Sequence alignment and homology

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Sequence alignment and homology

• Level 3 Molecular Evolution and Bioinformatics
• Jim Provan

Page Holmes Section 5.1
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Homology
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Homology and homoplasy

• Classic molecular example is the parallel
  evolution of lysozyme genes in langur monkeys and
  cows
• Both animals have independently evolved foregut
  fermentation and have recruited lysozyme to
  degrade fermenting bacteria
• Both lysozyme sequences share identical D14
  residue
• Carries out identical reaction
• Have different evolutionary histories
• Deciding whether two sequences are truly
  homologous requires knowledge of the evolutionary
  relationships among the sequences being compared

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Independent evolution of lysozyme
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Phylogeny of some lysozyme genes
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Homology among sequences
Sequence 1 ATGCGTCGTT Sequence 2 ATGCGTCGT
ATGCGTCGTT ATGCGTCGT
ATG---CGTCGTT ATGCGTCGT
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Homology among sequences
Sequence 1 ATGCGTCGTT Sequence 2 ATCCGTCAT
ATGCGTCGTT ATCCGTCAT
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Homology among sequences

• It is possible to align two non-identical
  sequences by inserting a number of gaps and/or
  substitutions
• We can compute the cost of a particular
  alignment
• D s wg
• where
• s number of substitutions
• g number of gaps
• w gap penalty
• If indels are thought to be rare, w should be
  higher
• Task is to find alignment with lowest cost

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Alternative alignments
ATGCGTCGTT 1 ATCCG-CGTC
AT--GCGTCGTT 2 ATCCGCGTC
If gaps have low cost (w 1) D1 2 (1 x 1)
3 D2 0 (1 x 2) 2 If gaps have high cost (w
3) D1 2 (3 x 1) 5 D2 0 (3 x 2) 6