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An MSA is constructed with respect to a phylogenetic tree, which can be
specified (TA) or is constructed (GTA) [36,30,21,31].
First the sequences at the leaves are aligned in a pairwise manner. Then in the next
step either a representative sequence is calculated or a
probabilistic ancestral sequence is determined.
The drawback here is that the correct evolutionary tree is
needed, something which is typically not available. We note that the calculation
of evolutionary trees is also still an open problem mainly due to the fact that
the problem is NP-complete .