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SPONTANEOUS MUTATIONS

The replication of DNA in all the organisms is generally performed very precisely, but, sometimes due to rare mistakes performed during the replication or repairing processes of DNA, generally at a very low frequency (107 to 10-12/organism), the mutations may occur, called spontaneous mutations. The reasons of these mutations may be many:

1. Base Substitutions. They can be of two types:

(i) Transitions: occurring due to tautomeric changes (tautomerism is the ability of a molecule to exist in more than one forms) in normal bases (Fig. 10.2).

Fig.10.2

Fig.10.2 Tautomeric shifts in bases to cause base substitutions.

(ii) Transversions: occurring due to mistaken pairing between two purines (e.g., A-G pairing) or two pyrimidines (e.g., C- T pairing).
Base substitutions may cause different types of mutations:

(a) Non-sense Mutations. Here, due to base substitution in DNA, an amino acid codon in the mRNA changes into a termination codon. This leads to the premature termination of polypeptide synthesis, the length of the polypeptide depending upon the position of the mutant termination codon (Fig. 10.3 and 10.4).

Fig. 10.3 Nonsense mutation.

Fig. 10.3 Nonsense mutation.

Fig. 10.4 Nonsense mutation in codon 4 to produce smaller polypeptide.

Fig. 10.4 Nonsense mutation in codon 4 to produce smaller polypeptide.

(b)   Reverse of Non-sense Mutation. Here, the normal termination codon in mRNA changes into an amino acid codon due to mutation in DNA. This leads to the formation of longer polypeptides than the normal size, e.g., many mutants in haemoglobin.

(c)    Missense Mutation. When due to base substitution in DNA, one amino acid is replaced by another amino acid, the mutation is called missense mutation. For example, the sickle cell anaemia disease in humans, where the RBC becomes sickle shaped due to poor O2 carrying capicity. Here, in β-globin polypeptide of haemoglobin the normal amino acid glutamic acid at the 6th position is replaced by valine amino acid (Fig. 10.5 and 10.6).

(The tetra mer haemoglobin is made up of two kinds of proteins- two molecules of α-globin and two molecules of β-globin)

Fig. 10.5 Missense mutation in β-globin gene of haemoglobin.

Fig. 10.5 Missense mutation in β-globin gene of haemoglobin.

Fig. 10.6 Sickle shaped red blood cells of a sickle cell anaemia patient.

Fig. 10.6 Sickle shaped red blood cells of a sickle cell anaemia patient.

2.Frame Shift Mutations

In this case, addition or deletion of bases in DNA may occur due to loop formation in the template DNA strand at the time of DNA replication, so that one or a few bases present in the loop may not be copied (deletions) or copied twice (additions). This may also occur due to breakage and reunion of DNA, leading to addition or deletion of some bases (Fig. 10.7).

Fig. 10.7 Frame-shift mutation due to loop formation in DNA.

Fig. 10.7 Frame-shift mutation due to loop formation in DNA.

Additions may also occur due to unequal crossing over between homologous chromosomes at
the time of meiotic Prophase (Fig. 10.8).

Fig.10.8

Fig. 10.8 Frame-shift mutation due to unequal crossing-over in
homologous chromosomes during meiosis.