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On the PAM matrix model of protein evolution
1National Institute of Arthritis, Diabetes, Digestive, and Kidney Diseases, Bethesda, Maryland 20205.
Molecular Biology and Evolution
|September 1, 1985
Summary
Investigating the PAM matrix model of protein evolution revealed significant discrepancies. The model requires modification, potentially by incorporating site-dependent mutation rates, to accurately reflect amino acid replacement data.
Area of Science:
- Molecular Biology
- Computational Biology
- Evolutionary Biology
Background:
- The PAM (Point Accepted Mutation) matrix model is fundamental to understanding protein evolution.
- It quantifies amino acid replacement probabilities based on observed sequence data.
- Internal consistency is crucial for the model's predictive power.
Purpose of the Study:
- To investigate the internal consistency of the 1 PAM matrix model.
- To identify discrepancies between predicted and observed amino acid replacements.
- To explore necessary modifications to the basic PAM matrix model.
Main Methods:
- Constructing the 1 PAM matrix from amino acid replacements in closely related sequences.
- Classifying replacements into types based on intermediate amino acid requirements.
- Using data from one type of replacement to predict data from another.
Main Results:
- A significant discrepancy, exceeding two orders of magnitude, was found between predicted and observed data.
- An error in matrix construction partially explains the discrepancy.
- The basic PAM matrix model appears insufficient without modifications.
Conclusions:
- The internal consistency of the 1 PAM matrix model is questionable.
- Model modifications, such as incorporating site-dependent mutability spectra, are necessary.
- Further research is needed to refine protein evolution models.