Genetic Code
Definition: The genetic code can be defined as the set of certain rules using which the living cells translate the information encoded within genetic material (DNA or mRNA sequences).
Codons: Each individual word in the code is composed of three nucleotide bases. These genetic words are called codons.
Each codon corresponds to a specific amino acid or stop signal.
Codons are presented in the messenger RNA (mRNA) language of adenine (A), guanine (G), cytosine (C), and uracil (U).
Their nucleotide sequences are always written from the 5′ end to the 3′ end.
The four nucleotide bases are used to produce the three-base codons. There are, therefore, 64 (43) different combinations of bases, taken three at a time.
Start and stop codons: AUG which codes for methionine is the start codon as translation always begins from this codon.
61 of the 64 codons code for the 20 common amino acids. Termination (“stop” or “nonsense”) codons: Three of the codons, UAG, UGA, and UAA, do not code for amino acids but rather are
termination codons. When one of these codons appears in a mRNA sequence, it signals that the synthesis of the protein is complete.
Characteristics of Genetic code
1. Specific: The genetic code is specific (unambiguous), that is, a particular codon always codes for the
same amino acid.
2. Universal: The genetic code is virtually universal, that is, the specificity of the genetic code has been
conserved from very early stages of evolution, with only slight differences in the manner in
which that code is translated. (Note: An exception occurs in mitochondria, in which a few codons have
meanings different than those shown in Figure e.g., UGA codes for Tryptophan)
3. Degenerate: 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 is specified by six different codons.
4. Nonoverlapping and comma less: The genetic code is nonoverlapping and commaless, that is, the code
is read from a fixed starting point as a continuous sequence of bases, taken three at a
time. For example, AUGCAAAAAUUUGGG is read as AUG/CAA/AAA/UUU/GGG without any
“punctuation” between the codons.
Consequences of altering genetic code
Point mutation: Changing a single nucleotide base on the mRNA chain.
1. Silent mutation: The codon containing the changed base may code for the same amino acid. For example, if the serine codon UCA is given a different
third base “U” to become UCU, it still codes for serine. 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 serine codon UCA is given a different
first base “C” to become CCA, it will code for a different amino acid, in this case, proline. The substitution of an incorrect amino acid is called a “missense”
mutation. E.g., Sickle cell anemia Glutamate replaced by Valine.
3. Nonsense mutation: The codon containing the changed base may become a termination codon. For example, if the serine codon UCA is given a different
second base “A” to become UAA, the new codon causes termination of translation at that point and the production of a shortened (truncated) protein. The
creation of a termination codon at an inappropriate place is called a “nonsense” mutation.
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 b. Splice site mutations: Mutations at splice sites can alter the
become amplified in number so that too many copies of the triplet occur. If this occurs within the coding region way in which introns are removed from the pre-mRNA molecules,
of a gene, the protein will contain many extra copies of one amino acid. For example, amplification of producing aberrant proteins.
the CAG codon leads to the insertion of many extra glutamine residues in the Huntington protein, causing the Myotonic dystrophy, a muscle disorder, gene silencing happens due to splicing site
neurodegenerative disorder, Huntington disease. The additional glutamines result in unstable proteins that cause alteration due to triplet expansion.
the accumulation of protein aggregates.
If the trinucleotide repeat expansion occurs in the untranslated portion of a gene, the result can be a decrease in
the amount of protein produced as seen, for example, in fragile X syndrome (most common cause of intellectual
disability in males)
c. Frame-shift mutations: If one or two nucleotides are either deleted from or
added to the coding region of a message sequence, a frame-shift mutation occurs
and the reading frame is altered. This can result in a product with a radically
different amino acid sequence or a truncated product due to the creation of a
termination codon.
If three nucleotides are added, a new amino acid is added to the peptide, or if
three nucleotides are deleted, an amino acid is lost. In these instances, the reading
frame is not affected. Loss of three nucleotides maintains the reading frame but
can result in serious pathology.
Cystic fibrosis (CF), a hereditary disease that primarily affects the pulmonary and
digestive systems, is most commonly caused by a deletion of three nucleotides
from the coding region of a gene, resulting in the loss of phenylalanine at the 508th
position (ΔF508) in the protein encoded by that gene. This ΔF508 mutation
prevents normal folding of the CF transmembrane conductance regulator
(CFTR) protein, leading to its destruction by the proteosome. CFTR normally
functions as a chloride channel in epithelial cells, and its loss results in the
production of thick, sticky secretions in the lungs and pancreas, leading to lung
damage and digestive deficiencies. In over seventy percent of patients with CF, the
ΔF508 mutation is the cause of the disease.