90
U N I T 1
Cell and Tissue Function
acid alanine (Table 5-1).
Start
and
stop codons,
which
signal the beginning or end of a protein molecule, are
also present.
Although there are only 20 amino acids, plus the
start and stop codons, mathematically, the four bases
can be arranged in 64 different combinations. As shown
in Table 5-1, several triplets code for the same amino
acid; therefore, the genetic code is said to be
redundant.
For example, there are four codons for the amino acid
valine. Codons that specify the same amino acid are
syn-
onymous.
Synonymous codons usually have the same
first two bases but differ in the third base. Because the
genetic code is a universal language used by most living
cells, the codons for an amino acid are the same whether
that amino acid is found in a bacterium, plant, or human
being. Also notice that AUG is the codon for the start sig-
nal as well as the codon for the amino acid methionine.
DNA Repair
Accidental errors in the replication of DNA do arise.
These errors are called
mutations
. Mutations can result
from the substitution of one base pair for another, the
loss or addition of one or more base pairs, or rearrange-
ments of base pairs. Many of these mutations occur
spontaneously through normal endogenous processes,
whereas others occur because of exogenous or environ-
mental agents such as chemical and radiation. Mutations
may arise in somatic cells or in germ cells. Only those
DNA changes that occur in germ cells can be inherited.
Considering the millions of base pairs that must be
duplicated in each cell division, it is not surprising that
random changes in replication occur. Most of these
defects are corrected by DNA repair mechanisms. Several
repair mechanisms exist, and each depends on specific
enzymes called
endonucleases
that recognize distor-
tions of the DNA helix, cleave the abnormal chain, and
remove the distorted region. The gap is then filled when
the correct nucleotides, identified by a DNA polymerase
using the intact complementary strand as a template, are
added to the cleaved DNA. The newly synthesized end
of the segment is then joined to the remainder of the
DNA strand by a DNA ligase. The normal regulation
of these gene repair mechanisms is under the control of
DNA repair genes. Loss of these gene functions renders
the DNA susceptible to accumulation of mutations,
which can play a role in cancer (see Chapter 7).
Genetic Variability
As the Human Genome Project progressed, it became
evident that the human genome sequence is almost
exactly (99.9%) the same in all people. It is the small
DNA sequence variation (one in every 1000 base pairs)
that is thought to account for the individual differ-
ences in physical traits, behaviors, and disease suscep-
tibility. These variations are sometimes referred to as
single nucleotide polymorphisms
(from the existence
of more than one morphologic form in a population),
or SNPs. An international effort has been organized to
develop a genome-wide map of these variations as hap-
lotypes (a combination of SNPs at adjacent locations
which are inherited together) with the intent of pro-
viding a link between genetic variations and common
complex diseases such as cancer, heart disease, diabe-
tes, and some forms of mental disease (the International
HapMap Project is discussed in the section under gene
technology).
TABLE 5-1
Triplet Codes for Amino Acids
Amino Acid
RNA Codons
Alanine
GCU
GCC
GCA
GCG
Arginine
CGU
CGC
CGA
CGG
AGA
AGG
Asparagine
AAU
AAC
Aspartic acid
GAU
GAC
Cysteine
UGU
UGC
Glutamic acid
GAA
GAG
Glutamine
CAA
CAG
Glycine
GGU
GGC
GGA
GGG
Histidine
CAU
CAC
Isoleucine
AUU
AUC
AUA
Leucine
CUU
CUC
CUA
CUG
UUA
UUG
Lysine
AAA
AAG
Methionine
AUG
Phenylalanine
UUU
UUC
Proline
CCU
CCC
CCA
CCG
Serine
UCU
UCC
UCA
UCG
AGC
AGU
Threonine
ACU
ACC
ACA
ACG
Tryptophan
UGG
Tyrosine
UAU
UAC
Valine
GUU
GUC
GUA
GUG
Start (CI)
AUG
Stop (CT)
UAA
UAG
UGA
