| The code of life is degenerate, not quite universal, and unpunctuated
|
| page 447 |  | | page 448 |
|
Table 32-1.
Amino acids specified by each of the codons. |
| Body_ID: None |
| The genetic code |
| Body_ID: T032001.50 |
| Codon | Amino acid | Codon | Amino acid | Codon | Amino acid | Codon | Amino acid |
| Body_ID: T032001.100 |
| AAA | lysine (Lys) | CAA | glutamine (Gln) | GAA | glutamic acid (Glu) | UAA | Stop |
| Body_ID: T032001.150 |
| AAG | | CAG | | GAG | | UAG | |
| Body_ID: T032001.200 |
| AAC | asparagine (Asn) | CAC | histidine (His) | GAC | aspartic acid (Asp) | UAC | tyrosine (Tyr) |
| Body_ID: T032001.250 |
| AAU | | CAU | | GAU | | UAU | |
| Body_ID: T032001.300 |
| ACA | threonine (Thr) | CCA | proline (Pro) | GCA | alanine (Ala) | UCA | serine (Ser) |
| Body_ID: T032001.350 |
| ACC | | CCC | | GCC | | UCC | |
| Body_ID: T032001.400 |
| ACG | | CCG | | GCG | | UCG | |
| Body_ID: T032001.450 |
| ACU | | CCU | | GCU | | UCU | |
| Body_ID: T032001.500 |
| AGA | arginine (Arg) | CGA | arginine (Arg) | GGA | glycine (Gly) | UGA | |
| Body_ID: T032001.550 |
| AGG | | CGC | | GGC | | | |
| Body_ID: T032001.600 |
| | | CGG | | GGG | | UGG | Stop |
| Body_ID: T032001.650 |
| AGC | serine (Ser) | CGU | | GGU | | | tryptophan (Trp) |
| Body_ID: T032001.700 |
| AGU | | | | | | UGC | cysteine (Cys) |
| Body_ID: T032001.750 |
| | | CUA | leucine (Leu) | GUA | valine (Val) | UGU | |
| Body_ID: T032001.800 |
| AUG | methionine (Met) | CUC | | GUC | | | |
| Body_ID: T032001.850 |
| | | CUG | | GUG | | UUA | leucine (Leu) |
| Body_ID: T032001.900 |
| AUA | isoleucine (Ile) | CUU | | GUU | | UUG | |
| Body_ID: T032001.950 |
| AUC | | | | | | | |
| Body_ID: T032001.1000 |
| AUU | | | | | | UUC | phenylalanine (Phe) |
| Body_ID: T032001.1050 |
| | | | | | | UUU | |
| Body_ID: T032001.1100 |
|
| Body_ID: T032001.1150 |
Note that the first and second positions of codons that specify the same amino acid are generally the same.
|
| MUTATION OF THE GENETIC CODE |
| Sickle cell anemia is an example of a disease in which a single nucleotide change within the coding region of the gene for the β-chain of hemoglobin A, the major form of adult hemoglobin, yields an altered protein that has impaired function. The mutation that causes this disease is a single nucleotide change in a codon that normally specifies glutamate (GAG), and which produces a codon that specifies valine (GUG). Under conditions of low oxygen tension, this single amino acid change causes the protein to polymerize into rod-shaped structures, resulting in deformation and altered rheological properties of red blood cells. This substitution of an acidic for a nonpolar, hydrophobic amino acid is known as a non-conservative mutation. Conservative mutations of one amino acid by another with similar physical and chemical properties usually have less severe consequences. |
|
| When one considers the transfer of information from RNA containing only four different bases (adenine, A; cytosine, C; guanine, G; and uracil, U) to a protein containing 20 different amino acids, it is apparent that there is not a one-to-one correspondence between nucleotide and amino acid sequence. In fact, three nucleotides in the mRNA, known as a codon, are required to specify each amino acid. There is thus a total of 64 possible codons when all combinations of four nucleotides are taken into account three at a time (Table 32.1). Three of these codons (UAA, UAG, UGA) are used as signals to stop the synthesis of a protein, and do not specify an amino acid. This leaves 61 codons to specify 20 amino acids, and illustrates a feature of the genetic code known as degeneracy, i.e. more than one codon can specify a specific amino acid. For example, codons GGU, GGC, GGA, and GGG all code for the amino acid, glycine. Indeed, all the amino acids, with the exception of methionine and tryptophan, have more than one codon. The codon AUG, which specifies only methionine, has a dual role: it encodes methionine anywhere
it occurs in the RNA, and it also marks the start of protein synthesis.
