The correlation of protein structure and evolution of a protein-coding gene: phylogenetic inference using cytochrome oxidase III

Discriminating phylogenetic signal from noise in DNA sequence data is adifficult problem in phylogenetic inference at higher systematic levels.For protein-coding genes, noise at synonymous (silent) positions can befiltered by deleting entire codon positions or types of change at a codonposition. This method is not appropriate for replacement sites, becausechanges at each site within a codon may not be independent. This researchpresents a method using information from protein structure to evaluatevariation in replacement sites. Analysis of the correlation of amino acidvariation with protein structure identified rapidly evolving codons in theCOIII gene. In a series of phylogenetic analyses attempting to recover aknown set of vertebrate relationships, downweighting these labile codonsproduced the most accurate results. Structural correlates of variable andinvariant residues identified in this study can be used to increase theaccuracy of models used for phylogenetic inference. Viewing amino acidvariation within a phylogenetic framework provided insight into residuechanges important in the secondary and tertiary structures of the molecule,changes that were correlated between pairs of neighboring residues orbetween residues in neighboring helices.