Multiple DNA and protein sequence alignment based on segment-to-segment comparison.
- 29 October 1996
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 93 (22), 12098-12103
- https://doi.org/10.1073/pnas.93.22.12098
Abstract
In this paper, a new way to think about, and to construct, pairwise as well as multiple alignments of DNA and protein sequences is proposed. Rather than forcing alignments to either align single residues or to introduce gaps by defining an alignment as a path running right from the source up to the sink in the associated dot-matrix diagram, we propose to consider alignments as consistent equivalence relations defined on the set of all positions occurring in all sequences under consideration. We also propose constructing alignments from whole segments exhibiting highly significant overall similarity rather than by aligning individual residues. Consequently, we present an alignment algorithm that (i) is based on segment-to-segment comparison instead of the commonly used residue-to-residue comparison and which (ii) avoids the well-known difficulties concerning the choice of appropriate gap penalties: gaps are not treated explicity, but remain as those parts of the sequences that do not belong to any of the aligned segments. Finally, we discuss the application of our algorithm to two test examples and compare it with commonly used alignment methods. As a first example, we aligned a set of 11 DNA sequences coding for functional helix-loop-helix proteins. Though the sequences show only low overall similarity, our program correctly aligned all of the 11 functional sites, which was a unique result among the methods tested. As a by-product, the reading frames of the sequences were identified. Next, we aligned a set of ribonuclease H proteins and compared our results with alignments produced by other programs as reported by McClure et al. [McClure, M. A., Vasi, T. K. & Fitch, W. M. (1994) Mol. Biol. Evol. 11, 571-592]. Our program was one of the best scoring programs. However, in contrast to other methods, our protein alignments are independent of user-defined parameters.This publication has 17 references indexed in Scilit:
- Sequence alignment and penalty choice: Review of concepts, case studies and implicationsJournal of Molecular Biology, 1994
- Motif-Biased Protein Sequence AlignmentJournal of Computational Biology, 1994
- Similarities between protein 3-D structures"Protein Engineering, Design and Selection", 1994
- Optimal alignment between groups of sequences and its application to multiple sequence alignmentBioinformatics, 1993
- CLUSTAL V: improved software for multiple sequence alignmentBioinformatics, 1992
- [14] Consensus methods for DNA and protein sequence alignmentMethods in Enzymology, 1990
- Fast and sensitive multiple sequence alignments on a microcomputerBioinformatics, 1989
- Progressive sequence alignment as a prerequisitetto correct phylogenetic treesJournal of Molecular Evolution, 1987
- A sensitive procedure to compare amino acid sequencesJournal of Molecular Biology, 1987
- A general method applicable to the search for similarities in the amino acid sequence of two proteinsJournal of Molecular Biology, 1970