Optimality of the genetic code with respect to protein stability and amino-acid frequencies 英文参考文献.docVIP

/2001/2/11/research/0049.1 Research Optimality of the genetic code with respect to protein stability and amino-acid frequencies Dimitri Gilis*, Serge Massar?, Nicolas J Cerf? and Marianne Rooman*? Addresses: *Biomolecular Engineering, and ?Ecole Polytechnique, Université Libre de Bruxelles, ave + D Roosevelt, 1050 Bruxelles, Belgium. ?Service de Physique Théorique, Université Libre de Bruxelles, Boulevard du Triomphe, 1050 Bruxelles, Belgium. Correspondence: Dimitri Gilis. E-mail: dgilis@ulb.ac.be Published: 24 October 2001 Received: 19 June 2001 Revised: 6 September 2001 Accepted: 28 September 2001 GenomeBiology 2001, 2(11):research0049.1–0049.12 The electronic version of this article is the complete one and can be found online at /2001/2/11/research/0049 ? 2001 Gilis et al., licensee BioMed Central Ltd (Print ISSN 1465-6906; Online ISSN 1465-6914) Abstract Background: The genetic code is known to be efficient in limiting the effect of mistranslation errors. A misread codon often codes for the same amino acid or one with similar biochemical properties, so the structure and function of the coded protein remain relatively unaltered. Previous studies have attempted to address this question quantitatively, by estimating the fraction of randomly generated codes that do better than the genetic code in respect of overall robustness. We extended these results by investigating the role of amino-acid frequencies in the optimality of the genetic code. Results: We found that taking the amino-acid frequency into account decreases the fraction of random codes that beat the natural code. This effect is particularly pronounced when more refined measures of the amino-acid substitution cost are used than hydrophobicity. To show this, we devised a new cost function by evaluating in silico the change in folding free energy caused by all possible point mutations in a set of protein structures. With this function, which