The structure of DNA, solved in 1953, set off a race to crack the genetic code. How do sequences of 4 nucleotides code for sequences of 20 amino acids? This coding problem lies at the heart of molecular biology. Physicist George Gamow of Big Bang fame contributed the first guess: Spaces between neighboring nucleotides might fit individual amino acids, directly templating protein assembly on the DNA. In Gamow's solution, each nucleotide must contribute to defining two amino acids–an overlapping code. The numerology looked good (there were exactly 20 possible combinations), but Gamow's solution turned out to be dead wrong: In 1957, Sydney Brenner devised a clever test that disproved this and all overlapping triplet codes. The true code was soon cracked based on beautiful frameshift experiments by Crick and colleagues (proving a triplet code), and by analysis of proteins synthesized from artificial RNAs (solving each codon).
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