cover up, swathing sunblock on any exposed skin to prevent
freckles, sores, and cancer. Special camps and programs
allow these children to play outdoors at night, away from
the danger of the sun.
The nature of the genetic code protects against muta-
tion, to a degree. Sixty-one codons specify the twenty types
of amino acids, and therefore, some amino acids correspond
to more than one codon type. Usually, two or three codons
specifying the same amino acid differ only in the third base
of the codon. A mutation that changes the third codon base
can encode the same amino acid. For example, the DNA trip-
lets GGA and GGG each specify the amino acid proline. If
a mutation changes the third position of GGA to a G, the
amino acid for that position in the encoded protein does not
change—it is still proline.
If a mutation alters a base in the second position, the
substituted amino acid is often similar in overall shape to
the normal one, and the protein is not changed signi± cantly
enough to affect its function. This mutation, too, would go
unnoticed. (An important exception is the mutation shown
g. 4.25.) Yet another protection against mutation is that
a person has two copies of each chromosome, and therefore
of each gene. If one copy is mutated, the other may provide
enough of the gene’s normal function to maintain health.
(This is more complicated for the sex chromosomes, X and
Y, discussed in chapter 24, pp. 927–928.)
Timing of a mutation influences effects on health.
A mutation in a sperm cell, egg cell, or fertilized ovum is
repeated in every cell of the individual. A mutation in an
embryo might be devastating because much of the body is
still to develop, and many cells inherit the mutation. In con-
trast, a mutation in a body cell of an adult would most likely
have no effect because it would be only one among trillions
of cells that do not have the mutation. However, if such a
somatic (body cell) mutation confers a faster cell cycle and
therefore cells bearing the mutation have a division advan-
tage, cancer can result.
Inborn Errors of Metabolism
The ± rst part of the chapter discussed enzymes that catalyze
the reactions of energy metabolism. Enzymes are also essen-
tial to many other reactions and pathways.
A type of disorder called an “inborn error of metabolism”
results from inheriting a mutation that alters an enzyme.
Such an enzyme block in a biochemical pathway has two
general effects: the biochemical that the enzyme normally
acts on builds up, and the biochemical resulting from the
enzyme’s normal action becomes scarce. It is similar to
blocking a garden hose: water pressure builds up behind the
block, but no water comes out after it.
The biochemical excesses and de±
ciencies that an inborn
error of metabolism triggers can drastically affect health. The
c symptoms depend upon which pathways and bio-
chemicals are affected.
shows how blocks of dif-
ferent enzymes in one biochemical pathway lead to different
sets of symptoms.
the muscle weakness of Duchenne muscular dystrophy
results from a mutation in the gene encoding the protein
dystrophin. This protein normally enables muscle cell mem-
branes to withstand the force of contraction. The mutation
may be a missing or changed nucleotide base or absence of
part or all of the dystrophin gene. Lack of the normal protein
causes muscle cells to collapse, and muscles throughout the
body weaken and break down.
shows how the
change of one base causes another inherited illness, sickle
Although mutations are commonly associated with dis-
eases or otherwise considered abnormal, they also can con-
fer an advantage. The opening vignette to chapter 3 (p. 76)
describes one such helpful mutation that protects against HIV
Once DNA changes, producing a mutation or a SNP or
copy number variant, the change is transmitted every time
the cell in which it originated divides. If that cell is an egg or
sperm, then the change is passed to the next generation. We
return to this point in the next section.
Protection Against Mutation
Cells detect many mutations and take action to correct the
errors. Special “repair enzymes” recognize and remove mis-
matched nucleotides and ±
ll the resulting gap with the accu-
rate, complementary nucleotides. This mechanism, called
DNA damage response,
restores the original structure of
the double-stranded DNA molecule.
Disorders of the DNA damage response can make life dif-
± cult. Xeroderma pigmentosum, for example, causes extreme
sun sensitivity. A child with the condition must completely
Direction of “reading” code
An example of mutation. (
) The DNA code for the
amino acid glutamic acid is CTT. (
) If something happens to change
rst T to A, the DNA code changes to CAT, which speciF
amino acid valine. The resulting mutation, when it occurs in the
DNA that encodes the sixth amino acid in a subunit of the protein
hemoglobin, causes sickle cell disease. The abnormal hemoglobin
bends the red blood cells containing it into sickle shapes. The cells
lodge in narrow blood vessels, blocking the circulation and causing