08. BLOSUM vs. PAM

As we have seen, there are two different log-odds scoring matrices available. When performing pairwise sequence alignments, you must specify the exact matrix to use - this depends on the suspected degree of identity between the query and its matches.

Let's do a quick summary of these two matrices and see how they differ.

PAM matrices summary

PAM (Accepted Point Mutations) matrices are:

  • Extrapolated using comparisons among closely related proteins based on an evolutionary model.
  • Based on data from alignments of closely related protein families.
  • Because they use the Markov model, the substitution probabilties for highly related proteins can be extrapolated to probabilties of distantly related proteins.

Some limitations of PAM matrices include the somewhat inaccuracy of the assumption model and each position being context dependent.

BLOSUM summary

  • Based on empirical observations of more distantly related protein alignments.
  • Not based on an evolutionary model - just empirically derived.
  • Sequence comparisons cover a broad range of divergences rather than just one subfamily of proteins.
  • Based on observed alignments from conserved regions of multiple sequence alignments (blocks). These blocks are from large protein databases, which give a large sampling site.

Limitations are that you are limited to a subset of conserved domains.

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