Although bioinformatics perceived is a new discipline, certain parts have a long history and could be viewed as classical bioinformatics. For example, application of string comparison algorithms to sequence alignment has a history spanning the last three decades, beginning with the pioneering paper by Needleman and Wunch, 1970. They used dynamic programming to maximize a similarity score based on a cost of insertion-deletions and a score function on matched amino acids. The principle of choosing solutions by minimizing the amount of evolution is also called parsimony and has been widespread in phylogenetic analysis even if there is no alignment problem. This situation is likely to change significantly in the coming years. After a pioneering paper by Bishop and Thompson (Bishop and Thompson, 1986) that introduced and approximated likelihood calculation, Thorne, Kishino and Felsenstein from 1991 proposed a well defined time reversible Markov model for insertion and deletions (denoted more briefly as the TKF91-model), that allowed a proper statistical analysis for two sequences. Such an analysis can be used to provide maximum likelihood
(pairwise) sequence alignments, or to estimate the evolutionary distance between two sequences. Steel and Hein generalized this to any number of sequences related by a star tree during my last NZ visit. This was subsequently generalized further to any phylogeny and more practical methods based on MCMC has been developed. We are presently developing this into a generally available program package. This talk will present the basic ideas behind this approach to sequence comparison data.

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