1. Introduction
The instructions for the manufacture of enzymes and all other proteins are located in the DNA found in the nucleus. Most proteins have a structural role or a functional role. It is the particular range of enzymes in the cell which determines what type of cell it becomes. This is the way in which DNA controls the activities of the cell.
2. Mutations
A mutation is a change in the genetic material of a cell or virus. Thus it is a change in the structure or number of chromosomes (chromosomal mutation) or DNA sequence of a gene (gene mutation).
Somatic mutations occur in cells in the body (soma) other than the germ cells. Mutations of this kind are not transmitted to the net generation, but they may be significant in the life of an organism if they contribute to the malfunctioning of the body. Somatic mutations tend to accumulate with age.
Germ cell mutations occur in the germ line cells that give rise to gametes. These may be transmitted to the offspring and to a succession of future generations. If the mutation has an adverse effect on the phenotype of a human, the mutant condition is referred to as a genetic disorder or hereditary disease.
2.1 Chromosomal Mutations
There are 2 types of chromosomal alterations: number or structure.
In alterations of chromosome number, for aneuploidy, one or several chromosomes are lost from or added to the normal set of chromosomes in the nucleus. Polyploidy is the possession of more than 2 complete sets of chromosome in the nucleus.
In alterations of chromosomal structure, there is: deletion (removal of a chromosomal segment), duplication (repeats a segment), inversion (reverses a segment within a chromosome) and translocation (moves a segment from one chromosome to another non-homologous one).
2.2 Gene Mutations
A gene mutation is a mutation in the gene sequence. Those gene mutations that affect only one or a few base pairs of DNA in a single gene are called point mutations. Point mutations within a gene can be divided into base pair substitutions of base pair insertions or deletions.
2.2.1 Base Pair Substitution
It is a change in a gene that one base pair is replaced by another base pair.
2.2.1.1 Transition Mutation
It is a change from one purine-pyrimidine base pair to the other purine-pyrimidine base pair. AT to GC, GC to AT, TA to CG, CG to TA.
2.2.1.2 Transversion Mutation
It is a change from a purine-pyrimidine base pair to a pyrimidine-purine base pair. AT to TA, GC to CG, AT to CG and GC to TA.
Mutations can also be classified according to their effects on amino acid sequences in proteins.
2.2.1.3 Silent Mutation
It is a base pair change in a gene that alters a codon in the mRNA such that the same amino acid is inserted in the protein (due to the redundancy of he genetic code). For example, a silent mutation results from an AT to GC transition mutation changes the codon from AAA to AAG both which specifies lysine.
2.2.1.4 Neutral Mutation
It is a base pair change that changes a codon in the mRNA such that the resulting amino acid substitution produces no detectable change in the function of he protein translated from that message. A new codon codes for a different amino acid that is chemically equivalent to the original and hence does not affect the protein’s function.
2.2.1.5 Nonsense Mutation
It is a point mutation that changes a codon for an amino acid into a stop codon, leading to a premature termination of translation. The resulting polypeptide will be shorter than the polypeptide encoded by the normal gene. Nearly all nonsense mutations lead to non-functional proteins.
2.2.1.6 Missense Mutation
It is a base pair change in the DNA that causes a change in an mRNA codon so that a different amino acid is inserted into the polypeptide in place of the one specified by the wild type codon, resulting in an altered phenotype.
2.2.2 Base Pair Insertions and Deletions
This occurs when there are additions or losses of one or more nucleotide pairs in a gene. Because mRNA is read as a series of nucleotide triplets during translation, the insertion or deletion of nucleotides may alter the reading frame of the genetic message. A frameshift mutation will occur whenever the number of nucleotides inserted or deleted is not a multiple of 3. Incorrect amino acids are added to the polypeptide chain after or downstream of the mutation site. Often, frameshift mutations generate new codons, resulting in a shortened protein, or they result in read-through of he normal stop codon, resulting in a longer than normal protein. In any case, frameshift mutation usually results in a non-functional protein.
2.3 Causes of Mutations
Mutations can occur spontaneously or they can be induced.
2.3.1 Spontaneous Mutations
Spontaneous mutations are mutations that occur naturally; that is, without the use of chemicals of physical mutagenic agents. They may result from errors during DNA replication, repair or recombinations and spontaneous chemical changes in DNA such as deamination and depurination
2.3.2 Induced Mutations
Since the rate of spontaneous mutations is so low, geneticists use mutagens to increase mutation frequency so that a significant number of organisms have mutations in the gene being studied. 2 classes of mutagens are often used – physical and chemical mutagens.
2.3.2.1 Radiation
X-rays are ionizing radiation. Collision of ionizing radiation with atoms in its path gives rise to ions and reactive chemical radicals that break chemical bonds in the DNA, inducing chromosome breakages, chromosome rearrangements and point mutations in DNA.
Ultra Violet Light is non-ionizing. However, it induces the formation of abnormal chemical bonds between adjacent pyrimidines in the same strand or between pyrimidines on the opposite strands of the double helix. This is mostly induced between adjacent thymines forming thymine dimmers.
2.3.2.2 Chemical Mutagens
Base analogues have molecular structures that are extremely similar to the bases normally found in DNA. They exist in alternate states; in each of the 2 states, they se-pair with a different base in DNA, producing base-pair substitutions.
Base modifying agents directly modify the chemical structure and the properties of the bases. This leads to mispairing during DNA replication and base-pair substitutions.
Intercalating agents
(proflavin, acridine, ethidium bromide) insert themselves between adjacent
bases in one or both strands of the DNA double helix. This leads to small
insertions or deletions during DNA synthesis and frameshift mutations.
