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An Isaac Newton Institute Workshop

Recent Advances in Statistical Genetics and Bioinformatics

Detecting natural selection with empirical codon models: a synthesis of population genetics and molecular phylogenetics

Authors: Carolin Kosiol (Cornell University), Nick Goldman (EMBL-European Bioinformatcs Institute)


The estimation of empirical codon models sheds new light on recently discussed questions about biological pressures and processes acting during codon sequence evolution (Averof et al., Science 287:1283 (2000), Bazykin et al., Nature 429:558 (2004), Friedman and Hughes, MBE 22:1285 (2005), Keightley et al., PLoS Biol 3:282 (2005)).

My results show that modelling the evolutionary process is improved by allowing for single, double and triple nucleotide changes; the affiliation between DNA triplets and the amino acid they encode is a main factor driving evolution; and the nonsynonymous-synonymous rate ratio is a suitable measure to classify substitution patterns observed for different proteins. However, comparing models estimated from genomic data and polymorphism data indicates that double and triple changes are not instantaneous.

This new view of how codon evolution proceeds leads to consequences for selection studies. I will discuss that under the new empirical codon model purifying selection is less purifying and that cases of positive selection are observed weaker than under the standard condon models (Yang et al.,Genetics 155: 431-449 (2000)).