Mutation is one of the basic phenomenon of life. Deep inside that spontaneous mutation is responsible for that. The reason is, the spontaneous mutation is a naturally occurring mutation. Any kind of human interaction is not involved in that.
Without that kind of mutation the gradual development of life from inorganic material who have been impossible. The most important thing the evolution of living being from the first group of the molecule to a highly refined and advance living organism could not have occurred without the mutation.
But what Max spontaneous mutation too difficult to understand?
The only one thing and that is a have known cause of spontaneous mutation. No specific agent is associated with their occurrence. because of that, they are generally assumed to be an accident.
Many of this nutrition arise as a result of normal biological or chemical processes in the organism, that alter the structure of nitrogen bases.
There are mainly five mechanism that leads spontaneous mutation.
- DNA replication error.
- Tautomeric shift.
- Depurination and Deamination
- Oxidative Damage
1) DNA replication Error.
However, DNA polymerase can correct most of these replication errors using their inherent or natural 3’prime 5’prime exonuclease proofreading capacity. The misincorporated nucleotide may persist (means continue) after replication.
If these errors are not detected and corrected by the DNA repair mechanism, in that case, that may lead to spontaneous mutations. These errors due to mispairing predominantly lead point mutation. The fact that bases can take several forms, known as tautomers, increases the chance of mispairing during DNA replication. That we discussed next.
In addition to mispairing and point mutations, DNA replication can lead to the introduction of small insertions or deletions. These spontaneous mutations can occur when one strand of the DNA template loops out and becomes displaced during replication, or when DNA polymerase slips or stutters during replication.
If a loop occurs in the template strand during replication, DNA polymerase may miss the looped out nucleotides, and a small deletion in the new strand will be introduced.
If DNA polymerase repeatedly introduces nucleotides that are not present in the template strand, insertion of one or more nucleotides will occur, creating an unpaired loop on the newly synthesized strand. Insertions and deletions may lead to frameshift mutations, or amino acid insertions or deletions in the gene product.
Slippage can occur anywhere in the DNA but seems distinctly more common in regions containing repeated sequences. Repeat sequences are hot spots for DNA mutation and in some cases contribute to hereditary diseases, such as fragile-X syndrome and Huntington disease.
The hypermutability of repeat sequences in noncoding regions of the genome is the basis for current methods of forensic DNA analysis.
Purines and pyrimidines can exist in tautomeric forms that are, in alternate chemical forms that differ by only a single proton shift in the molecule. The biologically important tautomers are the keto-enol forms of thymine and guanine and the amino–imino forms of cytosine and adenine.
These shifts change the bonding structure of the molecule, allowing hydrogen bonding with noncomplementary bases. Hence, tautomeric shifts may lead to permanent base-pair changes and mutations. Figure 15–2 compares normal base-pairing relationships with rare unorthodox pairings. Anomalous T ≡ G and C = A pairs, among others, may be formed.
Spontaneous Mutation occurs during DNA replication when a transiently formed tautomer in the template strand pairs with a non-complementary base. In the next round of replication, the “mismatched” members of the base pair are separated, and each becomes the template for its normal complementary base. The end result is a point mutation
3)Depurination and Deamination
Some of the most common causes of spontaneous mutations are two forms of DNA base damage: depurination and deamination. Depurination is the loss of one of the nitrogenous bases in an intact double-helical DNA molecule. Most frequently, the base is a purine—either guanine or adenine.
These bases may be lost if the glycosidic bond linking the 1′-C of the deoxyribose and the number 9 position of the purine ring is broken, leaving an apurinic site on one strand of the DNA. Geneticists estimate that thousands of such spontaneous lesions are formed daily in the DNA of mammalian cells in culture.
If apurinic sites are not repaired, there will be no base at that position to act as a template during DNA replication. As a result, DNA polymerase may introduce a nucleotide at random at that site. Deamination, an amino group in cytosine or adenine is converted to a keto group.
In these cases, cytosine is converted to uracil, and adenine is changed to hypoxanthine. The major effect of these changes is an alteration in the base-pairing specificities of these two bases during DNA replication. For example, cytosine normally pairs with guanine. Following its conversion to uracil, which pairs with adenine, the original G ≡ C pair is converted to an A = U pair and then, in the next replication, is converted to an A = T pair.
When adenine is deaminated, the original A = T pair is converted to a G ≡ C pair because hypoxanthine pairs naturally with cytosine. Deamination may occur spontaneously or as a result of treatment with chemical mutagens such as nitrous acid
4) Oxidative Damage
DNA may also suffer damage from the by-products of normal cellular processes. These by-products include reactive oxygen species (electrophilic oxidants) that are generated during normal aerobic respiration.
For example, superoxides (O2-), hydroxyl radicals (- OH), and hydrogen peroxide (H2O2) are created during cellular metabolism and are constant threats to the integrity of DNA. Such reactive oxidants, also generated by exposure to high-energy radiation, can produce more than 100 different types of chemical modifications in DNA, including modifications to bases, loss of bases, and single-stranded breaks.
Genetic elements, or transposons, are DNA elements that can move within, or between, genomes. These elements are present in the genomes of all organisms, from bacteria to humans, and often comprise large portions of these genomes. Transposons can act as naturally occurring mutagens.
If in moving to a new location they insert themselves into the coding region of a gene, they can alter the reading frame or introduce stop codons. If they insert into the regulatory region of a gene, they can disrupt the proper expression of the gene.
Transposons can also create chromosomal damage, including double-stranded breaks, inversions, and translocations. There is not much information about the disease that causes due to spontaneous mutation.
One famous example of disease is sickle cell anemia which cause by natural genetic alteration. It’s stuck around for the new generation because it’s beneficial to Cary sickle cell anemia gene in areas with a higher incidence of malaria.