Biology Now, 2e

(Ben Green) #1
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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