Evolution and Genetic Engineering - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 697

The large mutations involving whole chromosomes or sets of chromosomes usually occur
during cell division due to malfunctioning of the mitotic mechanism (e.g. spindle fibers mal-
functioning or centromere nondisjunction, etc.). Certain chemicals like Colchicine inhibit the
formation of a mitotic spindle, creating polyploid cells.
Depending upon the cause of mutations, there are two types: spontaneous and induced
mutations.
14.1.1.1. Spontaneous Mutations
Spontaneousmutations occur randomly in thegeneticmaterial of anorganismandarea result
of natural molecular decay or damage. There are four causes to these type of mutations:
1. Tautomerism d A base is changed by repositioning of a hydrogen atom, altering the
hydrogen bonding pattern of that base, resulting in an incorrect base pairing during
replication.
2. Depurination d Loss of a purine base (A or G) creating a purinic site.
3. Deamination d Hydrolysis can change a normal base to an atypical base containing
a keto group in place of the original amine group. For example, a conversion of
cytosine to uracil and adenine to hypoxanthine can be corrected by DNA repair.
Conversion of 5-methylcytosine to thymine cannot be corrected because thymine is
a natural base.
4. Slipped strand mispairing d Denaturation of the new strand from the template during
replication, followed by renaturation in a different spot is called “slipping”. It creates
“hairpin” like loops of DNA sections with unpaired bases. Repair of this defect can result
in deletions.
Natural (or spontaneous) mutation rates vary greatly from gene to gene (10 3 to 10 9 per
cell division), with 10 6 mutations in a gene per cell division being typical. Chemical agents
( mutagens ) or radiation is often used in the laboratory to increase mutation rates. Mutagens
are nonspecific and may affect any gene.
14.1.1.2. Induced Mutations
Induced mutations are results of environmental damages to DNA caused by chemical or
physical agents. There are three causes to these mutations:
1. Base analogs, alkylating reagents, DNA-adduct-forming chemicals, DNA-intercalating
agents, and DNA-cross linkers are examples of chemical damage to DNA.
2. Oxidative damage caused by free-radical-generating chemicals and radiations is another
source of induced mutations.
3. DNA damage caused by UV radiations (non-ionizing) and ionizing radiations is an
example of physical agents that can result into various types of mutations.
14.1.2. Types of Mutations
The genetic mutations can be classified into four types: (1) germ-line and somatic muta-
tions; (2) lethal, non-lethal, and neutral mutations; (3) point mutations; and (4) large-scale
mutations.