Document Detail

A combined empirical and mechanistic codon model.
MedLine Citation:
PMID:  17110464     Owner:  NLM     Status:  MEDLINE    
The evolutionary selection forces acting on a protein are commonly inferred using evolutionary codon models by contrasting the rate of synonymous to nonsynonymous substitutions. Most widely used models are based on theoretical assumptions and ignore the empirical observation that distinct amino acids differ in their replacement rates. In this paper, we develop a general method that allows assimilation of empirical amino acid replacement probabilities into a codon-substitution matrix. In this way, the resulting codon model takes into account not only the transition-transversion bias and the nonsynonymous/synonymous ratio, but also the different amino acid replacement probabilities as specified in empirical amino acid matrices. Different empirical amino acid replacement matrices, such as secondary structure-specific matrices or organelle-specific matrices (e.g., mitochondria and chloroplasts), can be incorporated into the model, making it context dependent. Using a diverse set of coding DNA sequences, we show that the novel model better fits biological data as compared with either mechanistic or empirical codon models. Using the suggested model, we further analyze human immunodeficiency virus type 1 protease sequences obtained from drug-treated patients and reveal positive selection in sites that are known to confer drug resistance to the virus.
Adi Doron-Faigenboim; Tal Pupko
Related Documents :
9548884 - Synthesis and stereochemistry of axinastatin 4
11594464 - Molecular cloning and the cdna-derived amino acid sequence of narcissus tazetta isolect...
11129594 - Some molecular and inhibitory specifications of a dipeptidyl carboxypeptidase from the ...
11922434 - Triclabendazole-resistant fasciola hepatica: beta-tubulin and response to in vitro trea...
20553554 - Lack of cbrb in pseudomonas putida affects not only amino acids metabolism but also dif...
24000204 - Microwave-accelerated pd-catalyzed desulfitative direct c2-arylation of free (nh)-indol...
Publication Detail:
Type:  Journal Article     Date:  2006-11-16
Journal Detail:
Title:  Molecular biology and evolution     Volume:  24     ISSN:  0737-4038     ISO Abbreviation:  Mol. Biol. Evol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-31     Completed Date:  2007-05-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8501455     Medline TA:  Mol Biol Evol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  388-97     Citation Subset:  IM    
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amino Acid Substitution
Anti-HIV Agents / therapeutic use
Carbamates / therapeutic use
Chloroplasts / genetics
Drug Resistance, Viral
Evolution, Molecular
Genes, Mitochondrial
Genes, Viral
HIV Infections / drug therapy
HIV Protease / chemistry,  genetics
HIV-1 / enzymology
Markov Chains
Models, Genetic*
Models, Statistical*
Selection, Genetic
Sulfonamides / therapeutic use
Reg. No./Substance:
0/Anti-HIV Agents; 0/Carbamates; 0/Codon; 0/Sulfonamides; 161814-49-9/amprenavir; EC 3.4.23.-/HIV Protease

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Expression of a non-DNA-binding isoform of Helios induces T-cell lymphoma in mice.
Next Document:  Defining a binding pocket for sulfonylureas in ATP-sensitive potassium channels.