Sequence alignment

A sequence alignment places sequences one above another and inserts gaps where needed so that equivalent letters fall in the same column. Matching positions show conservation, mismatches show substitutions, and gaps stand for insertions or deletions that happened after the sequences split from a common ancestor. Aligning two sequences is pairwise alignment; aligning three or more is multiple sequence alignment.

Alignments are scored. Matches earn points, mismatches lose points and gaps carry a penalty, with opening a gap usually costing more than extending one. For proteins, substitution matrices such as BLOSUM and PAM reward swaps between chemically similar amino acids. A global alignment, classically found with the Needleman-Wunsch method, stretches across the full length of both sequences. A local alignment, found with the Smith-Waterman method, picks out only the best-matching region, which suits sequences of different lengths or ones that share a single domain.

Alignment is the starting point for recognizing homologous genes, predicting protein function, finding mutations, designing PCR primers and building phylogenetic trees. Tools such as BLAST and Clustal Omega carry it out on a large scale.