What is a gene mutation and how do mutations occur?
A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size
from a single DNA building block (DNA base) to a large segment of a chromosome.
Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime.
Mutations that are passed from parent to child are called hereditary mutations or germ line mutations (because
they are present in the egg and sperm cells, which are also called germ cells). This type of mutation is present
throughout a person’s life in virtually every cell in the body.
Mutations that occur only in an egg or sperm cell, or those that occur just after fertilization, are called new (de
novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in
every cell, but has no family history of the disorder.
Acquired (or somatic) mutations occur in the DNA of individual cells at some time during a person’s life. These
changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a
mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than
sperm and egg cells) cannot be passed on to the next generation.
Mutations may also occur in a single cell within an early embryo. As all the cells divide during growth and
development, the individual will have some cells with the mutation and some cells without the genetic change.
This situation is called mosaicism.
Some genetic changes are very rare; others are common in the population. Genetic changes that occur in more
than 1 percent of the population are called polymorphisms. They are common enough to be considered a normal
variation in the DNA. Polymorphisms are responsible for many of the normal differences between people such
as eye color, hair color, and blood type. Although many polymorphisms have no negative effects on a person’s
health, some of these variations may influence the risk of developing certain disorders.
Mutations and Disease
We all start out our lives with some mutations. These germ-line mutations are inherited from your parents.
However, you can also acquire mutations during your lifetime. Some mutations happen during cell division,
when DNA gets duplicated. Still other mutations are caused when DNA gets damaged by environmental
factors, including UV radiation, chemicals, and viruses.
Few mutations are bad for you. In fact, some mutations can be beneficial. Over time, genetic mutations create
genetic diversity, which keeps populations healthy. Many mutations have no effect at all. These are called silent
mutations.
But the mutations we hear about most often are the ones that cause disease. Some well-known inherited genetic
disorders include cystic fibrosis, sickle cell anemia, Tay-Sachs disease, phenylketonuria and color-blindness,
among many others. All of these disorders are caused by the mutation of a single gene.
Most inherited genetic diseases are recessive, which means that a person must inherit two copies of the mutated
gene to inherit a disorder. This is one reason that marriage between close relatives is discouraged; two
genetically similar adults are more likely to give a child two copies of a defective gene.
Diseases caused by just one copy of a defective gene, such as Huntington's disease, are rare. Thanks to natural
selection, these dominant genetic diseases tend to get weeded out of populations over time, because afflicted
carriers are more likely to die before reproducing.
Scientists estimate that every one of us has between 5 and 10 potentially deadly mutations in our genes-the good
news is that because there's usually only one copy of the bad gene, these diseases don't manifest.
Cancer usually results from a series of mutations within a single cell. Often, a faulty, damaged, or missing p53
gene is to blame. The p53 gene makes a protein that stops mutated cells from dividing. Without this protein,
cells divide unchecked and become tumors.
Types of Mutations
There are many different ways that DNA can be changed, resulting in different types of mutation. Here is a
quick summary of a few of these:
Substitution
A substitution is a mutation that exchanges one base for another (i.e., a change in a
single "chemical letter" such as switching an A to a G). Such a substitution could:
1. change a codon to one that encodes a different amino acid and cause a small
change in the protein produced. For example, sickle cell anemia is caused by a
substitution in the beta-hemoglobin gene, which alters a single amino acid in the
protein produced.
2. change a codon to one that encodes the same amino acid and causes no change
in the protein produced. These are called silent mutations.
3. change an amino-acid-coding codon to a single "stop" codon and cause an
incomplete protein. This can have serious effects since the incomplete protein
probably won't function.
Insertion
Insertions are mutations in which extra base pairs are inserted into a new place in the
DNA.
Deletion
Deletions are mutations in which a section of DNA is lost, or deleted.
Frameshift
Since protein-coding DNA is divided into codons three bases long, insertions and
deletions can alter a gene so that its message is no longer correctly parsed. These
changes are called frameshifts.
For example, consider the sentence, "The fat cat sat." Each word represents a codon. If
we delete the first letter and parse the sentence in the same way, it doesn't make sense.
In frameshifts, a similar error occurs at the DNA level, causing the codons to be parsed
incorrectly. This usually generates truncated proteins that are as useless as "hef atc ats
at" is uninformative.
There are other types of mutations as well, but this short list should give you an idea of
the possibilities.