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Science

Dolly the Sheep not totally identical clone 115

Posted by Hemos
from the not-unexpected dept.
Marillion writes "Dolly, the first animal cloned from an adult mammal has variances in her DNA from her "Mother." " The variances in the DNA are actually in the mtDNA, or mitochondrial DNA. It's an interesting read if you are interested in cell biology/embryology.
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Dolly the Sheep not totally identical clone

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  • But what counts as a 'stupid genetic problem'? Anything that isn't the result of your enviroment? Who gets to decide if something is a problem?
  • by Anonymous Coward
    According to 'Vedas', human soul is positioned somewhere near the heart, the brain is only interface between body and soul. ;) (Chakras) I guess it's not that far from when we'll get proof of this point.

    We've swapped darn near every organ in the body, except the brain, amputated limbs, etc. Nothing affect who we are until you start fscking with the brain. But forget brain transplants, just wait until we get the tech to take a #D scan of the brain's cell structure, interconnections, and function and use that info to duplicate a functioning brain in software. Now that should sufficiently quash all remaining concepts of there being a 'soul'. And if the software brain can run within a really small computer case that can fit inside your skull, you can copy your mind to the machine, implant it into your freshly cloned body and be immortal! But it gets worse. The w4r3z kiddies of the future will create full clones of Cindy Crawford, etc. (when the tech becomes cheep) that could be created, "played with" and then disposed of (the matter reclaimed for the next "toy"). With cool remote 3D internal imaging equipment, someone could 'pirate' a copy of YOU, do what they will with it, then get rid of it untracebly. Is this a crime since the subjects aren't "real"? Ignoring this issue won't make it go away when the tech makes it feasible.

  • I thought they were "medigloricans" or something like that. I'm sure it probably was "mitochondria," and I was just hearing things, but oh well.... either way, I wonder what _their_ explanation is for how they get into the blood, since they mentioned them in the blood and not in the cells. I think. Any more thoughts on this?
  • by Anonymous Coward
    I pointed out immediately after the original announcement that the Hayflick limit (the cellular aging clock) was not reset in the cloning process, since it is only reset in the presence of telomerase, during gametogenesis.

    Note that telomerase is also present in many forms of cell immortalization, such as those which result in cancer.

    If you want to look to defeating aging, you should look to http://www.geron.com , since they are the holders of the patent on human telomerase encoding.

    In any case, it's well known in the biotechnology community that Dolly is going to be prematurely senescent due to the shortened telomers resulting in an advanced (by the age at which the cells were removed from the original "parent") cellular aging clock.

    If you are young, you might get away with cryogenic preservation of predominantly undifferentiaed cells, probably epithlial cells extracted from your intestine, but if not, no clone will be able to restore your lost youth.
  • Okay, in hair and nail clippings there is no DNA. They are both composed of proteins. Skin is a bit problematic in that the (surface) cells are already dead. You can still get some sequence from them using the Polymerase Chain Reaction (PCR) protocol, but that's more diagnostic than clinical. PCR has been developed to the point that, with the highest end setups, only one copy of the target sequence needs to be there for you to amplify and detect it.

    DNA is usually stored by extracting it from cells, supporting it in a buffer solution of correct pH and concentration, and freezing it at -80C. The thing is that while DNA as a molecule is rather robust, DNA as a storage medium is not. The information in it is rather fragile under chemical attack (free radicals or nitrites) enzymatic attack (from DNAse enzymes say) or harsh conditions (UV light). You only have to break two chemical bonds to sever the molecule. That's just as permanent as cutting a video tape with a pair of scissors. The best place to store DNA is in a living, respirating, cell that will take care of the DNA and make repairs to it.

    As to how long DNA can be stored with the sequence unaltered, we don't know yet. Watson and Crick published their paper about the physical structure of the DNA double helix in 1953. Large scale formal work with the information coded by DNA has only kicked into high gear since the late '70s, early '80s with PCR, Sanger sequencing, and restriction (DNA cutting) endonucleases. It's barely been 20 years so far.
  • Yes. While we have good statistical data to use for mutations and "genetic drift" in most chromosomal DNA, applying that to mtDNA is a bit questionable since it exists in a different chemical and enzymatic environment. Similar effects can be seen with the Y chromosome. Since the Y chromosome, with normal genetic segragation, never has a complementary chromosome to pair with, it lacks the final last ditch repair mechanism wherein the homoloqous chromosomes synapse and trade half their strands in hopes of patching over a damaged sequence. This has led to some rather bizarre gene arrangements accumulating over time like eight copies of the same gene in a row. Human mtDNA only codes for 13 genes. All other proteins used are imported from the cytosol. For sequenceing purposes, you can have a rather rapid mutation rate with individual bases changing. For genetic purposes you don't see much change in protein function because any large change tends to be catastrophic.
  • First, a number. For synonymous subsitutions (muations where a nucleotide changes but this change does not affect the protein product due to degeneracy), the rate in mammals has been estimated at 5.7 x 10^-8 subsitutions per site per year. Thats a pretty small number: most of yours and mine and everyone elses mtDNA is identical.

    As I read it, what you are asking about is what is known as a molecular clock. The idea of a molecular clock is using a macromolecule (DNA or protein) to date the time when an evolutionary event occured (like the most recent common ancestor of all humans today- mitochondiral eve.) In short, if we compare DNA sequences, we can find out how many sites they differ at. Then, if we know the rate of substiutions, we can figure out how long it has been since we all diverged.

    I say if because its not at all clear that rates of molecular evolution are constant between different groups. It seems that things like generation time, metabolic rate, body temperature and maybe even population size effect rates of molecular evolution. So our (human) rate of molecular evolution might be an order of magnitude different from the number I already gave. And the precise value of this rate will determine the value given for the age of Mitochondrial Eve.

  • Does that mean we have to make some kind of recolondria if we plan to visit other planets. I mean, what will our mitrocondria do to species that evolved somewhere other than earth?

