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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.

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.


Related in: MedlinePlus

Yersinia pestis: transposases. The alignment of two transposase variants from Yersinia pestis: [GenBank:167423046] - subsequence 4-167 of the back-translation, and [GenBank:EDR63673.1] - subsequence 225-389 of the back-translation. The frameshift mutation at position 115/336 corrects the reading frame. The frameshifted alignment fragment has an E-value of 10-7.
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Figure 7: Yersinia pestis: transposases. The alignment of two transposase variants from Yersinia pestis: [GenBank:167423046] - subsequence 4-167 of the back-translation, and [GenBank:EDR63673.1] - subsequence 225-389 of the back-translation. The frameshift mutation at position 115/336 corrects the reading frame. The frameshifted alignment fragment has an E-value of 10-7.

Mentions: Figure 7 displays the alignment of two transposase variants from Yersinia pestis. Both proteins are widely present on the NCBI nr database. The mechanism involved is (most probably) a programmed translational frameshifting since such mechanism has been quite frequently observed in several other transposases from related species, e.g. as in E. coli [36].


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

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

Yersinia pestis: transposases. The alignment of two transposase variants from Yersinia pestis: [GenBank:167423046] - subsequence 4-167 of the back-translation, and [GenBank:EDR63673.1] - subsequence 225-389 of the back-translation. The frameshift mutation at position 115/336 corrects the reading frame. The frameshifted alignment fragment has an E-value of 10-7.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Yersinia pestis: transposases. The alignment of two transposase variants from Yersinia pestis: [GenBank:167423046] - subsequence 4-167 of the back-translation, and [GenBank:EDR63673.1] - subsequence 225-389 of the back-translation. The frameshift mutation at position 115/336 corrects the reading frame. The frameshifted alignment fragment has an E-value of 10-7.
Mentions: Figure 7 displays the alignment of two transposase variants from Yersinia pestis. Both proteins are widely present on the NCBI nr database. The mechanism involved is (most probably) a programmed translational frameshifting since such mechanism has been quite frequently observed in several other transposases from related species, e.g. as in E. coli [36].

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.


Related in: MedlinePlus