Relative Rate Test, Li-Wu-Luo 1993

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A protein has evolved more rapidly than the neutral substitution rate requires more than simply counting non-synonymous and synonymous differences between sequences. Proper consideration of the genetic code requires a comparison of the number of nonsynonymous substitutions per non-synonymous site, noted by Ka, with the number of synonymous substitutions per synonymous site, noted by Ks between pairs of homologous protein-coding genes (Li et al. 1985; Li 1993). The value has been corrected for multiple hits by Jukes and Cantor's formula (1969)

Under the hypothesis of neutrality, Ka should be equal to Ks. Positive selection will cause Ka > Ks, while negative selection will lead to Ka < Ks. Statistical significance is calculated by t-test.