    You saw what the descoloda did to humans!
  • Yes my post wasn't in the same scientific vein as the original message, but it wasn't exactly off topic either. Star Wars may be silliness, but so is cloning sheep in my opinion. Perhaps humor is always 'off topic' ...and BTW I know it was 'miticlorians' or whatever in TPM. That was part of the joke. Sheesh, at least *some* people followed along. :p
  • >But what counts as a 'stupid genetic problem'?
    >Anything that isn't the result of your
    >enviroment? Who gets to decide if something is a
    >problem?

    I would say that you do for yourself. the point is moot however, unless we can figure out a way to keep the brain from decaying, there's no point in doing a brain transfer.

  • Ah, thank you for that explanation. I must say "miti-chlorite" sounds a heck of a lot better than my feeble "medigloricans" (or however I spelled that gosh-awful word).

    In response to what you said about Mitochondria, well, if you take any kind of worthwhile biology course (I mean, "biology," not the larger pool of highly diversified and specialized courses that fall under the scientific category of being a biology), you'll learn that mitochondrian are/were believed to have been seperate entities before being taken in by cells (they have their own DNA, etc.). So that I already knew. (Thank you for pointing it out, nonetheless.)

    And I'm assuming they did mean to imply all of the spiritual over/undertones that were implied by that statement... because, the whole of Star Wars is that it's another great myth explaining the universe and the world as we know it. yay Star Wars!
  • Actually, a sperm cell contains several mitochondria, positioned near its flagellum (tail). Now, the question becomes-- why is a sperms's contribution to mitochondrion makeup nil?

    A sperm cell is rather tightly compartmented. The sperm's "head" contains the acrosomal vesicle (enzymes and other proteins for bonding with an ova's zona pelucida, or egg coat.) and a nucleus, containing the genetic material to be delivered.

    Behind the head lies a midpiece, filled with mitochondria, and behind that, the flagellum. Basically, in fertilization, only the nucleus of the sperm merges with the cytoplasm of the egg, and the sperm's mitochondria don't get a chance to enter the fertilized egg.
  • There are cells in blood. I'm sure they were talking about the miti-chlorite count in these corpuscles, not floating around in the blood itself.

    For what it's worth, some people think the mitochondria might have started out as wholly autonomous organisms, little bacteria that were subsumed by early eukaryotic cells. This is the story they give in Star Wars: The miti-chlorites live in a "symbiot circle" with the cells. I'll bet this is supposed to have spiritual overtones: Cooperation is good, while gratuitous strife--like the strife that keeps the Sith at each other's throats and hence restricts their number to two--is bad. The good side of the Force is epitomized by caring for others.

    Beer recipe: free! #Source
    Cold pints: $2 #Product

  • Does that mean we have to make some kind of recolondria if we plan to visit other planets.
    A diffrent thought... If we could geneticly engenear Mitocondria could we add the features of a computer to it?
    Forget adding hardware go 100% wetware.. No more worrys about batterys...
    Of course if someone made a Mitocondria computer Virus the potental exists for a "Parasite Eve"

    Or worse.... GPF in Mitocondria
  • Oops. Sory. I should have read yet more about in Molecular Biology of the Cell.Basically in fertilization, the entire sperm eventually enters the egg, carrying its mitochondria. However, the egg's mitochondria do substantially outnumber those of the sperm. Perhaps there are other selective pressures that further limit the male derived mitochondria.
  • So they forked Dolly's process but the clone's PID was different?
  • There was an article just the other day about this on slashdot - search for "Head Transplants".

    Kris
  • So that's why they had to import the frog DNA! Or was that just a cheap plot device?
  • No problem: take a sample from the original, insert in clone's gut, let colonise.

    Worst case: some bad diahhorea for a few days.
  • Inquiring minds want to know...

    Do we know why a given set of mt survives? Could we just chalk it up to a chemical "host cell advantage" that favors the host mt?

    Has this method been tried with a host cell that has been cleaned of intracellular structures?

    Will this process work in Kansas?

  • Regarding "what they found in Anakin":

    1) It was "midichlorians" but--at least to me--it seemed pretty darned obvious they were trying to talk about mitochondria withut talking about mitochondria.

    2) I agree it was quite Lame; I rather liked the idea of the Force being some mystical power like ki, not like something out of a bad ripoff of "Parasite Eve". :P

    3) EVERYONE I know, when seeing TPM, made the comment "Does this mean Darth Vader is really Mitochondrial Eve in a man's body now? Does this mean Aya Brea was really a Jedi?"...taking the piss of the whole midichlorian thing. (Then again, it can be argued me and my circle of friends read too much manga, watch too much anime, and play too many Squaresoft games for it to be healthy. ;)

    Off to forget about the whole midichlorian fiasco and go play Final Fantasy VIII because it came out today (yay!)...

  • It's no big surprise also because one factor, I presume.

    One is that every egg cell has to face the risk of being injected foreign mitochondria during normal fecondation. If I'm not wrong, the plasma membrane of spermatozoa locks to the egg's one and opens up upon fecondation, allowing the nucleus (and possibly the mitochondria that lie behind it) to flow in. Therefore, the egg is likely to be exposed to male mtDNA which will not appear in the grown animal.
    My guess is that male mtDNA, if injected, eventually disappears as mitochondria replication is not allowed in a foreign environment (the egg plasma is originally filled with female-only proteins).
    It could be that male mitochondria in the female egg are not able to exchange proteins or other components (such as membrane lypids, for which they're not entirely indipendent), thus 'dying' for lack of 'maintenance'.
  • For more information on this read The Selfish Gene by Richard Dawkins.
    For an excerpt in another book that has a lot of good essays check out The Mind's I by Hofstadter and Dennett.
    They're both excellent.
    -lb

  • Normally you get mitochondrial DNA from your mother because she provides the egg and nuclear DNA from both parents. In the case of Dolly she got nuclear DNA from the prototype only, through cloning, and mitochondrial DNA from the sheep that provided the egg. The scientists could have taken an egg from the prototype as well (if it was a ewe), and thus have kept the right mitochondria, but I guess that would have confused the experiment.

    The point is that it doesn't matter. Mitochondrial DNA should be very well debugged by now, so it shouldn't matter which one you have.

