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J Mol Evol. 1976 Apr 9;7(3):167-83.

Evolutionary processes and evolutionary noise at the molecular level. I. Functional density in proteins.


The distinction between molecular sites that mainly carry out general functions and sites committed to specific functions is analyzed, notably in terms of different evolutionary variabilities. Functional density is defined as the proportion of sites involved in specific functions. Weighted functional density, by representing the relative variability at specific-function sites is to some extent a measure of the specificity of molecular interactions. The relationship between general- and specific-function sites on the one hand the covarions of Fitch on the other is discussed. The functional "degeneracy" of amino acids is described as increasing the interdependence of general functions. It is predicted that proteins tht do not possess general-function sites besides their specific-function sites tend to "freeze" their primary structure, according to an evolutionary process that is an autocatalytic function of the decrease in site variability. This limits the use of weighted functional density as an indicator of the overall degree of interaction specificity of a protein to values that are not close to unity.

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