pairwise-alignment-1

pairwise-alignment-1 - Pairwise Sequence Alignment BMI/CS...

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Pairwise Sequence Alignment BMI/CS 576 www.biostat.wisc.edu/bmi576/ Mark Craven [email protected] Fall 2011 Pairwise alignment: task definition Given – a pair of sequences (DNA or protein) – a method for scoring a candidate alignment Do – determine the correspondences between substrings in the sequences such that the similarity score is maximized
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DNA alignment example Maksimovic et al., Glycobiology 21:467-48, 2011 genomic sequence for part of the 6T6Gal gene in mouse and rat Protein alignment example Olivera et al., PNAS 95:6419-6424, 1998 Alignment of the PhaK protein from Pseudomonas putida and OprD protein from Pseudomonas aeruginos
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The role of homology in alignment homology : similarity due to descent from a common ancestor often we can infer homology from similarity thus we can sometimes infer structure/function from sequence similarity Homology example: evolution of the globins
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Homology homologous sequences can be divided into two groups orthologous sequences : sequences that differ because they are found in different species (e.g. human ! -globin and mouse ! -globin) paralogous sequences : sequences that differ because of a gene duplication event (e.g. human ! - globin and human " -globin, various versions of both ) DNA sequence edits substitutions: A C GA A G GA insertions: ACGA AC CGGA GA deletions: A CGGA GA AGA transpositions: A CGG AGA AAG CGG A inversions: AC GGA GA AC TCC GA
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Mismatches and gaps substitutions in homologous sequences result in mismatches in an alignment insertions/deletions in homologous sequences result in mismatches in an alignment CA--GATTCGAAT CGCCGATT---AT gap mismatch Alignment scales for short DNA sequences (gene scale) we will generally only consider – substitutions – insertions/deletions for longer DNA sequences (genome scale) we will consider additional events – transpositions – inversions in this course we will focus on the case of short sequences
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