Abstract
Protein or DNA motifs are sequence regions which possess biological importance. These regions are often highly conserved among homologous sequences. The generation of multiple sequence alignments (MSAs) with a correct alignment of the conserved sequence motifs is still difficult to achieve, due to the fact that the contribution of these typically short fragments is overshadowed by the rest of the sequence. Here we extended the PRALINE multiple sequence alignment program with a novel motif-aware MSA algorithm in order to address this shortcoming. This method can incorporate explicit information about the presence of externally provided sequence motifs, which is then used in the dynamic programming step by boosting the amino acid substitution matrix towards the motif. The strength of the boost is controlled by a parameter, α. Using a benchmark set of alignments we confirm that a good compromise can be found that improves the matching of motif regions while not significantly reducing the overall alignment quality. By estimating α on an unrelated set of reference alignments we find there is indeed a strong conservation signal for motifs. A number of typical but difficult MSA use cases are explored to exemplify the problems in correctly aligning functional sequence motifs and how the motif-aware alignment method can be employed to alleviate these problems.
Highlights
Sequence motifs are commonly described as relatively short conserved regions within a protein or DNA sequence [1]
We have developed a sequence alignment program named Motif-Aware PRALINE (MAPRALINE) that incorporates information about motifs explicitly
Motifs are provided to MA-PRALINE in the PROSITE pattern syntax; it scans the input sequences for instances of the pattern and provides a score bonus to matching sequence positions
Summary
Sequence motifs are commonly described as relatively short conserved regions within a protein or DNA sequence [1]. These regions are of functional importance: they serve as binding sites for ligands or transcription factors, and as catalytic sites or structural elements. In a typical protein sequence, only a small fraction of amino acids are associated with a motif, which results in an underrepresentation of the conservation signal encoded by the motif. Cases even exist where traditional amino acid conservation is almost non-existent, such as with hypervariable regions. In these instances only the presence or absence of motifs is conserved
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