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

Girdea M, Noe L, Kucherov G - Algorithms Mol Biol (2010)

Bottom Line: 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.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.

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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.

No MeSH data available.


Elapidae: neurotoxins (1). Two presynaptic neurotoxins from two higher snakes of the Elapidae family (Bungarus candidus and Naja kaouthia): [Swiss-Prot:Q8AY47.1] - subsequence 64-407 of the back-translation, and [PIR:PSNJ2K] - subsequence 13-354 of the back-translation. The sequences are aligned on the same reading frame up to position 186/135, and on a +1 reading frame from that point forward. The frameshifted fragment has an E-value of 10-9.
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Figure 9: Elapidae: neurotoxins (1). Two presynaptic neurotoxins from two higher snakes of the Elapidae family (Bungarus candidus and Naja kaouthia): [Swiss-Prot:Q8AY47.1] - subsequence 64-407 of the back-translation, and [PIR:PSNJ2K] - subsequence 13-354 of the back-translation. The sequences are aligned on the same reading frame up to position 186/135, and on a +1 reading frame from that point forward. The frameshifted fragment has an E-value of 10-9.

Mentions: In Figure 9, we show the alignment of two presynaptic neurotoxins from two higher snakes of the Elapidae family (Bungarus candidus and Naja kaouthia). Most of the sites are conserved: the primary metal binding site and the putative hydrophobic channel remain before the frameshift, and only the fourth (and last) part of the catalytic network seems changed. We also noticed that, in the original second sequence, the Cysteine regions are more conserved at the DNA level than other amino acids, even after the frameshift, which is a strong hint of the non randomness of this part of the alignment.


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

Girdea M, Noe L, Kucherov G - Algorithms Mol Biol (2010)

Elapidae: neurotoxins (1). Two presynaptic neurotoxins from two higher snakes of the Elapidae family (Bungarus candidus and Naja kaouthia): [Swiss-Prot:Q8AY47.1] - subsequence 64-407 of the back-translation, and [PIR:PSNJ2K] - subsequence 13-354 of the back-translation. The sequences are aligned on the same reading frame up to position 186/135, and on a +1 reading frame from that point forward. The frameshifted fragment has an E-value of 10-9.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821327&req=5

Figure 9: Elapidae: neurotoxins (1). Two presynaptic neurotoxins from two higher snakes of the Elapidae family (Bungarus candidus and Naja kaouthia): [Swiss-Prot:Q8AY47.1] - subsequence 64-407 of the back-translation, and [PIR:PSNJ2K] - subsequence 13-354 of the back-translation. The sequences are aligned on the same reading frame up to position 186/135, and on a +1 reading frame from that point forward. The frameshifted fragment has an E-value of 10-9.
Mentions: In Figure 9, we show the alignment of two presynaptic neurotoxins from two higher snakes of the Elapidae family (Bungarus candidus and Naja kaouthia). Most of the sites are conserved: the primary metal binding site and the putative hydrophobic channel remain before the frameshift, and only the fourth (and last) part of the catalytic network seems changed. We also noticed that, in the original second sequence, the Cysteine regions are more conserved at the DNA level than other amino acids, even after the frameshift, which is a strong hint of the non randomness of this part of the alignment.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

No MeSH data available.