Back-Translation for Discovering Distant Protein Homologies

  • Marta Gîrdea
  • Laurent Noé
  • Gregory Kucherov
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 5724)


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. To cope with this situation, we propose 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. This allows us to uncover evolutionary information that is not captured by traditional alignment methods, which is confirmed by biologically significant examples.


Frameshift Mutation Codon Substitution Model Substitution Score Overlap Reading Frame Translation Reading Frame 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Marta Gîrdea
    • 1
  • Laurent Noé
    • 1
  • Gregory Kucherov
    • 1
  1. 1.INRIA Lille - Nord Europe, LIFL/CNRSVilleneuve d’AscqFrance

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