C h a p t e r 5
Genetic Control of Cell Function and Inheritance
89
acid (RNA). These and other current findings have put to
rest the old hypothesis of “one gene–one protein.”
Packaging of DNA
The genome is distributed in chromosomes, discrete
bundles made up of one continuous, linear DNA helix.
Each human somatic cell (cells other than the gam-
etes) has 23 pairs of different chromosomes, with one
chromosome of each pair derived from the individual’s
mother and the other from the father. One of the chro-
mosome pairs consists of the sex chromosomes. Genes
are arranged linearly along each chromosome. When
unraveled, the DNA in the longest chromosome is more
than 7 cm in length. If the DNA of all 46 chromosomes
were placed end to end, the total DNA would span a
distance of about 2 m (more than 6 feet).
Because of their enormous length, the DNA double
helices are tightly coiled in a complex called
chroma-
tin
, which consists of proteins called
histones
along with
other less well-characterized proteins that appear to be
critical for ensuring normal chromosome behavior and
appropriate gene expression. The histones play a criti-
cal role in proper packaging of chromatin. They form
a core around which a segment of DNA double helix
winds, like thread around a spool (Fig. 5-3). About 140
base pairs of DNA are associated with each histone core,
making about two turns around the core. After a short
“spacer” segment of DNA, the next core DNA complex
forms, and so on, giving chromatin the appearance of
beads on a string. Each complex of DNA with a histone
core is called a
nucleosome,
which is the basic structural
unit of chromatin. Each chromosome contains several
hundred to over a million nucleosomes.
Although solving the structural problem of how to
fit a huge amount of DNA into the nucleus, the chro-
matin fiber, when complexed with histones and pack-
aged into various levels of compaction, makes the DNA
inaccessible during the processes of replication and gene
expression. To accommodate these processes, chroma-
tin must be induced to change its structure, a process
called
chromatin remodeling
. Several chemical interac-
tions are now known to affect this process. One of these
involves the acetylation of a histone amino acid group
that is linked to opening of the chromatin fiber and gene
activation. Another important chemical modification
involves the methylation of histone amino acids, which
is correlated with gene inactivation.
Genetic Code
Four bases—guanine, adenine, cytosine, and thymine—
make up the alphabet of the genetic code. A sequence of
three of these bases forms the fundamental triplet code
for one of the 20 amino acids used in protein synthe-
sis in humans. This triplet code is called a
codon
. The
molecular link between the DNA code of genes and the
amino acid sequence of proteins is RNA, a macromol-
ecule similar in structure to DNA, except that uracil
(U) replaces thymine (T) as one of the four bases. An
example is the nucleotide sequence GCU (guanine, cyto-
sine, and uracil), which is an RNA codon for the amino
Semiconservative Model
Conservative Model
original strand of DNA
newly synthesized strand of DNA
FIGURE 5-2.
Semiconservative versus conservative models of
DNA replication as proposed by Meselson and Stahl in 1958.
In semiconservative DNA replication, the two original strands
of DNA unwind and a complementary strand is formed along
each original strand.
Metaphase
chromosome
Linker
DNA
Histone
core
Supercoiled fiber
in chromatin
Nucleosomes
DNA
double
helix
Looped
domains
FIGURE 5-3.
Increasing orders of DNA compaction in
chromatin and mitotic chromosomes. (From Cormack DH.
Essential Histology. Philadelphia, PA: J.B. Lippincott; 1993.)
