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realistic amino acid subst. models

higgins at ebi.ac.uk higgins at ebi.ac.uk
Fri Jun 2 12:09:49 EST 1995

In article <1995Jun2.125633.38714 at ac.dal.ca>, aroger at ac.dal.ca writes:
> Des Higgins said:
>> 1) why is reversibility suspect here (biologically)???  I would have guessed
>> that the process could just as validly be treated as such (for almost
>> all cases) with real proteins.  For individual cases where natural
>> selection "drives" a substitution in one direction it will not hold
>> but for neutral substitutions it will be perfectly valid (or am I being
>> silly?).  By the looks of things, neutral changes are VERY common and
>> possibly the great majority of changes are such.
> I don't think that this argument is valid.  For instance if there is 
> a bias towards mutation (say a bias to mutate from a pyrimidine
> to a purine) and the change between two amino acids is neutral
> 9(say for the sake of argument that it is Asp and Glu). Then
> over a period of time the accumulation of neutral mutations
> in the third position will result in a bias of purines.  If you
> look at a codon usage table, you can see that Glu has purines
> in the third position and Asp has pyrimidines.  The accumlation
> of purines in the third position of the GAN codons will thus
> favour Glu over Asp.  Thus there could be a subsitution bias
> towards Asp-->Glu and against Glu-->Asp...and this substitution
> bias would be entirely the result of neutral changes.
> Andrew Roger
> aroger at ac.dal.ca

Hi Andrew:

I did say I was probably out of my depth :-).
Your point is taken.  All I can say is that such factors will
be important in specific cases (in this case for one species)
but surely, when you average out over all proteins and all species
it will be hard to see.  Hmmmmmmmm ..... I wonder if it would be
worth looking for such an effect??... and how you would try to see
it.  I vaguely remember people looking for how biased codon usage
would change amino acid composition (a similar effect to having
a bias towards purines).  Still, over many species, this would
surely be hard to see.   I also remember Steven Benner mention
that at very short evolutionary distances, the genetic code does
seem to influence the frequency of interchange of amino acids
(amino acids with similar codons change to each other more often)
but that at greater distance there is no effect: conservation of
amino acid property being far too dominant to see anything else.


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