    Pavlos

  • I should specify that the stuff I mentioned addresses the concept of humans being a patchwork of interconnected beings working in harmony for self-perpetuation.
    That's what I'm referring to as being some of the focus of the articles/books, etc.
    Sorry I didn't specify earlier. -lb
  • by mattc (12417)
    Does your CLONED SHEEP have a SOUL??? I'm selling them cheap-- only $500 each, while supplies last. Includes certificate of authenticity.
  • After thinking about it for a minute, the lack of mtDNA from Dolly's 'genetic' mother makes sense. Since only the female parent's mitochondria are present in offspring, there has to be a mechanism for recognizing 'native' mitochondria and either destroying or directing to self destruction 'foreign' mitochondria. All functioning spermatocytes from every animal contain at least one mitochondrion. It's usually coiled about the protein "engine housing" for the flagelum that drives the cell. So every sperm/egg fusion event brings with it a 'foreign' mitochondrion, whether it is easily liberated into the egg cell cytosol or not. So what is the mechanism? A possible MHC for cellular organelles or something simpler?
  • It seems to me that we aren't really cloning anything in the purist sense. What we are doing is really creating a 'twin'.
    Cloning always seemed to be to be the duplication of the body(or parts therof) with sped up growth and no mind/soul.
  • Sorry, just couldn't resist.

    Anyone else remember that demented little thread?
  • ...or perhaps this is more accurately called "splitting hairs." Ah well, an exercise in pedantry by any other name...

    I just felt obliged to point out that while mtDNA may mutate faster, it is generally very nearly identical to the female parent, whereas nuclear DNA differs more from the parent because it is mixed half-and-half with that of the male parent. It's obviously not mutation, but it might explain where the idea came from.

    Also, favorable mutations are propagated more quickly in nuclear DNA due to the advantages of sexual reproduction. If one defines mutation rate as changes in the genome over time, it might change the answer.

    And finally, I have a question: is this higher mutation rate per nucleotide, per molecule, or a per organism? Nuclear DNA may be more stable, but there are a lot more potentially mutated nucleotides in a set of human chromosomes than there are in a mitochondrion.
  • Ok, just me or this totally contradicting an earlier posting. Someone qualified mtDNA as mutating 5-10 times FASTER then DNA, while the posting I am replying to indicated very little if any mutation. Could someone in the know please clarify which of these posting is actually correct?
  • This is somewhat unsettling, because it means clones do not carry on genetical diseases of the original in totality.

    That means that cloning becomes a way to cure some genetical diseases.


    Do you really believe in this "scientific" propaganda ?

    Do you really think you and your clone are the same ???

    Just imagine you were cloned and you and your clone were alive. Can you see through its eyes ? Can you read its thoughts ? Can you feel its pain ?

    No ?????

    Then you are obviously two *different* persons. The clone might be physically identical to you but *NOT* psychologically. It's not your body that makes you a unique human being, it is your mind.

    Besides, what's the point of cloning ? I mean, *WHY* would anyone want to do it ?

    ----------------------------- Insert favourite quote here -----------------------------
  • Well, as long as we are being technical...
    Also, favorable mutations are propagated more quickly in nuclear DNA due to the advantages of sexual reproduction. If one defines mutation rate as changes in the genome over time, it might change the answer.
    Well regardless of if you fall into the neutralist or selectionist camp, nearly everyone who studies molecular evolution agrees that very, very few mutatations are advantagous- they are deleterious or at best neutral. So theory predicts that sex should not speed up rates of evolution, at least in this manner. (Though I'm not aware of a study comparing rates in sexual and asxual organisms of the same species - but it would be interesting.)

    And again, the mutation rates which have been measured are per nucleotide per year at silent sites.

  • I thought there was DNA in hair.

    Can't a DNA test be preformed on a strand of hair? Or perhaps do you mean that a 'good' complete strand of DNA cannot be extracted from hair or nails?

    -pos




  • Isaac Asimov once wrote a ditty,
    sung to the tune of "Home On The Range":

    Oh give me a clone,
    of my own flesh and bone,
    with the Y chromosone
    changed to X,
    and when I'm alone
    my very own clone
    will be of the opposite sex.

    I told ya it was apropos of very little,
    but for the subject of clones...

    --------------------------
    Your Favorite OS Sucks.
    ^D

  • I had thought that the Mitochondria inside the spermatozoa were locked into a segment between the nucleus and the tail (sort of a pre-tail energy-generation region), so that they couldn't actually be injected into the egg anyway???...

    Well, actually no one ever told me that happens, but why shouldn't it? Since the nucleus enters the cell intact, there's no obstacle to keep them from slipping in. Also, I seem too recall that, unlike with other mammal sperms, human male nuclei enter the egg with their tail still on. It eventually gets 'melted' by enzymes, and it's one example of the egg reacting to foreign structures. Another one is the male nucleus itself, which dissolves after having triggered the female one into completing meiosis.

    Isn't it more likely that the female mitochondria are THEMSELVES recognising and destroying the male mitochondria?

    I don't really think so. As I said before, mytochondria are not 'living things'. We have almost complete maps of mt genomes and there aren't any enzymes that could do such things. Mytochondria are not even self-sufficient when it comes to maintaining their membranes, exchanging ions and they lack some key enzymes for respiration (is that the right English word for their main function?).
    The fact itself that mytochondria relate to ancient prokaryotes is fascinating and certainly likely, but not yet proven. My hystology professor told me last year that there's still a circulating theory that there really aren't many mytochondria, but a single, long and crooked one that gets sliced so that it looks like many.
    Of course, this sounds at least exotic, but shows how little we know about that.
    If the key to male (in the case of Dolly, ewe's) mtDNA disappearing is in anyway related to the outnumbering of female mt's over male ones, it has to be related to the incapability to reproduce as female ones do.

    It'd be also very interesting to know how much foreign mtDNA could be found in a 4-, 8-, 16-cell embryo. That'd allow our speculations to be proven or ruled out...

