Pigs to the Rescue ■ 165
pair (known as a point mutation) to the addi-
tion or deletion of one or more whole chromo-
somes (a chromosomal abnormality, described
in Chapter 8).
Güell was developing techniques to artifi-
cially mutate genes, yet point mutations occur
naturally and randomly often, especially during
DNA replication. When DNA is copied right
before mitosis occurs in a cell, there are many
opportunities for mistakes to be made. The
enzymes that copy DNA sometimes insert an
incorrect nucleotide in the newly synthesized
strand. In addition, DNA in cells is constantly
being damaged by chemical, physical, and
biological agents, including energy from radi-
ation or heat, collisions with other molecules
in the cell, attacks by viruses (like PERVs), and
random chemical accidents (some of which are
caused by environmental pollutants, but most of
which result from normal metabolic processes).
Replication errors and damage to DNA—
especially to essential genes—disrupt normal
cell functions. If not repaired, DNA damage
leads to malfunctioning proteins, such as Felix’s
WAS protein in Chapter 8. DNA damage can
also cause the death of cells and, ultimately, the
death of an organism. Thankfully, cells have
a way to recover: DNA polymerase immedi-
ately corrects almost all mistakes during DNA
replication, “proofreading” complementary base
pairs as they form.
DNA polymerase is not infallible. When an
incorrect nucleotide is added but escapes proof-
reading by DNA polymerase, a mismatch error
has occurred. This happens about once in every
10 million nucleotides. But cells have another
backup safety program: repair proteins that
correct 99 percent of mismatch errors, reducing
the overall chance of an error to one mistake in
every billion nucleotides (Figure 9.10).
On the rare occasions when a mismatch error
is not corrected by repair proteins, the DNA
sequence is changed, and the new sequence is
reproduced the next time the DNA is replicated.
If the mutation occurs within a gene, it will
result in the formation of a new allele. Most new
alleles are either neutral or harmful, but occa-
sionally a mutation may be beneficial.
Three types of point mutations can alter a
gene’s DNA sequence: substitutions, insertions,
and deletions. In a substitution point muta-
tion, one nucleotide is substituted for another in
the DNA sequence of the gene. An insertion or
deletion point mutation occurs when a nucleo-
tide is, respectively, inserted into or deleted from
a DNA sequence. Sickle-cell disease, a human
genetic blood disorder, is caused by a substitu-
tion point mutation (Figure 9.11). Sometimes,
Figure 9.11
A point mutation in the hemoglobin
gene leads to sickle-cell disease
In people with the genetic disorder sickle-cell
disease, a single base in the gene that makes
hemoglobin, an important protein involved in
oxygen transport in red blood cells, is altered.
The red blood cells of people with sickle-cell
disease become curved and distorted under low-
oxygen conditions and can clog blood vessels,
leading to serious effects, including heart and
kidney failure.
Q1: What are the three types of point
mutations?
Q2: Sickle-cell disease is an autosomal
recessive genetic disorder. How many
mutated hemoglobin alleles do people with
sickle-cell disease have?
Q3: Because of improved treatments,
individuals with sickle-cell disease are now
living into their forties, fifties, or longer.
How might this extension of life span affect
the prevalence of sickle-cell disease in the
population?
G A C T C C T G A C A C C T
Normal
hemoglobin DNA
Sickle-cell
hemoglobin DNA
Normal hemoglobin Sickle-cell hemoglobin
Normal red blood cells A sickled red blood cell