How did Khorana crack the genetic code?
Cracking the genetic code was an exercise in precise chemical synthesis and biochemical experimentation. We began by synthesizing defined polymers of known repeating nucleotide sequences. For example, we created poly-U, poly-C, and poly-A. When these synthetic messengers were incubated with ribosomes and amino acids, we observed specific protein synthesis. Poly-U directed the synthesis of polyphenylalanine, poly-C directed polyproline, and poly-A directed polylysine. By using copolymers, such as alternating U and C, we could deduce the specific codon assignments. The specificity of the interaction between the messenger RNA codon and the aminoacyl-tRNA anticodon was the key. It was a matter of building the chemical keys to unlock the biological lock.
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