Thorne-Kishino-Felsenstein model (TKF)

The Thorne-Kishino-Felsenstein 1991 model (TKF91) is the first explicit derivation of a pairwise sequence alignment algorithm from a continuous-time Markov chain defined on whole sequences. It is a landmark paper in Statistical Alignment. Thorne JL, Kishino H, Felsenstein J.  An evolutionary model for maximum likelihood alignment of DNA sequences.  J Mol Evol. 1991 Aug;33(2):114-24. Alignment algorithms for the TKF91 model are implemented in the Handel Package. Empirical drawbacks of the TKF91 model revolve around its simplicity, in particular the assumption that each indel event involves only a single residue. This is the equivalent of the "linear gap penalty" in bioinformatics, and gives unrealistic (gappy) alignments. The followup "TKF92 model" attempts to introduce an "affine gap penalty" by breaking the sequence into indivisible fragments. Each indel event involves exactly one fragment; indel events never overlap, and the math turns out similar to the TKF91 model, but with "residues" replaced by "fragments". Thorne JL, Kishino H, Felsenstein J.  Inching toward reality: an improved likelihood model of sequence evolution.  J Mol Evol. 1992 Jan;34(1):3-16. TKF92 can be viewed as an approximation to a Long Indel model. (http://biowiki.org/ThorneKishinoFelsenstein)