In the first article of this series, I delineated four basic rules in regard to the bioselection and biousage of the elements (1). These rules are reiterated here. Rule 1 (abundance or availability rule) maintains that a more abundant - or rather, more readily available - element will be used preferentially. Rule 2 (efficiency rule) says that organisms would choose the more efficient entity as long as it is readily available and can perform the function. Rule 3 (basic fitness rule) asserts that a certain element is inherently - that is, chemically - fit for a certain kind of bioactivity. Rule 4 proposes that the efficiency and specificity of the biofunctions were improved through modification of genes. The last rule was designated as "evolutionary improvement of efficiency and specificity or effect of evolutionary pressure". The applications of rules 1 - 3 were the major concerns of the previous articles of this series (1 - 8). In this article we shall discuss rule 4: the evolutionary pressure on the bioinorganic chemistry of the elements (i.e., improvement of the functions of metal-containing proteins by "tuning"). The term tuning was used in ref 9. However, we know virtually nothing about the evolutionary processes themselves that led to invention of the biocompounds found in the earlier organisms. What we know of is the biomolecules in the organisms presently existing on earth. The only thing we can do then is to rationalize why a biomolecule found in contemporary organisms takes a specific structure and why it behaves the way it does (10).
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