MSA-Lec6-090904

MSA-Lec6-090904 - Lecture 6: Multiple sequence alignment...

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Unformatted text preview: Lecture 6: Multiple sequence alignment BioE 480 Sept 9, 2004 Comparing Multiple Sequences: Multiple Alignment We often need to compare several protein sequences that have similar functions. These proteins could come from different or the same species. Which parts are similar, and which parts are different. An example: A multiple alignment of 8 fragments from immunoglobulin sequences. VTISCTGSSSNIGAG-NHVKWYQQLPG VTISCTGTSSNIGS--ITVNWYQQLPG LRLSCSSSGFIFSS--YAMYWVRQAPG LSLTCTVSGTSFDD--YYSTWVRQPPG PEVTCVVVDVSHEDPQVKFNWYVDG-- ATLVCLISDFYPGA--VTVAWKADS-- AALGCLVKDYFPEP--VTVSWNSG--- VSLTCLVKGFYPSD--IAVEWESNG-- This alignment highlights: Conserved residues: a cysteine forming the disulphide bridges, and a conserved tryptophan Conserved regions: in particular, "Q.PG"at the end of the first 4 sequences. More sophisticated patterns: the dominance of hydrophobic residues at fragment positions 1 and 3. The alternating hydrophobicity pattern is typical for the surface beta-strand at the beginning of each fragment. Multiple alignments are helpful for protein structure prediction. Multiple alignment also helps to infer the evolutionary history of the sequences. The first 4 sequences and the last 4 sequences seem to be derived from 2 different common ancestors, which in turn are derived from a "root" ancestor. 4 fragments are from the variable regions, and 4 fragments from the constant regions of immunoglobulins. The sequences of the variable regions are about as conserved as the sequences of the constant regions, except for their antigen-binding subregions, which are composed of just a few amino acids each, and give the antibody its specificity We need to inspect longer fragments than shown here to make phylogenetic observations that are statistically significant! A Multiple Alignment of k sequences is a rectangular array, consisting of characters taken from the alphabet , that satisfies the following 3 conditions: 1. There are exactly k rows. 2. Ignoring the gap character, row number i is exactly the sequence s i . 3. Each column contains at least one character different from "-". Scoring Multiple Alignment Which one is better? VTISCTGSSSNIGAG-NHVKWYQQLPG VTISCTGTSSNIGS--ITVNWYQQLPG LRLSCSSSGFIFSS--YAMYWVRQAPG LSLTCTVSGTSFDD--YYSTWVRQPPG PEVTCVVVDVSHEDPQVKFNWYVDG-- ATLVCLISDFYPGA--VTVAWKADS-- AALGCLVKDYFPEP--VTVSWNSG--- VSLTCLVKGFYPSD--IAVEWESNG-- or VTISCTGSSSNIG-AGNHVKWYQQLPG VTISCTGTSSNIG--SITVNWYQQLPG LRLSCSSSGFIFS--SYAMYWVRQAPG LSLTCTVSGTSFD--DYYSTWVRQPPG PEVTCVVVDVSHEDPQVKFNW--YVDG ATLVCLISDFYPG--AVTVAW--KADS AALGCLVKDYFPE--PVTVSW--NS-G VSLTCLVKGFYPS--DIAVEW--ESNG or VTISCTGSSSNIGAG-NHVKWYQQLPG VTISCTGTSSNIGS--ITVNWYQQLPG LRLSCS-SSGFIFSS-YAMYWVRQAPG LSLTCT-VSGTSFDD-YYSTWVRQPPG PEVTCVVVDVSHEDPQVKFNWYVDG-- ATLVCLISDFYPGA--VTVAWKADS-- AALGCLVKDYFPEP--VTVSWNSG--- VSLTCLVKGFYPSD--IAVEWESNG-- Additive Functions: the alignment score is the sum of column scores....
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This note was uploaded on 02/13/2012 for the course CS 91.510 taught by Professor Staff during the Fall '09 term at UMass Lowell.

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MSA-Lec6-090904 - Lecture 6: Multiple sequence alignment...

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