Molecular Biology and Evolution, Vol 6, 649-668, Copyright © 1989 by Society for Molecular Biology and Evolution
J Hein
Among the fundamental problems in molecular evolution and in the analysis
of homologous sequences are alignment, phylogeny reconstruction, and the
reconstruction of ancestral sequences. This paper presents a fast, combined
solution to these problems. The new algorithm gives an approximation to the
minimal history in terms of a distance function on sequences. The distance
function on sequences is a minimal weighted path length constructed from
substitutions and insertions-deletions of segments of any length.
Substitutions are weighted with an arbitrary metric on the set of
nucleotides or amino acids, and indels are weighted with a gap penalty
function of the form gk = a + (bxk), where k is the length of the indel and
a and b are two positive numbers. A novel feature is the introduction of
the concept of sequence graphs and a generalization of the traditional
dynamic sequence comparison algorithm to the comparison of sequence graphs.
Sequence graphs ease several computational problems. They are used to
represent large sets of sequences that can then be compared simultaneously.
Furthermore, they allow the handling of multiple, equally good, alignments,
where previous methods were forced to make arbitrary choices. A program
written in C implemented this method; it was tested first on 22 5S RNA
sequences.
ORIGINAL ARTICLE
A new method that simultaneously aligns and reconstructs ancestral sequences for any number of homologous sequences, when the phylogeny is given
NIEHS, Research Triangle Park, North Carolina 27709.
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