From: french@RUST.ZSO.DEC.COM
Newsgroups: bionet.molbio.ageing
Subject: Re: the foutain of youth
Date: 15 Apr 92 18:30:06 GMT
Distribution: bionet

> Firstly, at least in reproduction, the complex patterns of methylation
> that have been seen in somatic cells (but not fully understood) are not
> necessarily maintained in germ cells.  

I would not expect the methlyation pattern of somatic cells to be maintained
in germ cells.  The methlyation pattern represents the state of the genetic
program and that state is reset to its embryonic form when fertilization
occurs.


> There are a few examples of nuclear transplantation experiments where somatic
> nuclei have been transplanted into enucleated/fertilized ova.  To the
> best of my knowledge, the most developed organism that this has been
> sucessful with has been amphibians and that was using nuclei from
> tadpole somatic cells (ie. not fully developed).  There have been some
> claims of experiments using mammalian nuclear transplants but as far
> as I know these are very controversial.  This should point out that
> the fertilization/early embryonic development does NOT 'renew' the
> potency of the hereditary material.

I would NOT expect such experiments to 'renew' the potency of the herediary
material.  In my hypothesis, the fertilization process only represents the 
error-correction mechanism.  Transplanting somatic nuclei into fertilized
ova would not produce positive results because the information source (DNA) in 
the ova would be the same as it was in the somatic cell.  In order to correct
errors, you must introduce a new information source.  For example, in
reproduction each parent provides an information source that has accumultated
errors independantly of each other.

I would also expect negative results if you used DNA from two widely differentiated
cells (such as from your toe and liver) because the large differences in the DNA's
methlyation state might easily swamp the error-correction mechanism.  A
much better choice 
of DNA would be from two adjacent cells.  Furthermore, I would expect
the cell's genetic
age to be reset only back to the point in time when the two source
cells differentiated -
not all the way back to the embryonic state.

> To the best of my knowledge, there is no mechanism for comparing DNA
strands between 
> parents.  If you think about this, first how would the replication
repair machinery 
> Know which was the correct strand, and secondly there is no reason to
believe that the
> genetic material from one parent would be identical to the other.

Each parent supplies a DNA duplex which implies that there are four corresponding
bases at each site on the chromosome.   As two chromosomes pass through a Holliday
junction, the identity of the four bases at the four-way junction of
the arms determines
which arms will pair with each other to provide the most favorable stacking energies
and the most stable conformation.  

Does a Holliday junction correct bases that are mis-paired and other
errors?  Perhaps not, 
but I would expect to find a mechanism similar to a Holliday junction
that does correct 
errors.  Such a mechanism may be more sophisticated than a simple
four-way bitwise comparison 
of the DNA strands from the parents. For example, an error-correction
mechanism may take advantage 
of redundant information encoded within the DNA strands in the form of
various conformations 
and so on.

I believe that a a near-perfect error correction mechanism must exist
because children
start out with essentially a clean slate of DNA and yet their parent's germ cells
are subject to the same radiation and radical damage as their somatic
cells.  If such a
mechanism did not exist, then I would expect such DNA damage to
accumulate in the germ 
line and thereby cause a species to degenerate over several generations.

I've considered the possibility that the viability of a species is ensured by an 
efficient error-detection mechanism that simply eliminates defective
germ cells.  However, 
this hypothesis is unworkable because most eggs remain fertile even
though they have spent a 
considerable length of time waiting in line in the ovaries.  If no
error-correction mechanism
existed, then errors would accumulate in the egg's DNA and such errors
would therefore accumulate 
in the germ line over several generations and the species would degenerate.