POINT MUTATIONS - INSERTIONS AND DELETIONS
Point mutations are changes that occur to one or more base-pairs in the DNA nucleotide sequence. This can occur by insertion or deletion of a nucleotide or nucleotides. This results in frameshift mutations, where the triplet codons by which the genetic code is read during transcription changes, leading to deletion, addition, or inclusion of wrong of amino-acids.
Genetic code is stored in DNA as nucleotides that have four bases. The complementary pairs are adenine and thymine, and guanine and cytosine.
Any permanent change that occurs in this sequence is called a mutation. Mutations can sometimes be useful, but are usually harmful, as they change the genetic code for amino-acids production. As they are part of the DNA, these mutations are passed on to the next generations.
Point mutations are mutations or changes caused in one or more of the base pairs. The changes are typically due to random mistakes during replication, but can be due to exposure to ultra-violet radiation, X-rays, and mutagenic chemicals. There are two types of point mutations: substitutions and insertions and deletions.
Substitution mutation occurs when one base is replaced incorrectly by another base, altering the genetic code, leading to silent mutations, missense mutations, and nonsense mutations. Insertions and deletions of bases leading to 'frameshift mutation' lead to changes that tend to be more serious.
The DNA nucleotide sequence are read in triplets called codons during transcription when RNA is formed. RNA in turn codes for the formation of amino-acids and proteins. Each codon codes for the synthesize of one amino-acid. There is also a special codon to signal the stop of synthesizes and it is called stop codon.
When the sequence of nucleotides changes, either due to insertion or deletion, the reading frame of this triplet codon is disturbed after the site of the point mutation. This change is called frameshift. The frameshift can result in a protein that is shorter, as the codon changes to a stop codon and the protein synthesis is stopped prematurely. This is similar to nonsense mutations. It can also be longer, or contain a string of wrong amino-acids, so that the protein produced is non-functional.
Sometimes, if the mutations involve deletion or insertion of three (or multiples of three) nucleotides, the frameshift could be preserved, in which case one (or more) codons are removed or added. So during protein formation one (or more) amino-acid is less or extra. In this case,depending on the position of the amino-acid, the protein could retain its functions.
Frameshift mutations can therefore be neutral or negative, and only rarely positive. In many cases, they lead to serious diseases.
Diseases due to insertions, deletions, and frameshift mutations
Insertion mutations cause Huntington's disease and 'fragile X syndrome' because of the addition or trinucleotide repeats. Deletion mutation causes '22q11.2 deletion syndrome',which leads to heart diseases and autoimmune disorders. Many diseases can arise due to frameshift mutations, like cystic fibrosis, Crohn' disease, and a variety of cancers.