    Getting always more intriguing!
  • Unfortunately, a late post, so probably nobody will read this... :-(

    A couple of things:

    1) It has been postulated (and is, I think, a necessary part of the prokaryote-decendant theory) that a lot of mitochondrial DNA was actually snarfed by the nucleus - support for this postulate is precisely the fact that you mentioned - the nucleus provides a lot of supporting proteins/enzymes/etc. to mitochondria.

    This means that the nucleus could easily also be producing the mitochondrial proteins for mitochondrial attack on self-non-similar mitochondria. Therefore this possibility is not ruled, at least not by that argument.

    (2) I seem to recall 2 years ago that our biochemistry lecturer was adamant that we STILL didn't know what the majority of those nifty little Mitochondrial proteins did.

    We have the genetic code, but certainly not the protein-encoded meaning!!! A statement "there aren't any enzymes that could do such things" is not necessarily true....there are a lot of proteins that still have unassigned actions.

    (3) WHY are male mitochondria incapable of reproducing is exactly the question we are all hypothesizing about.

    It isn't sufficient simply to say that they are (incapable) - of course they are, they're not present in Dolly!!!!! I'm simply trying to present one possibility (they get bashed by the other mitochondria).

    ** Sorry - that's just a little dig. If you shoot my theory down in flames, I'm gonna show you don't have one... ;-) **

    -Shane Stephens
  • I seem to remember this from an earlier (or later) episode of Star Wars.

    Yodafish speaks: It was a cool night on Tatooine, the cloned sheep was Schaermen we. We whipped from ours light Light sabers and began to shear it. They had higher mitokondriezaehlimpulse than VorlagenYoda all!

  • 1) It has been postulated (and is, I think, a necessary part of the prokaryote-decendant theory) that a lot of mitochondrial DNA was actually snarfed by the nucleus - support for this postulate is precisely the fact that you mentioned - the nucleus provides a lot of supporting proteins/enzymes/etc. to mitochondria.

    Mmmmh, I'd rather see that in a symbiontic key. I don't think it's easy to demonstrate the eukaryotic nucleus actually transcribes snarfed mtDNA, if not for the fact that mtDNA codons and tRNA differ from those the nucleus has. IMHO, it's more likely that mytochondria originally were 'smart' aerobic bacteria that found a convenient environment within an anaerobic one. Only the ones that were compatible with host cell structures, and that were able to take advantage of them while producing enough ATP, eventually came to 'live' in it. It looks like a gradual, Darwinian event to me, much more like a 'coincidence' than a transfer of nucleic acid.

    Therefore this possibility is not ruled, at least not by that argument.

    Of course it isn't! I'm sorry if I looked too assertive, but I'm sure that we don't have enough data yet to rule out anything. I just meant to make my point and, as i said before, we'd really need to take a look at what is or is not in early embryos to start understanding.

    (3) WHY are male mitochondria incapable of reproducing is exactly the question we are all hypothesizing about.

    It isn't sufficient simply to say that they are (incapable) - of course they are, they're not present in Dolly!!!!! I'm simply trying to present one possibility (they get bashed by the other mitochondria).

    ... Which implies a positive action... But male (ewe's) mytochondria might just be unable to reproduce, which is different from 'being bashed out', as is being infertile from being killed before you ever have sex... The result, of course, is the same.

    ** Sorry - that's just a little dig. If you shoot my theory down in flames, I'm gonna show you don't have one... ;-) **

    I do have one, yet I can't really be sure it's the right one! My theory comes down to this: transplant mytochondria from a somatic cell to an unfecundated (or recently fecundated) egg--- the mytochondria won't be able to reproduce in that environment, although they won't be destroyed by anything else... They'll simply age and disappear (or brcome undetectable) because of their inability to reproduce and to maintain theirselves...





  • Yeah, but that still isn't attempting to answer the question...

    Look - take it as given that these mitochondria don't reproduce (if they did, they'd be present in Dolly).

    Right, now - WHY don't they reproduce? That's the question that you don't have a theory on.

    WHY do they simply age and disappear? WHY are they unable to reproduce and maintain themselves?

    Oh - and there are certain amino acid sequences on some transcribed proteins that specifically target these proteins to the mitochondria, which at least suggests that these proteins were never part of the general cell mechanism that were taken advantage of, but instead specific, required proteins that the nucleus started to produce instead of the mitochondria.

    It is just as likely, in fact, that the DNA code changed AFTER mitochondria entered the cell, and not before - remember it's fairly likely that the prototype eukaryotic cell and the prototype mitochondrial invader looked pretty similar.

    -Shane Stephens
  • Mmmmh the fact that a protein attaches to another structure doesn't imply it was built with that structure 'in mind'.

    Think of allergies. Random-generated antibodies eventually bind to molecules they've never encountered before. One might say, shit happens.

    The fact that some anaerobic prokaryotic cells produced proteins that were compatible with foreign aerobic invaders, thus setting up/contributing to a symbiontic system, is simply Darwinian. Some other didn't, and didn't make it to eukaryotes.

    Maybe you're right, I don't have a theory, if thinking that they might have receptors incompatible with carrier proteins isn't enough to make one. However, I don't really think I'll go any further in this discussion, as I have no evidence to answer basic questions:

    1) How many cell divisions does it take male/ewe mtDNA to become undetectable? This is important to assess whether mitochondria get rapidly eliminated or slowly, steadily degrade and decrease in number.

    2) Would mitochondria transplants from a somatic cell to one of another individual work? That could determine once and for all if an egg cell is a different environment than a somatic cell with respect to mitochondria (it is in 90% all other respects, actually).

    3) Would the same happen with a family in-breeding? That'd help understand if there's an in-cell 'hystocompatibility' system which differs from individual to individual, has a hereditary basis, or doesn't differ at all.

    I realize that if I don't have an experimental answer to these questions, I really can't say anymore than: "It just so happens that they die of 'natural' death. I don't really think they get killed."
  • Shit happens


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  • YEah


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  • This is somewhat unsettling, because it means clones do not carry on genetical diseases of the original in totality.