|
| The genetic code as specified by the triplet nucleotides is, for the most part, the same for bacteria and humans, and is referred to as 'universal'. However, there are notable exceptions. In bacteria, if the codons GUG and UUG occur at the beginning of protein synthesis, they can be read as a methionine codon. In addition, the protein synthesis stop-codon, UAA, can encode a tryptophan amino acid in some lower eukaryotic organisms such as Paramecium and Tetrahymena. There are also minor differences in the genetic code in mitochondria.
|
| Another aspect of the genetic code is that it is translated without punctuation. This means that, once synthesis has started at an AUG codon for methionine, each successive triplet from that start point will be read without interruption until a termination codon is encountered. Thus the 'reading frame' of the mRNA will be dictated by the AUG codon. This means that mutations that cause the addition or deletion of single nucleotides will cause a frame shift, resulting in a protein with a different (nonsense) amino acid sequence after the mutation, or a protein that is prematurely terminated (Table 32.2).
|
| page 448 | | | page 449 |
|
Table 32-2.
Effect of mutations on the primary sequence of the encoded protein. |
| Body_ID: None |
| Effect of mutations on protein synthesis |
| Body_ID: T032002.50 |
| Normal | AUG | GCA | UUA | CAG | GUA | UUA | CUA | CGA | GGC | ACA | CCU | GAA . . . | functional |
| Body_ID: T032002.100 |
| gene | Met | Ala | Leu | Gln | Val | Leu | Leu | Arg | Gly | Thr | Pro | Glu | protein |
| Body_ID: T032002.150 |
| insertion | AUG | GCA | UUU | ACA | GGU | AUU | ACU | ACG | AGG | CAC | ACC | UGA A . . . | premature |
| Body_ID: T032002.200 |
| | Met | Ala | Phe | Arg | Gly | Ile | Thr | Thr | Arg | His | Thr | Stop | termination |
| Body_ID: T032002.250 |
| | | | ↓ | | | | | | | | | | |
| Body_ID: T032002.300 |
| deletion | AUG | GCA | UAC | AGG | UAU | UAC | UAC | GAG | GCA | CAC | CUG | AAA . . . | different |
| Body_ID: T032002.350 |
| | Met | Ala | Tyr | Arg | Tyr | Tyr | Tyr | Glu | Ala | His | Leu | Lys | protein |
| Body_ID: T032002.400 |
| altered base | AUG | GCA | UUA | CAG | GAA | UUA | CUA | CGA | GGC | ACA | CCU | GAA . . . | single amino |
| Body_ID: T032002.450 |
| | Met | Ala | Leu | Gln | Glu | Leu | Leu | Arg | Gly | Thr | Pro | Glu | acid change |
| Body_ID: T032002.500 |
| altered base | AUG | GCA | UUA | CAG | GUA | UUA | CUG | CGA | GGC | ACA | CCU | GAA . . . | no change |
| Body_ID: T032002.550 |
| | Met | Ala | Leu | Gln | Val | Leu | Leu | Arg | Gly | Thr | Pro | Glu | |
| Body_ID: T032002.600 |
|
| Body_ID: T032002.650 |
Note that the location of the mutation will dictate the extent of change observed in the primary sequence. Insertion and deletion mutations cause frame shifts that lead to synthesis of nonsense proteins with either premature or delayed termination.
|
|
