The universal genetic code was constructed in two phases. A predecessor code for environmentally derived Phase 1 amino acids underwent expansion to include biosynthetically derived Phase 2 amino acids. In the process the Phase 2 product amino acids received codons from their Phase 1 precursors. This expansion, by breaking up the original codon domains of the precursors, created a strangely structured code with seemingly irrational features such as the unequal allocations of one to six codons to different amino acids, split codon domains for Ser, placement ofthe codons ofphysi-cally dissimilar Cys and Trp in the same UGN box and the partial use of a codon by Pyl and Sec. Despite this strange structure, the reigning objective of the expansion, viz. to enhance the capabilities of the encoded ensemble of amino acid sidechains, was superbly accomplished. This ensemble has provided the variety and balance of sidechains for the remarkable performance of proteins manifest in the catalytic perfection of diffusion controlled enzymes where the rate of catalyzed reaction is only limited by diffusion of substrate into the enzyme active site,71 the development of multicellular life and the advent of human intelligence, arts and sciences. After a deep freeze for three billion years, the code is experimentally thawed since 1983 and its intrinsic mutability is once again making possible code expansion to yield synthetic life forms using synthetic genetic codes.
In evolution, although natural selection based on competition between organisms is of pivotal importance, it has been suggested that developmental constraints could play a significant role jointly with competition in limiting and channeling evolution, e.g., the reduced front legs of Tyrannosaurus might have been selected as a by-product of other adaptations such as larger hind legs.72,73 The emergence ofa unique genetic code clearly illustrates the workings of channeling: disallowance ofalternate codes by developmental constraints is even more important than elimination of alternate-coded species in achieving the one out of2 x 1019 selection ofthe universal code. In Chance and Necessity, Jacques Monod74 defined three frontiers that represent the foremost challenges of biology: the problem of life's origins, the riddle of the code's origins and the central nervous system. In this regard, the proving ofthe coevolution theory establishes the subdivision of the codon domains of precursor amino acids to accommodate the influx ofproduct amino acids from biosynthesis as the key to deciphering the riddle of genetic code structure. Just as the map of a country so often tells the story ofits history, the universal genetic code is a lasting inscription ofthe history of its coevolution with the primordial pathways of amino acid biosynthesis.
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