Biology Now, 2e

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

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