Genetic Mutations: From DNA to Chromosomes
Genetic or Molecular Mutations
1. Mutations
These are mutations that affect one or more of the nucleotides of DNA. They are not visible microscopically and can be of two types:
- Base substitution mutations: They occur in a position to change one base pair for another. Depending on the base exchange, these mutations are classified as:
- Transitional mutations: A purine base is changed by another purine (A↔G), or a pyrimidine by another pyrimidine (T↔C).
- Transversional mutations: A purine base is changed to a pyrimidine (A, G↔T, C) or a pyrimidine for a purine (T, C↔A, G).
- Structural shift mutations: They occur when base pairs are added or removed, altering the length of the string. In turn, they are classified as:
- Loss Mutation or deletion of bases: when one or more nucleotides are lost in the chain.
- Mutation by insertion of bases: if, on the contrary, extra nucleotides are inserted into the DNA chain, interposed between the existing ones.
Gene mutations can have four effects on the protein:
- Silent mutation: It does not alter the amino acid sequence of the protein, either because it occurs in introns or because there are synonymous codons that code for the same amino acid: AGA (Arg) ↔ AGG (Arg).
- Missense mutation: A new triplet codes for a different amino acid; the protein has an amino acid change. This is what happens to the chain of hemoglobin in sickle cell disease, in which the sixth amino acid is valine instead of glutamic acid: GAG (Glu) ↔ GUG (Val).
- Nonsense mutation: A stop codon appears, CAG (Gln) ↔ UAG (STOP), so that the protein is shorter.
- Frameshift mutation: It takes place by addition or deletion of a number of nucleotides that is not a multiple of three, making the reading frame shift, and the protein is completely different from the point of mutation.
Chromosomal Mutations
2. Mutations
Chromosomal mutations are changes in the internal structure of the chromosomes and therefore are visible under the microscope. They often disrupt the proper pairing of chromosomes during meiosis, which reduces fertility.
They can be of four types:
- Mutation by inversion of a chromosome fragment. It is the reversal of a fragment within its chromosome.
- Mutation by deletion or loss of a chromosome fragment.
- Mutation by duplication of a chromosome fragment.
- Mutation by translocation or shifting of a chromosome fragment. The translocation can be reciprocal if fragments are exchanged between two chromosomes, and non-reciprocal, in which case it is called transposition.
Karyotypic and Genomic Mutations
3. Mutations
Affect the number of chromosomes and are also visible under the microscope.
They can be of two types:
- Euploidy: These are mutations affecting the haploid number of chromosomes. It can be:
- Polyploidy: if there are more than two haploid sets of chromosomes. Thus we speak of individuals triploid (3n), tetraploid (4n)… Polyploidy in plants is often accompanied by an increase in the size of the specimens. In humans, triploidy is responsible for many spontaneous abortions; this is the case of the triploid 69, XXX or 69, XXY.
- Monoploidy or haploidy: if there is a single set of chromosomes (n).
- Aneuploidy: These are mutations that affect only the number of copies of a chromosome pair. It can be:
- Nulisomies (lack of a complete pair).
- Monosomies (missing one chromosome of a pair). In humans, the most common is Turner syndrome or sexual monosomy XO.
- Trisomies (there is an extra chromosome in the pair). In humans, the most common are trisomy 21 or Down syndrome, trisomy 18 or Edwards syndrome, trisomy 13 or Patau syndrome, trisomy XXX sexual or triple X syndrome, sexual trisomy XXY or Klinefelter syndrome, and XYY syndrome or sexual trisomy double Y.
- Tetrasomy (there are two more chromosomes in the pair).