Mutation-absorption model of the enzyme

Abstract

Gradual changes in function of proteins in response to single changes in primary structure are often observed to occur and are a necessary condition for evolution by variation and natural selection at the protein level. A probabilistic (entropy theory) analysis of the effect of changes in primary structure on three-dimensional shape and function shows that such gradualism is based on the presence of a control system in the molecule involving a definite general form of structure-function degeneracy. The assumptions of the analysis are that primary structure determines tertiary structure (or a thermal distribution of tertiary configurations and allosteric forms), tertiary structure determines function (characterized by rate and other parameters), and that certain features of tertiary structure may be specialized for particular functions. The main conclusion is that embodied in the molecule is a subsystem which serves as a buffer, absorbing mutation or other forms of genetic variation and expressing these as graceful variations in features of the shape critical for function. This buffer system may be realized by numerical redundancy of amino acids or other mechanisms which increase the redundancy of weak interactions responsible for folding, utilization of amino acids having a greater number of analogs with redundant features, or local and global structural formats which allow for more effective utilization of redundancy. The mutation-absorption model has implications for the interpretation of structure-function relations in biology, the topology of the adaptive landscape, the interpretation of isoenzymes and allozymes, the relationship between selection and neutralism in evolution, and the relation between the complexity of and energy required by biological systems and the effectiveness of evolutionary optimization.