Biology Reference
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For example, this could be done if the sequences have some
known domains with known boundaries. An added advan-
tage in such cases is that no undesirable overlaps will occur
between these pre-marked regions if aligned separately.
Finally, the whole alignment can be built by concatenating
the aligned blocks. It should be stressed that each of the
separate alignment operations is likely to follow a different
evolutionary scenario, as for example the guide tree or the
additionally homologous background sequences in the
homology-extended strategy in PRALINE can well be dif-
ferent in each case. It is entirely possible, however, that these
different scenarios reflect true evolutionary differences, such
as unequal rates of evolution of the constituent domains.
(b)
Altering amino acid exchange weights
. Multiple alignment
programs make use of amino acid substitution matrices in
order to score alignments. Therefore, it is possible to
change individual amino acid exchange values in a substitu-
tion matrix. Referring to the disulfide bond example men-
tioned above, one could decide to up-weight the
substitution score for a cysteine self-conservation. As a
result, the alignment will obtain a higher score when
cysteines are matched, and as a consequence the method
will attempt to create an alignment where this is the case.
However, some protein families have a number of known
pairs of Cys residues that form disulfide bonds, where
mixing up of the Cys residues involved in different disulfide
bridges might happen in that Cys residues involved in
different disulfide bonds become aligned at a given single
position. To avoid such incorrect matches in the alignment,
one can add a few extra amino acid designators in the amino
acid exchange matrix that can be used to identify Cys
residue pairs in a given bond (for example J, O, or U).
The exchange scores involving these “alternative” Cys resi-
dues should be identical to those for the original Cys, except
for the cross-scores between the alternative letters for Cys
that should be given low (or extremely negative) values to
avoid cross alignment. It must be stressed that such altera-
tions are heuristics that may compromise the evolutionary
model underlying a given residue exchange matrix.
References
1. Sankoff D, Cedergren RJ (1983) Simultaneous
comparison of three or more sequences related
by a tree, time warps, string edits and macro-
molecules. The theory and practice of sequence
comparison. Addison-Wesley, Reading, MA,
pp 253-263
2. Hogeweg P, Hesper B (1984) The alignment
of sets of sequences and the construction of
phyletic trees: an integrated method. J Mol
Evol 20:175-186
3. Feng DF, Doolittle RF (1987) Progressive
sequence alignment as a prerequisite to correct
phylogenetic trees. J Mol Evol 25:351-360
4. Thompson JD, Higgins DG, Gibson TJ
(1994) CLUSTALW: improving the sensitivity
of progressive multiple sequence alignment
