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Dolly the Sheep not totally identical clone
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.
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.
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?
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
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?
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
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."
If tits were wings it'd be flying around.
sporty
---
And I shall call him, mini-me
-
ping -f 255.255.255.255 # if only
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
-AS
*Pikachu*
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.
I am that that is, not that that is not, that is.
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
Check out JoshJitsu.info for Brazilian Ji
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.
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.
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..
.sig: Now legally binding!
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
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.
Unbreakable toys can be used to break other toys.
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.)
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?