Multiple base substitution corrections in DNA sequence evolution

We discuss the Jukes and Cantor's one-parameter model and Kimura's two-para meter model unability to describe evolution of asymmetric DNA molecules. Th e standard distance measure between two DNA sequences, which is the number of substitutions per site, should include the effect of multiple base subst itutions separately for each type of the base. Otherwise, the respective ta bles of substitutions cannot reconstruct the asymmetric DNA molecule with r espect to the composition. Basing on Kimura's neutral theory, we have deriv ed a linear law for the correlation of the mean survival time of nucleotide s under constant mutation pressure and their fraction in the genome. Accord ing to the law, the corrections to Kimura's theory have been discussed to d escribe evolution of genomes with asymmetric nucleotide composition. We consider the particular case of the strongly asymmetric Borrelia burgdor feri genome and we discuss in detail the corrections, which should be intro duced into the distance measure between two DNA sequences to include multip le base substitutions.