Multiple Sequence Alignment

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Multiple Sequence Alignment
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An alignment of heads
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Sequence Alignment

• A way of arranging the primary sequences of DNA,
  RNA and amino acid to identify the regions of
  similarity that may be a consequence of
  functional, structural or evolutionary
  relationship between the sequences.

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Goals

• To establish an hypothesis of positional homology
  between bases/amino acids.
• To generate a concise, information-rich summary
  of sequence data.
• Sometimes used to illustrate the dissimilarity
  between a group of sequences.
• Alignments can be treated as models that can be
  used to test hypotheses.

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Sequence Alignment

• Aligned sequences of nucleotide or amino acid
  residues are typically represented as rows within
  a matrix.
• Gaps (symbol -) are inserted between the
  residues so that residues with identical or
  similar characters are aligned.

GGGAATCTAGGACTATACCGGATCTA GGGAATCTA--ACTATA--GGAT
CTA GGG--TCTAGGACTATACCGGAT--A
Taxon A Taxon B Taxon C
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Alignment can be easy or difficult
Easy
Difficult due to insertions or deletions
(indels)
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(No Transcript)
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Protein Alignment may be guided by Tertiary
Structure Interactions
Homo sapiens DjlA protein
Escherichia coli DjlA protein
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Multiple Sequence Alignment- Approaches

• 3 main approaches of alignment
• Manual
• Automatic
• Combined

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Manual Alignment

• Might be carried out because
• Alignment is easy.
• There is some extraneous information
  (structural).
• Automated alignment methods have encountered the
  local minimum problem.
• An automated alignment method can be improved.

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Automatic AlignmentProgressive Approach

• Devised by Feng and Doolittle in 1987.
• Essentially a heuristic method and as such is not
  guaranteed to find the optimal alignment.
• Requires n-1n-2n-3...n-n1 pairwise alignments
  as a starting point.
• Most successful implementation is CLUSTAL.

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Overview of ClustalW Procedure
ClustalW
Hbb_Human 1 -
Hbb_Horse 2 .17 -
Hba_Human 3 .59 .60 -
Quick pairwise alignment calculate distance
matrix
Hba_Horse 4 .59 .59 .13 -
Myg_Whale 5 .77 .77 .75 .75 -
Hbb_Human
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2
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Hbb_Horse
Hba_Human
Neighbor-joining tree (guide tree)
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Hba_Horse
Myg_Whale
alpha-helices
1 PEEKSAVTALWGKVN--VDEVGG
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2
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Progressive alignment following guide tree
2 GEEKAAVLALWDKVN--EEEVGG
3 PADKTNVKAAWGKVGAHAGEYGA
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4 AADKTNVKAAWSKVGGHAGEYGA
5 EHEWQLVLHVWAKVEADVAGHGQ