Some of the most important properties of genetic codes are as follows:
1. The code is a triplet codon:
The nucleotides of mRNA are arranged as a linear sequence of codons, each codon consisting of three successive nitrogenous bases, i.e., the code is a triplet codon. The concept of triplet codon has been supported by two types of point mutations: frame shift mutations and base substitutions.
(i) Frameshift mutations:
Evidently, the genetic message once initiated at a fixed point is read in a definite frame in a series of three letter words. The framework would be disturbed as soon as there is a deletion or addition of one or more bases.
When such frame shift mutations were intercrossed, then in certain combinations they produce wild type normal gene. It was concluded that one of them was deletion and the other an addition, so that the disturbed order of the frame due to mutation will be restored by the other (Fig. 38.26).
(ii) Base substitution:
If in a mRNA molecule at a particular point, one base pair is replaced by another without any deletion or addition, the meaning of one codon containing such an altered base will be changed. In consequence, in place of a particular amino acid at a particular position in a polypeptide, another amino acid will be incorporated.
For example, due to substitution mutation, in the gene for tryptophan synthetase enzyme in E. coli, the GGA codon for glycine becomes a missence codon AGA which codes for arginine. Missence codon is a codon which undergoes an alteration to specify another amino acid.
A more direct evidence for a triplet code came from the finding that a piece of mRNA containing 90 nucleotides, corresponded to a polypeptide chain of 30 amino acids of a growing haemoglobin molecule. Similarly, 1200 nucleotides of “satellite” tobacco necrosis virus direct the synthesis of coat protein molecules which have 372 amino acids.
2. The code is non-overlapping:
In translating mRNA molecules the codons do not overlap but are “read” sequentially (Fig. 38.27). Thus, a non-overlapping code means that a base in a mRNA is not used for different codons. In Figure 38.28, it has been shown that an overlapping code can mean coding for four amino acids from six bases.
However, in actual practice six bases code for not more than two amino acids. For example, in case of an overlapping code, a single change (of substitution type) in the base sequence will be reflected in substitutions of more than one amino acid in corresponding protein. Many examples have accumulated since 1956 in which a single base substitution results into a single amino acid change in insulin, tryptophan synthelase, TMV coat protein, alkaline phosphatase, haemoglobin, etc.
However, it has been shown that in the bacteriophage ɸ × l74 there is a possibility of overlapping the genes and codons (Barrel and coworkers, 1976; Sanger, et al., 1977).
3. The code is commaless:
The genetic code is commaless, which means that no codon is reserved for punctuations. It means that after one amino acid is coded, the second amino acid will be automatically, coded by the next three letters and that no letters are wasted as the punctuation marks (Fig. 38.29).
4. The code is non-ambiguous:
Non-ambiguous code means that a particular codon will always code for the same amino acid. In case of ambiguous code, the same codon could have different meanings or in other words, the same codon could code two or more than two different amino acids. Generally, as a rule, the same codon shall never code for two different amino acids.
However, there are some reported exceptions to this rule: the codons AUG and GUG both may code for methionine as initiating or starting codon, although GUG is meant for valine. Likewise, GGA codon codes for two amino acids glycine and glutamic acid.
5. The code has polarity:
The code is always read in a fixed direction, i.e., in the 5’→3′ direction. In other words, the codon has a polarity. It is apparent that if the code is read in opposite directions, it would specify two different proteins, since the codon would have reversed base sequence:
6. The code is degenerate:
More than one codon may specify the same amino acid; this is called degeneracy of the code. For example, except for tryptophan and methionine, which have a single codon each, all other 18 amino acids have more than one codon. Thus, nine amino acids, namely phenylalanine, tyrosine, histidine, glutamine, asparagine, lysine, aspartic acid, glutamic acid and cysteine, have two codons each. Isoleucine has three codons. Five amino acids, namely valine, proline, threonine, alanine and glycine, have four codons each. Three amino acids, namely leucine, arginine and serine, have six codons each (see Table 38.5).
The code degeneracy is basically of two types: partial and complete. Partial degeneracy occurs when first two nucleotides are identical but the third (i.e., 3′ base) nucleotide of the degenerate codons differs, e.g., CUU and CUC code for leucine, Complete degeneracy occurs when any of the four bases can take third position and still code for the same amino acid (e.g., UCU, UCC, UCA and UCG code for serine).
Degeneracy of genetic code has certain biological advantages. For example, it permits essentially the same complement of enzymes and other proteins to be specified by microorganisms varying widely in their DNA base composition. Degeneracy also provides a mechanism of minimising mutational lethality.
7. Some codes act as start codons:
In most organisms, AUG codon is the start or initiation codon, i.e., the polypeptide chain starts either with methionine (eukaryotes) or N- formylmethionine (prokaryotes). Methionyl or N-formylmethionyl-tRNA specifically binds to the initiation site of mRNA containing the AUG initiation codon. In rare cases, GUG also serves as the initiation codon, e.g., bacterial protein synthesis. Normally, GUG codes for valine, but when normal AUG codon is lost by deletion, only then GUG is used as initiation codon.
8. Some codes act as stop codons:
Three codons UAG, UAA and UGA are the chain stop or termination codons. They do not code for any of the amino acids. These codons are not read by any tRNA molecules (via their anticodons), but are read by some specific proteins, called release factors (e.g., RF-1, RF-2, RF-3 in prokaryotes and RF in eukaryotes). These codons are also called nonsense codons, since they do not specify any amino acid.
The UAG was the first termination codon to be discovered by Sidney Brenner (1965). It was named amber after a graduate student named Bernstein (= the German word for ‘amber’ and amber means brownish yellow) who help in the discovery of a class of mutations. Apparently, to give uniformity the other two termination codons were also named after colours such as ochre for UAA and opal or umber for UGA. (Ochre means yellow red or pale yellow; opal means milky white and umber means brown). The existence of more than one stop codon might be a safety measure, in case the first codon fails to function.
9. The code is universal:
Same genetic code is found valid for all organisms ranging from bacteria to man. Such universality of the code was demonstrated by Marshall, Caskey and Nirenberg (1967) who found that E. coli (Bacterium), Xenopus laevis (Amphibian) and guinea pig (mammal) amino acyl-tRNA use almost the same code. Nirenberg has also stated that the genetic code may have developed 3 billion years ago with the first bacteria, and it has changed very little throughout the evolution of living organisms.
Recently, some differences have been discovered between the universal genetic code and mitochondrial genetic code (Table 38.6).
Table 38.6. Differences between the ‘universal genetic code’ and two mitochondrial genetic codes:
|Codon||Mammalian mitocondrial code||Yeast mitochondrial code”||“Universal Code|
|1. UGA||Trp *||Trp||Stop|
* Italic type indicates that the code differs from the ‘universal’ code.