From: robison1@husc10.harvard.edu (Keith Robison)
Newsgroups: sci.bio
Subject: Re: Gene Imprinting ???
Keywords: Genes
Date: 8 Oct 92 14:55:21 GMT
Article-I.D.: husc10.robison1.718556121

mytelka@codon6 (Daniel Mytelka;612 Barker;x2-5110) writes:

>In article <2133@grivel.une.edu.au> jjuanyse@neumann.une.edu.au (El pescador ) writes:
>>
>>	But I need more information about it, like in what sorts of 
>>developmental processes are the "imprinted" genes involved, what sorts of 
>>explanations have been advanced for the evolution of imprinting, what could
>>be the mechanism for these changes in the male and female genes, etc.

I believe that it has been suggested that in mammals at least some
imprinting has evolved as an arms race between males and females.
There is a growth factor and its receptor which are both known to be
imprinted, but in opposite manners -- paternal inheritance ups the
activity of the one, while maternal inheritence drops the activity of the
other.  Since in many mammals it is common for a female to be carrying the
offspring of multiple fathers, males which produce large offspring are
more likely to propagate their genes (as their offspring will crowd
out the others).  On the other hand, females weighted down with an
oversize pregnancy are at a severe disadvantage, and so there would
be selective pressure to prevent the male's trick from getting out of hand.
(apologies for lack of reference).

>>
>There actually hasn't been too much work done in this area, though it's been
>known for quite a while based on the observation that a cell in which one
>pronuclei (pre-first division) is replaced by a copy of the other one (eg two
>maternal or paternal pronuclei) won't develop properly.

Actually, a lot of work has been done on imprinting but the answers are 
not clear.  In addition to the nuclear transplantation experiments, 
another key piece of evidence is that the expression of some
transgenes (artificially introduced genes) is affected by which
parent they are inherited from.  Additionally, there is a known pair
of mental retardation syndromes (sorry -- names have slipped me) which
are caused by the same defect -- which one you get depends on which
parent you inherit the defect from.

>There are at least two ways in which parent specific gene activation occurs.
>In some of the early embryonic tissues, X inactivation always deactivates 
>the paternal X-chromosome, rather than at random, as is true in later
>stages. The mechanism given is usually methylation.

X-inactivation in mice is paternal chromosome specific (except in some
neat re-arranged chromosomes), but in humans it is random.  This was
documented a long ways back by the fact that women heterozygous for 
an X-linked deficiency show a mosaic pattern of enzyme expression.

>As to a specific gene, you could look at Fragile-X syndrome (work mostly
>of Charles Laird), and references therein.

Fragile-X is probably not a good example -- the mechanisms at work here
may include imprinting but several others are at work here (triplet
repeat amplification).  _Science_ had a good review back in the spring.

>I think that most of the rest of your questions can at best be answered by
>speculation right now.

>Dan Mytelka, mytelka@mendel.berkeley.edu


A good place to start looking for this sort of information is 
_Annual Review of Genetics_ -- it has a five-year index in each
volume so you can quickly find out if they recently published a 
review.  Trends in Genetics is another good place to look.

Keith Robison
Harvard University
Department of Cellular & Developmental Biology
Department of Genetics / HHMI

robison@ribo.harvard.edu