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mouse/human mRNAs are 85% similar/NA and protein

Douglas Rhoads drhoads at MERCURY.UARK.EDU
Sun Mar 9 07:55:21 EST 1997


Why the concern?  Is it that both coding and protein sequence 
divergence was measured to be 85%.  You were expecting higher 
divergence at the NA level than AA.  Several things will come into 
this number.  First, you only theoretically have to diverge 33% at 
the NA level to be 100% divergent at the AA level.  However, we are 
used to variation at codon third positions giving most of the NA 
divergence with little variation at the AA level because of genetic 
code degeneracy.  One also has to take into account codon bias which 
I have not studied but with significant overlap of mouse and human 
then this will minimize variation at the 3rd position from selective 
pressures.

> To:            mol-evol at net.bio.net
> From:          grewal at OCELOT.RUTGERS.EDU ("Grewal, Anoop")
> Subject:       mouse/human mRNAs are 85% similar/NA and protein
> Date:          8 Mar 1997 23:15:21 -0800

> I just a read an article, -Comparative analysis of 1196 orthologous mouse and
> human full-length mRNA and protein sequences+ by Makalowski W et al (Genome
> Research, 9/96; http://207.22.83.2:443/cshl/journals/gr/nih/article.html).
> I had been assuming that amino acid sequence conservation (avg 85% between mouse
> and human orthologs) would be much higher on average than corresponding
> conservation at the nucleic acid level because of redundancy in codon
> specification of amino acids. But the authors+ analysis reveals that nucleic
> acid conservation in the coding sequence also averages 85%.
> Is this a surprise to any readers of this newsgroup? Or is my assumption only a
> common misconception held among biologists outside the molecular
> evolution/comparative genetics realm?
> Certainly, this suggests that nucleic acid structure is a way significant
> constraint on sequences that are selected for. But would it be fair to see that
> mutations selected for because of their effects at the nucleic acid sequence
> level may +direct+ amino acid sequence and hence, protein structure (ie esp. in
> cases where nuclei acid sequence conservation is higher than corresponding amino
> acid conservation). What mechanism is considered to play such a strong force -
> is it the topological structure of the DNA, the way sequence affects its
> interaction with histones, the structure and stability of the transcribed RNA?
> 
> 
> 
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||                  Douglas Rhoads                        ||                             ||
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