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Science 20 June 2008:
Vol. 320. no. 5883, pp. 1632 - 1635
DOI: 10.1126/science.1158395
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Reports

Phylogeny-Aware Gap Placement Prevents Errors in Sequence Alignment and Evolutionary Analysis

Ari Löytynoja* and Nick Goldman

Genetic sequence alignment is the basis of many evolutionary and comparative studies, and errors in alignments lead to errors in the interpretation of evolutionary information in genomes. Traditional multiple sequence alignment methods disregard the phylogenetic implications of gap patterns that they create and infer systematically biased alignments with excess deletions and substitutions, too few insertions, and implausible insertion-deletion–event histories. We present a method that prevents these systematic errors by recognizing insertions and deletions as distinct evolutionary events. We show theoretically and practically that this improves the quality of sequence alignments and downstream analyses over a wide range of realistic alignment problems. These results suggest that insertions and sequence turnover are more common than is currently thought and challenge the conventional picture of sequence evolution and mechanisms of functional and structural changes.

European Molecular Biology Laboratory—European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SD, UK.

* To whom correspondence should be addressed. E-mail: ari{at}ebi.ac.uk

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