ABSTRACT
The genetic code was first decoded during the middle part of the twentieth century. For these early experiments, the length of the codon was unknown. No one knew whether a single nucleotide, dinucleotide, trinucleotide, or longer codon encoded each of the amino acids. Initially, poly-U RNAs were synthesized and used in cell-free in vitro translation systems. Only poly-phenylalanine peptides were produced. Similar experiments using poly-C and poly-A RNAs produced poly-proline and poly-lysine polypeptides, respectively. Analogous experiments using RNAs with alternating bases (e.g., UCUCUCUC) produced polypeptides with alternating amino acids (e.g., threoninehistidine). These all indicated that the codon consisted of a triplet of nucleotides. For example, in the previous example of the UCUCUCUCUC synthesized RNA, the triplets would be UCU (which encodes threonine) and CUC (which encodes histidine). While some of the codons were more challenging to deduce, eventually all of the codons were determined to elucidate the genetic code, including the fact that most amino acids were encoded by more than one triplet codon. Also, it became clear that the first and second nucleotides were the primary determiners of the amino acids, while the third nucleotide could vary without altering the amino acid sequence. During the first few decades after the genetic code was solved, it was thought to be a universal genetic code, and for the majority of organisms, it is universal (Figure 6.1). However, while most bacterial, archaeal, and nuclear genes use the universal genetic code, there are many organisms whose nuclear and/or organellar genes utilize slightly different codons for some amino acids, as well as different start and stop signals (Figure 6.2). For example, some of the stop codons in the universal code encode for amino acids in some genomes, and the standard methionine start codon is instead isoleucine for some genomes. Additionally, a number of different start and stop codons have been identified in a variety of organisms. However, these variations in the genetic code likely occurred after the evolution of the universal genetic code, because the variations usually appear in the organellar or nuclear genomes of a limited number of organisms.
