Re: Fwd: Single and double strand DNA breaks -Reply

[denison.8@osu.edu (Eric Denison)]

Andy Karam wrote:
>
>Another corollary comes to mind, too:  Does the degeneracy of the DNA code
>(ie multiple code sequences for many amino acids) reflect the environment
>in which DNA and its repair evolved?  For example, there are more codons
>for arginine (5) than there are for Methionine (1).  Is this just the way
>things happened to turn out, or is methionine (or the bases that code for
>it) more resistant to mutation than arginine?  Or could methionine have
>evolved at a different time in the history of life when mutations were less
>likely to occur?
>
Aha!  A chance to put the biochem degree to use again!  Needless to say, we
discussed DNA/amino acid coding pretty extensively in Molecular Genetics
and a few other courses.  Please bear in mind that a lot of this is theory,
and all of it depends on my memory being correct.  If there's a real expert
out there who finds errors, please feel free to let me (us) know.

First, quick and dirty dictionary entries for those not familiar with terms.
DNA = DeoxyriboNucleic Acid.  The "double helix" or "twisted ladder" molecule
      that carries genetic information; backbones, formed of alternating
      sugar (deoxyribose) and phosphate groups, are held together by
      hydrogen-bonding between complimentary bases.
BASE = one of the "rungs" of the DNA ladder.  Can be A, C, G or T; bond in
       limited pairs, A always with T, C always with G (there are very rare
       exceptions to that rule).
RNA = RiboNucleic Acid.  Related to DNA, has several varieties that perform
      different functions; ribose replaces deoxyribose in the backbone and U
      replaces T in the base pairings.
mRNA = memory RNA.  Type of RNA which brings amino acids floating in the cell
       to the sites of protein synthesis and arranges them in the order
       dictated by the DNA codons.
CODON = a sequence of three DNA bases that tells mRNA which amino acid to
        bring into the assembly area next in order to make a desired protein.

As I recall, the degeneracy of the DNA/RNA coding tables reflects an
evolutionary attempt to minimize the effects of botched or missed repair
attempts.  If one looks at the sequences in tabular form, it becomes
apparent that the amino acids are grouped to allow some errors, primarily
in the third base of the three-base codon group.  I don't have the table
handy, but I seem to recall that 4 of the 5 arginine codons are identical
in the first and second bases.  As a result, you can put anything in the
third spot (possibly even nothing) and still get arginine.  Definitely
looks to me (and a lot of others) like a mechanism to protect against
screw-ups caused by poor binding mechanics in the region of the third base.

I think if you look at the table statistically, you could get the idea that
the number of codons per amino acid is something of a random distribution.
This is entirely possible.  However, it seems more likely that the number
of times an amino acid appears on the table is related to its importance in
building a range of functional proteins.  I'll have to check with some of
the lab folks here to see if my memory is correct, but I seem to recall
hearing a professor mention that the acids with the greatest number of
codon triplets are the most common and/or the most important to promote
folding of the protein into its proper three-dimensional shape.  In many
cases, changing one amino acid in a protein can make that protein
non-functional.*  It makes sense, then, that there is a redundant system
for getting these critical amino acids into their proper places in the
proteins.

Another consideration is the fact that some amino acids, like methionine,
which contains a sulfur atom, make a protein structures do wierd things.
In most cases, the peculiar functions are needed in only a few proteins and
are most certainly unwanted in the rest.  If you only need a
double-back-half-twist in 1% of your proteins, you don't need a lot of
codons that get it for you.  If that same double-back-half-twist will
destroy the usefulness of the other 99% of your proteins, you definitely
don't want to increase the probability of getting it in there by accident.

Hope this helps (and that it wasn't too much).  Let me know if you need
references on this stuff.  It might take a while to dig them out, but I
still have all of my textbooks and class notes.

Eric

* Perhaps the best example of this is Sickle-Cell anemia -- change one
particular amino acid in normal hemoglobin and you ruin its capacity to
carry oxygen through the blood stream effectively.  Put the sickle-cell
sufferer under  stress (sometimes walking briskly up stairs is enough), and
the demand for oxygen soars past the sickle-heme's ability to deliver.  The
result is a warping of the red blood cells into a shape that clogs the
capillaries, starving muscles of oxygen and causing severe pain and loss of
muscle function.  Severe cases can be fatal in a matter of minutes due to
system shock and brain death.  Getting the sickling gene from both parents
results in sickle cell anemia.  Getting one sickling gene and one normal
gene makes one a carrier (symptoms show generally only under the most
severe stress).  Interestingly, being a carrier also makes one immune to
(or at least *highly* resistant to) infection by malaria parasites.  This
fact leads us to believe that the sickling gene evolved as a defense
against malaria and is still around because at some point, it saved more
Africans than it killed.


J. Eric Denison
Program Assistant to the Director
Neurobiotechnology Center
The Ohio State University
206 Rightmire Hall
1060 Carmack Road
Columbus, Ohio  43210
ph: 614-292-5682
fax:614-292-5379
e-mail: denison.8@osu.edu