A THOUGHTFUL CONCEPTION
Building Cells
The generalized cell emphasizes aspects of a human
somatic cell important to a discussion of genetics.
The drawing of it does not represent any single cell
type; in fact it is a cartoon. All cells exist in a watery
environment; the cell membrane separates the cell
contents from this environment. Receptors in cell
membranes act as mailboxes for chemical messages
in the environment. The cell contents act as a
chemical factory to perform the specialized functions
of the cell. Energy for the factory is managed by
mitochondria in the cell. Hereditary material for the
cell is mostly on chromosomes in the cell nucleus,
but some is in the mitochondria. Human somatic
Generalized Cell and Sperm Cell.
cells have 23 pairs of chromosomes in each nucleus,
Figure 1
but this illustration has only two pairs: a large and a
small pair. Ordinarily chromosomes cannot be seen with a light microscope, but they can be
seen here. During cell division such as meiosis the chromosomes shorten or condense,
becoming tight, fat structures easily seen with a light microscope (Figure 3). Sperm cells are
among the smallest cells in humans, and each has a long whip-like tail that thrashes to
propel the sperm. The sperm nucleus has one chromosome from each pair of
chromosomes found in somatic cells.
CELL STRUCTURE (See Fig. 1) Cells have a
structure appropriate to their function. Cells come in
many different sizes and shapes, but each cell in an
animal, including all human cells, is contained within a
sac called a cell membrane. The cell membrane is a
chemical structure that actively influences passage of
materials into and out of its cell. Materials entering the
cell may be nutrients, drugs, chemical messages (such
as hormones), toxins, or even complex particles such as
a virus. Materials leaving the cell may be waste
products or chemical messages intended for other cells.
Genes made of DNA (the hereditary material) are found in two places in cells. A few
genes are in the mitochondria (energy producers) but most genes are in the cell nucleus. The
nucleus contains chromosomes, which are DNA complexed with protein. In the nucleus of most
cells are 23 pairs of microscopic chromosomes that make a total of 46 chromosomes. Each
chromosome carries a specific portion of the total genetic material in a cell. For each pair of
chromosomes, one chromosome comes from the mother and one from the father.
CHEMICAL BLUEPRINTS. A cell manufactures all its constituent parts from
chemicals. Proteins are assembled by linking various amino acids into a sequence specific for
each protein. There are two major kinds of protein: structural proteins and enzymes. Structural
proteins exist to ensure that cells accomplish their function, for example, the proteins that cause
muscles to move or to carry oxygen in the blood. Enzymes help catalyze reactions, for example,
converting sugar and fat to energy or linking amino acids into proteins.
Obviously, a pattern or blueprint is needed to manufacture hundreds of identical copies of
any protein. Each copy of a protein must be assembled in the same way, linking together many
different amino acids in the proper sequence. One error in an amino acid can result in a faulty
protein. Since cells make every protein needed, each cell must have a blueprint for the amino
acid sequence of all its proteins. The amino acid sequence for each protein is written in genetic
chemistry.
Each gene is a blueprint for one protein. A blueprint, like written words, is a collection
of symbols. Each gene consists of a sequence of symbols representing the amino acid sequence
of a protein.
In genes, the symbols that give rise to proteins are chemical units called nucleotides or
bases. A string of nucleotides linked together, regardless of the sequence, forms a single strand
of DNA. A single strand is not the same as DNA; DNA is formed of two interconnected parallel
nucleotide strands that match each other in a complementary manner. Parallel nucleotide strands
form a coil, the famous double helix of DNA.
Each chromosome (found in a cell’s nucleus) is
composed of a folded coil of DNA much like a thread in
a ball of yarn. When the DNA thread is pulled from a
chromosome, one sees that the thread filament (called
chromatin) is a double helix wrapped around protein
beads. The double helix, DNA, has cross members
consisting of a pair of nucleotides. The four
nucleotides in DNA are shown in the cartoon as four
interlocking building blocks labeled A, C, G, and T. T
and A link together and C and G link with each other.
A set of three nucleotides (a “triplet”), called a codon,
represents one amino acid in a protein sequence
(see text); note that codons do not overlap.
