Genetic code

The genetic code is the set of instructions in a gene that tell the cell how to make a specific protein. A codon is a trinucleotide sequence of DNA or RNA that corresponds to a specific amino acid. There are 64 different codons of which 61 specify amino acids while the remaining three are used as stop signals. The start codon is the first codon of a mRNA transcript translated by a ribosome and it is AUG which codes for the amino acid methionine. Stop codons halt translation and are UAA, UGA and UAG.

Features of the genetic code

Nonoverlapping and contiguous: codons are continuous

Unambiguous: each codon specifies only one amino acid

Degenerate: an amino acid may be coded by more than one codon. The wobble position of a codon refers to the 3rd nucleotide in a codon. Changes are seen in wobble position in codons for a single amino acid.

Universal: the same code is used everywhere, including plants, humans, and microbes.

Mutations: A mutation is a change in the base sequence of DNA.

1. Point mutations are changes in a single nucleotide base. Point mutations can be of the following types:

   i) Silent: New mutation still codes for the same amino acid as before, so there is practically no change.

   ii) Missense: New mutation changes the codon in a way that it now specifies another amino acid, e.g., in sickle cell anemia due to a missense mutation (GAG to GTG), amino acid valine is formed instead of glutamic acid

   iii) Nonsense: New mutation produces a stop codon, which prematurely stops translation and leads to the formation of a truncated protein product.

2. A frameshift mutation is a type of mutation involving the insertion or deletion of a nucleotide in which the number of deleted/inserted base pairs is not divisible by three. “Divisible by three” is important because the cell reads a gene in groups of three bases. Frameshift mutation disrupts the reading frame due to which the entire DNA sequence following the mutation will be read incorrectly.

3. Trinucleotide repeats are caused by errors in DNA replication leading to an abnormal number of repeated nucleotide triplets. Seen in Huntington’s disease, Friedrich’s ataxia. Fragile X syndrome and myotonic dystrophy.
4. Translocation is a type of chromosomal abnormality in which a chromosome breaks and a portion of it reattaches to a different chromosome. It is seen in cancers like Burkitt’s lymphoma, Philadelphia chromosome in CML, etc.
5. Aneuploidy is a change in chromosome number due to loss or gain of an entire chromosome. It is seen in Down’s syndrome (trisomy 21). Most cases result from nondisjunction when homologous chromosomes or chromatids fail to separate in meiosis. This causes some cells to have extra chromosomes while others will have fewer chromosomes.
6. Microdeletions involve deletion of a small portion of a chromosome and are seen in Angelman and Prader-Willi syndromes.