Learning Objectives
The effect of a mutation will depend upon the function of the DNA sequence. Mutations in non-protein coding regions could occur in regulatory regions that affect genes or have no effect on a cell or organism.
When mutations occur in coding sequences, we can predict the effect on the primary structure of the protein using the codon table.
- Silent mutations: do not change the encoded amino acid
- Nonsense mutations: change a codon to a STOP codon
- Missense mutations: change a codon to a codon for a DIFFERENT amino acid
- Frameshift mutations: add or remove bases to change all downstream codons
Figure \(\PageIndex{1}\): Mutations can lead to changes in the protein sequence encoded by the DNA. (OSC_Microbio_11_05_EffMut.jpg "Mutations" by OpenStax, LibreTexts is licensed under CC BY.)
Multiples of three
Adding or removing bases in multiples of three, will not cause a frameshift mutation. Why not?
Would mutations like this affect the protein? What additional information would you need to make a prediction about such a mutation?
Do mutations affect protein function?
Both frameshift and nonsense mutations are likely to affect protein function by producing a shortened or extremely altered peptide that is unlikely to retain enough structure to perform the intended function. However, a frameshift or nonsense mutation that occurs near the 3' end of the gene might allow the protein to retain the ability to function.
Silent mutations are least likely to affect protein function.
Missense mutations are often difficult to predict. If the change is to a similar amino acid or in a non-critical amino acid, the mutation protein may continue to function. However, if the amino acid is changed to a different type of amino acid or removes a critical amino acid (in terms of structure or activity), then the mutant protein may change in activity.
Mutations that reduce the function of a gene product are called loss-of-function. If the gene product is completely non-functional, the allele is termed a null allele. Loss-of-function and null alleles are usually (but not always) recessive in diploid organisms, because one functional allele can usually supply enough protein product.
Some mutations actually make proteins more active, for example, by altering an inhibitory domain; these mutations are called gain-of-function. Gain-of-function alleles are often dominant alleles because their new function or activity is produced independently of the other allele.
Definition
A nonsense mutation occurs in DNA when a sequence change gives rise to a stop codon rather than a codon specifying an amino acid. The presence of the new stop codon results in the production of a shortened protein that is likely non-functional.
Narration
A nonsense mutation, or its synonym, a stop mutation, is a change in DNA that causes a protein to terminate or end its translation earlier than expected. This is a common form of mutation in humans and in other animals that causes a shortened or nonfunctional protein to be expressed.
Search
The DNA sequence of a gene can be altered in a number of ways. Gene variants (also known as mutations) can have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. Variant types include the following:
Substitution
This type of variant replaces one DNA building block (nucleotide) with another. Substitution variants can be further classified by the effect they have on the production of protein from the altered gene.
- Missense: A
missense
variantis a type of substitution in which the nucleotide change results in the replacement of one protein building block (amino acid) with another in the protein made from the gene. The amino acid change may alter the function of the protein.
- Nonsense: A
nonsense
variantis another type of substitution. Instead of causing a change in one amino acid, however, the altered DNA sequence results in a stop signal that prematurely signals the cell to stop building a protein. This type of variant results in a shortened protein that may function improperly, be nonfunctional, or get broken down.
Insertion
An insertion
Deletion
A deletion
Deletion-Insertion
This variant occurs when a deletion and insertion happen at the same time in the same location in the gene. In a deletion-insertion variant, at least one nucleotide is removed and at least one nucleotide is inserted. However, the change must be complex enough to differ from a simple substitution. The resulting protein may not function properly. A deletion-insertion (delins) variant may also be known as an insertion-deletion (indel) variant.
Duplication
A duplication
Inversion
An inversion changes more than one nucleotide in a gene by replacing the original sequence with the same sequence in reverse order.
Frameshift
A reading frame consists of groups of three nucleotides that each code for one amino acid
Repeat expansion
Some regions of DNA contain short sequences of nucleotides that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of sequences of three nucleotides, and a tetranucleotide repeat is made up of sequences of four nucleotides. A repeat expansion