Using gaps and gap penalties to optimize pairwise sequence alignments

INTRODUCTIONTo obtain the best possible alignment between two sequences, it is necessary to include gaps in sequence alignments and use gap penalties. For aligning DNA sequences, a simple positive score for matches and a negative score for mismatches and gaps are most often used. To score matches and mismatches in alignments of proteins, it is necessary to know how often one amino acid is substituted for another in related proteins. In addition, a method is needed to account for insertions and deletions that sometimes appear in related DNA or protein sequences. To accommodate such sequence variations, gaps that appear in sequence alignments are given a negative penalty score reflecting the fact that they are not expected to occur very often. Mathematically speaking, it is very difficult to produce the best-possible alignment, either global or local, unless gaps are included in the alignment. This article discusses how to use gaps and gap penalties to optimize pairwise sequence alignments.