A mutation is a change in the nucleotide sequence of a gene. This gives rise to a new genetic trait or a changed genotype. A cell or an organism that shows the effect of a mutation is called a mutant. A mutant differs from its parental strain in its genotype (nucleotide sequences of the genome). In addition, there may be changes in observable properties of the mutant relative to its parent, called the phenotype. The effect of mutations in an organism leads to changes, some good, some bad but mostly neutral.
Types of Mutations
Mutations can be either spontaneous or induced.
- Spontaneous mutations can result from errors in DNA replication during cell division. Mutation rates in cells are remarkably low, between 10^-8 and 10^-11 errors per base pair inserted because of the proofreading activity of DNA polymerase.
- Induced mutations are those that are due to agents in the environment and include mutations made deliberately by humans. Exposure to ionizing radiation or carcinogens, exposure to chemicals called mutagens, or infection by viruses may cause mutations.
Germline mutations are heritable mutations that occur in the eggs and sperm and can be passed on to offspring, while somatic mutations occur in body cells and are not passed on.
At the molecular level, there are several ways in which changes in the purine-pyrimidine base sequence of a gene can occur, resulting in a mutation. Two common types are point mutations and frameshift mutations.
Point mutations occur as a result of the substitution of one nucleotide for another in the specific nucleotide sequence of a gene.
- The substitution of one purine (A or G) base for another purine or one pyrimidine (C or T) base for another pyrimidine is termed as transition type of point mutation.
- A transversion is the replacement of a purine by a pyrimidine or vice versa.
This base-pair substitution may result in one of three kinds of effects.
- Silent mutation: altered codon corresponds to the same amino acid
- Missense mutation: altered codon corresponds to a different amino acid
- Nonsense mutation: altered codon corresponds to a stop signal.
Neutral Mutation or Silent Mutation
The altered gene triplet produces an mRNA codon that specifies the same amino acid because the codon resulting from mutation is a synonym for the original codon. This is a neutral mutation or silent mutation, that is, a mutation that does not affect the phenotype of the cell. Silent mutations in coding regions are almost always in the third base of the
codon. For example, a change in the RNA from UAC to UAU would have no apparent effect because UAU is also a tyrosine codon.
In the missense mutation, the altered gene triplet produces a codon in the mRNA which specifies different amino acids different than the one present in the normal protein. Altered proteins formed after missense mutation may be functionally inactive or less active or more active than the normal one or the amino acid substitution may have no effect on its function. Changes in the first or second base of the codon more often lead to significant changes in the polypeptide.
A good example of a missense mutation in humans is the disease sickle cell anemia. Sixth amino acid of normal hemoglobin A is glutamic acid (GAG). A single base substitution in the codon of this amino acid, the substitution of U in the place of A, changes amino acid to valine (GUG), forming characteristic hemoglobin S of sickle cell anemia.
For instance, a single base change from GGU to GCU results in an amino acid change within the polypeptide from Glycine to Alanine at a specific site.
A nonsense mutation is the substitution of a single base pair that leads to the formation of an altered gene triplet which produces a chain-terminating codon in mRNA. For example, a single base change from UAC to UAA results in an amino acid change within the polypeptide from Tyrosine to stop the codon at a specific site.
Unless the nonsense mutation is very near the end of the gene, the result is the premature termination of protein during translation forming incomplete or shortened polypeptide that is most likely nonfunctional.
Frameshift mutations result from the addition or deletion of one or more nucleotides (the number of added or deleted base pairs is not divisible by three) in a gene.
The reading of the genetic code starts from one end of the protein template, mRNA, and is read in consecutive blocks of three bases. Each group of three bases corresponds to one of 20 different amino acids.
This results in a shift in the reading frame. Frameshift reading of the nucleotide sequences of mRNA generally leads to premature termination or formation of non-functional proteins because an entirely new sequence of amino acids is synthesized from the changed DNA sequence.
References and further readings
- Mutation. Genome.Gov. Retrieved June 19, 2021, from https://www.genome.gov/genetics-glossary/Mutation
- Madigan Michael T, Bender, Kelly S, Buckley, Daniel H, Sattley, W. Matthew, & Stahl, David A. (2018). Brock Biology of Microorganisms (15th Edition). Pearson.
- Pelczar, M. J., Chan, E. C. S., & Krieg, N. R. (2001). Microbiology: Concepts and applications. New York: McGraw-Hill.