Never one to shrink from philosophizing, I wonder generally why the codon
conventions are the way they are? Is it like the QWERTY keyboard--basically
an historical accident--or is there some more beautiful reason? One might
argue that since basically all organisms share the convention (are there
exceptions, even?), that it must be the "best of all possible" conventions.
I have often wondered whether maybe this particular convention allows for
the most effective pathways between proteins of significant function, e.g.,
through the fewest mutations perhaps? One certainly cannot maintain that
every possible protein sequence has been made at some time or another in
the history of the biological world (go quantitate!) so there must be a way
to ensure that mostly the "best" ones got made. On the other hand, since
many organisms share DNA, maybe they had to "agree" on a system (I think
this is the dogma?). Was there a "United Organisms" convention at some
point, reminiscent of "Les Immortels" of the French language or POSIX or
something, to ensure compliance? What was the penalty for non-compliance?

Anyway, I like the question about the methionines,

Jacob

On Tue, Mar 19, 2013 at 9:46 AM, Edward A. Berry <ber...@upstate.edu> wrote:

> Opher Gileadi wrote:
>
>> Hi Theresa,
>>
>> To add to Anat's comments: Although the AUG codon for the first
>> methionine and all other methionines in a protein coding sequence look the
>> same, they are read in a very different way by the ribosomal machinery. The
>> first AUG is recognized by the initiation complex, which includes the
>> separate small ribosomal subunit (40s), a special tRNA-methionine, and
>> initiation factors (proteins) including eIF2. This leads to assembly of a
>> complete ribosome and initiation of protein synthesis. Subsequently, in the
>> process of elongation, AUG codons are read by a different tRNA, which is
>> brought to the 80s ribosome bound to a protein called elongation factor 1a.
>> This is an oversimplification, of course, but the point is that the
>> initiation codon (=the first amino acid to be incorporated to the protein)
>> is read by a special tRNA, hence the universal use of methionine.
>>
>> Opher
>>
>>  Yes, but why methionine? Half the time it has to be removed by
> N-terminal peptidase to give a small first residue, or by leader sequence
> processing. Why use a big expensive amino acid instead of choosing one of
> the glycine codons? Is there an obvious reason, or just "it had to be
> something, and Met happened to get selected"?
>
> And why sometimes alternate start codons can be used? and why doesn't
> initiation occur also at methionines in the middle of proteins? I'm
> guessing it has to do with 5' untranslated region and ribosome binding
> sites. So could the start codon actually be anything you want, provided
> there is a strong ribosome binding site there?
>
> Just being philosophical, and not afraid to display my ignorance,
> eab
>



-- 
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Jacob Pearson Keller, PhD

Looger Lab/HHMI Janelia Farms Research Campus

19700 Helix Dr, Ashburn, VA 20147

email: kell...@janelia.hhmi.org

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