From: Koonin, Eugene (NIH/NLM/NCBI) [E]
Sent: Friday, April 24, 2009 5:13 PM
To: NLM/NCBI List ncbi-seminar
Cc: Claus Wilke
Subject: Seminar on May 8

Follow Up Flag: Follow up
Flag Status: Red

Friday, May 8, 11 AM
Bldg. 38A, B2 conference room


Mistranslation-Induced Protein Misfolding as a Dominant Constraint on Coding-
Sequence Evolution

Claus Wilke

University of Texas-Austin
Center for Computational Biology and Bioinformatics and Institute for Cell and Molecular Biology

Strikingly consistent correlations between rates of coding-sequence evolution 
and gene expression levels are apparent across taxa, but the biological causes 
behind the selective pressures on coding-sequence evolution remain 
controversial. We demonstrate conserved patterns of simple covariation between 
sequence evolution, codon usage, and mRNA level in E. coli, yeast, worm, ?y, 
mouse, and human that suggest that all observed trends stem largely from a 
uni?ed underlying selective pressure. In metazoans, these trends are strongest 
in tissues composed of neurons, whose structure and lifetime confer extreme 
sensitivity to protein misfolding. We propose, and demonstrate using a 
molecular-level evolutionary simulation, that selection against toxicity of 
misfolded proteins generated by ribosome errors suf?ces to create all of the 
observed covariation. The mechanistic model of molecular evolution that
emerges yields testable biochemical predictions, calls into question the use 
of nonsynonymous-to-synonymous substitution ratios (Ka/Ks) to detect
functional selection, and suggests how mistranslation may contribute to 
neurodegenerative disease.



On Tuesday 21 April 2009, you wrote:
> Dear Claus,
>
>
>
> Time flies as it always does, and your much anticipated visit  to the
> NCBI is approaching.
>
> I would now like to announce your seminar and so would be most grateful
> for a title and a brief
>
> abstract.
>
>
>
> Thank you in advance,
>
>
>
> See you in May,
>
>
>
> Eugene
>
>
>
> Eugene V. Koonin, PhD
>
> Senior Investigator
>
> NCBI, NLM, NIH
>
> Bethesda, MD 20894
>
> Bldg. 38a, Rm. 5N503
>
> Telephone:
>
> 301-435-5913 (o)
>
> 301-233-7294 (cell)


-- 
Claus Wilke
Section of Integrative Biology 
 and Center for Computational Biology and Bioinformatics 
University of Texas at Austin
1 University Station C0930
Austin, TX 78712
cwilke@mail.utexas.edu
512 471 6028