest (and in the right direction) will pass on their DNA, their IS survival of the fittest and passing on of genes. What I wonder though at the moment.. are the mitochondria genes on the autosomes or on the X chromosome? Does that even matter?
     
  16. Feb 6, 2004 #15
    Re: Re: Swim Lessons?

    As to your observation vis a vis "survival of the fittest";

    ____________________________
    Since only sperm which swim the fastest (and in the right direction) will pass on their DNA, their IS survival of the fittest and passing on of genes.
    ____________________________

    My reference was to the (non) passing on of performance enhancing mutations in the sperm's organelles (mDNA) not to the sucessful nDNA propagation.

    I guess the assumption is that the "motor" (organelle) is more important to a sperm's success than the "brain" (nucleus).

    On the other issue you raise;

    _____________________________
    What I wonder though at the moment.. are the mitochondria genes on the autosomes or on the X chromosome? Does that even matter?
    _____________________________

    Not sure... aren't the mitochondrial genes in the organelles, not the nucleus?
     
  17. Feb 6, 2004 #16

    Monique

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    Re: Re: Re: Swim Lessons?

    Some time during evolution there was a transfer of mitochrial genes to the nuclear DNA, so part of them reside there. At some point this transfer stopped, not sure why.
     
  18. Feb 6, 2004 #17

    Monique

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    My textbook says that the nucleus has to provide at least 90 genes just to maintain the organelle's genetic system. The diversity in the location of the genes coding for the subunits of functionally equivalent proteins in different organisms is difficult to explain by any hypothesis that postulates a specific evolutionary advantage of present-day mitochondrial or chloroplast genetic systems.

    Perhaps the organelle genetic systems are an evolutionary dead-end. In terms of the endosymbiont hypothesis, this would mean that the process whereby the endosymbionts transferred most of their genes to the nucleus stopped before it was complete.

    Further transfers may have been ruled out, for the mitochondria, by recent alterations in the mitochondrial genetic code that made the remaining mitochondrial genes nonfunctional if they were transferred to the nucleus.

    From Alberts et al, molecular biology of the cell.
     
  19. Feb 7, 2004 #18
    As I understood it, the gene transfer was an "efficiency move" to eliminate redundancies and occurred relatively soon after the symbiosis event. It seems logical that if the same cellular function could be performed by two genes (one in the nucleus and one in the organelle) that a transfer of that job would occur under evolutionary pressures and that the larger, more complex nDNA's gene
    would get the job (sort of like in some company mergers today).

    Yet, your quote seems to imply an actual physical migration of genes from the mDNA into the nDNA... not an atrophy. Is there evidence of movement in the other direction... genes in the present mDNA which perform jobs originally done by genes in the nDNA (aside from the obvious next-step in metabolism)?

    As it relates to the swim lesson question, the fact remains that the organelles perform the necessary cellular function of metabolism and that swimming requires efficient metabolism... do you agree?

    To the extent that efficient metabolism in the organelles is governed by genes in the nDNA I agree that mutations in those genes DO get passed on as a reward for superior swimming... but what about a mutation in the mDNA of a given sperm cell which enhanced its performance...

    Quoting myself - new emphasis:
    In other words; "survival of the fittest" relies upon the passing on of successful mutations when they occur and yet such performance enhancing mutations as may have occured in a sperm's ORGANELLES which allowed it to sucessfully join with an egg, are lost to subsequent generations.

    Do you understand now why I said the preceeding?

    Oh, as to Whohooo! ... statistics! don't you love it?:)
     
  20. Feb 7, 2004 #19
    Huh it's not our sperm that learned to swim it's old evolutional characteristic existing from primordial animal life in water (same thing is with plants-just they reduced that characteristic with stepping from water ferns to larches )
     
  21. Feb 7, 2004 #20

    Monique

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    Yes, the genes physically migrated from the mDNA to the nDNA. We know that because of their resemblence to bacterial genes and the existance of non-coding DNA sequences that seem to be of recent mitochondrial origin.

    You are right for the genes encoded in the mDNA, which are 2 ribosomal RNAs, 22 transfer RNAs, and 13 different polypeptide chains. None of these will be passed on by the father to subsequent generations (although it is said that some portion of the sperm mDNA DOES get passed down).

    But a fertilized egg has very high energy requirements, since it has to grow so fast, so there definately IS an evolutionary feedback which selects for organisms with good functioning mitochondria. It is well documented that some females are infertile because of bad mitochondria in their eggs, and that cytoplasmic transfer from a healthy female overcomes the problem :)

    :P did you get a chance to read it? I did my very best to make it readable for a non-initiated biology person, but that ain't easy ;)
     
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