    That means that cloning becomes a way to cure some genetical diseases. Rich Man has genetical defect. Rich Man gets cloned. Clone ages as fast as Rich Man (remember that? Dolly's cells show signs as aging as fast as her progenitor.) Rich Man transplants his brain without chance of reject.

    Now that is a scary possibility.

    That, or maybe I've played Parasite Eve too much and I'm gittery when the word "Mitochondria" gets mentioned. :)

    "There is no surer way to ruin a good discussion than to contaminate it with the facts."

  • I don't think that this should come as a huge surprise. The egg used to create the clone had its DNA removed and replaced with the ewe's DNA; however it did not have its mitochondria replaced, thus the mtDNA of the egg would continue to be replicated and become Dolly's mtDNS

    ~Caliban
  • Now we don't have to worry about them showing up for just a little bit longer...

    At least they have some clues about that weird cell aging that they found before.
    Rick Rezinas
  • Hmmmm. There's an analogy I think....

    The mitochondria are small sort of independant cell-like structures contained within our cells. The thinking is that simple cells evolved into complex cells by subsuming other simple cells around them. It's a borg-like thing I guess. Anyway, these cells which started to live together took over different jobs within the cells, and the mitochondria got the job of converting molecules into energy for the rest of the cell.

    So, on a strictly cellular level, the mitochondria are the mitigators of the "force."

  • What they didn't tell you is that there is one other difference, this sheep... it is an EVIL clone!

    sporty
    ---
    And I shall call him, mini-me

  • Exactly.

    This idea of Lucas, to recycle the scientific fact that the Mitochondria (the power plants of the cell) have their own DNA and thus might be symbionts to us in his fictive religion was far more annoying to me than the Jar Jar binks character.

    I wonder if another fact, that Mitochondric DNA is passed from the mother only to the child, will be used too. This was useful to determine the gentic ancestor of humanity, BTW.

  • As far as I understand things, this makes it harder for a healthy clone to come from an older donor. The most successful clones will be from cells taken during the donor's youth because DNA tends to loose its accuracy and vitality as it ages from radiation and tiny, undetectible freak accidents. This aging puts widescale cloning back a fair bit in that cells have to be collected and frozen for years before the cloners know whether or not they wish to clone them. Alot more than just DNA goes into the formation of individuals, but the early keeping of cells can provide a fairly good reference point for trying to duplicate the organism they were from.
  • Actually, they were called mitochlorians (guessed spelling; I didn't read the book).
  • Not even a small surprise. Two years ago, people have pointed out that only the nucleus dna was copied. This new study only confirms this. A quick search on google found only a dead link of a 1997 article, cached here [google.com].
  • It's a scary thought, but mtDNA only accounts for a small percentage of genetic diseases. To eliminate most genetic diseases would require changing the DNA of the cell's nucleus; with this, the clone is no longer identical thus increasing the chances that the clone would reject the transplant.

    ~Caliban
  • Yes, I know it would be a real pain in the microscope... But this could perhapse be one of those instances where those nano-tools could be put to some use. I believe the original cloning procedure physically removed the nucleus from the mother cell, and put it into the empty egg membrane, thus the mitochindria that were not touched at all. Possible to suck out the little mitochondria and replace them too? Probably, but nobody cares enough to try for the 100% clone job.
  • Shouldn't be that scarry.
    I recall the article saying that the vast majority of genetic deseases/defects are carried by the nuclear DNA rather than the mtDNA. So, most likely, you would still have the same genetic defects as before. Hooptie
  • Just because the genetic material is not all exactly the same does not mean that the diseases are not the same. The way that they do the cloning is not very accurate, and will result in adding some new disease, or a third arm or what-have-you just as often as taking a disease out.
    I'm not trying to deny that they might be able to do what you are talking about eventually, but we are no closer than we were in the first place to having the forever man.
    We still have to learn how to replace parts of the DNA with other parts, (genetic surgery), and THEN clone.
  • Nothing contributed by the mtDNA makes it to the surface of the cell- thus there is no contribution by the mtDNA to anything that is linked to rejection. Thus- cloning is still a viable step in the fixing of genetic diseases (except those carried in mtDNA)
  • (..) however it did not have its mitochondria replaced, thus the mtDNA of the egg would continue to be replicated and become Dolly's mtDNS

    I have read (don't know how true it is) that our digestive system is working only if a certain collection of bacteria settles in our intestines. A new born is supposed to get this bacteria from his mother.

    I have no idea, about how individual that inteestine flora is, but it could form another factor to consider that has to be duplicated for a perfect clone.

  • And if the software brain can run within a really small computer case that can fit inside your skull, you can copy your mind to the machine, implant it into your freshly cloned body and be immortal!

    Then you'll have to start worrying about psychiatrists of the Redmond school, of course, but I wouldn't recommend open source for your brain, either.
    And how about Active XX/XY? If your mother chooses Windows 3000 as an OS when you're born, you might feel a compelling urge to talk about your most intimate secrets whenever she asks, then pass out and reboot...

  • Anyway, how about (as distasteful as it is) inbreeding?

    If two siblings bred then the sperm's mitochondria should, hypothetically, be identical to the egg's mitochondria, no? If so, would we still see the destruction of the sperm's mitochondria within the first cycle?

    Or if not, how man degrees of separation(genetically) is necessary before the egg decides to reject the sperm's mitochondria? Cousin? Cousin once removed? Etc?

    -AS
  • But what counts as a 'stupid genetic problem'? Anything that isn't the result of your enviroment? Who gets to decide if something is a problem?

    I do.
    It's my code. I can recompile myself if I want.
  • Uhm, it's late, here... I forgot to add that mitochondria incompatibility with the host egg environment might also be related to the differences in proteins/enzymes the mt's are 'accustomed' to.
  • To say that the cells age "as fast as" the originator is correct but I don't think that's what you meant.

    Well, that's what I meant, but rather than explain it all, I decided to cut corners for dramatic effect, if you will. Of course, Rich Man would have to wait 20 years (I mean, who wants to live through puberty again? Wait, I could drink Coke all I want, consider a McExtra health food and play D&D all day? I take that BACK!) and then get a brain transplant. Of course, he wouldn't get any more life expectancy, which is perhaps the Universe's way of telling us we can't be immortals just yet... :)

    Love the nick btw, I've got about 100 pages left to the Cryptonomicon. Gotta see if I can finish that up tonight.

