Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens.
Spontaneous mutations on the molecular level can be caused by:
Tautomerism – A base is changed by the repositioning of a hydrogen atom, altering the hydrogen bonding pattern of that base resulting in incorrect base pairing during replication. Depurination – Loss of a purine base (A or G) to form an apurinic site (AP site). Deamination – Hydrolysis changes a normal base to an atypical base containing a keto group in place of the original amine group. Examples include C ? U and A ? HX (hypoxanthine), which can be corrected by DNA repair mechanisms; and 5MeC (5-methylcytosine) ? T, which is less likely to be detected as a mutation because thymine is a normal DNA base. Slipped strand mispairing - Denaturation of the new strand from the template during replication, followed by renaturation in a different spot ("slipping"). This can lead to insertions or deletions. A covalent adduct between benzo pyrene, the major mutagen in tobacco smoke, and DNA Induced mutations on the molecular level can be caused by:
Spontaneous mutations on the molecular level can be caused by:
Tautomerism – A base is changed by the repositioning of a hydrogen atom, altering the hydrogen bonding pattern of that base resulting in incorrect base pairing during replication. Depurination – Loss of a purine base (A or G) to form an apurinic site (AP site). Deamination – Hydrolysis changes a normal base to an atypical base containing a keto group in place of the original amine group. Examples include C ? U and A ? HX (hypoxanthine), which can be corrected by DNA repair mechanisms; and 5MeC (5-methylcytosine) ? T, which is less likely to be detected as a mutation because thymine is a normal DNA base. Slipped strand mispairing - Denaturation of the new strand from the template during replication, followed by renaturation in a different spot ("slipping"). This can lead to insertions or deletions. A covalent adduct between benzo pyrene, the major mutagen in tobacco smoke, and DNA Induced mutations on the molecular level can be caused by:
Chemicals Hydroxylamine NH2OH Base analogs (e.g. BrdU) Alkylating agents (e.g. N-ethyl-N-nitrosourea) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions. Agents that form DNA adducts (e.g. ochratoxin A metabolites)[25] DNA intercalating agents (e.g. ethidium bromide) DNA crosslinkers Oxidative damage Nitrous acid converts amine groups on A and C to diazo groups, altering their hydrogen bonding patterns which leads to incorrect base pairing during replication. Radiation Ultraviolet radiation (nonionizing radiation). Two nucleotide bases in DNA – cytosine and thymine – are most vulnerable to radiation that can change their properties. UV light can induce adjacent pyrimidine bases in a DNA strand to become covalently joined as a pyrimidine dimer. UV radiation, particularly longer-wave UVA, can also cause oxidative damage to DNA. Ionizing radiation Viral infections DNA has so-called hotspots, where mutations occur up to 100 times more frequently than the normal mutation rate. A hotspot can be at an unusual base, e.g., 5-methylcytosine.
Mutation rates also vary across species. Evolutionary biologists have theorized that higher mutation rates are beneficial in some situations, because they allow organisms to evolve and therefore adapt more quickly to their environments. For example, repeated exposure of bacteria to antibiotics, and selection of resistant mutants, can result in the selection of bacteria that have a much higher mutation rate than the original population (mutator strains).