ABSTRACT
Natural selection can be detected by comparing sequences at the nucleotide and amino acid levels. Some changes in DNA codons will change the structure of proteins (nonsynonymous or replacement changes), while other changes in DNA codons will have no effect on protein structure (synonymous or silent changes). The ratio of nonsynonymous to synonymous changes, dN/dS or ω, can be used to quantitate whether a protein experiences purifying natural selection, is under neutral evolution, or is experiencing positive Darwinian selection. The dN/dS ratio may be determined by approximate or model-based methods. Approximate approaches determine the actual and potential numbers of synonymous and nonsynonymous changes between two sequences and their proportionality. Redundancy in the genetic code, and the different pathways by which codon change can occur, also must be taken into account in calculating dN/dS.