From Chromosomes to DNA
Figure 2
There are four different nucleotides in DNA (see Fig. 2). Each nucleotide is symbolized
by a letter: A, C, G or T respectively. A sequence of three nucleotides, called a codon, specifies
one amino acid in a protein. For example, the nucleotide sequence GTG specifies the amino acid
valine; GAG, glutamate. So a single nucleotide strand in DNA with GTGGAG would specify
valine and glutamate linked together. A group of DNA codons that “expresses” or “codes for” a
protein is called a gene. It may be helpful to think of DNA nucleotides as letters, triplet codons
as words and genes as sentences. Just as a sentence forms a complete thought, genes specify a
complete protein. The order of the words is important for a sentence to make sense just as the
order of the triplet codes is necessary to make a specific protein. A single strand of DNA may
have thousands of codons forming the genes that code for many proteins. Experts estimate that
the number of genes in the human genome is approximately 25,000.
Although double-stranded DNA is too thin to be seen even with a microscope, its length
is necessarily very long in order to carry all the genetic information contained in a cell. The total
length of DNA contained in each human cell is about 6 feet or 2 meters!
The total DNA in a cell is attached to protein and packaged onto 46 chromosomes.
Double-stranded DNA is coiled, and this coil is then coiled upon itself. These supercoils are
then twisted and twisted again to make a single chromosome. The coiling and twisting at times
can make chromosomes thick enough to be seen with a microscope. Unraveled chromosomes
are called chromatin (see Fig. 3).
Each chromosome has one double-stranded DNA. Each of the two chromosomes in a
pair normally carries the blueprint for identical proteins, but the two blueprints do not necessarily
produce exactly the same proteins. Proteins produced by either blueprint usually have variations
in the amino acid sequence; sometimes these variations have profound effects on the function of
the protein.
A DNA segment within a chromosome serves as the blueprint for a protein. When a cell
must replenish itself with a particular protein, a copy is made of the protein’s DNA segment or
gene. The blueprint travels from the nucleus to the cytoplasm where proteins are synthesized.
HEMOGLOBIN. Let us look at an example of the powerful effect DNA has on the
assembly of one protein, hemoglobin, which carries oxygen to all cells in the body. Hemoglobin
is found in red blood cells. Each hemoglobin is made of four separate globin chains of amino
acids, actually two pairs of chains. In most people, one pair consists of two identical chains,
each with 141 amino acids; these alpha chains are coded on chromosome 16. The second pair
consists of two identical chains each with 146 amino acids; these beta chains are coded on
chromosome 11. Attached to each chain is a complex chemical, called a heme group, which
carries oxygen.
Assembly of hemoglobin, like that of other proteins, is directed by DNA. A specific
DNA sequence codes for each of the amino acids for alpha and beta globin chains. As each
amino acid is linked to the next one in the sequence specified by the gene, the chain of amino
acids forms a coil. Finally, the various chains (e.g., 2 alpha and 2 beta globins) constitute the
finished protein.
Most adults have hemoglobin A. The sequence for all 141 amino acids in alpha globin
and the sequence for all 146 amino acids in beta globin for hemoglobin A are well known.
Variations, however, do occur in the codons. More than 200 variations are known to occur in the
codon for beta globin.
Sometimes changes in proteins have little consequence, while at other times they can
have dramatic consequences. Some people have hemoglobin in which the sixth amino acid in
the beta globin is different from what is found in the majority of people: valine (DNA code
GTG) is substituted for glutamate (DNA code GAG). This causes sickle cell anemia.
Hemoglobin with this change in beta globin is called “S” because its red blood cells take on the
shape of a curved sickle, like the tool for cutting wheat or grass. Unlike deoxygenated
hemoglobin A, deoxygenated hemoglobin S tends to stick together and form fibers that cause red
blood cells to become sickled. These sickled cells are fragile and clog blood vessels, which
results in anemia, jaundice and damage to joints, kidneys and heart. We will talk more about this
condition later.
In contrast to amino acid substitutions that have little or no effect at all on the function of
hemoglobin, substitution of valine for glutamate has a profound effect. Similarly with other
proteins, the substitution or deletion of amino acids may have profound or no effect on the
protein’s actual function.
Many genetic variations occur in humans, yet even with variations people are still human
beings. In human communities, people exchange genes with others continuously through the
process of conception so that the gene pool is consistently and thoroughly mixed. Each person
has similar genes, variations on the same theme.
Now the question is …how does the blueprint for cellular proteins get from parent to
child, how do both parents take part in this? The answer is, of course, sex.