Alternate Genetic Codes
The genetic code is the correspondence between the information carried in a sequence of deoxyribonucleic acid (DNA) nucleotide building blocks, and the amino acid sequence of the protein product. Three major types of ribonucleic acid (RNA) utilize DNA information to construct the protein. Messenger RNA (mRNA) carries the DNA sequence information. An mRNA's sequence is complementary to one side of the DNA double helix, with each of the DNA bases adenine (A), guanine (G), thymine (T) and cytosine (C) represented in the mRNA as the complementary bases uracil (U), C, A and G, respectively. Ribosomal RNA (rRNA) associates with ribosomal proteins to form the ribosome, a structural and enzymatic support for protein synthesis. Finally, transfer RNA (tRNA) pairs a particular amino acid consistently with a particular mRNA triplet, or codon, via its own triplet anticodon sequence. When tRNAs align opposite the mRNA, the amino acids join.
Researchers deciphered the genetic code in the early 1960s with a series of experiments that translated simple synthetic RNAs into peptides in vitro. Because 64 possible codons specify 20 types of amino acids, some amino acids correspond to more than one codon. In addition, UGA, UAA, and UAG provide stop signals, to which no tRNAs correspond.
Cells of all species use the same codon-amino acid assignments. It is this universality that makes possible biotechnologies in which one type of organism expresses a gene of another. In the 1980s, automated DNA sequencing enabled researchers to discover exceptions to the universality of the genetic code. This seems impossible, for if a codon assignment were to change, it would affect all proteins, and results could devastate a cell. Two peculiarities of the deviations known are consistent with this idea that more pervasive changes would not have been compatible with life. First, most often the alteration is limited to a stop codon specifying a particular amino acid. Also, these changes are most often seen in mitochondrial genomes and in certain ciliated protozoans. Mitochondrial genomes may have tolerated the deviations because they are small, and very few genes would be affected. The ciliates often have two types of nuclei, so that a deviation from the code in one might be overshadowed by adherence to the universal code in the other.
Biochemistry may explain why most of the exceptions to the genetic code involve stop codons. The normal stop codons--UGA, UAA, and UAG--are rich in U and A. UA base pairs, held together by two hydrogen bonds, are easier to break apart than are GC base pairs, with their three bonds. Therefore, these codons are the most vulnerable to change. Other clues lay in possible sites of origin of genetic code deviations-- the tRNA's anticodon; the enzyme that places the amino acid onto the tRNA (an amino acyl tRNA synthetase), and protein releasing factors that help to terminate protein synthesis. Although not much is known about how alternate codes arise, there is some experimental evidence to support the hypothesis that two mutations set the stage for the deviation to persist. First, an abnormal eukaryotic releasing factor 1 ignores certain stop codons. Instead of terminating protein synthesis by physically blocking a tRNA from entering, the releasing factor provides space for a mutant tRNA to bring in an amino acid. The tRNA has to be mutated in a way that enables it to recognize a stop codon and bring in an amino acid. In this way, a stop codon comes to specify a particular amino acid.
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