Feng-Doolittle 1987

In this algorithm (Feng and Doolittle, 1987 [1]), the key idea is that the pair of strings with minimum distance is almost likely to having been obtained from the pair of objects that had most recently diverged, and that the pairwise alignment of these two specific strings provides the most "reliable" information that can be extracted from the input strings. Therefore any spaces (gaps) that appear in the optimal pairwise alignment of those two strings should be preserved in the overall multiple alignment. The algorithm is as follows:

1.

Calculate the $k \choose 2$ pairwise alignment scores, and convert then to distances.

2.

Use an incremental clustering algorithm (Fitch and Margoliash, 1967 [2]) to construct a tree from the distances.

3.

Traverse the nodes in their order of addition to the tree, repeatedly align the child nodes (sequences or alignments).

Features of this heuristic:

• Highest scoring pairwise alignment determines the alignment to two groups.
• "Once a gap, always a gap": replace gaps in alignments by a neutral character.