Back-translation for discovering distant protein homologies in the presence of frameshift mutations

Marta Gîrdea, Laurent Noé, Gregory Kucherov

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    Background: Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins' common origin. Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level.Results: We developed a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences. We design a dynamic programming alignment algorithm over memory-efficient graph representations of the complete set of putative DNA sequences of each protein, with the goal of determining the two putative DNA sequences which have the best scoring alignment under a powerful scoring system designed to reflect the most probable evolutionary process. Our implementation is freely available at http://bioinfo.lifl.fr/path/.Conclusions: Our approach allows to uncover evolutionary information that is not captured by traditional alignment methods, which is confirmed by biologically significant examples.

    Original languageEnglish
    Article number6
    JournalAlgorithms for Molecular Biology
    Volume5
    Issue number1
    DOIs
    Publication statusPublished - 4 Jan 2010

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