Natural selection at single amino acid sites models and estimation for the validation of SNP'S phenotypes

DUCHI S., L. ARBIZA AND H. DOPAZO

Zaragoza, España

Congreso; XXVIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular; 2005

Sociedad Española de Bioquímica y Biología Molecular

NATURAL SELECTION AT SINGLE AMINO ACID SITES MODELS AND ESTIMATIONS FOR THE VALIDATION OF SNP´S PHENOTYPE Serena Duchi, Leonardo Arbiza and Hernán Dopazo Pharmacogenomics and Comparative Genomics Unit Bioinformatics Department Centro de Investigación Príncipe Felipe. Valencia. Spain hdopazo@ochoa.fib.es Natural selection can be divided into positive and negative selection. Positive selection is the evolutionary mechanism whereby newly produced mutants have higher fitness than the average in the population, and the frquencies of the mutants increase in the following generations. On the other hand negative selection is the evolutionary mechanism whereby newly produced mutants have lower fitness han the average in the population, and the frquencies of the mutants decrease in the following generations. Neutral theory predicts that the greath majority of the evolutionary change is selectively neutral or nearly neutral and mutants increase or decrease according to a randon drift process. Parsimony and maximum likelihood methods have been developed in order to detect positive and negative natural selection at single amino acid sites. Here we study the model´s predictions for each amino acid sites on different genes related to human diseases. When the frequency of patiens carrying specific amino acid mutations versus the selection coeficient values estimated for each amino acid sites were plotted, L shape graphics were obtained. We conclude that models of natural selection at single amino acid sites would be used as good predictors of the phenotype effect of particular SNP´s. A high-throughput analysis using all the human proteins and all the coding SNP´s will be done. and results will be available in the PupaSNP´s tool(http://pupasnp.bioinfo.ochoa.fib.es/)