    Thanks. Enjoy it!

    "There is no surer way to ruin a good discussion than to contaminate it with the facts."

  • either you've been reading to much Greg Egan recently, or you need to go out (no, not go: run) and grab a few of his books, with a virtual guarantee that you'll love them.
  • Cloning always seemed to be to be the duplication of the body(or parts therof) with sped up growth and no mind/soul.
    that's the SF definition of cloning (for some SF authors; not that there's anything wrong with it as a fiction premise anyway). in biology, cloning is pretty much exactly what was done to Dolly.
  • by Fishy (17624)
    Does that mean I should light the barbecue?

    F
  • by Anonymous Coward
    It probably doesn't matter in most cases, but there are some genetic deseases that come from mtDNA.
  • Several people have noted that this is not 'new' news, as the insertion of DNA into nucleas-free egg doesn't affect the mitochondria already present. BUT, it goes further than that. We already know that even in the traditional method of reproduction, (read: SEX) only the mother's Mitochondrial DNA is passed on anyway. The mitochodria in the sperm cell is destroyed by enzymes in the egg. This will make creating a *true* clone *very* difficult. unless of course you clone a female by using one of her own eggs. Note: i'm not a biologist, i just play one on the internet.
  • True, but he said "rid our race of stupid geneitic problems".

    It sounded like he was advocating species-wide recoding, not something on a individual basis. You could never convince everyone (ie, the species) to voluntarily alter their DNA; some of us are quite happy with our flawed genes.

    *shrug* It doesn't look like that's what he meant after all, but it's what I read.
  • Agreed. My complaint was about the comment:

    rid our race of stupid geneitic problems

    Which sounds like you mean species-wide recoding, not changes to individuals. Perhaps I misunderstood.
  • If you want to look to defeating aging, you should look to http://www.geron.com [geron.com] , since they are the holders of the patent on human telomerase encoding.
    Does anyone else have problems with the morality of
    • the fact that one can hold patents on these sorts of things, including afaik, gene sequences?
    • the fact that a for-profit corporations are holding patents on key scientific aspects of the biology of life?
    Does anybody know of an 'open source' movement in fields other than CompSci? How do we go about starting one?

    --
    People who say "the best thing since sliced bread" have never lived without indoor plumbing.

  • Metachlorians.

    Kintanon
  • 1 in 200 is at least as effective as the traditional cloning process, aka copulation.
    Just think about all the people having sex every day, if they all got it right 1 in 200 times we'd be swamped with little babies... Anyone know the actual statistics for that? 1 in 1000? more? less?

    Kintanon
  • Absolutely, but since most national (at least European and North American, which is where most mol-biol research is done) and international law is written solely for the benefit of corporations rather than the individual, there's not a lot we can do about it.

    It's been fun watching Monsanto, duPont et al. squirming in Europe recently though. Their party line appears to be: GM crops are safe ... and if they ain't safe you can't ban them 'cos of WTO rules ... and if you do ban them it won't help you 'cos everything coming from US-Ca is mixed GM and normal so you're stuffed no matter what.

    Our poxy government kow-towed before them - it's been particularly unpleasant watching the spectacle of the Rev. A.R.P. Blair toadying up to Monsanto and telling the British public that they weren't to worry and if it weren't for GM the third world would starve and anyway all these important people hav promised him it's safe. Thankfully, the masses have revolted (and after salmonella, BSE et al. it's hardly suprising), those evil anarchists in Genetix Snowball and similar organisations have been destroying crops and it looks like GM in this country is going to have an even harder ride than anticipated (and remember, Monsanto hired Burston Marsteler (sp?) to do their PR - these were the guys who tried to tell the world that the Exxon Valdez was an unfortunate accident, no-one was culpable and it wasn't serious anyway).

    Zaibatsu? Who needs 'em...
    --
    Cheers

    Jon
  • This is an interesting result - it supports the theory that mitochondria were originally unicellular organisms that passed into ancestral animal cells, so becomming intracellular symbiotes. This would explain the observed behviour very nicely.
  • Essentially this has always been known about dolly. Majority of DNA, and therefore genes are stored in the nucleus, about 60,000 to 100,000 genes(depending on species). The mitochondria have a small genome, of maybe 9 to 20 working genes (depending on species). And are transferred from the mother by the mitochondria left hangin around in the egg cell. The way the small amount of mitochondria from the ewe being cloned is destroyed is very similar to how mitochondria from sperm, which does make it into the egg on fertilisation, is destroyed soon after. The most abundant wins. Still, you can still have a dinosaur, if you can find a host with the right makeup of mtDNA.
  • by Anonymous Coward on Tuesday September 07, 1999 @07:07AM (#1697275)
    This result was not wholly unexpected - in fact it would have been a much bigger surprise if Dolly had managed to hang on to the mitochondrial DNA of her "nuclear" mother. The technique used here was to extract the nuclear DNA and from one cell and stick it into an egg cell which had its original nuclear DNA removed. Mitochondria live outside the cell nucleus and have their own, cut down, DNA genomes. In fact they're really bacteria that invaded, and became symbiotic with, our cellular ancestors about 1.1 billion years ago. We're all mosaic creatures... In any case before people start making speculations about human cloning please note cloning is amazingly unreliable, Dolly was 1 success out of about 200 attempts. Nobody's really improved on that success rate despite all the goats, mice and cows we've seen cloned. Imagine needing 200 pregancies to guarantee one healthy child in a ninth month period and you'll see why human cloning is a ways off.
  • mtDNA and aging of nuclear DNA are not linked events/objects. While the rest of what you say is true- there is a bit of controversy in the field about how much it matters and whether or not it can be overcome. Work in mice get differant results than the work in sheep- leading to the question of whether or not it is a global truth.
  • Now, scientists have inspected Dolly's mtDNA and found no trace of the ewe's contribution at all. That's a surprise, and it suggests the egg destroyed the ewe's mtDNA
    I'm no scientist, but neither am I clueless on the subject of genetics, and I'm sure I'm not the only one that was fully aware of the mitochondrial differences in Dolly. In fact, I'm surprised that this is news. If there was anything other than the egg's mtDNA I'd have been astonished.
    Remember the 'mitochondrial eve' story that first surfaced a couple of decades ago? The idea that a common ancestor could be traced through DNA is only possible because mtDNA is passed almost solely from the mother. Dolly didn't have a mother per se, so the mtDNA comes from the egg.
  • by technos (73414) on Tuesday September 07, 1999 @07:18AM (#1697280) Homepage Journal
    Some background:

