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Q: individual dna variation ( No Answer,   5 Comments )
Question  
Subject: individual dna variation
Category: Science > Biology
Asked by: brick66-ga
List Price: $2.00
Posted: 01 Dec 2005 04:04 PST
Expires: 31 Dec 2005 04:04 PST
Question ID: 599944
How much nuclear DNA within an individual's cells is "different"?  I
often see percentages quoted for differences between species and
organisms but have never seen anything for within an individual except
a statement that each cell contains dna for every part of an
individual which implies all of an individual's cells have the same
DNA.  I understand a number of mutation and copying error mechanisms 
exist so this led me to ask what percentage of an individuals DNA
varies at birth and over time.
Answer  
There is no answer at this time.

Comments  
Subject: Re: individual dna variation
From: pforcelli-ga on 01 Dec 2005 10:26 PST
 
Hey;

I'm not sure I'm understanding your question.

Are you asking what percentage of DNA in one cell varies from the DNA
in another cell?

If so, think of it this way, we have about 3billion base pairs in our genome

The error rate in DNA synthesis approximately 1 in a billion after proofreading.  

If you have a 3 basepair change every time a cell divide...

So some cells will have a greater difference than otherrs, but an
average of 10^-9% variation.

I haven't really thought this through, but that seems logical.

Mikewa, Dops? Any thoughts/comments? I'm not a geneticist.
Subject: Re: individual dna variation
From: pforcelli-ga on 01 Dec 2005 10:31 PST
 
Two other quick thoughts, those numbers don't take into account T or B
lymphocytes which undergo somatic cell hypermutation, nor do they take
into account haploid cells (spermatozoa or oocytes)
Subject: Re: individual dna variation
From: mikewa-ga on 02 Dec 2005 04:46 PST
 
I think pforcelli has got it right. Although cells arise through
mitosis (other than gametes)the spontaneous errors in replication will
tend to produce slightly differnt results each time. You also need to
add in the mutation rate due to chemical and physical factors. The
result is that probaly most cells in your body have a unique base
sequence. However, since only a very small % of the DNA is coding for
proteins, this will not mean that every cell looks/behaves
differently.
Subject: Re: individual dna variation
From: brick66-ga on 02 Dec 2005 07:14 PST
 
Thanks, you have helped to quantify and clarify my question - Within
an organism, each cell has nuclear dna, some of which is significant
in that cell's form and function, so within those exons how much
variation exists?

A side question - When numbers are quoted that humans are 99.9% the
same or humans are 9X% the same as chimps or mushrooms, is this
referring to only to DNA that codes for proteins?

Based on your comments, this is what I understand now, the genome that
would be produced by each cell is different by the accumulated
mutation rate of its predecessors within the organism and any
environmental (chemical and physical) driven changes. Every cell
replication from the gamete produces ~3 base changes (1/10^9 rate *
3e9 bases).

Also I understand that the rate is higher due to the
chemical,physical, and hypermutation.

So I figure that the 47 doublings from the single starting cell
produces >~1e14 single base errors in the 7e13 cells indicating that
most cells are very slightly different from the starting cell. 
Somewhere I read 47 doublings occur from single cell to birth and
using excel, this computes to 7e13 cells with 1e14 errors.

I understand that the majority of these differences would be within
introns since introns are the majority of the bases so these changes
apparently don't change form or function of the cells.

There does seem (to me) to be significant variation here. 

Would this very slight variation be a cellular evolutionary mechanism
within an organism?  I could envision occasionally these errors could
create a cell replicative advantage when they happened within exons if
the error was an improvement.

Or perhaps the error could create a disadvantage and the cell would
terminate instead of replicating the disadvantaged DNA.

If there was an cellular replicative advantage could it create an
organism reproductive advantage?

How would the cells with a beneficial mutation communicate this
advantage to the reproductive cells for organism evolution?

Thanks for your thoughts.
Subject: Re: individual dna variation
From: pforcelli-ga on 04 Dec 2005 10:08 PST
 
A side question - When numbers are quoted that humans are 99.9% the
same or humans are 9X% the same as chimps or mushrooms, is this
referring to only to DNA that codes for proteins?

--> To the best of my knowledge: No.  This is talking about total genomic DNA

I understand that the majority of these differences would be within
introns since introns are the majority of the bases so these changes
apparently don't change form or function of the cells.

--> There are other stretches of non-coding DNA which could be
effected, and a change in any place is capable (in theory) of
producing a change in protein expression - it can effect packaging of
DNA, it can effect regulatory regions...

There does seem (to me) to be significant variation here. 

--> I suppose it depends on your definition of significant.  

Would this very slight variation be a cellular evolutionary mechanism
within an organism?  I could envision occasionally these errors could
create a cell replicative advantage when they happened within exons if
the error was an improvement.

-->  I think you thinking of this in the wrong way.  The variation is
the means by which evolution occurs.  However, this isn't going to
make even the slightest difference unless it occurs early enough in
development to effect all gametes, or if it occurs during
gametogenesis.

Or perhaps the error could create a disadvantage and the cell would
terminate instead of replicating the disadvantaged DNA.

--> Don't think of individual cells in terms of disadgantaged,
certainly there are mechanisms to induce apoptosis if there is an
unrepareable error in DNA synthesis.  The cell could certainly die if
a vital enzyme was made inactive by a mutation.  The same can apply in
reverse, this is the mechanism of cancer, a cell undergoes mutations,
allowing it to replicate ad infinitum.

If there was an cellular replicative advantage could it create an
organism reproductive advantage?

--> It would have to be very early in development for the change to
effect enough cells to make any sort of differnece in overall
organismal functioning.

How would the cells with a beneficial mutation communicate this
advantage to the reproductive cells for organism evolution?

--> The cannot.  100% Cannot.  There is no mechanism by which one cell
tells another cell to change its dna in a specific and directed way. 
What you are suggesting is something akin to what Lamarck believed. 
When you think of this, remember evolution isn't planned for in cells,
organisms, or anything else.  It is chance changes in genotype and
phenotype which, will have an impact on reproductive viability in a
given niche.

I think i've done all of that justice, again, comments...

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