Comparing orthologs or homologous genes between different species.
D_N = fraction of sites that differ at non-synonymous sites (nucleotides that change codon/amino acid).
D_S = fraction of sites that differ at synonymous sites (different nucleotides but same codon).
DN/DS = 1 indicates neutral selection (genetic drift).
DN/DS < 1 indicates negative selection (purifying selection).
DN/DS > 1 indicates positive selection.
Rates of nonsynonymous and synonymous mutations are species-specific.
Example in drosophila: half the differences evolved via positive selection.
Example: In humans, less than 15% evolve via positive selection.