Long lived clones!

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Wed May 24 11:27:29 EST 2000

Christina Wing, or possibly Iuval Clejan, wrote:

> if there is no selection mechanism during meiosis itself, there should
> be no difference in mtDNA from randomly selected pre-ovulatory egg
> cells and randomly selected other tissue cells from same organism. Has
> anyone ever looked into that?

Oocyte mtDNA mutations have indeed been looked for and their levels are
pretty low: some studies have failed to detect them.  But your inference
is wrong, because there is a huge difference in the level of mutant mtDNA
in different tissues.  In general, the cell types that have the most are
those which are both postmitotic and highly oxidative: particularly nerve
and muscle cells.  Egg stem cells (the cells that give rise to oocytes)
are neither of these, so one would expect them (and, consequently, their
descendent oocytes) to have very few mutations.  Representative studies
include Mol Hum Reprod 2(12):951-958 and Am J Hum Genet 57(2):239-247.

This is not to say that there is no selection of mutation-free oocytes
between meiosis and ovulation, only that there is no need to postulate
one based on current evidence.  The bottleneck that I mentioned is not
strictly a selection against mutant mtDNA, but it is presumed to cause
such selection later on (at ovulation).  See Nature Genet 14(2):146-151,
for example.

> Is there less mtDNA damage in post-ovulatory eggs than in other cells
> in the same organism?

I don't know of any study of this.  Getting enough such eggs to measure
mtDNA mutations is probably difficult.

Aubrey de Grey

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