Re: Symmetry of DNA replication

On Jan 21, 10:52 pm, "Graham Jones" <x...@xxx> wrote:
"Ron O" <rokim...@xxxxxxx> wrote in message

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On Jan 17, 12:34 pm, "Graham Jones" <x...@xxx> wrote:
Given a double strand of DNA, it seems at first sight that the
replication
process could start just as easily at one end as the other. Does this
actually happen in cell division? That is, is each end equally likely to
be
the starting point or is there a preferred (or only) direction? What
about
circular DNA - is there a preferred way to go round during replication?

The reason for asking is that if there is a symmetry, it puts a
constraint
on the pattern of mutations that can arise.

Graham Jones

There are sequences that act as origins of DNA replication.  In
circular molecules replication most often occurs bidirectionally from
this origin.  All DNA replication has to occur 5' to 3'.  The
antiparallel nature of the DNA strands dictates the direction of
replication and which strand leading and lagging strand synthesis has
to occur.  In either direction using the 3' to 5' template strand
leading strand replication can occur and continuously replicate.
Lagging strand (the 5' to 3' template) has to wait for single strand
sequence to open up due to replication of the leading strand, prime
the single strand template and synthesize DNA back toward the origin
of replication.

There is a rolling circle replication for some plasmids where
replication from the origin is leading strand that goes completely
around the circular plasmid and then peels off the newly replicated
strand and it comes off like toilet paper as the plasmid continues to
replicate in that one direction.  Lagging strand synthesis occurs and
circles have to be formed by recombination of the tandem repeats
formed.

In mitochondria there may be assymetric DNA replication where one
strand is replicated for more than the usual Okazaki fragment length.
There was a proposal that more mutations occurred on the exposed
single strand.  This might be something like you are looking for.

Ron Okimoto

Thanks for your reply. I knew about leading and lagging strands but not most
of the other details. I am interested in what substitution models should be
used for phylogenetic analysis (for nucleotides, amino acids, codons, etc).
Barry Hall has a simulation of molecular evolution "EvolveAGene 3" based on
observations of mutations in E. Coli. These are spontaneous mutations of
base-pairs, before selection has had an effect, not accepted mutations, and
the figures he has are

AT to GC  8%
GC to AT 40%
GC to TA 29%
GC to CG  4%
AT to CG 10%
AT to TA 10%

Recheck your figures, my guess is that it should be CG to TA 29% and
TA to CG 10%.

"EvolveAGene 3: A DNA coding sequence evolution simulation program" by Barry
G. Hall.http://precedings.nature.com/documents/1230/version/1/files/npre20071...

"Comparison of the Accuracies of Several Phylogenetic Methods
Using Protein and DNA Sequences" Barry G. Hallhttp://mbe.oxfordjournals.org/cgi/reprint/msi066v1.pdf

No mention is made of whether it matters if a base pair such as AT is
replicated with A on the leading strand, and T on the lagging strand, or
vice-versa. I am trying to  figure out whether it does matter. To rephrase
my original question: if you  are looking at the replication of a particular
gene, is it equally likely that the antisense strand is the leading strand
or the lagging strand? From your answer, I think it depends on where the
sequences that act as origins of DNA replication are in relation to the
gene.

CpG sites mutate at a much higher rate than other DNA positions. This
may occur due to the spontaneous deamination of cytosine which can
cause an A instead of a G to be put in on the replicating strand using
the deaminated Cytosine as a template.

Ron Okimoto


Just thinking out loud here... If you have a unicellular organism, and a
particular gene which always gets the antisense strand as the leading
strand, and assume the leading and lagging strands make very different
numbers of errors, then presumably, focussing on this gene, you get a
"lagging daughter cell" and a "leading daughter cell". Even this assymmetry
wouldn't matter at the population level, except that selection acts on the
two daughter cells, so it might...

Graham- Hide quoted text -

- Show quoted text -



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