Introduction to Bioinformatics

Chapter 4: Alignments and Phylogenetic Trees

Introduction to sequence alignment

Given two or more sequences, we initially wish to

  • measure their similarity

  • determine the residue-residue correspondences

  • observe patterns of conservation and variability

  • infer evolutionary relationships

If we can do this, we will be in a good position to go fishing in databanks for related sequences. A major application is to the annotation of genomes, involving assignment of structure and function to as many genes as possible.

How can we define a quantitative measure of sequence similarity? To compare the nucleotides or amino acids that appear at corresponding positions in two or more sequences, we must first assign those correspondences. Sequence alignment is the identification of residue-residue correspondences. It is the basic tool of bioinformatics.

Any assignment of correspondences that preserves the order of the residues within the sequences is an alignment. Gaps may be introduced.

Given two text strings:

  • first string = a b c d e

second string = a c d e f

a reasonable alignment would be

a b c d e -

a - c d e f

We must define criteria so that an algorithm can choose the best alignment. For the sequences gctgaacg and ctataatc:

An uninformative alignment

- - - - - - - g c t g a a c g

c t a t a a t c - - - - - - -

An alignment without gaps

g c t g a a c g

c t a t...

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