A formal mathematical analysis of the substitution process in nucleoti
de sequence evolution was done in terms of the Markov process. By usin
g matrix algebra theory, the theoretical foundation of Barry and Harti
gan's (Stat. Sci. 2:191-210, 1987) and Lanave et al.'s (J. Mol. Evol.
20:86-93, 1984) methods was provided. Extensive computer simulation wa
s used to compare the accuracy and effectiveness of various methods fo
r estimating the evolutionary distance between two nucleotide sequence
s. It was shown that the multiparameter methods of Lanave et al.'s (J.
Mol. Evol. 20:86-93, 1984), Gojobori et al.'s (J. Mol. Evol. 18:414-4
22, 1982), and Barry and Hartigan's (Stat. Sci. 2:191-210, 1987) are p
referable to others for the purpose of phylogenetic analysis when the
sequences are long. However, when sequences are short and the evolutio
nary distance is large, Tajima and Nei's (Mol. Biol. Evol. 1:269-285,
1984) method is superior to others.