Practical methods for multiple sequence alignment based on a tree have been developed in several laboratories . The principle is that since the alignment of two sequences can be achieved very easily, multiple alignments should be built by the successive application of pairwise methods.
The steps are summarised here and illustrated in Figure 5:
This family of methods gives good usable alignments with gaps it can be applied to large numbers of sequences, and with the exception of the initial pairwise comparison step is very fast.
Although based on the successive application of pairwise methods, multiple alignment will often yield better alignments than any pair of sequences taken in isolation. This effect was illustrated by Barton and Sternberg  for the alignment of immunoglobulin and globin domains. Figure 6 shows that for some alignment pairs there is a marked improvement in accuracy over optimal pairwise aligment (e.g. variable versus constant domains).