Specificity: The genetic code is specific (unambiguous), because a particular codon always codes for the same amino acid.
2.
Universality: The genetic code is virtually universal insofar as its specificity has been conserved from very early stages of evolution, with only slight differences in the manner in which the code is translated. [Note: An exception occurs in mitochondria, in which a few codons have meanings different than those shown in Figure 32.2. For example, UGA codes for tryptophan (Trp).] 3.
Degeneracy: The genetic code is degenerate (sometimes called redundant). Although each codon corresponds to a single amino acid, a given amino acid may have more than one triplet coding for it. For example, arginine (Arg) is specified by six different codons (see Fig. 32.2). Only Met and Trp have just one coding triplet.
4.
Nonoverlapping and commaless: The genetic code is nonoverlapping and commaless, meaning that the code is read from a fixed starting point as a continuous sequence of bases, taken three at a time without any punctuation between codons. For example, AGCUGGAUACAU is read as AGC UGG AUA CAU.
C. Consequences of altering the nucleotide sequence
Changing a single nucleotide base (a point mutation) in the coding region of an mRNA can lead to any one of three results (Fig. 32.3).
1.
Silent mutation: The codon containing the changed base may code for the same amino acid. For example, if the serine (Ser) codon UCA is changed at the third base and becomes UCU, it still codes for Ser. This is termed a silent mutation.
2.
Missense mutation: The codon containing the changed base may code for a different amino acid. For example, if the Ser codon UCA is changed at the first base and becomes CCA, it will code for a different amino acid (in this case, proline [Pro]). This is termed a missense mutation.
3.
Nonsense mutation: The codon containing the changed base may become a termination codon. For example, if the Ser codon UCA is changed at the second base and becomes UAA, the new codon causes premature termination of translation at that point and the production of a shortened (truncated) protein. This is termed a nonsense mutation. [Note: The nonsense-mediated degradation pathway can degrade mRNA containing premature stops.] 4.
Other mutations: These can alter the amount or structure of the protein produced by translation.
a. Trinucleotide repeat expansion: Occasionally, a sequence of three bases that is repeated in tandem will become amplified in number so that too many copies of the triplet occur. If this happens within the coding region of a gene, the protein will contain many extra copies of one amino acid. For example, expansion of the CAG codon in exon 1 of the gene for huntingtin protein leads to the insertion of many extra glutamine residues in the protein, causing the neurodegenerative disorder Huntington disease (Fig. 32.4). The additional glutamines result in an abnormally long protein that is cleaved, producing toxic fragments that aggregate in neurons. If the trinucleotide repeat expansion occurs in an untranslated region (UTR) of a gene, the result can be a decrease in the amount of protein produced, as seen in fragile X syndrome and myotonic dystrophy. Over 20 triplet expansion diseases are known. [Note: In fragile X syndrome, the most common cause of intellectual disability in males, the expansion results in gene silencing through DNA hypermethylation (see p. 476).] b.
Splice site mutations: Mutations at splice sites (see p. 443) can alter the way in which introns are removed from pre-mRNA molecules, producing aberrant proteins. [Note: In myotonic dystrophy, a muscle disorder, gene silencing is the result of splicing alterations due to triplet expansion.] c.