Gene and Chromosome Mutations: Types, Causes, and Repair
Gene Mutations: Definition and Impact
Gene mutations are alterations in the nucleotide sequence of a gene. Thus, they are called mutations.
Types of Gene Mutations
Base Substitution Mutations
These are produced by changing one base for another. These mutations alter a single gene triplet. Sometimes, the new triplet encodes the same amino acid, or a different amino acid that does not alter the protein’s function, meaning the mutation has no harmful consequences. In other cases, the mutation causes an amino acid change that affects the active site of an enzyme or a stop codon. In other cases, the mutation can be harmful.
Nucleotide Loss or Insertion Mutations
These may be deletions, when a nucleotide is lost, or insertions, when a new nucleotide is added. In both cases, the process of protein synthesis is affected. The consequence of these mutations is a shift in the reading frame of the triplets from the point where the mutation occurs, and therefore all subsequent triplets are altered. The consequences are often severe.
Causes of Gene Mutations
Gene mutations result from three main causes:
Replication Errors
These errors appear spontaneously during DNA replication.
Accidental DNA Damage
These are changes in the structure of one or more nucleotides that appear spontaneously even when DNA is not replicating. The most common are:
Depurination
This is the loss of purine bases by bond cleavage between them and deoxyribose.
Deamination
This is caused by losing amino groups in nitrogenous bases.
Thymine Dimerization
This is formed by linking two adjacent thymines, which form a thymine dimer. Generally, this is caused by ultraviolet rays from solar radiation.
Transpositions
These are due to the existence of DNA segments that change position spontaneously, causing mutations.
Repair Mechanisms for Gene Mutations
DNA replication is a very precise process. This is facilitated by the proofreading performed by DNA polymerase. The enzyme, before adding a new nucleotide, checks whether the previously added is correct. If not, it removes it and replaces it with the correct one.
Despite this activity, DNA polymerase leaves one wrong nucleotide per 107 nucleotides added. To reduce this number, several enzymatic repair systems review the newly synthesized DNA and repair these lesions.
One significant DNA repair system is:
DNA Excision Repair
This process is initiated by an endonuclease, which detects the error and produces two cuts, one on each side of it. Afterward, an exonuclease enzyme removes the segment containing the incorrect nucleotides. Finally, a DNA ligase joins the ends.
Chromosomal Mutations
These are mutations that cause changes in the internal structure of chromosomes, meaning they affect the sequence of genes within chromosomes. There are various types of chromosomal mutations:
Deletions
Occur due to the loss of a chromosome fragment. If the fragment contains many genes, the deletion can have serious or even fatal consequences.
Duplications
Are a repetition of a segment of a chromosome, which increases the amount of genetic material.
Inversions
Arise when a segment changes direction on the chromosome. If the inverted segment includes the centromere, it is called a pericentric inversion; if not, it is called a paracentric inversion. Inversions are not usually negative for the individual, but they can affect the offspring.
Translocations
Consist of a change in the position of a chromosome segment. If the exchange of segments takes place between two non-homologous chromosomes, it is called a reciprocal translocation. When there is only a transfer of one segment to another part of the same chromosome or to other chromosomes, it is called a transposition. Translocations are not negative for the individual who has them, but they may affect their offspring.