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Reply to Chromosomes

Graham Dellaire popa0206 at PO-Box.McGill.CA
Thu Jun 1 16:47:40 EST 1995

Keith Robinson wrote:

....plenty of things about sex chromosomes and dose compensation clipped
(no doubt spered on by the recent review in Cell <grin>)

>The other complication worth mentioning is that some genes are
>intertwined with their neighbors, and so it may not be possible
>to move individual genes to another chromosome (and retain
>function) but it would then be possible to move the entire
>block of genes to another chromosome (unless, of course, the
>block consists of all the genes on the chromosome!).
good point...
 I would also like to add that it may not just be that the genes are "intertwined" as you put
it , which I believe is rare*, there may be a structuarl reason too..
* (In general in higher organisms as there is not such a size constraint
as in viruses where overlapping reading frames are common.)  
Often the promoters or enhancer sequences that help a gene function appropriately 
(proper tissue and time in development for example).  Without transplanting these 
sequences with the gene you may get abberant or no expression at all of your gene....
such is the bane of attempts at gene therapy for diseases like muscular distrophy where the
actual gene spans more than a megabase!

So you can't just plop a gene anywhere and expect it to be functional.  

The previous question as to chromosome stability that was original asked has still not
been touched <grin>.  This is a much sticker point and of great debate.

To go from the most concrete reasons for stability you can look at the physical characteristics of
a chromosome.  
1. has telomeres that prevent degredation of DNA and ensure complete replication of the
 chromosome each time
    - in addition prevent recombination occurring as the free ends of the chromosomes are no longer accessible

2. A chromosome has one (yeast artificial chromosomes) or several origins of replication that ensure the 
chromosome is replicated during mitosis and meiosis and can be passed on to the daughter cells
 or gametes respectively.

3. There is a centromere which enables the proper segregation at mitosis and meiosis
 so that each daughter cell or gamete recieves a full compliment of chromosomes.

No as for the actual integrity of the sequence this is maintained by
1. Packaging around nucleosomes and histone 1 
	-which excludes the DNA some what from the action of DNases and
 UV light etc ( and any other potential destructor of DNA)
2. During replication and recombination event there are other DNA binding proteins 
that prevent degredation
	-when DNA is without histones and/or unwound, nicked etc
3.  We also have several repair systems that "scan" our DNA for mismatches, thymidine dimers, crosslinks, 
adducts etc... and general make sure the genetic house is in order.

Now all this is not full proof and mistakes do occur and mutations can accumulate

To go beyond this quick physical look at chromosomes is where you enter uncharted and very
 "theoretical" country

One tidbit for everyone to chew on mentally...

One theory is that line-1 and Alu sequences (and perhaps other moderate repeats) are 
are involved in not only driving "evolution" by retropostion into coding sequences and 
through gene conversion which may join exons....but also in genome stability!

Theses sequences may also maintaini stability of the genome through
gene conversion events and recombination between these sequences.

For instance at meiosis there is thought to be an homology search prior to synapsis
which  then results in areas of crossing over (and eventually visable chiasmata ) between
chromosome homologs.   Gene conversion initiated by repeat sequences may be involved 
in this homology search.


Graham Dellaire			Snail Mail:
                                  Red Cross, Research		
McGill Univeristy                 Montreal Blood Services	  	
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Div. of Experimental Medicine     Montreal, QC, Canada           
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