    Mitochondria are cellular components that produce energy for the cell. The best scientific guess on their origin is that they were one invasive bacteria, but they enhanced some cellular function and evolved into a symbiotic role within the cell.
    As decendants of cells, they carry their own unique DNA and RNA sequences. Their DNA data set is much smaller than that of the host cell, mutates at a slower rate, and is only passed down the female line. The scientists are running into the part of the mitochondrial mechanism that ensures that mtDNA is passed along the female line. Simply, the mitochondria of the host egg are more numerous and better equipped to deal with intruding foreign mitochondria. It will only be a matter of time before scientists flood the host egg with healthy mitochondria from the cell(s) to be cloned, or deal with them by removal much in the way they deal with the nucleus..
  • by chandoni (28843) on Tuesday September 07, 1999 @07:23AM (#1697281) Homepage
    All the nuclear DNA came from one sheep, but because of the way the clone was made, the mitochondria came from both the egg (most of them) and the cell that was fused with it (a smaller number). Mitochondria replicate some time in the cell cycle (along with all the other organelles), so one would probably expect all cells in Dolly to have the same ratio of mtDNA types as the original fused cell.

    What's interesting and surprising about this research is that NO mtDNA except that from the egg was found. This implies that the "foreign" mitochondria originally present were either actively killed off by something, or more likely, were not signaled to replicate at the same time all the "native" mitochondria from the egg cell were (because if they didn't replicate, they would become randomly segregated into the billions of cells making up Dolly, and would be lost). This would mean the signaling pathways telling mitochondria when to replicate are more complicated than we thought they were; i.e. we could now try to figure out what signal turns on the replication and why it only affects some mitochondria.

    JMC

  • why scary? sounds like a damn good idea to me. rid our race of stupid geneitic problems...

  • What makes this interesting is that you could get around this, and make a "true" clone, by using a donor egg cell from the creature you are trying to clone.

    This interesting part is that this only works for females!

    Though I suppose that in theory, you could get much the same effect by using donor egg-cells by a female relative, as mitochondrial DNA is preserved pretty well through the generations. (i.e. you've got pretty much what your mother has, barring mutations.)
  • Hmmm.... that would be a good test for which mechanism is used. Two other possibilities that I did not mention are:
    1: Mitochondria are tagged upon the production of the spermatozoa, thus dooming them. This has interesting implications in that it would be a different mechanism that what would destroy those mitochondria in the fused egg.
    2: Perhaps cellular mitochondria have a particular cytoskeletal connection needed to operate that foreign mitochondria cannot receive on fusion.
    However, it is not yet know (AFAIK) which mechanism is used; perhaps it's something I have not listed.
  • I had thought that the Mitochondria inside the spermatozoa were locked into a segment between the nucleus and the tail (sort of a pre-tail energy-generation region), so that they couldn't actually be injected into the egg anyway???...

    ...there shouldn't really be that much reason why male mitochondria can't exchange nutrients with the egg - remember that the female mitochondria end up thriving in a half-male/half-female environment...which may also preclude recognition of male mitochondria by the female egg.

    Isn't it more likely that the female mitochondria are THEMSELVES recognising and destroying the male mitochondria? This also fits in with the whole theory that mitochondria are adapted prokaryotic cells - presumably prokaryotic implantation into eukaryotes began as a parasitic attack, and prokaryotes that actively ejected other prokaryotic attacks would have a selective benefit.

    Intriguing, anyway!

    -Shane Stephens
  • To nitpick for a moment- mtDNA actually mutates faster than nuclear DNA: most molecular evolution studies come up with values of 5 to 10 times faster. There are probably several reasons for this.

    One of the major factors is that oxygen radicals (which are potent mutagens) are produced in high quantities in the mitochondira as ATP is produced to power the cell. Mitochondira also seem to lack some of the error checking mechanisms in DNA replication that nuclear DNA has avaliable to it.

  • First off, a brain transplant is way too futuristic to even consider (Unless something big happened and I missed it.)
    Growing a brainless clone is probably the simplest element. Regulator (homeobox) mutations can defeat the growth of most of the brain; although more developments must be made to keep the mutant from dying.
    Gene therapy is not enough to cure aging (unless a radical method which can fix mutations in an entire genome is developed.)
    Plants live for a long time because they are not as intradependent as a human. Plants often have giant tumors in certain parts, but because they are much more of a parallel structure, the rest of the plant can live; a human, on the other hand, is far more internally organized and possesses little redundancy. Thus, a plant can have half of its roots die off, and still have half the plant operate, while a human can hardly live with half its body.
    Gene-based gamete selection is already developed, and has succeeded for not only simple things like gender, but in the avoidance of Hunnington's disease gametes. The major holdback is the primitiveness of artificial insemination (it takes many many tries to get it right.)
    One must keep in mind that cloning, gene selection, etc... are merely scientific developments. They can be used for the betterment or for the destruction of society. Not developing the technology because some uses of it may be bad is not a wise thing to do.
  • Mitochondrial DNA is pretty well preserved over the generations. In other words, it would be almost identical in third cousins that share the same great-great-grandmother. It isn't like nuclear DNA, which is rapidly diluted from one generation to another.

    In other words, it should be pretty simple to test such a case. You wouldn't necessarily need a couple that would traditionally be considered incestuous.

