The Tamura-Nei distance (1993) estimated by the composite likelihood method (Tamura et al. 2004) corrects for multiple hits, taking into account the substitution rate differences between nucleotides and the inequality of nucleotide frequencies. When the nucleotide frequencies between the sequences are different, the expected proportions of observed differences (P1, P2, and Q) in the computation of the composite likelihood can be obtained by the modified formulas according to Tamura and Kumar (2002) to relax the assumption of the substitution pattern homogeneity. See related Tamura-Nei distance (Heterogeneous Patterns).