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Amino acid substitution during functionally constrained divergent evolution of protein sequences
S A Benner1, M A Cohen, G H Gonnet
1Institute for Organic Chemistry, Swiss Federal Institute of Technology, Zurich.
Protein Engineering
|November 1, 1994
Summary
Protein sequence alignment assumes mutations are independent over time. This study reveals mutation patterns change with divergence, showing genetic code influence at low divergence and side-chain chemistry at high divergence.
Area of Science:
- Bioinformatics
- Molecular Evolution
- Computational Biology
Background:
- Homologous protein sequence alignment typically assumes time-independent mutation patterns.
- This assumption implies similar mutation rates across varying sequence divergence levels.
Purpose of the Study:
- To investigate the validity of the time-independence assumption in protein sequence evolution.
- To analyze how mutation patterns change with increasing sequence divergence.
Main Methods:
- Construction of separate mutation matrices for protein sequence pairs at divergences from 5 to 100 PAM units.
- Normalization of derived log-odds (Dayhoff) matrices to 250 PAM units.
Main Results:
- Mutation patterns are not constant across different sequence divergence levels.
- The genetic code significantly influences accepted point mutations at early divergence stages.
- Chemical properties of amino acid side chains become dominant factors at later divergence stages.
Conclusions:
- The assumption of time-independent amino acid substitutions in protein alignment is incorrect.
- Evolutionary pressures on protein sequences vary dynamically with divergence.
- Understanding these changing patterns is crucial for accurate sequence alignment and phylogenetic analysis.