    Another possibility concerning why this happens is that the mitochondrial DNA is somehow packaged differently in the egg than in any other cell. Perhaps it gets tagged somehow when the egg is produced.
  • Just one thing - the aging problem may not be as solvable as you think...

    ...you pointed out that plants can live for a very long time. If you notice, plants that live for extended periods of time either get very LARGE (eg trees) or grow very SLOWLY (eg blackboys), but the point is that plants never stop growing.

    And the stuff that is old; dies anyway. If you cut a tree down (please don't) you will notice the large section in the middle known as deadwood. This _is_ dead wood.

    I don't know if the aging problem is truly surmountable, but the fact that tree parts grow old and die, and that to survive trees have to keep growing, may suggest that it's not.

    -Shane Stephens
  • Thank you for correcting me! I was only confident in that the mitochondrial mutation rate was an order different from that of the average cell. It has been a few years since my one course in genetics. One question though; Wouldn't the prodigious mutation rate be a detremental factor when determining maternal ancestry, in that with the comparably limited pool of information and the high mutation resulting in sports or fallback? I've heard quite a few different results on the timespan of 'Mitochondrial Eve', and seriously wonder how accurate any possible answer could be.
  • Think of how long plants live--there's no fundamental reason why animals must age.

    True, but natural selection has favored genomes which produce children and then get out of the way at a certain point (and thus stop competing for limited resources.) We've got many millions of years of evolution with this selection pressure, and I'd be surprised if we don't find that we have a much harder task stopping/reversing the aging process than appears. In other words, aging may be actively selected for rather just being the eventual result of accumulation of errors, etc.

  • There has been a okay go ahed that in australia they will bring back the tasmainian tiger ( distinct.... no not the spinning one - thats a a devil)
  • To say that the cells age "as fast as" the originator is correct but I don't think that's what you meant. DNA can be said to have a counter on it like a integer decrementer in a standard "for" loop. Every time the cell divides the DNA gets truncated and various Bad Things have their probability of being triggered raised (for the derived cells in the division).

    So loosely, the cloned being starts of with cells the *same* age as the originator and then those cells age "normally". One of the problems with this is that clones start out with basically the same resources as a newborn, but are genetically coded to be older. This could theoretically cause stunted developement and a host of defects.

    Besides that, there is the issue of neural aging and degeneration in the originators brain if there is a transplant. Not to mention the fact that a cloned genetically defective human will still have the genetic defect.

    All those things aside, the scary thing to me is that somebody would consider cloning a human that would age prematurely. Seems particularly cruel.

    Love the nick btw, I've got about 100 pages left to the Cryptonomicon. Gotta see if I can finish that up tonight.
  • by crow (16139) on Tuesday September 07, 1999 @07:44AM (#1697296) Homepage Journal
    A lot of people are very intrigued by the idea of creating a clone of themselves and then doing a brain transplant so as to cure diseases and defeat aging.

    What does this mean? This means that the clone might have different mtDNA, which generally doesn't matter. In a case where you care, you get an egg from someone with identical mtDNA (e.g., your sister).

    Of course, there are a lot more issues here:

    The ethics of the whole thing.
    Being able to grow a brainless clone (or being willing to kill the brain of the clone).
    Being able to transplant a brain without causing paralysis.
    Defeating aging of the brain.

    Personally, I think this is the wrong approach to this sort of thing.

    Aging can probably be defeated through much less drastic measures (e.g., gene theorapy) once the process is fully understood. Think of how long plants live--there's no fundamental reason why animals must age.

    Genetic disorders, excluding those caused by mutations, can be eliminated through controlled reproduction. Consider that we all have far more reproductive cells than we need. Hence, if I carry both a good and bad gene for something, why not eliminate all of my reproductive cells that carry the bad gene?

    Of course, all this genetic engineering stuff already has a bad feeling associated with it, based on the last major attempt to eliminate "bad" genes. (I'm referring to WWII, of course.)
  • Quite correct. However, differences in mitochondrial DNA are not really all that exciting. We have known for quite a long time that mitochondria are basically totally separate organisms that have evolved {except in Kansas} in a symbiotic relationship with eukariotic cells.

    As such, their genitic makeup is totally separate from the host. You could remove all the mitochondia from a given cell, and stick in new ones... why? I have no idea... mitochondria are basically glorified power supplies...so long as they work, they do very little to influence the overall makeup of the underlying system... (I haven't ever heard of someone surving long enough to even be aborted with malfunctioning mitochondria)

    Finally, mitochondria are passed down the female line for the simple reason that male sperm don't have mitochondria. Male sperm are not designed [in Kansas, evolved elsewhere] to do oxidative reduction, (Make ATP via Citric Acid Cycle) and therefore do not need mitochondria...

    Finaly, as near as I can remember, (I haven't studied this part of biology in a while) foreign mitochondria are attacked, not by the mitochondria inside, but by the host cell itself... (if they even manage to get inside, which is highly unlikely...)

    I guess I really don't see this as a great revelation that the scientists did not have a complete clone, and I am pretty sure that the scientists did not either... they probably were just verifying in a new way something that had been known for quite some time.



    Don Armstrong -".naidnE elttiL etah I"

  • The force is strong in this sheep.

    Not even Master Yoda has a reading that high.
  • You make a good point, I think I can add to it. A recent study on the fusion of sperm and egg cells has revealed that the sperm mitochondria (which are very numerous) enter the egg cell; however, these are destroyed. It is not yet clear what the system of identification is; however, flourescent markers in the sperm mitochondria revealed that the entering mitochondria were destroyed after the first cycle.
    A current explanation for this phenomenon deals with the fact that mitochondria do not have complete genomes. Many of the genes of mitochondria have migrated to the main genome; thus, mitochondrial structures are a combined product of host and mitochondrial synthesis. A mechanism could exist that disallows foreign mitochndria from receiving the nuclear support needed to support and reproduce themselves.
    Another theory is that there is a special differentiating flag on each type of mitochondrion. A glycoprotein on the surface could be used to identify the mt, much like human cells get identified.
  • Does this mean I get dinosuars or not?

"There is nothing new under the sun, but there are lots of old things we don't know yet." -Ambrose Bierce

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