What kinds of gene mutations are possible? [Talking Glossary of Genetic Terms]
Mutations can occur in any organism, from people and other animals to plants, bacteria, fungi, and protists. A mutation
is any change in the nucleotide sequence of an organism's DNA. Some mutations are more drastic than others. The DNA
sequence of a gene can be altered (changed) in a number of ways. Gene mutations have varying effects on health,
depending on where they occur and whether they alter the function of essential proteins. The types of mutations
include: missense, nonsense, insertion, deletion, frameshift, duplication, and repeat expansion.
Missense mutation: This type of mutation is a change in one DNA base pair that results in the substitution of one
amino acid for another in the protein made by a gene.
In this example, the nucleotide adenine is replaced by cytosine in the genetic code, introducing an incorrect amino acid
into the protein sequence.
Nonsense mutation: A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid
for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of
mutation results in a shortened protein that may function improperly or not at all.
In this example, the nucleotide cytosine is replaced by thymine in the DNA code, signaling the cell to shorten the
protein.
Insertion: An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein
made by the gene may not function properly.
In this example, one nucleotide (adenine) is added in the DNA code, changing the amino acid sequence that follows.
Deletion: A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or
a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The
deleted DNA may alter the function of the resulting protein(s).
In this example, one nucleotide (adenine) is deleted from the DNA code, changing the amino acid sequence that
follows.
[Point mutations are changes in the genetic sequence that occur at a specific point along the DNA strand.]
Duplication: A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of
mutation may alter the function of the resulting protein.
A section of DNA is accidentally duplicated when a chromosome is copied.
Frameshift mutation: This type of mutation occurs when the addition or loss of DNA bases changes a gene’s reading
frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the
grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional.
Insertions, deletions, and duplications can all be frameshift mutations.
A frameshift mutation changes the amino acid sequence from the site of the mutation.
Repeat expansion: Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For
example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-basepair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is
repeated. This type of mutation can cause the resulting protein to function improperly.
In this example, a repeated trinucleotide sequence (CAG) adds a series of the amino acid glutamine to the
resulting protein.
What causes mutations?
Mutations can be caused by external (exogenous) or endogenous (native) factors, or they may
be caused by errors in the cellular machinery. Physical or chemical agents that induce mutations
in DNA are called mutagens and are said to be mutagenic.
Exogenous factors: environmental factors such as sunlight, radiation, and smoking can cause
mutations.
Endogenous factors: errors during DNA replication can lead to genetic changes as can toxic byproducts of cellular metabolism.
What are the consequences of mutations?
Mutations can be advantageous and lead to an evolutionary advantage of a certain genotype.
Mutations can also be deleterious, causing disease, developmental delays, structural abnormalities,
or other effects. There are several classes of mutations described below. The original sequence is
shown on the top with the mutated sequence below it. The genetic sequence is shown in black while
the protein sequence is in blue. Changes in sequence are highlighted by yellow.
Deletion
Frameshift
Genetic material is removed or deleted. A few bases can be
deleted (as shown on the left) or it can be complete or partial loss
of a chromosome (shown on right).
The insertion or deletion of a number of bases that is not a
multiple of 3. This alters the reading frame of the gene and
frequently results in a premature stop codon and protein
truncation.
Insertion
When genetic material is put into another region of DNA. This
may be the insertion of 1 or more bases, or it can be part of one
chromosome being inserted into another, non-homologous
chromosome.
Missense
A change in DNA sequence that changes the codon to a different
amino acid. Not all missense mutations are deleterious (harmful),
some changes can have no effect. Because of the ambiguity of
missense mutations, it is often difficult to interpret the
consequences of these mutations in causing disease.
Nonsense
A change in the genetic code that results in the coding for a stop
codon rather than an amino acid. The shortened protein is
generally non-function or its function is impeded.
Point
A single base change in DNA sequence. A point mutation may be
silent, missense, or nonsense.
Silent
A change in the genetic sequence that does not change the protein
sequence. This can occur because of redundancy in the genetic
code where an amino acid may be encoded for by multiple
codons.
Splice Site
A change in the genetic sequence that occurs at the boundary of
the exons and introns. The consensus sequences at these
boundaries signal where to cut out introns and rejoin exons in the
mRNA. A change in these sequences can eliminate splicing at
that site which would change the reading frame and protein
sequence.
Translocation
A structural abnormality of chromosomes where genetic material
is exchanged between two or more non-homologous
chromosomes.