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Genetic Code - Exceptions To The Universal Genetic Code

codon stop tryptophan uga

After the original genetic code of E. coli was completed in 1968, the genetic code was subsequently determined for many other organisms ranging from bacteria to mammals, including humans. The codons were found to be the same for all organisms, leading to the idea that the genetic code is "universal." Furthermore, it also suggested that life on Earth had a single evolutionary origin, otherwise there would have been numerous genetic codes. The code was established during evolution, probably by chance, as there are no compelling reasons one codon should prevail over another. After it was established, any subsequent changes in the code would prove to be lethal, for if one codon changed, then all similar codons in the entire organism's genome would have to change simultaneously—a highly unlikely possibility.

Thus, it was surprising to find that there are, in fact, a few rare exceptions to the universal code. These exceptions are listed in Table 2. Most of these exceptions are found in the mitochondrial genome. The mitochondrion is thought to have evolved from an endosymbiotic bacterium at the time when the eukaryotic cell first arose. The mitochondrial genome is small, and most of the genes of the original endosymbiont have migrated to the nucleus.

Table 2.

Organism Normal codon Usual meaning New meaning
Mammalian AGA, AGG Arginine Stop codon
mitochondria AUA Isoleucine Methionine
UGA Stop codon Tryptophan
Drosophila AGA, AGG Arginine Serine
mitochondria AUA Isoleucine Methionine
UGA Stop codon Tryptophan
Yeast AUA Isoleucine Methionine
mitochondria UGA Stop codon Tryptophan
CUA, CUC, CUG, CUU Leucine Threonine
Higher plant UGA Stop codon Tryptophan
mitochondria CGG Arginine Tryptophan
Protozoan nuclei UAA, UAG Stop codons Glutamine
Mycoplasma capricolum bacteria UGA Stop codon Tryptophan

In examining the exceptions to the universal genetic code in Table 2, you can see that there are only a few changes, most notably the use of a standard "stop" codon to encode an amino acid. For example, UGA normally is a stop codon. But in the mitochondria of the fruit fly Drosophila melanogaster, it encodes the amino acid tryptophan.

A few additional exceptions to the universal genetic code have also been identified. These include the nuclear genome of a few protozoan species and also in the bacterium Mycoplasma capricolum. These exceptions, however, do not imply multiple evolutionary origins of life. What is most striking is that the "exceptional" meanings of most of the codons are identical across all the organisms in which they are found, not different. Had there been multiple origins, we would expect to see drastically different genetic codes in these exceptional organisms.

Ralph R. Meyer


"The Genetic Code." Cold Spring Harbor Symposia on Quantitative Biology, vol. 31. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1966.

Kay, Lily E. Who Wrote the Book of Life? A History of the Genetic Code. Stanford, CA: Stanford University Press, 2000.

Nirenberg, M. W., and J. H. Matthaei. "The Dependence of Cell-Free Protein Synthesis in E. coli upon Naturally Occurring or Synthetic Polyribonucleotides." Proceedings of the National Academy of Sciences 47 (1961): 1588-1602.

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