ESTIMATING THE PATTERN OF NUCLEOTIDE SUBSTITUTION

Knowledge of the pattern of nucleotide substitution is important both to our understanding of molecular sequence evolution and to reliable e stimation of phylogenetic relationships. The method of parsimony analy sis, which has been used to estimate substitution patterns in real seq uences, has serious drawbacks and leads to results difficult to interp ret. In this paper a model-based maximum likelihood approach is propos ed for estimating substitution patterns in real sequences. Nucleotide substitution is assumed to follow a homogeneous Markov process, and th e general reversible process model (REV) and the unrestricted model wi thout the reversibility assumption are used. These models are also app lied to examine the adequacy of the model of Hasegawa et al. (J. Mol. Evol, 1985;22:160-174) (HKY85). Two data sets are analyzed. Far the ps i eta-globin pseudogenes of six primate species, the REV model fits th e data much better than HKY85, while, for a segment of mtDNA sequences from nine primates, REV cannot provide a significantly better fit tha n HKY85 when rate variation over sites is taken into account in the mo dels. It is concluded that the use of the REV model in phylogenetic an alysis can be recommended, especially for large data sets or for seque nces with extreme substitution patterns, while HKY85 may be expected t o provide a good approximation. The use of the unrestricted model does not appear to be worthwhile.