Amino Acid Properties, Substitution Rates, and the Nearly Neutral Theory

Area of Science:

• Evolutionary biology
• Molecular evolution
• Biochemistry

Background:

• The neutral theory of molecular evolution posits that most evolutionary changes are driven by random genetic drift.
• Selective constraint, where changes are detrimental to organismal fitness, is expected to slow down evolutionary rates.
• Amino acid physicochemical properties (e.g., charge, size) are crucial for protein structure and function, suggesting differences may impact substitution rates.

Purpose of the Study:

• To investigate whether amino acid physicochemical properties influence their rates of substitution.
• To test the prediction that greater differences between amino acids lead to lower substitution rates due to selective constraint.
• To determine the relative importance of physicochemical properties versus mutation properties in predicting substitution rates.

Main Methods:

• Utilized empirical amino acid exchangeability matrices to estimate substitution rates.
• Quantified amino acid differences based on two uncorrelated physicochemical properties: charge and size.
• Analyzed the relationship between substitution rates and differences in charge, size, and combined properties, as well as mutation properties (e.g., number of mutations, transition/transversion bias).

Main Results:

• Amino acid pairs with larger differences in charge and size exhibited significantly lower substitution rates.
• Amino acids differing in both charge and size showed the lowest substitution rates, supporting selective constraint on both properties.
• Mutation properties, including the number of mutations and type (transitions vs. transversions), were also significant predictors of substitution rates.
• The observed relationship between physicochemical differences and substitution rates was consistent across multiple taxonomically restricted datasets.

Conclusions:

• Physicochemical properties of amino acids, specifically charge and size, play a significant role in determining their evolutionary substitution rates.
• Purifying selection acts to maintain protein structure and function by constraining substitutions between amino acids with dissimilar properties.
• The influence of selective constraint on amino acid substitution rates appears to be conserved across different taxonomic groups, irrespective of effective population size.