A maximum likelihood method for detecting functional divergence at individual codon sites, with application to gene family evolution

Journal of Molecular Evolution
Joseph P Bielawski, Ziheng Yang

Abstract

The tailoring of existing genetic systems to new uses is called genetic co-option. Mechanisms of genetic co-option have been difficult to study because of difficulties in identifying functionally important changes. One way to study genetic co-option in protein-coding genes is to identify those amino acid sites that have experienced changes in selective pressure following a genetic co-option event. In this paper we present a maximum likelihood method useful for measuring divergent selective pressures and identifying the amino acid sites affected by divergent selection. The method is based on a codon model of evolution and uses the nonsynonymous-to-synonymous rate ratio (omega) as a measure of selection on the protein, with omega = 1, < 1, and > 1 indicating neutral evolution, purifying selection, and positive selection, respectively. The model allows variation in omega among sites, with a fraction of sites evolving under divergent selective pressures. Divergent selection is indicated by different omega's between clades, such as between paralogous clades of a gene family. We applied the codon model to duplication followed by functional divergence of (i) the epsilon and gamma globin genes and (ii) the eosinophil cationic protein (...Continue Reading

Citations

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