This isn’t anything new, but I think it’s interesting and I happened to have a reason to look it up recently, so here goes. If you know enough biology to know what mitochondrial DNA is, skip to the second-to-last paragraph.
There are basically two kinds of DNA. The DNA everybody knows about, that determines your hair color and skin color and tells whether O.J. is guilty is “nuclear DNA.” Nothing to do with nuclear weapons; it’s called that because it “lives” in the nucleus of each cell of your body. Half of it comes from each parent, which is why you inherit some characteristics from each of your parents. This is the type of DNA responsible for the inheritance patterns discovered by Gregor Mendel (1822-1884).
The other kind is called “mitochondrial DNA.” Inside every cell in your body, but outside the nucleus, are these things called mitochondria. They produce energy for the rest of the cell by converting ADP to ATP. They self-replicate like cells do. And, they have their own DNA, which is smaller and therefore simpler than nuclear DNA, but it is real DNA and it determines how the mitochondria do their jobs. Which means, if affects your body’s characteristics, much like nuclear DNA does. For more details, see this excellent web page on mitochondrial DNA.
Now, here’s the other interesting thing about mitochondrial DNA: It is inherited completely from the mother. Nuclear DNA comes half from each parent — each egg cell and each sperm cell has half the DNA of a normal cell, and when they come together, the DNA are brought together, the pairs of chromosomes are matched up, and you have one cell with a full set of DNA. That cell divides and grows into a new human (or other) being. However, the sperm cell and the egg cell are not equal in anything except their nuclear DNA contribution. The egg cell is a mostly fully-formed cell, with a nucleus and mitochondria and all the other things cells have — except a full complement of nuclear DNA. The sperm cell is basically just a nuclear DNA transport device — it takes the DNA to the egg cell and attaches itself, then its DNA finds the egg cells nucleus, the two half-sets of DNA combine, and then the cell is complete and starts growing. Now if you’ve been paying attention, you should be asking, where does this new cell get its mitochondrial DNA? Well, it already had it — in the mitochondria of the unfertilized egg cell. Which means, mitochondrial DNA comes only from the mother. Which means, any traits dependent on mitochondrial DNA are inherited only from the mother.
Now, here’s the question I want to ask. Suppose they make a “clone,” like Dolly the Sheep. The way this works is, they take an unfertilized egg cell, and replace its nucleus with the nucleus of a normal (not egg or sperm) cell of the animal they want to clone. They then take that egg cell, which has a full complement of DNA, as if it had been fertilized, and implant it in the womb of a (surrogate?) mother, to develop and be born like any “normal” individual. Note that while all of the nuclear DNA came from the “nucleus donor” being cloned, the mitochondrial DNA came from the egg cell donor, not the individual being cloned. The only exception to this would be if the egg cell came from the same individual as the nucleus. I don’t know if this is possible at all, but it’s certainly not possbile if the nucleus donor is male.
My question is: If the mitochondrial DNA doesn’t “match” (the source of the nuclear DNA), then the clone is not really a perfect copy of the original, right? Could this mismatch cause some trouble? Could this be why clones seems to have some serious problems? Dolly the Sheep was not the first clone, but was the first clone to survive for a reasonable period. Even so, she died young for a sheep. Could a mismatch of mitochondrial DNA have something to do with this?
If anyone knows any answers, or has some knowledge of the research literature in the field, please leave a comment or send me an e-mail (to blog AT differentriver DOT com). Thanks!
UPDATE (2/14/05 1:35pm):
In response to an e-mail from a reader, I’ve corrected the statement above about the role of mitochondria in the ADP-ATP process. The same reader answer both the question I was thinking about and didn’t ask (but should have), and the question I did ask:
Sperm cells certainly have mitochondria; they have a good number relative to the size of the cell. They are needed to produce the burst of energy-on-demand that the sperm requires. At some point (before fertilization) the sperm’s mitochondria are marked with ubiquitin which is a protein that marks other proteins and organelles for destruction. Occasionally this process fails and paternal mitochondria do survive. This only happens very, very rarely (without human intervention).
And now to your question:
Your intuition is right — when the mitochondrial DNA and nuclear DNA do not match, undesireable behavior is the result. Cellular processes need to “recognize” the mitochondria, probably most importantly to govern the various signals the encode for their replication.
To combat this, when the embryo that became Dolly was created, a technique known as egg cytoplasmic donation was used. This technique is sometimes used in humans (though it is pretty far down on the list of fertilization treatments to try). It involves injecting the cytoplasm (everything outside the nuclear membrane) of an oocyte (the female’s cell that goes through meiosis and ends up as an unfertilized egg) with the cytoplasm from the nuclear donor. Thus the new nuclear DNA has some mitochondria it can work with. Presumably the mitochondria donated from the original egg are either recognized, perhaps as they undergo fission, or they are actively destroyed, or they eventually die on their own.
So, the mitochondiral DNA problem probably has nothing to do with Dolly’s early demise. That problem is actually (probably) from the chromosomal DNA.
Oh, and the current best hope for understanding Dolly’s apparently premature aging is telomere cropping. Telomeres are long, non-coding segments of DNA that appear at the end of chromosomes. These caps shrink with age and apparently restrict the number of times a cell can viably undergo mitosis without its DNA falling apart. Since Dolly’s original DNA came from an older cell (ie with already-shortened telomere sequences) the thought is that her cells operated as older cells might, i.e. undergoing mitosis fewer times and with more time between divisions.